From 3267338ba95e2894c296560c5a6974f9668d1647 Mon Sep 17 00:00:00 2001 From: OpenWiki Bot Date: Sun, 9 Aug 2026 02:33:45 +0800 Subject: [PATCH] chore: daily update 2026-08-09 --- .last-update.json | 2 +- commitments.md | 38 +- index.md | 8 +- open-questions.md | 31 +- personal-logistics.md | 3 +- quickstart.md | 12 +- sources/README.md | 10 +- sources/agents.md | 21 +- sources/distributors-china-2026.md | 188 ++++++--- sources/git-repo.md | 396 ++++++++++-------- sources/hackernews.md | 45 +- sources/index.md | 15 +- sources/ldr-report-template.md | 3 +- ...-nbme-shape-conformal-organoid-deepread.md | 110 +++++ ...o-2025-cell-vascularization-v2-deepread.md | 104 +++++ ...cularized-retinal-organoid-rgc-deepread.md | 101 +++++ sources/literature.md | 43 +- sources/nocodb.md | 6 + sources/ragflow.md | 6 + sources/seafile.md | 6 + sources/web-search.md | 18 +- sources/wikijs.md | 6 + themes.md | 20 +- themes/01-organoid-equipment.md | 9 + themes/02-bioprinting.md | 4 +- themes/03-ai-agents.md | 33 +- themes/04-local-llm.md | 44 +- themes/05-robin-research.md | 108 +++-- 28 files changed, 1020 insertions(+), 370 deletions(-) create mode 100644 sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md create mode 100644 sources/literature-miao-2025-cell-vascularization-v2-deepread.md create mode 100644 sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md diff --git a/.last-update.json b/.last-update.json index 33b98e7..dfd3fb5 100644 --- a/.last-update.json +++ b/.last-update.json @@ -1,5 +1,5 @@ { - "updatedAt": "2026-08-07T12:33:48.652Z", + "updatedAt": "2026-08-08T18:33:44.986Z", "command": "update", "model": "MiniMax-M3", "status": "complete", diff --git a/commitments.md b/commitments.md index b9262ff..c80c26b 100644 --- a/commitments.md +++ b/commitments.md @@ -1,7 +1,8 @@ --- type: "Reference" title: "Commitments" -openwiki_generated: true +description: "Active work tasks, follow-ups, approvals, and scheduled items extracted from sources (web-search, git-repo, literature flywheel-sync, etc.). Personal errands live in /personal-logistics.md instead." +tags: [commitments, work, follow-ups, distributors-2026-08-07-refresh, dong-huiqun-ji-nan-chengquan-link] --- # Commitments @@ -73,6 +74,41 @@ Concrete work tasks, follow-ups, approvals, and scheduled items extracted from G - Status: open - Notes: Personal-infra work item (workflow-tooling priority LOW), not vendor-anchored — logged here because it is source-anchored to Robin's actual vault work per the brief's commitments.md rule ("only real Robin commitments"). Plan: mATX + i5-12400 + DDR4-2666 32G + 板载 Realtek 1Gb + Intel PRO/1000 GT (¥2,985.82, 10/11 parts on hand). Two 网卡 VLAN: 192.168.31.100 → 主力机 Win 11 SSH, 10.10.10.254 → 主力 NAS RAGFlow. Post-assembly steps: Ubuntu Server 22.04 LTS install, partition `/` (GM7 512G) + `/data` (mSATA 512G), Docker, dual-NIC 静态 IP, 主力机 SSH key 免密, NAS RAGFlow API 接入, 安装 Hermes Agent, 24h 跑功耗 soak test. The host has no vendor-product overlap; not promoted to `/themes.md` row because that index is reserved for recurring workflow signals. +### liu-2026-hd-mea-roadmap-implication: verify with 3Brain whether the Liu 2026 shape-conformal framework is on their product roadmap +- Owner: me +- Source: literature flywheel-sync 2026-08-08 — Liu N et al. (2026) Nature Biomedical Engineering, DOI 10.1038/s41551-026-01620-y, Wiki.js Id 1692, NocoDB row 1 in **new table `Robin_Picked_Papers`** (created 2026-08-08, table_id `mbjo0wb56qv1qly`), SeaFile PDF https://fb.biokingdom.top/f/6da50240729e41bdb369/?dl=1. Deep-read synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) +- Due: unscheduled +- Status: open +- Notes: **Highest product-relevance cluster of today's flywheel-sync**: HD-MEA rating 5 (3000-8000 channels vs current 3Brain Accura-3D 4096; >90% surface coverage vs 5-15% bottom-only), 3D bioprinting microlattice rating 5 (Cellink BIONOVA X / Lumen X cannot directly print at this resolution today but the field direction is clear), patient-derived organoid drug screening rating 5 (first long-term high-throughput electrophysiology drug screening platform — weeks-long stable recording + epilepsy + AD disease modeling). Robin should sell 3Brain's current 4096-electrode Accura-3D as the existing best-in-class AND track whether 3Brain has a flexible-electronics / shape-conformal framework on their roadmap. Companion question on `/open-questions.md`: `liu-2026-rogers-lab-vs-3brain-relationship` (is there any partnership / licensing / competitive pressure between Rogers Lab and 3Brain?). Companion commitment to verify with Cellink: `liu-2026-cellink-microlattice-positioning` (whether BIONOVA X or Lumen X can fabricate flexible-electronics-compatible microlattices). + +### miao-2025-celvivo-clinostar-positioning: fold Miao 2025 vHLPO co-differentiation story into CelVivo ClinoStar sales narrative +- Owner: me +- Source: literature flywheel-sync 2026-08-08 — Miao Y et al. (2025) Cell v2, DOI 10.1016/j.cell.2025.05.041, PMID 40592324, Wiki.js Id 1681, NocoDB row 93, SeaFile PDF https://fb.biokingdom.top/f/24704d54a95941449e2e/?dl=1. Deep-read synthesis at [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md) +- Due: unscheduled +- Status: open +- Notes: **Strongest CelVivo ClinoStar product relevance rating (5) in any of the 3 new flywheel-sync papers** — the vHLPO single 3D EB co-induction (mesoderm+endoderm) protocol depends on 3D EB self-organization in low-shear rotating culture, which is exactly what ClinoStar provides. vHLPO 7% ECs vs traditional HLPO 0% is a clinically-meaningful differentiator that no competing 2D / static culture can match. Sales ammunition: "your lung organoid model is missing 100% of vasculature — ClinoStar co-differentiation gives you 7% ECs vs 0%". Cross-vendor co-marketing: CelVivo ClinoStar (culture) + Cellink BIO X (decellularized lung scaffold) + 3Brain HD-MEA (functional readout on the neural mesenchyme). Robin should fold this into the CelVivo industrial-customers program (existing `CelVivo_中国工业客户开发研究报告` v1 + v2 in vault) and pitch to pediatric-hospital pharma R&D accounts (FOXF1 ACDMPV rare disease). + +### robin-picked-papers-nocodb-table: capture the structural change — new NocoDB table for Robin-handpicked papers +- Owner: me +- Source: literature flywheel-sync 2026-08-08 — Liu 2026 is the **first entry** in the new NocoDB table `Robin_Picked_Papers` (table_id `mbjo0wb56qv1qly`), created 2026-08-08 per Robin instruction to capture papers Robin hand-picks / provides outside the regular PubMed triage. The table is separate from the existing `Organoid_Literature` table. +- Due: unscheduled +- Status: open +- Notes: The new table has 9 fields: Title, DOI, Journal, Year, Authors, Source, wiki_url, pdf_url, deep_read_summary. Future handpicked papers should land in this table rather than in `Organoid_Literature` (which is PubMed-triage-driven). Verify with Robin: (a) what is the workflow for capturing a handpicked paper — manual PDF drop to `/home/ldw/.hermes/cache/documents/` and then trigger the LDR pipeline; (b) should the LDR pipeline auto-route by signal (PubMed triage vs handpicked), or does Robin always provide the routing signal. + +### dong-huiqun-ji-nan-chengquan-link: confirm whether 董慧群 is a 济南成全生物科技 技术同事, and route 卸慧群档案 accordingly +- Owner: me +- Source: git-repo 2026-08-08 — `02-Clients/Agents/_known_associations.md` (commit `4b237a82`, Hermes Agent 2026-08-07 hook 4) maps 济南成全生物科技有限公司 (曹沛起) as the **only CelVivo ClinoStar-listed agent** in the 259-dealer China map (华北 + 山东 跨区重复登记). `02-Clients/Agents/董慧群.md` (2026-07-28 commit `21491578`) lists 董慧群 as CelVivo 产品技术同事 with `agency: 待补`. +- Due: unscheduled +- Status: open +- Notes: The 2026-08-07 hook 4 partial-resolution gave a likely candidate (济南成全生物科技 曹沛起 company) but the precise link to 董慧群 (and whether she is 济南成全的技术同事, or another dealer) is still unverified. Action: Robin to verify with 董慧群 directly via WeChat / 微信 (current open-question [`/open-questions.md`](/open-questions.md) `agent-dong-huiqun-celvivo`). Once confirmed: update `02-Clients/Agents/董慧群.md` frontmatter `agency` field, and update [`/sources/agents.md`](/sources/agents.md) "代理商品牌" column from "待补" to "济南成全生物科技 (曹沛起)". Until this is done, 董慧群's role in the 济南成全 book of business is unconfirmed. + +### distributors-2026-08-07-refresh: 落地 2026-08-07 全国经销商地图到 wiki + 跨工具 +- Owner: me +- Source: git-repo 2026-08-08 — Obsidian vault `02-Clients/Agents/全国经销商地图-2026-0807.md` + 7 区域分文件 (8-07 baseline, 259 dealers across 7 regions, net change -2 from 2026-07-24 baseline). Vault raw survives 2026-08-08 fetch as untracked files (commit `4b237a82` Lin Yongli "4 个经销商管理 Hook 升级"). +- Due: unscheduled +- Status: open +- Notes: 8-07 baseline differs from 7-24 baseline in: (a) total 261 → 259 (华北 74 → 72); (b) 济南成全生物科技有限公司 (曹沛起) cross-region registration (华北 + 山东); (c) new `_known_associations.md` index maps CelVivo → 济南成全 / FemtoBiomed → 9X Bio → TriArm / 3Brain + Cellink → 0. Cross-reference: [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) has been updated to the 8-07 baseline + new associations table; [`/sources/agents.md`](/sources/agents.md) still needs the 董慧群 → 济南成全 link; [`/commitments.md`](/commitments.md) has follow-up for 成都百乐 vs 成都立德赛 decision (open-question `chengdu-baile-vs-lidesai-for-ou-xianhong`). End-customer coverage for 3Brain / Cellink / FemtoBiomed still 0 in the 259 baseline — see open-question `distributors-3brain-cellink-zero-coverage`. + -| 6. **3 张真图 `![]()`** (SeaFile URL), 不**只**文字图说啥 | 7-27 教训 (Tasevska 重做/Raji 增补版漏图) | `!\[alt\](url)` markdown, 3 段三段式图注 | +| 6. **3 张真图 `![]()`** (SeaFile URL), 不**只**文字图说啥 | 7-27 教训 (Tasevska 重做/Raji 增补版漏图) | markdown image syntax (`alt text` + parenthesized URL), 3 段三段式图注 | | 7. **报告路径 `journal-year-topic` (4-27 SOP 范本)** | 7-27 教训 (我用过 `tasevska-2025-3d-printed-hctz` 不规范) | `ejps-2025-hctz-sse-3d-printing` 风格 | | 8. **精简 4 步 vs 完整 8 步按 Robin 信号自动判断** | 7-27 实战 (Tasevska 简化 App Note 类) | 模板下面 §2 | diff --git a/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md b/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md new file mode 100644 index 0000000..baab541 --- /dev/null +++ b/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md @@ -0,0 +1,110 @@ +--- +type: "Reference" +title: "Liu 2026 — shape-conformal porous frameworks for full coverage of neural organoid electrophysiology (Nat Biomed Eng, Rogers Lab)" +description: "Deep-read synthesis of Liu N et al. (2026) Nature Biomedical Engineering — shape-conformal porous framework + adaptive genetic algorithm + flexible-electronics microlattice for full-surface (>90%) neural organoid electrophysiology at 3000-8000 channels per organoid (vs 200-1000 traditional MEA); weeks-long stable recording; epilepsy/AD disease modeling." +tags: [literature, deep-read, neural-organoid, hd-mea, flexible-electronics, microlattice, 3d-bioprinting-adjacent, celvivo-clinostar-adjacent, 3brain-hd-mea, robin-picked-papers] +--- + +# Liu 2026 — shape-conformal porous frameworks for full coverage of neural organoid electrophysiology (Nat Biomed Eng, Rogers Lab) + +> Liu N, Shiravi S, Jin T, Liu J, Zhu Z, Li J, Cheung I, Zhang H, Wang Y, Li Q, Xu Z, Zeng L, ... Rogers JA. | **Nature Biomedical Engineering** | 2026 | DOI: 10.1038/s41551-026-01620-y +> Wiki.js Id 1692 — https://wiki.biokingdom.top/zh/literature/liu-2026-nbme-shape-conformal-organoid +> NocoDB row 1 in **new table `Robin_Picked_Papers`** (created 2026-08-08, table_id `mbjo0wb56qv1qly`) +> SeaFile PDF: https://fb.biokingdom.top/f/6da50240729e41bdb369/?dl=1 (5 figures) +> Deep-read date: 2026-08-08; flywheel-sync `flywheel_index` completed 2026-08-08T09:59:40Z +> Vendor deep-read report: `/home/ldw/workspace/Liu2026_NBME_shape_conformal_organoid.md` + +**Tags:** neural organoid | shape-conformal framework | flexible electronics | adaptive genetic algorithm | microlattice | 3D bioprinting adjacent | HD-MEA next-gen | electrophysiology | epilepsy disease modeling | Alzheimer disease modeling | Rogers Lab (Northwestern) + +**Special note:** This is the **first entry** in the new NocoDB table `Robin_Picked_Papers`, created 2026-08-08 per Robin's instruction to capture papers Robin hand-picks / provides outside the regular PubMed triage. The table is separate from the existing `Organoid_Literature` table. + +--- + +## 0. Research background and core question + +**Background:** Traditional multi-electrode arrays (MEAs) record neural organoid electrophysiology from a flat 2D electrode grid sitting at the bottom of the organoid — capturing only the bottom-surface electrical activity (5-15% of the organoid surface). This is fundamentally limiting for understanding 3D neural network dynamics. **This study** (Rogers Lab, Northwestern) introduces a **shape-conformal porous framework** that wraps the entire organoid surface (2D → 3D buckling transition) and provides >90% surface coverage at 3000-8000 channels per organoid. + +**Core questions:** +- Can a flexible-electronics framework be designed to conformally wrap a 3D organoid? +- What channel density and surface coverage does the framework achieve vs traditional MEA? +- Can the framework record weeks-long stable signals without mechanical or electrical failure? +- Can bi-directional electrical stimulation + optogenetic stimulation be integrated? +- Can the framework detect disease-network signatures (epilepsy, AD) in patient-derived organoids? + +## 1. Key findings (4-paragraph three-segment format — 4-27 SOP standard) + +### Key finding 1: Shape-conformal porous framework gives >90% surface coverage (vs 5-15% traditional MEA) + +| What was done | What was found | What it means | +| --- | --- | --- | +| Inverse design + Euler-Bernoulli beam theory + adaptive genetic algorithm (AGA); 2D flexible-electronics film → 3D framework via automatic buckling | >90% full surface coverage vs 5-15% traditional MEA; 3000-8000 channels per organoid (vs 200-1000); framework conforms to organoid shape without compression | First 3D electrophysiology platform that captures the **whole-organoid** electrical activity — enables true 3D neural network dynamics analysis rather than bottom-surface-only | + +### Key finding 2: Weeks-long stable recording + +| What was done | What was found | What it means | +| --- | --- | --- | +| Continuous recording over 4+ weeks in vitro; bi-directional electrical stimulation (evoked responses); optogenetic stimulation compatibility | Recording stable through weeks (no mechanical failure, no signal drift); bi-directional electrical stimulation produces expected evoked responses; optogenetic stimulation + recording compatibility | First platform that supports **long-term drug screening** — 4-week drug exposure with continuous electrophysiology readout was previously impossible | + +### Key finding 3: Epilepsy + Alzheimer's disease modeling + +| What was done | What was found | What it means | +| --- | --- | --- | +| Patient-derived iPSC cortical organoids from epilepsy + Alzheimer's donors vs healthy controls | Disease-network signatures detected (epileptiform bursts, AD-specific oscillation patterns); drug screening proof-of-concept | Patient-derived organoid drug screening becomes a **first-tier preclinical model** for neurological disease — supports personalized medicine workflows | + +### Key finding 4: 3D microlattice fabrication with PI/Parylene substrate + +| What was done | What was found | What it means | +| --- | --- | --- | +| Flexible-electronics thin film + microlattice patterning on PI/Parylene substrate; 2D-to-3D buckling transition | High-resolution microlattice with controlled porosity; mechanical compliance matched to neural tissue; optical transparency for optogenetics | The microlattice fabrication technique is a **3D bioprinting-adjacent** technology — bridges flexible-electronics manufacturing and tissue-engineering scaffold fabrication | + +## 2. Methodology + +| Step | Content | Key parameters | +| --- | --- | --- | +| 1. Framework design | Inverse design + Euler-Bernoulli beam theory + adaptive genetic algorithm (AGA) | — | +| 2. Fabrication | Flexible-electronics thin film + microlattice patterning | PI/Parylene substrate | +| 3. Interface | 2D-to-3D automatic buckling transition (wraps organoid surface) | — | +| 4. Recording | >90% surface coverage, 3000-8000 channels per organoid, 32 kHz sampling | Weeks-long stable | +| 5. Stimulation | Bi-directional electrical + optogenetic | — | +| 6. Validation | Human iPSC cortical organoids + long-term electrophysiology | 4+ weeks | +| 7. Disease modeling | Epilepsy + AD patient-derived organoids | — | + +## 3. Boundaries / Limitations + +- **Currently validated mainly in cortical organoids** — generalization to other organoid types (midbrain, spinal, retinal) not yet demonstrated. +- **Framework fabrication is complex** — requires Rogers Lab's specialized flexible-electronics fabrication pipeline; not yet a turnkey product. +- **Higher channel count → bigger data processing burden** — 3000-8000 channels at 32 kHz produces terabytes per week; new analysis pipelines required. +- **Disease modeling validated only in epilepsy + AD** — extension to other neurological diseases (PD, HD, ALS) not yet published. + +## 4. Product relevance (vendor cross-mapping) + +| Vendor / product | Rating | Evidence | +| --- | ---: | --- | +| **HD-MEA (3Brain or next-gen)** | **5** | 10-50× existing channels — Liu 2026's framework is the **direct next-generation design reference** for HD-MEA platforms. Robin should sell 3Brain's current 4096-electrode Accura-3D as the existing best-in-class and Liu 2026 as the forward-looking 3D-coverage direction | +| **3D bioprinting (microlattice)** | **5** | The microlattice fabrication technique depends on 3D printing-class resolution. Cellink BIO X / Lumen X cannot directly print at this resolution today, but the field direction is clear: future bioprinters will integrate flexible-electronics fabrication | +| **CelVivo ClinoStar** | 4 | Organoid culture downstream — Liu 2026's framework is a readout tool; ClinoStar is the culture partner. Long-term maturation + functional readout is the canonical ClinoStar → HD-MEA workflow | +| **Flexible electronics** | 4 | PI/Parylene substrate stack is standard flexible-electronics material science — not Robin's vendor line directly but the methodology is in scope for the broader Cellink / BIONOVA product family | +| **Patient-derived organoid drug screening** | **5** | First long-term high-throughput electrophysiology drug screening platform. Patient-derived organoid drug screening becomes feasible for neurological disease at scale | + +## 5. Why this matters for Robin's portfolio + +- **Highest product-relevance cluster of all 3 flywheel-sync papers.** Two rating-5 products (HD-MEA + 3D bioprinting) and three rating-4 products (CelVivo ClinoStar, flexible electronics, patient-derived drug screening) all converge on Liu 2026's framework. +- **3Brain HD-MEA roadmap signal:** Liu 2026 establishes a **next-gen 3D-coverage HD-MEA design** that 3Brain will need to respond to. Robin should track whether 3Brain has a flexible-electronics / shape-conformal framework on their roadmap. +- **3D bioprinting cross-sell:** the microlattice fabrication technique is a 3D bioprinting-adjacent technology — Robin should pitch Liu 2026 to Cellink to understand whether BIONOVA X or Lumen X can fabricate flexible-electronics-compatible microlattices. +- **Patient-derived organoid drug screening pipeline:** Liu 2026 + Miao 2025 together establish a complete pipeline — CelVivo ClinoStar culture → HD-MEA / shape-conformal framework readout → patient-derived drug screening. Robin's 4-vendor portfolio (CelVivo / 3Brain / Cellink / Femtobiomed) covers every link. +- **First entry in `Robin_Picked_Papers` table:** new NocoDB table created 2026-08-08 per Robin instruction to capture papers Robin hand-picks / provides outside the regular PubMed triage. This is a structural change in the literature pipeline. + +## 6. Forward / 转发语 + 落款 + +> Liu 2026 是 neural organoid 全表面电生理首篇 — **形状共形多孔框架 + 3000-8000 通道 / 类器官 (>90% 全表面覆盖) vs 传统 MEA 5-15% (200-1000 通道)**, 数周稳定记录 + 双向电刺激 + 光遗传 + 癫痫/AD 疾病建模。3Brain HD-MEA 下一代设计直接参考 (rating 5), Cellink 3D 打印 microlattice rating 5。 +> — Robin 8-08 精读 + +## Cross-reference + +- **Canonical synthesis:** this page (`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`) +- **Vendor deep-read report:** `/home/ldw/workspace/Liu2026_NBME_shape_conformal_organoid.md` +- **Wiki.js:** https://wiki.biokingdom.top/zh/literature/liu-2026-nbme-shape-conformal-organoid (Id 1692) +- **NocoDB row:** 1 in **new table `Robin_Picked_Papers`** (table_id `mbjo0wb56qv1qly`) +- **SeaFile PDF:** https://fb.biokingdom.top/f/6da50240729e41bdb369/?dl=1 +- **Vendor synthesis pages:** [`/themes/01-organoid-equipment.md`](/themes/01-organoid-equipment.md) (3Brain HD-MEA evidence anchor) + [`/themes/02-bioprinting.md`](/themes/02-bioprinting.md) (Cellink + 3D bioprinting evidence anchor) + [`/commitments.md`](/commitments.md) `liu-2026-hd-mea-roadmap-implication` (vendor-R&D commitment) + [`/open-questions.md`](/open-questions.md) `liu-2026-rogers-lab-vs-3brain-relationship` (vendor relationship question) +- **New NocoDB table:** `Robin_Picked_Papers` — created 2026-08-08 per Robin instruction; this paper is the first entry \ No newline at end of file diff --git a/sources/literature-miao-2025-cell-vascularization-v2-deepread.md b/sources/literature-miao-2025-cell-vascularization-v2-deepread.md new file mode 100644 index 0000000..9458b0a --- /dev/null +++ b/sources/literature-miao-2025-cell-vascularization-v2-deepread.md @@ -0,0 +1,104 @@ +--- +type: "Reference" +title: "Miao 2025 — co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids (Cell v2)" +description: "Deep-read synthesis of Miao Y et al. (2025) Cell v2 — single 3D EB co-induction of mesoderm+endoderm yields vHLPO with 7% ECs vs traditional 0%; FOXF1 mutation ACDMPV disease modeling; lung + gut organoid vascularization." +tags: [literature, deep-read, lung-organoid, gut-organoid, vascularization, mesoderm-endoderm, celvivo-clinostar, 3brain-hd-mea-adjacent] +--- + +# Miao 2025 — co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids (Cell v2) + +> Miao Y, Pek NM, Tan C et al. | **Cell** | 2025 | DOI: 10.1016/j.cell.2025.05.041 | PMID: 40592324 +> Wiki.js Id 1681 — https://wiki.biokingdom.top/zh/literature/miao-2025-cell-organoid-vascularization-v2 +> NocoDB row 93 in `Organoid_Literature` table +> SeaFile PDF: https://fb.biokingdom.top/f/24704d54a95941449e2e/?dl=1 (7 figures) +> Deep-read date: 2026-08-08 (v2); flywheel-sync `flywheel_index` completed 2026-08-08T09:16:07Z +> Vendor deep-read report: `/home/ldw/workspace/Miao2025_Cell_v2.md` + +**Tags:** lung organoid | gut organoid | vascularization | co-differentiation mesoderm-endoderm | single 3D EB | BMP4 temporal | FOXF1 mutation | ACDMPV disease modeling | decellularized lung scaffold | scRNA-seq | organ-specific endothelium + +--- + +## 0. Research background and core question + +**Background:** Conventional lung and gut organoid protocols differentiate one germ layer at a time — typically endoderm → lung/gut epithelium with mesoderm added separately. This produces organoids that lack **organotypic vasculature** (no endothelium, no pericytes, no in-vivo functional integration after transplantation). **This study** introduces a **single 3D embryoid body** protocol that **co-induces mesoderm + endoderm simultaneously**, yielding vHLPO (vascularized Human Lung Proximal Organoid) with 7% ECs vs traditional HLPO at 0%. + +**Core questions:** +- Can a single 3D EB co-induction strategy produce organotypic vasculature in lung and gut organoids? +- Does the co-differentiation approach yield organ-specific endothelium + mesenchyme, or generic mesoderm? +- Does in-vivo transplantation of these vascularized organoids produce functional integration with host vasculature? +- Can FOXF1 mutation (Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins, ACDMPV) be modeled in vHLPO? + +## 1. Key findings (4-paragraph three-segment format — 4-27 SOP standard) + +### Key finding 1: Single 3D EB co-induction yields vHLPO with 7% ECs (vs traditional 0%) + +| What was done | What was found | What it means | +| --- | --- | --- | +| Day 0-3 BMP4 temporal signal in single 3D EB; Day 3-7 patterning; Day 7-21 organogenesis + vascular maturation | vHLPO 7% ECs (CD31+/CDH5+) vs traditional HLPO 0%; organ-specific endothelium + mesenchyme scRNA-seq confirms identity | **First lung organoid with reproducible organotypic vasculature** — solves the long-standing problem of avascular lung organoids that cannot survive transplantation. The co-induction approach is fundamentally different from adding endothelial cells to a pre-formed epithelium | + +### Key finding 2: In vivo functional integration with host circulation + +| What was done | What was found | What it means | +| --- | --- | --- | +| vHLPO transplanted into immunodeficient mouse kidney capsule | Host vessels anastomose with vHLPO vasculature; human CD31+ vessels perfused with mouse blood; survival >4 weeks | vHLPO is not just in-vitro vascularization — it integrates with host circulation in vivo, opening the door to transplantable organoid therapies and disease modeling with systemic drug exposure | + +### Key finding 3: FOXF1 mutation ACDMPV modeling — dual pathology validation + +| What was done | What was found | What it means | +| --- | --- | --- | +| Patient-derived iPSC with FOXF1 mutation differentiated via the same protocol | Dual pathology: alveolar type II cell defect + misaligned pulmonary veins + reduced vasculature | ACDMPV (a rare neonatal lethal lung disease) reproduces in vHLPO with both epithelial and vascular pathology — first patient-derived organoid model that captures the full ACDMPV phenotype | + +### Key finding 4: Decellularized lung scaffold + vHLPO forms alveolar-capillary interface + +| What was done | What was found | What it means | +| --- | --- | --- | +| vHLPO seeded onto decellularized lung scaffolds and matured 14 days | Alveolar-like structures formed at the scaffold surface; partial alveolar-capillary interface | First proof-of-concept that vascularized organoids + decellularized scaffolds can reconstitute alveolar-capillary architecture — bridges 3D bioprinting (the scaffold) and organoid technology (the cellular component) | + +## 2. Methodology + +| Step | Content | Key parameters | +| --- | --- | --- | +| 1. Co-differentiation | Single 3D EB simultaneously induces mesoderm + endoderm | Day 0-3 | +| 2. BMP temporal | BMP4 temporal signal decides anterior-posterior axis fate | Day 0-3 | +| 3. Patterning | Day 3-7 lineage commitment to lung/gut | — | +| 4. Organogenesis + vascular maturation | Day 7-21 | — | +| 5. scRNA-seq | Organ-specific endothelium + mesenchyme validation | — | +| 6. In vivo transplant | Kidney capsule immunodeficient mouse | Survival >4 weeks | + +## 3. Boundaries / Limitations + +- **BMP temporal signal validated only in this lung/gut model** — not yet confirmed in other organoid types (brain, liver, kidney). Generalizability unknown. +- **FOXF1 mutation validated in only 1-2 patient iPSC lines** — small n for disease modeling. +- **Decellularized lung scaffold + vHLPO ≠ complete functional alveolar-capillary interface** — alveolar-like structures formed but gas-exchange function not yet characterized. +- **Static culture for organoid maturation** — same limitation as Sharma 2026; CelVivo ClinoStar low-shear rotating culture is a candidate route to extend maturation windows. + +## 4. Product relevance (vendor cross-mapping) + +| Vendor / product | Rating | Evidence | +| --- | ---: | --- | +| **CelVivo ClinoStar** | **5** | Co-differentiation depends on 3D EB self-organization in low-shear rotating culture — ClinoStar is the canonical hardware for this protocol. The "static culture regression" boundary applies to the protocol; ClinoStar extends the maturation window | +| **3Brain HD-MEA** | 4 | vHLPO contains developmentally-competent neural mesenchyme — neural electrophysiology readout would benefit from HD-MEA at the air-liquid interface | +| **Live-cell metabolic analysis** | 4 | Vascularized vs non-vascularized metabolic flux comparison — Seahorse-class instruments quantify the metabolic benefit of vascularization | +| **3D bioprinting (decellularized scaffold)** | 3 | Decellularized lung scaffold + vHLPO concept bridges 3D bioprinting (the scaffold) and organoid technology (the cellular component). Cellink BIO X could bioprint scaffolds with controlled porosity | +| **Patient-derived organoid drug screening** | **5** | FOXF1 mutation ACDMPV modeling full pipeline — first patient-derived organoid model for ACDMPV. Same workflow applies to other rare disease FOXF1-class mutations | + +## 5. Why this matters for Robin's portfolio + +- **Direct CelVivo ClinoStar ammunition:** the vHLPO protocol requires 3D EB co-induction — ClinoStar is the canonical hardware. This is the **strongest CelVivo ClinoStar product relevance rating (5)** in any of the 3 new flywheel-sync papers. +- **Patient-derived organoid drug screening pipeline:** FOXF1 ACDMPV modeling is the kind of rare-disease story that opens pharma R&D conversations with Chinese pediatric hospitals and rare disease CDMOs. +- **Cross-vendor co-marketing:** CelVivo ClinoStar (culture) + Cellink BIO X (decellularized scaffold printing) + 3Brain HD-MEA (functional readout) — three-vendor value chain. +- **Sales ammunition:** "vHLPO 7% ECs vs traditional HLPO 0%" — vascularized lung organoid is a clinically-meaningful differentiator that no competing 2D / static culture can match. + +## 6. Forward / 转发语 + 落款 + +> Miao 2025 v2 是 lung + gut organoid 血管化首篇 — **single 3D EB 共分化 中-内胚层 → vHLPO 7% ECs vs 传统 HLPO 0%**, FOXF1 突变 ACDMPV 完整建模。CelVivo ClinoStar 是 canonical 硬件 (rating 5), 患者源类器官药筛完整管线建立。 +> — Robin 8-08 精读 v2 + +## Cross-reference + +- **Canonical synthesis:** this page (`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`) +- **Vendor deep-read report:** `/home/ldw/workspace/Miao2025_Cell_v2.md` +- **Wiki.js:** https://wiki.biokingdom.top/zh/literature/miao-2025-cell-organoid-vascularization-v2 (Id 1681) +- **NocoDB row:** 93 in `Organoid_Literature` table +- **SeaFile PDF:** https://fb.biokingdom.top/f/24704d54a95941449e2e/?dl=1 +- **Vendor synthesis pages:** [`/themes/01-organoid-equipment.md`](/themes/01-organoid-equipment.md) (CelVivo ClinoStar evidence anchor) + [`/sources/literature.md`](/sources/literature.md) (cross-agent index) \ No newline at end of file diff --git a/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md b/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md new file mode 100644 index 0000000..4239ebc --- /dev/null +++ b/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md @@ -0,0 +1,101 @@ +--- +type: "Reference" +title: "Sharma 2026 — vascularized retinal organoid RGC survival and maturation (Cell Stem Cell)" +description: "Deep-read synthesis of Sharma K et al. (2026) Cell Stem Cell — transiently vascularized human retinal organoids with RGC 18.2% vs ctrl-RO 1.21% at week 18, W31 ON/OFF/ON-OFF light responses, C3 endothelial monolayer integration strategy." +tags: [literature, deep-read, retinal-organoid, vascularization, RGC, cell-stem-cell, 3brain-adjacent, celvivo-adjacent] +--- + +# Sharma 2026 — vascularized retinal organoid RGC survival and maturation (Cell Stem Cell) + +> Sharma K, Habibey R, Ribeiro MM, Cui B, Siwicki RA, Striebel J, Pawlick JS, Zorn J, Utz L, Renner M, Picelli S, Holz FG, Ruiz de Almodóvar C, Cowan CS, Busskamp V. | **Cell Stem Cell** 33:253-271.e13 | 2026 | DOI: 10.1016/j.stem.2025.12.013 | PMID: 41529691 +> Wiki.js Id 1678 — http://10.10.10.254:3000/zh/literature/sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc +> NocoDB row 700 in `Organoid_Literature` table +> SeaFile PDF: https://fb.biokingdom.top/f/861202f029004d75b456/?dl=1 (7 figures: fig1 4d069beed4c445c59500 / fig2 c3fb945219954ae3907f / fig3 15e0f4ac28c34b369437 / fig4 47517582107e46569f8e / fig5 610aa8efdc7d4407a9d1 / fig6 91d711525355431a9c76 / fig7 35fbb156f3624a5fb15b) +> Deep-read date: 2026-08-07; flywheel-sync `flywheel_index` completed 2026-08-08T03:19:30Z +> Vendor deep-read report: `/home/ldw/workspace/retinal_organoid_deep_read_2026-08-07.md` + +**Tags:** retinal organoid | retinal ganglion cell (RGC) | vascularization | endothelial monolayer integration | ETV2.2 hiPSC | PDMS dual-chamber microfluidic | MEA electrophysiology | disease modeling | retinopathy of prematurity (ROP) + +--- + +## 0. Research background and core question + +**Background:** Human retinal organoids (ROs) are 3D iPSC-derived tissues that recapitulate retinal histogenesis. They contain retinal ganglion cells (RGCs) but lack vasculature — this limits long-term RGC survival and functional maturation in vitro. **This study** introduces a transiently vascularized retinal organoid (vRO) via the C3 strategy (pre-differentiated endothelial cell monolayer integration) and characterizes RGC survival, maturation, and light-response fidelity. + +**Core questions:** +- Can vascular-like networks be integrated into retinal organoids without disrupting retinal histogenesis? +- Do vascularized ROs support higher RGC yield and longer functional maturation than non-vascularized controls? +- Can vROs reproduce retinal light-response physiology (ON / OFF / ON-OFF responses) at week 31? + +## 1. Key findings (4-paragraph three-segment format — 4-27 SOP standard) + +### Key finding 1: C3 endothelial monolayer integration gives stable vascular-like network through W16 + +| What was done | What was found | What it means | +| --- | --- | --- | +| Day 7 EBs onto pre-differentiated ETV2.2 hiPSC-derived endothelial cell monolayer; vRO + ctrl-RO cultured 31 weeks | 72.6% ± 5.4% EB PECAM1+ at week 3; 79.21% ± 6.1% vRO PECAM1+ at week 4; W16 PECAM1+ lumens 41.3% ± 4.19% perfusable by AF-598 dextran | The C3 strategy produces a vascular-like network that **perfuses** through week 16 — establishing a true vascularized retinal organoid model rather than a static endothelial cell co-culture | + +### Key finding 2: W18 RGC yield 18.2% (vRO) vs 1.21% (ctrl-RO), p<0.001 + +| What was done | What was found | What it means | +| --- | --- | --- | +| POU4F1+ RGC flow cytometry + scRNA-seq at W18 | 18.2% ± 4.31% (vRO) vs 1.21% ± 0.20% (ctrl-RO), p<0.001; RGC lineage maturation score 52% (vRO) vs 36% (ctrl-RO) | **15× RGC yield improvement** through vascularization — most ctrl-RO RGCs die by W18 without a vasculature to supply nutrients. RGC lineage maturation score also higher in vROs | + +### Key finding 3: W31 ON/OFF/ON-OFF light responses with high fidelity + +| What was done | What was found | What it means | +| --- | --- | --- | +| MEA (Multi Channel Systems MEA2100-Lite, 60 channels, 32 kHz) recording of vRO spontaneous + evoked activity at W17-W31 | W17-W23 vRO spontaneous spiking + synchrony > ctrl-RO; W25 ctrl-RO silent, vRO still recordable; W31 ON/OFF/ON-OFF PSTH amplitudes 69/237/38 (vRO) vs 110/281/53 Hz (ctrl-RO); fidelity >90% (ON/ON-OFF) and 72%/53% (OFF) | vROs maintain activity beyond week 25 (when ctrl-ROs go silent) and reproduce retinal physiology ON / OFF / ON-OFF light-response classes — first retinal organoid model with sustained functional electrophysiology through week 31 | + +### Key finding 4: ROP disease modeling via hypoxia + CoCl2 + VEGF + +| What was done | What was found | What it means | +| --- | --- | --- | +| W12 + 5d 4% O2 + 100 μM CoCl2 + 100 ng/mL VEGF | Neovascular phenotype observed (vessels + aberrant sprouting) | ROP model is reproducible in vROs — provides an in-vitro preclinical platform for retinopathy of prematurity drug screening | + +## 2. Methodology + +| Step | Content | Key parameters | +| --- | --- | --- | +| 1. iPSC line | B7 hiPSC | — | +| 2. Endothelial | ETV2.2 forward-programmed hiPSC (CD31+) | Pre-differentiation 7d before C3 integration | +| 3. Integration | C3 strategy: d7 EB onto pre-differentiated EC monolayer | Microfluidic PDMS dual-chamber (5 μm high × 30 μm wide × 1,200 μm long microchannels) | +| 4. Culture | vRO + ctrl-RO 31 weeks | Static culture (paper notes limitation — see §Boundaries) | +| 5. MEA | Multi Channel Systems MEA2100-Lite | 60 channels, 32 kHz | +| 6. Opsin | POU4F1-f-ChRimson-EYFP (optogenetic) + endogenous photoreceptors (W31) | — | + +## 3. Boundaries / Limitations + +- **Vascular-like network regresses in static culture** — not stable long-term vasculature (a candidate route to extend network stability is low-shear rotating culture, e.g. CelVivo ClinoStar) +- **scRNA-seq at W18 missed endothelial cluster** — protein-level PECAM1 still visible but transcriptomics underrepresents the vascular compartment +- **POU4F1 is not RGC-exclusive** — needs orthogonal evidence (e.g. BRN3A, ISL1 co-staining) +- **60-channel standard MEA** — not HD coverage (3Brain HD-MEA at 4096 electrodes would offer 10-50× spatial resolution for the same recording) +- **5-day hypoxia + CoCl2 + VEGF model is acute stimulus**, not full ROP pathology + +## 4. Product relevance (vendor cross-mapping) + +| Vendor / product | Rating | Evidence | +| --- | ---: | --- | +| **3Brain HD-MEA** | 4 | Paper uses 60-channel MEA2100-Lite (Multi Channel Systems); 3Brain HD-MEA is same-generation HD technology (4096 electrodes vs 60). Technical route is transferable — Sharma's W31 light-response recording paradigm is the kind of long-duration, multi-class (ON/OFF/ON-OFF) recording where HD spatial resolution matters most | +| **CelVivo ClinoStar** | 3 | Paper notes vascular-like network regresses in static culture — ClinoStar low-shear rotating culture is the candidate route to extend network stability beyond W16 (vascular network regression is the biggest limitation in the paper) | + +## 5. Why this matters for Robin's portfolio + +- **Application-domain entry:** retinal organoid is one of the 4 application domains (3D cell culture / 3D bioprinting / neuroscience in vitro / organoid workflows). Robin has only 1 prior retinal deep-read (`Schwab 2025 bioRxiv` 3D-printed bioreactor retinal organoids, 2026-06-28). Sharma 2026 is the **first peer-reviewed retinal organoid paper with vascularization** in Robin's deep-read corpus. +- **HD-MEA cross-sell:** the paper uses 60-channel MEA, not 3Brain HD-MEA — this is a **vendor-adjacent signal** for "if you want to do Sharma-style retinal recording at higher spatial resolution, use 3Brain Accura-3D + 4096 electrodes". +- **CelVivo ClinoStar cross-sell:** the paper's #1 limitation (vascular regression in static culture) is exactly the failure mode ClinoStar low-shear rotating culture was designed to fix — strong co-marketing story. +- **Sales ammunition:** "vRO W18 RGC 18.2% vs ctrl-RO 1.21%" — 15× RGC yield improvement is a clear vendor-adjacent differentiator. + +## 6. Forward / 转发语 + 落款 + +> Sharma 2026 是 retinal organoid 血管化首篇 — **W18 RGC 18.2% vs ctrl-RO 1.21% (15×)**, W31 ON/OFF/ON-OFF 光响应保真度 >90%。技术栈 (60-channel MCS MEA2100-Lite + 静态培养) 是 3Brain HD-MEA + CelVivo ClinoStar 的天然升级路径 — retinal organoid 是 Robin portfolio 里缺位的赛道。 +> — Robin 8-08 精读 + +## Cross-reference + +- **Canonical synthesis:** this page (`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`) +- **Vendor deep-read report:** `/home/ldw/workspace/retinal_organoid_deep_read_2026-08-07.md` +- **Wiki.js:** http://10.10.10.254:3000/zh/literature/sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc (Id 1678) +- **NocoDB row:** 700 in `Organoid_Literature` table +- **SeaFile PDF:** https://fb.biokingdom.top/f/861202f029004d75b456/?dl=1 +- **Vendor synthesis pages:** [`/themes/01-organoid-equipment.md`](/themes/01-organoid-equipment.md) (3Brain HD-MEA evidence anchor) + [`/sources/literature.md`](/sources/literature.md) (cross-agent index) \ No newline at end of file diff --git a/sources/literature.md b/sources/literature.md index 23eb5b4..da9485b 100644 --- a/sources/literature.md +++ b/sources/literature.md @@ -13,14 +13,26 @@ tags: [literature, deep-read, flywheel, celvivo, 3brain, cellink, femtobiomed] ## Last 30 days of deep reads (mtime descending) -### 2026-08-08 (3 papers — flywheel-sync completed today) +### 2026-08-08 (4 papers — flywheel-sync completed today) | DOI | Vendor | Application | Title (short) | Vault path | | --- | --- | --- | --- | --- | | `10.1038/s41551-026-01620-y` | 3Brain (HD-MEA) + Cellink (microlattice) | Neural organoid e-phys drug screen | Liu N et al. (2026) Shape-conformal porous frameworks for full coverage of neural organoids and high-resolution electrophysiology (Nat Biomed Eng, Rogers Lab; >90% surface coverage vs 5-15% MEA; 3000-8000 channels per organoid; weeks-long stable recording; epilepsy/AD modeling) — first entry in NocoDB table `Robin_Picked_Papers` | `Liu2026_NBME_shape_conformal_organoid.md` (in `/home/ldw/workspace/`) | | `10.1016/j.cell.2025.05.041` | CelVivo (ClinoStar) + 3Brain (HD-MEA adjacent) | Lung/gut organoid vascularization | Miao Y et al. (2025) Co-development of Mesoderm and Endoderm Enables Organotypic Vascularization in Lung and Gut Organoids (Cell; vHLPO 7% ECs vs traditional HLPO 0%; single 3D EB co-induction of mesoderm+endoderm; FOXF1 mutation ACDMPV modeling) — NocoDB row 93 in `Organoid_Literature` | `Miao2025_Cell_v2.md` (in `/home/ldw/workspace/`) | | `10.1016/j.stem.2025.12.013` | 3Brain (HD-MEA, adjacent) + CelVivo (ClinoStar, adjacent) | Retinal ganglion cell / vascularized retinal organoid | Sharma K et al. (2026) Retinal ganglion cell survival and functional maturation in transiently vascularized human retinal organoids (Cell Stem Cell 33:253-271.e13, PMID 41529691; C3 endothelial integration strategy; W18 POU4F1+ RGC 18.2% vs 1.21% p<0.001; W31 ON/OFF/ON-OFF light responses >90%/72%/53% fidelity) — NocoDB row 700 in `Organoid_Literature` | `Retina-StemCell/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc.md` (planned) | -| `10.3389/fbioe.2026.1854988` | CelVivo (ClinoStar adjacent) + Cellink (BIO X adjacent) + FemtoBiomed (CellShot adjacent) | Microbioreactor design for eukaryotic cell-based biomedical applications | Rosero G et al. (2026) Microbioreactor design for eukaryotic cell-based biomedical applications (Front Bioeng Biotechnol, Mini Review; 6x productivity vs T-flask; organoid size 140% vs static control; 4 applications: CAR-T / mAb / iPSC / organoid) — NocoDB: `Robin_Picked_Papers` (PMID 42516424, Wiki.js ID 1694) | `Microbioreactor_2026_Rosero_FrontBioeng.md` (in `/home/ldw/workspace/`) | +| `10.3389/fbioe.2026.1854988` | CelVivo (ClinoStar adjacent) + Cellink (BIO X adjacent) + FemtoBiomed (CellShot adjacent) | Microbioreactor design for eukaryotic cell-based biomedical applications | Rosero G et al. (2026) Microbioreactor design for eukaryotic cell-based biomedical applications (Front Bioeng Biotechnol, Mini Review; 6x productivity vs T-flask; organoid size 140% vs static control; 4 applications: CAR-T / mAb / iPSC / organoid) — NocoDB: `Robin_Picked_Papers` (PMID 42516424, Wiki.js ID 1696) | `Microbioreactor_2026_Rosero_FrontBioeng.md` (in `/home/ldw/workspace/`) | + +### 2026-08-08 (Fernandez Vallone 2026 — untracked, deep-read commit `6c16dc05` + `d7df3830`) + +| DOI | Vendor | Application | Title (short) | Vault path | +| --- | --- | --- | --- | --- | +| `10.3390/cells15110963` | CelVivo (ClinoStar adjacent) + 3Brain (HD-MEA adjacent) | hiPSC brain organoid Thyroid Hormone System Disrupting Chemicals (THSDC) platform | Fernandez Vallone V et al. (2026) Comparative Evaluation of hiPSC-Derived Brain Organoids as Platforms for Assessing Thyroid Hormone System Disrupting Chemicals (Cells 15:963, PMID 42274556; COs vs NSCOs; LC-MS/MS T3代谢; qRT-PCR HR/KLF9/DIO3/SEMA3C; HCA; THSDC = iopanoic acid + silychristin) — NocoDB row 3263 in `Robin_Picked_Papers`, Wiki.js Id 1698, v2 (5 张真图 + 双 H1) | `obsidian-vault/04-Literature/Deep-Reads/Cells/fernandez-vallone-2026-thsdc-brain-organoids.md` | + +### 2026-08-06 (Parfitt 2024 Nat Commun — untracked deep-read, hiPSC midbrain organoid DJ1 LOF PD model) + +| DOI | Vendor | Application | Title (short) | Vault path | +| --- | --- | --- | --- | --- | +| `10.1038/s41467-024-44732-2` | CelVivo (ClinoStar adjacent) + 3Brain (HD-MEA adjacent) | DJ1 LOF / midbrain organoid / Parkinson disease model | Parfitt GM et al. (2024) DJ1 缺失破坏星形胶质溶酶体蛋白降解，引发中脑类器官蛋白稳态崩溃（Nat Commun 15:1071, PMID 38200091; DJ1 KO + L166P 突变 iPSC hMIDOs; 星形胶质 α-synuclein 旁分泌毒性放大 DA 神经元死亡) | `04-Literature/Deep-Reads/Brain/2026-08-06_Parfitt_GM_et_al_NatCommun_2024_DJ1_LOF_midbrain_organoid_PD.md` | ### 2026-07-29 @@ -80,6 +92,9 @@ tags: [literature, deep-read, flywheel, celvivo, 3brain, cellink, femtobiomed] | **Cellink** | 1 | 2026-07-27 | — | | **CelVivo + 3Brain cross** | 1 | 2026-07-27 | Miao 2025 v2 (CelVivo ClinoStar rating 5, HD-MEA rating 4) | | **Cellink + 3Brain cross** | 0 | — | Liu 2026 (3D bioprinting microlattice rating 5) | +| **Across all 4 vendors** (Microbioreactor review) | 1 | 2026-08-08 | Rosero 2026 Front Bioeng Biotechnol (CAR-T / mAb / iPSC / organoid — 4 applications) | +| **Brain organoid + THSDC** (NAMs adjacent) | 1 | 2026-08-08 | Fernandez Vallone 2026 Cells (hiPSC brain organoid THSDC platform, v2 5 张真图 + 双 H1; Wiki.js Id 1698) | +| **Brain organoid + PD model** | 1 | 2026-08-06 | Parfitt 2024 Nat Commun (DJ1 LOF midbrain organoid PD model, untracked) | | **Ronawk Bio-Block** (KB 0 hit) | 1 | 2026-07-28 | — | ## 4-week MSC long-term-culture keyword hits (cumulative) @@ -121,10 +136,30 @@ The `Robin_Picked_Papers` table is **new as of today** — created per Robin's 2 - "Latest ClinoReactor research" → read this page's ClinoReactor keyword hits + Miao 2025 v2 (vascularization cross-reference) - "What new papers in the past week?" → read this page's "Last 30 days" section, top 3 rows - "Liu 2026 shape-conformal neural organoid HD-MEA — what is it?" → [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) +- "Fernandez Vallone 2026 hiPSC brain organoid THSDC — what is it?" → deep-read at `obsidian-vault/04-Literature/Deep-Reads/Cells/fernandez-vallone-2026-thsdc-brain-organoids.md` (Wiki.js Id 1698, NocoDB row 3263, v2 with 5 张真图 + 双 H1) +- "Parfitt 2024 DJ1 LOF midbrain organoid PD model — what is it?" → deep-read at `04-Literature/Deep-Reads/Brain/2026-08-06_Parfitt_GM_et_al_NatCommun_2024_DJ1_LOF_midbrain_organoid_PD.md` (Nat Commun 15:1071, PMID 38200091) -| `10.3389/fbioe.2026.1854988` | CelVivo (ClinoStar adjacent) + Cellink (BIO X adjacent) + FemtoBiomed (CellShot adjacent) | Microbioreactor design for eukaryotic cell-based biomedical applications | Rosero G et al. (2026) Microbioreactor design for eukaryotic cell-based biomedical applications (Front Bioeng Biotechnol, Mini Review; 6x productivity vs T-flask; organoid size 140% vs static control; 4 applications: CAR-T / mAb / iPSC / organoid) — NocoDB: `Robin_Picked_Papers` (PMID 42516424, Wiki.js ID 1695) | `Microbioreactor_2026_Rosero_FrontBioeng.md` (in `/home/ldw/workspace/`) | +## 8-07 vault mtime additions (working-tree deep-reads — not yet on `main`) -| `10.3389/fbioe.2026.1854988` | CelVivo (ClinoStar adjacent) + Cellink (BIO X adjacent) + FemtoBiomed (CellShot adjacent) | Microbioreactor design for eukaryotic cell-based biomedical applications | Rosero G et al. (2026) Microbioreactor design for eukaryotic cell-based biomedical applications (Front Bioeng Biotechnol, Mini Review; 6x productivity vs T-flask; organoid size 140% vs static control; 4 applications: CAR-T / mAb / iPSC / organoid) — NocoDB: `Robin_Picked_Papers` (PMID 42516424, Wiki.js ID 1696) | `Microbioreactor_2026_Rosero_FrontBioeng.md` (in `/home/ldw/workspace/`) | +> Observed in the 2026-08-08 git-repo connector pull as **untracked files in the working tree**. These are working-tree deep-reads that the next LDR commits will fold onto `main`. + +| Path | Status | Note | +| --- | --- | --- | +| `Liu2026_NBME_shape_conformal_organoid.md` | untracked @ `/home/ldw/workspace/` | canonical 2026-08-08 paper; v2-v11 已经 commit `1614ccf9` to `main` | +| `Miao2025_Cell_v2.md` | untracked @ `/home/ldw/workspace/` | canonical 2026-08-08 paper; v2 已 commit `1c05eee7` to `main` | +| `Miao2025_Cell_vascularized_organoid.md` | untracked @ `/home/ldw/workspace/` | 出处未明 working copy | +| `Microbioreactor_2026_Rosero_FrontBioeng.md` | untracked @ `/home/ldw/workspace/` | 2026-08-08 论文 working copy; v2 with SeaFile links 已 commit `65fef021` to `main` | +| `04-Literature/Deep-Reads/Brain/2026-08-06_Parfitt_GM_et_al_NatCommun_2024_DJ1_LOF_midbrain_organoid_PD.md` | untracked (2026-08-06) | DJ1 LOF midbrain organoid PD model (Parfitt 2024 Nat Commun) | +| `obsidian-vault/04-Literature/Deep-Reads/Cells/fernandez-vallone-2026-thsdc-brain-organoids.md` | untracked (2026-08-08) | Fernandez Vallone 2026 Cells hiPSC 脑类器官 THSDC (commits `6c16dc05` + `d7df3830`) | +| `retinal_organoid_deep_read_2026-08-07.md` | untracked @ `/home/ldw/workspace/` | Sharma 2026 working copy | +| `rustdesk-selfhosted-2026-08-05.md` | untracked @ `/home/ldw/workspace/obsidian-vault/` | 独立的 RustDesk 自建部署笔记 (related to `/sources/rustdesk-sop.md`) | +| `dify精读进度-20260805.md` | untracked @ `/home/ldw/workspace/` | Dify 文档精读进度追踪 | +| `literature_deepread_v6.py` + `__pycache__/` | untracked @ `/home/ldw/workspace/` | LDR pipeline v6 脚本 (脚本源) | +| `文悦精读流程线.yml` v1-v5-clean | untracked @ `/home/ldw/workspace/` | Dify 精读流程线 workflow YAML (5 版迭代) | + +## 8-07 _known_associations.md 接续 + +> 2026-08-07 added Obsidian vault `02-Clients/Agents/_known_associations.md` 是 4 个经销商管理 Hook 升级 (commit `4b237a82`) 的输出。这页 index 是新引入的 cross-product mapping — connector 证据已在 [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) § "8-07 新增：_known_associations.md 索引" 索引。 ## Maintenance diff --git a/sources/nocodb.md b/sources/nocodb.md index 566a69a..fb84896 100644 --- a/sources/nocodb.md +++ b/sources/nocodb.md @@ -1,3 +1,9 @@ +--- +type: "Reference" +title: "NocoDB 文献库索引 — 跨 agent 数据层" +openwiki_generated: true +--- + # NocoDB 文献库索引 — 跨 agent 数据层 > 数据源: NocoDB 13 个文献库 + 2 个公司库 (实时,每次 OpenWiki cron 跑时更新) diff --git a/sources/ragflow.md b/sources/ragflow.md index d5eab93..c77f2b4 100644 --- a/sources/ragflow.md +++ b/sources/ragflow.md @@ -1,3 +1,9 @@ +--- +type: "Reference" +title: "RAGFlow 全文检索索引 (Robin KB system)" +openwiki_generated: true +--- + # RAGFlow 全文检索索引 (Robin KB system) > 数据源: RAGFlow (http://10.10.10.254:9980/) 14 个 KB 全文检索结果 diff --git a/sources/seafile.md b/sources/seafile.md index 55cebd8..dc347b3 100644 --- a/sources/seafile.md +++ b/sources/seafile.md @@ -1,3 +1,9 @@ +--- +type: "Reference" +title: "SeaFile 大文件存储索引" +openwiki_generated: true +--- + # SeaFile 大文件存储索引 > 数据源: SeaFile (http://10.10.10.254:9898/) 共 N 个资料库 diff --git a/sources/web-search.md b/sources/web-search.md index cfce9c0..4d89d69 100644 --- a/sources/web-search.md +++ b/sources/web-search.md @@ -1,14 +1,24 @@ --- type: "Reference" title: "Web Search Evidence" -openwiki_generated: true +description: "Compact, source-backed evidence and ingestion coverage for the web-search-1 Tavily lane tracking CelVivo, 3Brain, Cellink, and related organoid news." +tags: [source, web-search, tavily, celvivo, 3brain, cellink, organoids] --- # Web Search Evidence -> Connector: `web-search-1` (Tavily). This page records compact, relevant evidence from Tavily pulls; search results are discovery leads, not vendor-confirmed announcements. Latest pull: 2026-08-03 18:08 UTC. +> Connector: `web-search-1` (Tavily). This page records compact, relevant evidence from Tavily pulls; search results are discovery leads, not vendor-confirmed announcements. Latest successful pull: 2026-08-03 18:08 UTC. The 2026-08-08 update attempt was skipped because the connector is disabled and `TAVILY_API_KEY` is not present; no new 24-hour evidence was available. -## 2026-07-26 pull +## 2026-08-08 attempted update — skipped + +- **Status:** skipped. `web-search-1` is not enabled; the connector reports that `enabled=true` must be set in `~/.openwiki/connectors/web-search/config.json`. +- **Authentication:** `TAVILY_API_KEY` is not present, so no Tavily request was made. +- **Coverage:** no raw data files were written for this attempted 24-hour window. No new CelVivo, 3Brain, Cellink, or organoid findings were available for synthesis; the latest successful pull remains 2026-08-03 18:08 UTC. +- **Synthesis:** no changes were made to `/themes.md`, `/commitments.md`, `/open-questions.md`, or `/personal-logistics.md` from this source attempt. + +## Historical successful pulls + +The detailed pull records below preserve the prior evidence trail in chronological order. ### 3D spheroid automation and assay standardization — source-backed @@ -115,7 +125,7 @@ Third Tavily pull on the same day, after the 2026-07-27 `~/.openwiki/INSTRUCTION ### Coverage note for next update The China CDE regulatory lane is no longer being refreshed on every Tavily pull. The existing `/commitments.md` item pins it as `source-backed` with one credible cisema.com source. If a future Tavily or HN pull surfaces an NMPA / CDE-direct corroboration, promote from watchlist to `source-backed` and move into `/themes.md` as a confirmed row. -ll +## 2026-07-27 18:04 pull Fourth Tavily pull on the 2026-07-27 cycle, run as a stand-alone `openwiki personal --update` source ingest. All 10 queries were re-run. Two lanes produced genuinely new material evidence (CelVivo / ClinoReactor vendor-anchored signal; Hermes Agent v0.19 Quicksilver workflow-tooling release). One lane (3D-bioprinted-organoid reviews) added supporting evidence to the existing `class-organoid-3d-bioprinting` row. The Tavily answer-text mis-attribution pattern recurred on the 3Brain, Cellink, and MiniMax-M3 lanes — flagged again below. diff --git a/sources/wikijs.md b/sources/wikijs.md index 7476591..c1efc3c 100644 --- a/sources/wikijs.md +++ b/sources/wikijs.md @@ -1,3 +1,9 @@ +--- +type: "Reference" +title: "Wiki.js 索引 — 跨 agent 文档发布层" +openwiki_generated: true +--- + # Wiki.js 索引 — 跨 agent 文档发布层 > 数据源: Wiki.js (http://10.10.10.254:3000/graphql) Biokingdom 实例 diff --git a/themes.md b/themes.md index c0bcecd..0d13fc6 100644 --- a/themes.md +++ b/themes.md @@ -1,7 +1,8 @@ --- type: "Reference" title: "Themes" -openwiki_generated: true +description: "Recurring topics, signals, and trends observed across Robin's sources. Index of theme rows with confidence labels and source citations; details live on the linked source and synthesis pages." +tags: [themes, recurring, signals, synthesis] --- # Themes @@ -12,18 +13,13 @@ Index kept narrow by design: only themes that map to Robin's actual work (life-s | Topic key | Theme / Signal | First seen | Last seen | Confidence | Sources | Evidence count | Status | Evidence | | --- | --- | --- | --- | --- | --- | --- | --- | --- | - -| `class-organoid-3d-bioprinting` | Recurring organoid, 3D bioprinting, and 3D-cell-culture automation coverage; this window adds a 2026-07-28 HN drug-discovery essay (owlposting "Why haven't organoids solved all of drug discovery?", 9 pts), a 2026-07-27 Oxford Academic review on 3D-bioprinted organoids, a 2026-07-22 Sage review on bioprinting-enabled organoids, a 2026-07-27 Pluristyx iPSC + aerospace clinical-grade hepatocyte manufacturing partnership, the first vendor-anchored CelVivo ClinoReactor co-marketing signal (TheWell Bioscience xeno-free workflow pages), the first vendor-anchored Cellink BIO X Gen 3 / BIO X6 signal (Nuclear Mechano-Oncology install + CELLINK LinkedIn U. Miami reference + third-party market report), and the third vendor-anchored Cellink signal — **CELLINK × Volumetric new Lumen X release** (3DPrint.com 2026-07-28) — plus GEN "Large Bioprinted Tissues Get a Precision Boost" (2026-07-29) and MDPI Cells "Rapid Volumetric Bioprinting Coupled with Dynamic Perfusion Enhances Human Hepatic Organoid Toxicity Testing" (2026-07-27) on top of the prior Nature / HN evidence; pull 7 (2026-07-30) adds FDA NAMs framework (2026-07-27, organ-on-chip included among New Approach Methodologies alongside June 2026 cell/gene-therapy draft guidance), Molecular Cancer patient-derived 3D-bioprinted primary liver cancer (Peking Union Medical College Hospital, 2026-07-28), and npj Biomedical Innovations microvasculature bioprinting review (2026-07-29); pull 11 (2026-08-03) re-anchors the HepatoBiliary Surgery and Nutrition "Spatial architecture and dynamic surveillance: 3D bioprinting and microfluidics converge" review (2026-08-01) as the strongest same-week cross-anchor between organ-on-chip and 3D-bioprinting; still mostly application-domain plus three vendor-channel signals (CelVivo+TheWell; Cellink BIO X Gen 3 / BIO X6; Cellink Lumen X) | 2026-07-16 | 2026-08-03 | source-backed | hackernews, web-search | 23+ | active | [HN: 49083799 drug-discovery essay 2026-07-28](/sources/hackernews.md#class-organoid-3d-bioprinting-refreshed-this-run); [Tavily: 3D bioprinted organoid reviews + Pluristyx + CelVivo+TheWell 2026-07-27](/sources/web-search.md#2026-07-27-1804-pull); [Tavily: Cellink BIO X Gen 3 / BIO X6 + CN Bio / NASA AVATAR OOC + GEN bioprinting 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: FDA NAMs + Peking Union 3D-bioprinted liver cancer + npj microvasculature 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: Cellink × Volumetric new Lumen X + 3Brain Utrecht Summer School + CelVivo ClinoStar 2 / Thailand Lab 2026 + HBSN bioprinting+microfluidics 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull) | - -| `china-cde-cell-gene-therapy-rules-2026` | China CDE (under NMPA) published technical guidelines defining scope & classification of cell and gene therapy drugs; standardizes CMC planning for Chinese pharma/CDMO/biotech customers | 2026-07-24 | 2026-07-24 | source-backed | web-search | 1 | watchlist | [Tavily: cisema.com 2026-07-24](/sources/web-search.md#china-cde-cell-gene-therapy-classification-source-backed) | -| `china-order-no-818-clinical-translation` | China's Order No. 818 (effective 2026-05-01) creates an accelerated pathway for advanced biomedical technologies — including cell therapy and 3D bioprinting — towards regulated clinical translation at qualified hospitals after demonstrating safety and preliminary efficacy; the clinical-translation counterpart to the CDE classification item and directly relevant to Robin's Chinese pharma R&D / CDMO / biotech customer base | 2026-07-28 | 2026-07-28 | source-backed | web-search | 1 (+ Tavily synthesis) | watchlist | [Tavily: BetaLife LinkedIn 2026-07 + Roots Analysis re-mention 2026-07-28](/sources/web-search.md#china-order-no-818--accelerated-clinical-translation-pathway--source-backed) | - - - -| `MiniMax-m3` | MiniMax-M3 (1M context multimodal) HuggingFace model card + Twitter launch; the daily-driver inference provider behind every OpenWiki run and most of Robin's agent work; haimaker.ai July 2026 third-party eval ranks models for Hermes Agent usage; MyClaw.ai 2026-07-29 confirms M3 + M2.7 are the operational models for both OpenClaw and Hermes, with M3 supporting multimodal (image, video, music, speech, web search); pull 11 (2026-08-03) adds **unsloth/MiniMax-M3-GGUF** (HuggingFace 2026-08-01) confirming quantized local-LLM run path + **benchlm.ai "DeepSeek V4 Flash vs MiniMax M3: Benchmarks & Cost"** (2026-08-01) reframing M3 as "1M context window at $0.30…"; this 2026-08-03 HN pull surfaces the **MiniMax-H3 launch cluster** (item `49155629` 167pts top-feed ComfyUI Day-0 support with open weights + native audio + 2K video; item `49150583` 8pts "MiniMax-H3 weights are up" on HuggingFace model card; item `49150861` 2pts "Run MiniMax-H3 Locally with SGLang Diffusion on 2× RTX 5090s or 1× RTX Pro 6000" via LMSYS Twitter) — three distinct primary sources on the same day confirming H3 as the next frontier model release after M3 | 2026-07-16 | 2026-08-03 | source-backed | hackernews, web-search | 8+ | active | [HN: M3 model cluster (huggingface + twitter)](/sources/hackernews.md#MiniMax-m3-watchlist); [Tavily: Hermes Agent best-models eval](/sources/web-search.md#hermes-agent-best-models-eval-source-backed-workflow-tooling-low-priority); [Tavily: MyClaw OpenClaw vs MiniMax Agent 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: unsloth/MiniMax-M3-GGUF + BenchLM M3 vs DeepSeek V4 Flash 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull); [HN: MiniMax-H3 launch cluster 2026-08-03](/sources/hackernews.md#MiniMax-h3-launch-cluster-refreshed-this-run) | -| `hermes-agent-v0-19-quicksilver` | Hermes Agent v0.19 "Quicksilver" release (2026-07-25): first-token delay 4.3s → 0.9s, profile routing, live subagent, delivery ledger, 1Password/Bitwarden integration; relevant to Robin's daily-driver stack; MCP 2026-07-28 revision finalization (not backward-compatible) is a related protocol-layer signal; `configuration.md` (2026-07-26) documents the iteration-budget behavior change (April 2026: removed premature 70%/90% warnings, now single wrap-up at 500/500 with grace call) and `features/api-server.md` (2026-07-27) documents new `/v1/runs/{run_id}/stop` + `/approval` endpoints with MiniMax-M3 as the documented default model; pull 7 (2026-07-30) re-anchors `api-server.md` with a new per-profile `API_SERVER_KEY` breaking-change warning and a runs API for long-form sessions, and adds a third-party Hermes Atlas "State of Hermes Agent — July 2026" report; this 2026-08-03 HN pull surfaces **Hermes Agent v0.20.0** (item `49159200`, NousResearch GitHub releases tag `v2026.8.3`, 1pt on HN day-of — the next major version after v0.19 Quicksilver); pull 11 (2026-08-03) adds a **Hermes Agent 0.19.1 GitHub bug report** (NousResearch issues/77000, 2026-08-02, score 0.790, "gpt-5.6-luna + opencode-go") confirming patch-version activity on the v0.19.x track between the v0.19 Quicksilver release and the v0.20.0 release; Tavily answer text on the Hermes/M3 lane was partially fabricated ("release date of June 1, 2026") and should be ignored — the underlying GitHub issue URL is the credible signal | 2026-07-25 | 2026-08-03 | source-backed | hackernews, web-search | 10 | active | [Tavily: Hermes v0.19 Quicksilver + MCP revision 2026-07-27](/sources/web-search.md#hermes-agent-v019-quicksilver-release--source-backed-workflow-tooling-low-priority); [Tavily: hermes-agent configuration.md + api-server.md + MyClaw 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: api-server.md API_SERVER_KEY break + Hermes Atlas state report 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: Hermes Agent 0.19.1 GitHub bug report 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull); [HN: Hermes Agent v0.20.0 release 2026-08-03](/sources/hackernews.md#hermes-agent-v0200-release-refreshed-this-run) | +| `class-organoid-3d-bioprinting` | Recurring organoid, 3D bioprinting, and 3D-cell-culture automation coverage; this window adds a 2026-07-28 HN drug-discovery essay (owlposting "Why haven't organoids solved all of drug discovery?", 9 pts), a 2026-07-27 Oxford Academic review on 3D-bioprinted organoids, a 2026-07-22 Sage review on bioprinting-enabled organoids, a 2026-07-27 Pluristyx iPSC + aerospace clinical-grade hepatocyte manufacturing partnership, the first vendor-anchored CelVivo ClinoReactor co-marketing signal (TheWell Bioscience xeno-free workflow pages), the first vendor-anchored Cellink BIO X Gen 3 / BIO X6 signal (Nuclear Mechano-Oncology install + CELLINK LinkedIn U. Miami reference + third-party market report), and the third vendor-anchored Cellink signal — **CELLINK × Volumetric new Lumen X release** (3DPrint.com 2026-07-28) — plus GEN "Large Bioprinted Tissues Get a Precision Boost" (2026-07-29) and MDPI Cells "Rapid Volumetric Bioprinting Coupled with Dynamic Perfusion Enhances Human Hepatic Organoid Toxicity Testing" (2026-07-27) on top of the prior Nature / HN evidence; pull 7 (2026-07-30) adds FDA NAMs framework (2026-07-27, organ-on-chip included among New Approach Methodologies alongside June 2026 cell/gene-therapy draft guidance), Molecular Cancer patient-derived 3D-bioprinted primary liver cancer (Peking Union Medical College Hospital, 2026-07-28), and npj Biomedical Innovations microvasculature bioprinting review (2026-07-29); pull 11 (2026-08-03) re-anchors the HepatoBiliary Surgery and Nutrition "Spatial architecture and dynamic surveillance: 3D bioprinting and microfluidics converge" review (2026-08-01) as the strongest same-week cross-anchor between organ-on-chip and 3D-bioprinting; **flywheel-sync 2026-08-08** adds 3 deep-read papers: Liu 2026 Nat Biomed Eng (shape-conformal porous framework for full-coverage neural organoid e-phys, Rogers Lab — microlattice fabrication rate 5 for Cellink, HD-MEA rate 5 for 3Brain), Miao 2025 Cell v2 (co-differentiation mesoderm+endoderm for vascularized lung/gut organoids — ClinoStar rate 5, organotypic vascularization), Sharma 2026 Cell Stem Cell (vascularized retinal organoid RGC survival — HD-MEA rate 4, CelVivo ClinoStar rate 3 for extending vascular network stability); still mostly application-domain plus three vendor-channel signals (CelVivo+TheWell; Cellink BIO X Gen 3 / BIO X6; Cellink Lumen X) + three literature flywheel-sync application-domain signals (Liu/Miao/Sharma) | 2026-07-16 | 2026-08-08 | source-backed | hackernews, web-search, literature-flywheel | 26+ | active | [HN: 49083799 drug-discovery essay 2026-07-28](/sources/hackernews.md); [Tavily: 3D bioprinted organoid reviews + Pluristyx + CelVivo+TheWell 2026-07-27](/sources/web-search.md#2026-07-27-1804-pull); [Tavily: Cellink BIO X Gen 3 / BIO X6 + CN Bio / NASA AVATAR OOC + GEN bioprinting 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: FDA NAMs + Peking Union 3D-bioprinted liver cancer + npj microvasculature 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: Cellink × Volumetric new Lumen X + 3Brain Utrecht Summer School + CelVivo ClinoStar 2 / Thailand Lab 2026 + HBSN bioprinting+microfluidics 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull); [Flywheel: Liu 2026 NBME shape-conformal framework + Miao 2025 Cell v2 vascularized organoids + Sharma 2026 Cell Stem Cell vascularized retinal organoids 2026-08-08](/sources/literature.md) | +| `china-cde-cell-gene-therapy-rules-2026` | China CDE (under NMPA) published technical guidelines defining scope & classification of cell and gene therapy drugs; standardizes CMC planning for Chinese pharma/CDMO/biotech customers | 2026-07-24 | 2026-07-24 | source-backed | web-search | 1 | watchlist | [Tavily: cisema.com 2026-07-24](/sources/web-search.md) | +| `china-order-no-818-clinical-translation` | China's Order No. 818 (effective 2026-05-01) creates an accelerated pathway for advanced biomedical technologies — including cell therapy and 3D bioprinting — towards regulated clinical translation at qualified hospitals after demonstrating safety and preliminary efficacy; the clinical-translation counterpart to the CDE classification item and directly relevant to Robin's Chinese pharma R&D / CDMO / biotech customer base | 2026-07-28 | 2026-07-28 | source-backed | web-search | 1 (+ Tavily synthesis) | watchlist | [Tavily: BetaLife LinkedIn 2026-07 + Roots Analysis re-mention 2026-07-28](/sources/web-search.md) | +| `MiniMax-m3` | MiniMax-M3 (1M context multimodal) HuggingFace model card + Twitter launch; the daily-driver inference provider behind every OpenWiki run and most of Robin's agent work; haimaker.ai July 2026 third-party eval ranks models for Hermes Agent usage; MyClaw.ai 2026-07-29 confirms M3 + M2.7 are the operational models for both OpenClaw and Hermes, with M3 supporting multimodal (image, video, music, speech, web search); pull 11 (2026-08-03) adds **unsloth/MiniMax-M3-GGUF** (HuggingFace 2026-08-01) confirming quantized local-LLM run path + **benchlm.ai "DeepSeek V4 Flash vs MiniMax M3: Benchmarks & Cost"** (2026-08-01) reframing M3 as "1M context window at $0.30…"; this 2026-08-03 HN pull surfaces the **MiniMax-H3 launch cluster** (item `49155629` 167pts top-feed ComfyUI Day-0 support with open weights + native audio + 2K video; item `49150583` 8pts "MiniMax-H3 weights are up" on HuggingFace model card; item `49150861` 2pts "Run MiniMax-H3 Locally with SGLang Diffusion on 2× RTX 5090s or 1× RTX Pro 6000" via LMSYS Twitter) — three distinct primary sources on the same day confirming H3 as the next frontier model release after M3 | 2026-07-16 | 2026-08-03 | source-backed | hackernews, web-search | 8+ | active | [HN: M3 model cluster + H3 launch cluster 2026-08-03](/sources/hackernews.md); [Tavily: Hermes Agent best-models eval](/sources/web-search.md); [Tavily: MyClaw OpenClaw vs MiniMax Agent 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: unsloth/MiniMax-M3-GGUF + BenchLM M3 vs DeepSeek V4 Flash 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull) | +| `hermes-agent-v0-19-quicksilver` | Hermes Agent v0.19 "Quicksilver" release (2026-07-25): first-token delay 4.3s → 0.9s, profile routing, live subagent, delivery ledger, 1Password/Bitwarden integration; relevant to Robin's daily-driver stack; MCP 2026-07-28 revision finalization (not backward-compatible) is a related protocol-layer signal; `configuration.md` (2026-07-26) documents the iteration-budget behavior change (April 2026: removed premature 70%/90% warnings, now single wrap-up at 500/500 with grace call) and `features/api-server.md` (2026-07-27) documents new `/v1/runs/{run_id}/stop` + `/approval` endpoints with MiniMax-M3 as the documented default model; pull 7 (2026-07-30) re-anchors `api-server.md` with a new per-profile `API_SERVER_KEY` breaking-change warning and a runs API for long-form sessions, and adds a third-party Hermes Atlas "State of Hermes Agent — July 2026" report; this 2026-08-03 HN pull surfaces **Hermes Agent v0.20.0** (item `49159200`, NousResearch GitHub releases tag `v2026.8.3`, 1pt on HN day-of — the next major version after v0.19 Quicksilver); pull 11 (2026-08-03) adds a **Hermes Agent 0.19.1 GitHub bug report** (NousResearch issues/77000, 2026-08-02, score 0.790, "gpt-5.6-luna + opencode-go") confirming patch-version activity on the v0.19.x track between the v0.19 Quicksilver release and the v0.20.0 release; Tavily answer text on the Hermes/M3 lane was partially fabricated ("release date of June 1, 2026") and should be ignored — the underlying GitHub issue URL is the credible signal | 2026-07-25 | 2026-08-03 | source-backed | hackernews, web-search | 10 | active | [Tavily: Hermes v0.19 Quicksilver + MCP revision 2026-07-27](/sources/web-search.md); [Tavily: hermes-agent configuration.md + api-server.md + MyClaw 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: api-server.md API_SERVER_KEY break + Hermes Atlas state report 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: Hermes Agent 0.19.1 GitHub bug report 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull); [HN: Hermes Agent v0.20.0 release 2026-08-03](/sources/hackernews.md) | | `openwiki-brand` | `langchain-ai/openwiki` (96 pts) — same product family as Robin's OpenWiki; high-engagement on HN | 2026-07-16 | 2026-07-16 | source-backed | hackernews | 1 (+ 2 adjacent wrappers) | watchlist | [HN: openwiki cluster](/sources/hackernews.md#openwiki-brand-signal) | -| `agent-memory-architecture` | Shared agent-memory architecture using Karpathy's LLM Wiki + Google's Open Knowledge Format (OKF) + MCP — let "every Local AI share ONE permanent memory"; this 2026-07-29 Tavily pull adds four more corroborated sources (Hackernoon Moorcheh.ai "Agent Memory Has a Lock-In Problem. Open Formats Are How We Fix It." with diffability / reviewability / auditability framing; Towards Data Science "Usage-Reinforced Decay Engine for AI Agent Memory" using Ebbinghaus forgetting curve; The Register / MinIO AIStor Memory for long-running multi-step workflows; HPCwire Exabase M-1 BEAM benchmark numbers 76.9% / 75.0% / 68.0% at 100K/1M/10M tokens) on top of the prior HN + Tavily sources; the Hackernoon piece is the strongest OpenWiki-aligning source yet; pull 7 (2026-07-30) adds arXiv 2607.24759v1 "A Templated Substrate for Heterogeneous Collaborative" + rohitg00 LLM Wiki v2 (extending Karpathy's LLM Wiki pattern with lessons from building agentmemory) + Pi `@zosmaai/pi-llm-wiki` package + MinIO AIStor Memory (HPCwire 2026-07-29 + SiliconANGLE 2026-07-30); pull 11 (2026-08-03) adds **akitaonrails/ai-memory `docs/research-karpathy-llm-wiki.md`** (GitHub 2026-07-28, score 0.601) — a third-party research write-up of the Karpathy LLM Wiki pattern — bringing the cluster to 15+ distinct sources | 2026-07-26 | 2026-08-03 | source-backed | hackernews, web-search | 15+ | active | [HN: 49059959, 49059889, 49060215](/sources/hackernews.md#agent-memory-architecture-watchlist--new); [Tavily: LLM Wiki + OKF cluster 2026-07-28](/sources/web-search.md#llm-wiki--okf--shared-agent-memory-cluster--source-backed-workflow-tooling-low-priority); [Tavily: Moorcheh.ai + TDS + MinIO + Exabase cluster 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: arXiv 2607.24759v1 + LLM Wiki v2 + Pi pi-llm-wiki + MinIO AIStor 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: akitaonrails/ai-memory research write-up 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull) | +| `agent-memory-architecture` | Shared agent-memory architecture using Karpathy's LLM Wiki + Google's Open Knowledge Format (OKF) + MCP — let "every Local AI share ONE permanent memory"; this 2026-07-29 Tavily pull adds four more corroborated sources (Hackernoon Moorcheh.ai "Agent Memory Has a Lock-In Problem. Open Formats Are How We Fix It." with diffability / reviewability / auditability framing; Towards Data Science "Usage-Reinforced Decay Engine for AI Agent Memory" using Ebbinghaus forgetting curve; The Register / MinIO AIStor Memory for long-running multi-step workflows; HPCwire Exabase M-1 BEAM benchmark numbers 76.9% / 75.0% / 68.0% at 100K/1M/10M tokens) on top of the prior HN + Tavily sources; the Hackernoon piece is the strongest OpenWiki-aligning source yet; pull 7 (2026-07-30) adds arXiv 2607.24759v1 "A Templated Substrate for Heterogeneous Collaborative" + rohitg00 LLM Wiki v2 (extending Karpathy's LLM Wiki pattern with lessons from building agentmemory) + Pi `@zosmaai/pi-llm-wiki` package + MinIO AIStor Memory (HPCwire 2026-07-29 + SiliconANGLE 2026-07-30); pull 11 (2026-08-03) adds **akitaonrails/ai-memory `docs/research-karpathy-llm-wiki.md`** (GitHub 2026-07-28, score 0.601) — a third-party research write-up of the Karpathy LLM Wiki pattern — bringing the cluster to 15+ distinct sources | 2026-07-26 | 2026-08-03 | source-backed | hackernews, web-search | 15+ | active | [HN: 49059959, 49059889, 49060215](/sources/hackernews.md); [Tavily: LLM Wiki + OKF cluster 2026-07-28](/sources/web-search.md); [Tavily: Moorcheh.ai + TDS + MinIO + Exabase cluster 2026-07-29](/sources/web-search.md#2026-07-29-1803-pull); [Tavily: arXiv 2607.24759v1 + LLM Wiki v2 + Pi pi-llm-wiki + MinIO AIStor 2026-07-30](/sources/web-search.md#2026-07-30-1804-pull); [Tavily: akitaonrails/ai-memory research write-up 2026-08-03](/sources/web-search.md#2026-08-03-1808-pull) | ## Notes diff --git a/themes/01-organoid-equipment.md b/themes/01-organoid-equipment.md index e3c2e04..d5336ce 100644 --- a/themes/01-organoid-equipment.md +++ b/themes/01-organoid-equipment.md @@ -59,6 +59,8 @@ The state diagram shows the canonical CelVivo → 3Brain workflow: 3D suspension - **Whitepaper: "Breaking the Bias" (2026, 16 pp)** — CelVivo's official vendor narrative on brain organoid long-term culture. Key data: ~110 day / 8 mm diameter brain organoid (Univ. Groningen, Trombetta-Lima); sc-RNA-seq 17,738 cells at Day 90 (Univ. Lausanne, Bagni); Day 30/45 dorsal forebrain comparison vs orbital shaker (Drexel, Qiang); hiPSC → cortical organoid + Omicron BA.5 (QIMR Berghofer, Stewart 2022). 4 patents: WO 2021/001472, WO 2021/245117, WO 2022/008292, WO 2022/144461. Full synthesis at [`/sources/literature-celvivo-brain-whitepaper-2026.md`](/sources/literature-celvivo-brain-whitepaper-2026.md). - **Bosnjakovic 2025 bioRxiv (PAH HepG2 3D spheroid, ClinoStar dynamic culture)** — 21-day maturation + 24h/96h BaP/BBF exposure; **4 metabolic markers (phenylalanine, TCA intermediates, GSH depletion, sphingolipid dysregulation) only appear in 3D, completely invisible in 2D**. Sales ammunition: "your 2D model is missing 100% of environmental toxicology early signals". Synthesis at [`/sources/literature-cel-bosnjakovic-2025-pah-deepread.md`](/sources/literature-cel-bosnjakovic-2025-pah-deepread.md). +- **Miao 2025 Cell v2 (co-differentiation mesoderm + endoderm, vascularized lung/gut organoids, ClinoStar rotating culture)** — single 3D EB co-induction strategy yields **vHLPO with 7% ECs vs traditional HLPO 0%**, organ-specific endothelium + mesenchyme scRNA-seq validation, in-vivo functional integration with host circulation, FOXF1 mutation ACDMPV dual-pathology disease modeling. Product relevance: CelVivo ClinoStar rating 5 (co-differentiation depends on 3D EB self-organization in low-shear rotating culture — ClinoStar is the canonical hardware), HD-MEA rating 4, 3D bioprinting rating 3, patient-derived organoid drug screening rating 5. Synthesis at [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md). +- **Liu 2026 Nat Biomed Eng (shape-conformal porous framework for neural organoid e-phys, Rogers Lab)** — CelVivo ClinoStar rating 4 (organoid culture downstream of the shape-conformal framework; long-term maturation + functional readout is the canonical ClinoStar → HD-MEA workflow). Synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md). See 3Brain evidence for the HD-MEA read side. - **Sales ammunition kit (CelVivo pricing + 8 Protocols + 5 app notes + 5 brand/whitepapers)** — Demo kit `10005-6` lists at €300 (Global Distributor Price, with special discount). 8 ClinoReactor Protocols cover prepare / media change / gardening / plate config / rotation-speed / alginate embed / VitroGel embed. 5 application notes cover HepG2/C3A liver, FTC-133 thyroid, NCI-H69V SCLC, TNBC, ClinoStar vs Orbital Shaker. Synthesis at [`/sources/sales-ammunition.md`](/sources/sales-ammunition.md). - **260528_CS vs OS app note (2026-07-17 deep read)** — ClinoStar vs Orbital Shaker shear-stress comparison for long-term 3D construct performance; ClinoStar has lower shear + long-term growth + better consistency. This is the **vs-competitor killer document** for "why not use an orbital shaker" customer questions. - **111_Planimetry app note (2026-07-17 deep read)** — Planimetry measurements of spheroids in ClinoReactor using FIJI (open-source). Standard answer for "how to quantify spheroids". @@ -66,6 +68,8 @@ The state diagram shows the canonical CelVivo → 3Brain workflow: 3D suspension ### 3Brain evidence - **Raji 2026 Mol Psychiatry (hMOs + 3Brain HD-MEA, 2026-07-27 deep read)** — WNT-modulated human midbrain organoids + 3Brain BioCAM DupleX + Accura-3D (4096 electrodes) + BrainWave 5. **TH+ 58% at 12 weeks** (vs 2D 18%, 3D static 32%). DA release 76 pg/mL (vs 2D 12, 3D static 28). α-synuclein PFF → DA neurons -35% / TH -40% / DA release -45% — establishes the **PD drug screening platform**. Shear-stress 15x lower than orbital shaking (0.13 dyn/cm² vs 2.03 dyn/cm²). Synthesis at [`/sources/literature-raji-2026-deepread.md`](/sources/literature-raji-2026-deepread.md). +- **Liu 2026 Nat Biomed Eng (shape-conformal porous framework, full-coverage neural organoid e-phys, Rogers Lab)** — HD-MEA rating 5: **3000-8000 channels per organoid vs traditional MEA 200-1000 (10-50× improvement), >90% surface coverage vs 5-15%, weeks-long stable recording + bi-directional electrical + optogenetic stimulation, epilepsy + AD disease modeling**. The framework is the **direct next-generation design reference** for 3Brain's current 4096-electrode Accura-3D; Robin should sell Accura-3D as the existing best-in-class and Liu 2026 as the forward-looking 3D-coverage direction. Synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md). Tracks as `liu-2026-hd-mea-roadmap-implication` commitment (verify with 3Brain whether flexible-electronics / shape-conformal framework is on their roadmap). +- **Sharma 2026 Cell Stem Cell (vascularized retinal organoids, RGC survival)** — HD-MEA rating 4: paper uses 60-channel MCS MEA2100-Lite; 3Brain HD-MEA is same-generation HD technology, technical route is transferable. The W31 ON/OFF/ON-OFF light-response recording paradigm is the kind of long-duration, multi-class recording where HD spatial resolution matters most. CelVivo ClinoStar rating 3 (vascular network regresses in static culture → ClinoStar low-shear route candidate). W18 RGC yield **18.2% vs ctrl-RO 1.21% (15× improvement)** through C3 endothelial monolayer integration. Synthesis at [`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`](/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md). - **3Brain Sample Holder Set / PressNet (UK GB2624872)** — Mechanical net-press device for CorePlate 1W/6W; load force 250–1250 µN. Recorded 2026-07-07 (untracked in vault). Carryover evidence in [`/sources/git-repo.md`](/sources/git-repo.md) Notable entities. - **3Brain end-customer dossiers** — 11+ dossiers under `03-Resources/End-Customers/` covering 神经所 (上海), 北京大学, 北京天坛医院, 浙大一附院, 中科院昆明动物所, 西南医科大学, 贵州医科大学, plus TCM accounts at 云南中医药大学 and 天津创新中药. Listed in [`/sources/git-repo.md`](/sources/git-repo.md) Notable entities. - **Vendor-channel strand (Tavily 2026-07-30 → 2026-08-03)** — 3Brain's official website + LinkedIn (booth 412 at ISSCR 2026; booth 4 at ELRIG Drug Discovery; Utrecht Summer School "Human Brain Models" course 2026-07-29). Tracks in `/commitments.md` as `3brain-coreplate-2026-conference-positioning` (verify which conference posts are current and pull application notes). @@ -73,6 +77,8 @@ The state diagram shows the canonical CelVivo → 3Brain workflow: 3D suspension ## Cross-vendor workflow links - **CelVivo + 3Brain joint workflow** (from Raji 2026): hMOs are cultured in a **bioreactor** (CelVivo-class, low-shear rotating-wall) for 12 weeks; transplanted to **3Brain Accura-3D** (4096-electrode HD-MEA chip) for 24h spike-train recording via BrainWave 5. Two pieces of hardware from two vendors compose the **PD drug screening platform** Robin sells. +- **CelVivo + 3Brain next-gen workflow** (from Liu 2026): the shape-conformal porous framework (Rogers Lab, next-gen HD-MEA design) records 3000-8000 channels per organoid vs current 4096 — **forward-looking direction** for the CelVivo → 3Brain pipeline. Track in `/commitments.md` as `liu-2026-hd-mea-roadmap-implication`. +- **CelVivo + 3Brain vascularized organoid workflow** (from Miao 2025 v2 + Sharma 2026): vHLPO and vRO use single 3D EB co-induction (mesoderm+endoderm) or C3 endothelial monolayer integration. The vascular-like networks regress in static culture — **CelVivo ClinoStar low-shear rotating culture is the candidate route to extend maturation**. Functional readout remains 3Brain HD-MEA territory (60-channel MEA in Sharma; future HD-MEA for vascularized organoids). - **CelVivo + TheWell Bioscience xeno-free workflow** (Tavily 2026-07-21/23/25): TheWell's hydrogel-media workflow pages position **ClinoReactor as the scale-up vessel for apical-out organoids + hMSC expansion**. Tracks in `/commitments.md` as `celvivo-clinoreactor-thewell-bioscience-xeno-free` (verify whether sanctioned co-marketing). - **CelVivo + Femtobiomed** (small but complementary): Femtobiomed CellShot / CellPick / TriArm for hiPSC electroporation upstream of CelVivo 3D culture. @@ -101,6 +107,9 @@ The state diagram shows the canonical CelVivo → 3Brain workflow: 3D suspension | What is ClinoReactor's pricing? | [`/sources/sales-ammunition.md`](/sources/sales-ammunition.md) | | What does the CelVivo brain organoid whitepaper actually say? | [`/sources/literature-celvivo-brain-whitepaper-2026.md`](/sources/literature-celvivo-brain-whitepaper-2026.md) | | What is Raji 2026's PD drug screening story? | [`/sources/literature-raji-2026-deepread.md`](/sources/literature-raji-2026-deepread.md) | +| What is Miao 2025's vascularized lung/gut organoid story? | [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md) | +| What is Liu 2026's shape-conformal neural organoid e-phys story? | [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) | +| What is Sharma 2026's vascularized retinal organoid RGC story? | [`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`](/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md) | | What distributors am I actually working with? | [`/sources/agents.md`](/sources/agents.md) | | Which Chinese dealers carry our brand? | [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) | | What regulatory shifts affect our Chinese pharma deals? | [`/commitments.md`](/commitments.md) China CDE / Order No. 818 / China CGT items | diff --git a/themes/02-bioprinting.md b/themes/02-bioprinting.md index abacd65..7c216c5 100644 --- a/themes/02-bioprinting.md +++ b/themes/02-bioprinting.md @@ -48,6 +48,7 @@ This is the synthesis page for **3D 生物打印** — Robin's 3D bioprinting pr The 3D bioprinting lane also captures application-domain papers that bioprint scaffolds for organoid culture — these are **vendor-adjacent** signals that fold into the [`/themes/01-organoid-equipment.md`](/themes/01-organoid-equipment.md) organoid culture theme rather than into Cellink hardware sales: +- **Liu 2026 Nat Biomed Eng (shape-conformal porous framework, Rogers Lab, 2026-08-08 deep read)** — flexible-electronics microlattice fabrication as a 3D-bioprinting-adjacent technology for neural organoid scaffolds. **3D bioprinting rating 5** — the microlattice fabrication technique depends on 3D printing-class resolution (Cellink BIO X / BIONOVA X / Lumen X cannot directly print at this resolution today, but the field direction is clear: future bioprinters will integrate flexible-electronics fabrication). The framework records 3000-8000 channels per organoid (>90% surface coverage, weeks-long stable recording, epilepsy + AD disease modeling) — Robin should pitch Liu 2026 to Cellink to understand whether BIONOVA X or Lumen X can fabricate flexible-electronics-compatible microlattices. Synthesis at [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md). First entry in the new NocoDB table `Robin_Picked_Papers` (created 2026-08-08). - **MDPI Cells 2026-07-27** — "Rapid Volumetric Bioprinting Coupled with Dynamic Perfusion Enhances Human Hepatic Organoid Toxicity Testing" - **GEN 2026-07-29** — "Large Bioprinted Tissues Get a Precision Boost" - **HepatoBiliary Surgery and Nutrition 2026-08-01** — "Spatial architecture and dynamic surveillance: 3D bioprinting and microfluidics converge" (strongest same-week cross-anchor between organ-on-chip and 3D-bioprinting) @@ -94,4 +95,5 @@ The bioprinting theme is **evidence-light compared to theme 1 (organoid-equipmen | Is the New Lumen X product release verified? | [`/commitments.md`](/commitments.md) `cellink-volumetric-lumen-x-release` | | Are there BIO X Gen 3 / BIO X6 customer installs in China? | [`/commitments.md`](/commitments.md) `cellink-bio-x-gen3-customer-evidence` | | What distributors carry Cellink in China? | [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) | -| What 3D bioprinted-organoid reviews have come out this month? | [`/sources/web-search.md`](/sources/web-search.md) 2026-07-29 / 2026-07-30 / 2026-08-03 pulls | \ No newline at end of file +| What 3D bioprinted-organoid reviews have come out this month? | [`/sources/web-search.md`](/sources/web-search.md) 2026-07-29 / 2026-07-30 / 2026-08-03 pulls | +| What is Liu 2026's shape-conformal neural organoid framework story (microlattice + flexible electronics)? | [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) | \ No newline at end of file diff --git a/themes/03-ai-agents.md b/themes/03-ai-agents.md index 9960f21..71c0467 100644 --- a/themes/03-ai-agents.md +++ b/themes/03-ai-agents.md @@ -19,30 +19,29 @@ This is the synthesis page for **AI Agent 工具** — Robin's daily-driver stac ## Agent stack architecture - -```text +```mermaid flowchart TD User[Robin · desktop / mobile] subgraph DesktopWSL[WSL · primary host] Hermes[Hermes Agent v0.19 Quicksilver] - Cron1["cron 02:00
openwiki-update.sh"] + Cron1["cron 02:00 (openwiki-update.sh)"] end subgraph DesktopPC[Windows desktop · secondary] - MiniMaxCode[MiniMax code
+ 4 bridge skills] + MiniMaxCode["MiniMax code (+ 4 bridge skills)"] CodexCLI[Codex CLI fallback] end subgraph Remote[ITX 24h host · future] - ITXHermes[Hermes Agent
on Ubuntu 22.04] + ITXHermes["Hermes Agent (on Ubuntu 22.04)"] end subgraph Memory[Memory substrate] - OpenWiki[(OpenWiki
local markdown wiki)] - Gitea[Gitea public mirror
10.10.10.254:3080] + OpenWiki[("OpenWiki (local markdown wiki)")] + Gitea["Gitea public mirror (10.10.10.254:3080)"] end subgraph KB[Knowledge backends · NAS] - RAGFlowKB[RAGFlow
18 KB · 32709 docs] - NocoDBDB[NocoDB
13 lit tables] - SeaFileStore[SeaFile
4 repos · 77 GB] - WikiJS[Wiki.js
1500+ pages] + RAGFlowKB["RAGFlow (18 KB · 32709 docs)"] + NocoDBDB["NocoDB (13 lit tables)"] + SeaFileStore["SeaFile (4 repos · 77 GB)"] + WikiJS["Wiki.js (1500+ pages)"] end subgraph LLM[Local inference · see theme 04] MiniMaxM3[MiniMax-M3 1M context] @@ -96,8 +95,7 @@ The architecture shows three agent surfaces sharing the OpenWiki memory substrat - **OpenWiki = LangChain 7/10 open-source "personal brain" framework.** Local markdown wiki rooted at `~/.openwiki/wiki`, mirrored to Gitea public `http://10.10.10.254:3080/Robin/openwiki-wiki`. Cron pipeline: every night 02:00 `openwiki-update.sh` (HN + Tavily + git-repo + M3 agent synthesis) → commit → push to Gitea. Every 02:30 `openwiki-update-sources.sh` (NocoDB + SeaFile + Wiki.js + RAGFlow health checks) → commit → push. - **Five canonical synthesis pages** — [`/quickstart.md`](/quickstart.md), [`/themes.md`](/themes.md), [`/commitments.md`](/commitments.md), [`/open-questions.md`](/open-questions.md), [`/personal-logistics.md`](/personal-logistics.md). Five detailed theme pages under [`/themes/`](/themes/). - **Evidence layer** — 21 source pages under [`/sources/`](/sources/), one per active connector or subsystem. - -- **Activation manual:** [`/sources/README-ACTIVATION.md`](/sources/README-ACTIVATION.md) (2026-07-27 update). 8 sections covering TL;DR / connectors not yet on / daily operations / what Robin manually does / what Robin never touches / cross-tool cheat sheet / today's real system status / changes from 7-26 / next steps. +- **Activation manual:** [`/README-ACTIVATION.md`](/README-ACTIVATION.md) (2026-07-27 update). 8 sections covering TL;DR / connectors not yet on / daily operations / what Robin manually does / what Robin never touches / cross-tool cheat sheet / today's real system status / changes from 7-26 / next steps. - **Cheat sheet:** [`/sources/OpenWiki速查手册.md`](/sources/OpenWiki速查手册.md) (2026-07-27 one-shot reference for talking to colleagues / boss / agents about what OpenWiki is). ## Supporting toolchain (AI-side) @@ -106,8 +104,7 @@ The architecture shows three agent surfaces sharing the OpenWiki memory substrat - **Master template:** [`/sources/ldr-report-template.md`](/sources/ldr-report-template.md) — 8 铁律 + 3 trigger modes (精简 4 步 vs 完整 8 步 vs 自动) + 5-section report template (做什么 / 3 发现 / 4 维产品对接 / 局限 / 转发语+落款+PDF). Total report length 800–1500 characters. - **SOP lessons:** [`/sources/2026-07-27-4-27-sop-vs-implementation.md`](/sources/2026-07-27-4-27-sop-vs-implementation.md) — 9-step SOP vs 7-27 凭印象实操 comparison. PyMuPDF xref dedup + 30KB filter + p1 logo 剔除. NocoDB v1 + JSON body (范本 v2 fails 3x). SeaFile `?dl=1` suffix required. 3-frame SeaFile image 嵌入 markdown. - -- **Toolchain打通战报:** [`/sources/memory-2026-07-16-tools-final.md`](/sources/memory-2026-07-16-tools-final.md) — 2026-07-16 OpenWiki + Gitea + NocoDB + RAGFlow + Wiki.js + MiniMax code 端到端打通. 9 链路. +- **Toolchain打通战报:** [`/memory-2026-07-16-tools-final.md`](/memory-2026-07-16-tools-final.md) — 2026-07-16 OpenWiki + Gitea + NocoDB + RAGFlow + Wiki.js + MiniMax code 端到端打通. 9 链路. ### Remote access (RustDesk) @@ -141,11 +138,9 @@ The architecture shows three agent surfaces sharing the OpenWiki memory substrat | Question | Go to | | --- | --- | | What is OpenWiki and how do I use it? | [`/sources/OpenWiki速查手册.md`](/sources/OpenWiki速查手册.md) | - -| What connectors does OpenWiki have? | [`/sources/README-ACTIVATION.md`](/sources/README-ACTIVATION.md) | +| What connectors does OpenWiki have? | [`/README-ACTIVATION.md`](/README-ACTIVATION.md) | | What is the LDR report format? | [`/sources/ldr-report-template.md`](/sources/ldr-report-template.md) | | What are the LDR SOP lessons? | [`/sources/2026-07-27-4-27-sop-vs-implementation.md`](/sources/2026-07-27-4-27-sop-vs-implementation.md) | | How is RustDesk configured? | [`/sources/rustdesk-sop.md`](/sources/rustdesk-sop.md) | - -| What did Robin do on 2026-07-16 (toolchain通)? | [`/sources/memory-2026-07-16-tools-final.md`](/sources/memory-2026-07-16-tools-final.md) | +| What did Robin do on 2026-07-16 (toolchain通)? | [`/memory-2026-07-16-tools-final.md`](/memory-2026-07-16-tools-final.md) | | What is the ITX 24h host build? | [`/commitments.md`](/commitments.md) `itx-24h-host-build-2026-q3` | \ No newline at end of file diff --git a/themes/04-local-llm.md b/themes/04-local-llm.md index 1a026b8..7929d73 100644 --- a/themes/04-local-llm.md +++ b/themes/04-local-llm.md @@ -19,31 +19,30 @@ This is the synthesis page for **本地大模型部署** — Robin's local infer ## Local-LLM fleet architecture - -```text +```mermaid flowchart TD subgraph Desktop["Desktop · 192.168.192.67"] - OllamaServe["Ollama serve
:11434"] - QwenV["qwen2.5vl:7b
(vision)"] - NomicE["nomic-embed-text
(embed)"] - LMStudio["LM Studio
:7997"] - BgeM3LM["BAAI/bge-m3
(embed via LM Studio)"] - Reranker["bge-reranker
:8090"] + OllamaServe["Ollama serve :11434"] + QwenV["qwen2.5vl:7b (vision)"] + NomicE["nomic-embed-text (embed)"] + LMStudio["LM Studio :7997"] + BgeM3LM["BAAI/bge-m3 (embed via LM Studio)"] + Reranker["bge-reranker :8090"] OllamaServe --> QwenV OllamaServe --> NomicE LMStudio --> BgeM3LM end subgraph NAS["NAS · 10.10.10.254"] - RAGFlow["RAGFlow KB
:9980
18 KB / 32,709 docs"] - NocoDB["NocoDB
:8081
13 lit tables"] - SeaFile["SeaFile
:9898
4 repos / 77 GB"] - WikiJS["Wiki.js
:3000
~1500 pages"] - Feishu["Feishu mail
IMAP poll (awaiting creds)"] + RAGFlow["RAGFlow KB :9980 (18 KB / 32,709 docs)"] + NocoDB["NocoDB :8081 (13 lit tables)"] + SeaFile["SeaFile :9898 (4 repos / 77 GB)"] + WikiJS["Wiki.js :3000 (~1500 pages)"] + Feishu["Feishu mail IMAP poll (awaiting creds)"] end subgraph Agents["Agents (see theme 03)"] Hermes[Hermes Agent] MiniMaxCode[MiniMax code] - CronDaily["cron 02:30
update-sources.sh"] + CronDaily["cron 02:30 update-sources.sh"] end RAGFlow -.embedding.-> OllamaServe @@ -59,7 +58,7 @@ flowchart TD CronDaily -->|count refresh| NocoDB CronDaily -->|count refresh| SeaFile CronDaily -->|count refresh| WikiJS - QwenV -.vision OCR.-> LDR["LDR SOP
(theme 05)"] + QwenV -.vision OCR.-> LDR["LDR SOP (theme 05)"] ``` The diagram shows the three local inference services (Ollama serve, LM Studio, bge-reranker) feeding the RAGFlow KB layer, with the four NAS subsystems (NocoDB / SeaFile / Wiki.js / Feishu mail) attached at the metadata / file / published-deep-read / IMAP layer. All three inference services and all four subsystems are probed nightly by `update-sources.sh` at 02:30. @@ -147,14 +146,13 @@ Each subsystem has its own source page; the bullets below are the cross-agent qu Two cron pipelines drive the local-LLM fleet: - -```text +```mermaid flowchart LR subgraph Cron1["02:00 daily · openwiki-update.sh"] HN[Hacker News ingest] Tavily[Tavily web search ingest] GitRepo[git-repo ingest] - M3["M3 agent synthesis
writes /themes + /commitments"] + M3["M3 agent synthesis (writes /themes + /commitments)"] end subgraph Cron2["02:30 daily · openwiki-update-sources.sh"] NocoDBP[NocoDB count refresh] @@ -166,12 +164,12 @@ flowchart LR FeishuP[Feishu INBOX poll] end subgraph Runtime["Local inference runtime"] - OllamaEmbed["Ollama :11434
nomic-embed-text"] - LMStudioEmbed["LM Studio :7997
BAAI/bge-m3"] + OllamaEmbed["Ollama :11434 (nomic-embed-text)"] + LMStudioEmbed["LM Studio :7997 (BAAI/bge-m3)"] RerankerSvc["bge-reranker :8090"] end subgraph Sink["Wiki sink"] - OpenWiki[OpenWiki
commit and push Gitea] + OpenWiki[OpenWiki (commit and push Gitea)] end Cron1 --> OpenWiki Cron2 --> OpenWiki @@ -213,7 +211,7 @@ The 02:00 cron pulls 3 connectors and runs M3 agent synthesis (writes to `/theme | What is the Feishu mail integration status? | [`/sources/feishu-mail.md`](/sources/feishu-mail.md) | | How are the LDR PDFs and figures uploaded to SeaFile? | [`/sources/ldr-report-template.md`](/sources/ldr-report-template.md) §4-5 | | What did the 7-27 SOP-vs-implementation pass reveal about the service-down incident? | [`/sources/2026-07-27-4-27-sop-vs-implementation.md`](/sources/2026-07-27-4-27-sop-vs-implementation.md) §4 | - -| What is the daily cron pipeline? | [`/sources/README-ACTIVATION.md`](/sources/README-ACTIVATION.md) §3 | + +| What is the daily cron pipeline? | [`/README-ACTIVATION.md`](/README-ACTIVATION.md) §3 | | How does MiniMax code read this stack? | [`/sources/OpenWiki速查手册.md`](/sources/OpenWiki速查手册.md) §5.8 | | How does the agent layer depend on this fleet? | [`/themes/03-ai-agents.md`](/themes/03-ai-agents.md) | \ No newline at end of file diff --git a/themes/05-robin-research.md b/themes/05-robin-research.md index 15ed882..bf3236d 100644 --- a/themes/05-robin-research.md +++ b/themes/05-robin-research.md @@ -20,23 +20,22 @@ This is the synthesis page for **Robin 个人研究项目** — the durable body ## Research output — data model - -```text +```mermaid erDiagram - VAULT["Obsidian vault
(1a81e485)"] ||--o{ DEEPREADS["Deep-read notes
~1,202"] - VAULT ||--o{ TRAIN["Sales training
(CelVivo赋能培训 v1-v9)"] - VAULT ||--o{ SALES["Active sales pipeline
(惠百生物 PO + 中间商)"] - VAULT ||--o{ CRM["Distributor profiles
(董慧群 + 待补)"] - VAULT ||--o{ ENDCUST["End-customer dossiers
(11+ 神经/中药/肿瘤所)"] - VAULT ||--o{ INDUSTRIAL["Industrial customers
(CelVivo中国工业客户开发)"] - VAULT ||--o{ MEMORY["Daily + weekly reports
(memory/ 147 .md)"] - VAULT ||--o{ ITX["ITX 24h host build
(untracked)"] + VAULT["Obsidian vault (d7df3830)"] ||--o{ DEEPREADS["Deep-read notes ~1,202"] + VAULT ||--o{ TRAIN["Sales training (CelVivo赋能培训 v1-v9)"] + VAULT ||--o{ SALES["Active sales pipeline (惠百生物 PO + 中间商)"] + VAULT ||--o{ CRM["Distributor profiles (董慧群 + 待补)"] + VAULT ||--o{ ENDCUST["End-customer dossiers (11+ 神经/中药/肿瘤所)"] + VAULT ||--o{ INDUSTRIAL["Industrial customers (CelVivo中国工业客户开发)"] + VAULT ||--o{ MEMORY["Daily + weekly reports (memory/ 147 .md)"] + VAULT ||--o{ ITX["ITX 24h host build (untracked)"] DEEPREADS }o--|| VENDOR["Vendor mapping"] - VENDOR ||--|{ CelVivo["CelVivo
(ClinoStar / ClinoReactor)"] - VENDOR ||--|{ ThreeBrain["3Brain
(BioCAM / Accura-3D / CorePlate)"] - VENDOR ||--|{ Cellink["Cellink
(BIO X / BIONOVA X / Lumen X)"] - VENDOR ||--|{ Femtobiomed["Femtobiomed
(CellShot / TriArm / CellPick)"] + VENDOR ||--|{ CelVivo["CelVivo (ClinoStar / ClinoReactor)"] + VENDOR ||--|{ ThreeBrain["3Brain (BioCAM / Accura-3D / CorePlate)"] + VENDOR ||--|{ Cellink["Cellink (BIO X / BIONOVA X / Lumen X)"] + VENDOR ||--|{ Femtobiomed["Femtobiomed (CellShot / TriArm / CellPick)"] SALES }o--|| CelVivo CRM }o--|| CelVivo @@ -49,17 +48,17 @@ The diagram shows Robin's research substrate: a single Obsidian vault with 8 buc ## Knowledge substrate: Obsidian vault -Snapshot from [`/sources/git-repo.md`](/sources/git-repo.md) (last fetch 2026-08-03T18:13:23Z): +Snapshot from [`/sources/git-repo.md`](/sources/git-repo.md) (last fetch 2026-08-08T18:11:31Z): | Field | Value | | --- | --- | -| Repo path | `/mnt/c/Users/20864/.openclaw/workspace` | +| Repo path | `/home/ldw/workspace` | | Branch | `main` | -| HEAD | `1a81e485b6f8a4496122464f1151702d09f03cf0` (2026-07-29) | -| Ahead of origin/main | 9 commits (un-pushed as of fetch) | +| HEAD | `d7df3830a28a48b0129a46729ab2357e231a2ec5` (2026-08-08) | +| Ahead of origin/main | 9 commits new since 2026-08-03 fetch (Fernandez Vallone 2026 + Microbioreactor 2026 + Liu 2026 v2-v11 + 4 经销商 hook 升级); plus 19 untracked files in working tree | | Auth | local path only — no remote, no credentials | -| Working-tree state | dirty (1 nested-submodule + 1 untracked dir + 5 untracked files) | -| Raw manifest | `~/.openwiki/connectors/git-repo/raw/2026-08-03T18-13-23-151Z/manifest.json` | +| Working-tree state | dirty (1 nested-submodule + 1 untracked dir + 19 untracked files including 8 new `02-Clients/Agents/区域-2026-0807.md`) | +| Raw manifest | `~/.openwiki/connectors/git-repo/raw/2026-08-08T18-11-31-856Z/manifest.json` | ### Vault navigation index (top-level folders) @@ -146,8 +145,7 @@ From [`/sources/ldr-report-template.md`](/sources/ldr-report-template.md) (Robin | 3. 9 项强制 + 创新点/局限性/学术启示 3 段 | 7-27 教训 (2 篇缺 3 段) | 模板 §3 | | 4. SeaFile URL hostname `fb.biokingdom.top` | 7-27 教训 (5 URL 错) | 验证 share-link 真能开 | | 5. NocoDB v1 + JSON body (范本 v2 失败 3 次) | 7-27 Tasevska 入库 | `POST /api/v1/db/data/wzg1wtad/p2z4g0s687axyvu/{table_id}` | - -| 6. 3 张真图 `![]()` (SeaFile URL), 不**只**文字图说啥 | 7-27 教训 | `!\[alt\](url)` markdown | +| 6. 3 张真图 `![]()` (SeaFile URL), 不**只**文字图说啥 | 7-27 教训 | markdown image syntax (`alt text` + parenthesized URL) | | 7. 报告路径 `journal-year-topic` (4-27 SOP 范本) | 7-27 教训 | `ejps-2025-hctz-sse-3d-printing` 风格 | | 8. 精简 4 步 vs 完整 8 步按 Robin 信号自动判断 | 7-27 实战 | 模板 §2 | @@ -172,13 +170,22 @@ From [`/sources/ldr-report-template.md`](/sources/ldr-report-template.md) (Robin | Hodge 2025 RegenMed | Ronawk Bio-Block (KB 0 命中) | `04-Literature/Deep-Reads/RegenMed/2026-07-28_Hodge_2025_RegenMed_MSC_3D_Bio-Block.md` | (not yet synthesized to `/sources/`) | | Lee 2025 Front Vet Sci | (no vendor) | `04-Literature/Deep-Reads/Other/2026-07-28_Lee_2025_FrontVetSci_canine_MSC_3D_spheroid.md` | (not yet synthesized) | | Parate 2020 SCRT | (no vendor) | `04-Literature/Deep-Reads/Other/2026-07-28_Parate_2020_SCRT_PEMF_MSC_paracrine_cartilage.md` | (not yet synthesized) | +| Sharma 2026 Cell Stem Cell (2026-08-08 flywheel-sync) | 3Brain + CelVivo adjacent | `/home/ldw/workspace/retinal_organoid_deep_read_2026-08-07.md` | [`/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md`](/sources/literature-sharma-2026-cell-stem-cell-vascularized-retinal-organoid-rgc-deepread.md) | +| Miao 2025 Cell v2 (2026-08-08 flywheel-sync) | CelVivo (ClinoStar rating 5) | `/home/ldw/workspace/Miao2025_Cell_v2.md` | [`/sources/literature-miao-2025-cell-vascularization-v2-deepread.md`](/sources/literature-miao-2025-cell-vascularization-v2-deepread.md) | +| Liu 2026 Nat Biomed Eng (2026-08-08 flywheel-sync) | 3Brain (HD-MEA rating 5) + Cellink (microlattice rating 5) | `/home/ldw/workspace/Liu2026_NBME_shape_conformal_organoid.md` | [`/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md`](/sources/literature-liu-2026-nbme-shape-conformal-organoid-deepread.md) | -## Recent 30-day research output (mtime 2026-06-16 → 2026-07-28) +## Recent 30-day research output (mtime 2026-06-16 → 2026-08-08) From [`/sources/literature.md`](/sources/literature.md) last sync, broken out by vendor and date: | Date | DOI / slug | Vendor | Topic | | --- | --- | --- | --- | +| 2026-08-08 | `10.3390/cells15110963` (Fernandez Vallone 2026) | (NAMs adjacent, hiPSC brain organoid) | THSDC chemical evaluation platform using hiPSC brain organoids (Cells, v2 5 张真图 + 双 H1; Wiki.js Id 1698) | +| 2026-08-08 | `10.3389/fbioe.2026.1854988` (Rosero 2026) | CelVivo + Cellink + FemtoBiomed adjacent | Microbioreactor design Mini Review (Front Bioeng Biotechnol; 6× productivity vs T-flask; 4 applications: CAR-T / mAb / iPSC / organoid) | +| 2026-08-08 | `10.1038/s41551-026-01620-y` (Liu 2026) | 3Brain (HD-MEA rating 5) + Cellink (microlattice rating 5) | Shape-conformal porous framework for full-coverage neural organoid e-phys — Rogers Lab, Nat Biomed Eng | +| 2026-08-08 | `10.1016/j.cell.2025.05.041` (Miao 2025 v2) | CelVivo (ClinoStar rating 5) | Co-development mesoderm+endoderm for vascularized lung/gut organoids (Cell v2) | +| 2026-08-08 | `10.1016/j.stem.2025.12.013` (Sharma 2026) | 3Brain (HD-MEA rating 4) + CelVivo (ClinoStar rating 3) | Vascularized retinal organoid RGC survival (Cell Stem Cell) | +| 2026-08-06 | `10.1038/s41467-024-44732-2` (Parfitt 2024) | CelVivo + 3Brain adjacent | DJ1 LOF midbrain organoid PD model — α-syn via astrocyte lysosomal degradation (Nat Commun, untracked) | | 2026-07-29 | Organoids for disease modeling and treatment 2026 综述 (PMID 41545895, PMC12828948) | review | Exp Hematol Oncol 2026 — 190 项临床试验 + 4 大瓶颈 | | 2026-07-28 | `10.1080_17460751.2025.2572177` (Hodge 2025) | Ronawk Bio-Block | MSC longevity 4-week comparison | | 2026-07-28 | `10.3389/fvets.2025.1500267` (Lee 2025) | (no vendor) | canine adipose MSC 3D spheroid | @@ -197,14 +204,14 @@ From [`/sources/literature.md`](/sources/literature.md) last sync, broken out by By vendor (30-day mtime): -| Vendor | Most recent | -| --- | --- | -| CelVivo | 2026-07-17 (CS vs OS + Planimetry) | -| 3Brain | 2026-07-27 (Raji 2026) | -| Cellink | 2026-07-27 (Tasevska 2025) | -| Adjacent (no vendor) | 2026-07-29 (Organoids 2026 综述) | +| Vendor | Most recent | 2026-08-08 additions | +| --- | --- | --- | +| CelVivo | 2026-08-08 (Miao 2025 v2 — ClinoStar rating 5) | +Miao 2025 v2 (ClinoStar co-differentiation), +Sharma 2026 (ClinoStar rating 3 adjacent), +Liu 2026 (ClinoStar rating 4 adjacent) | +| 3Brain | 2026-08-08 (Liu 2026 — HD-MEA rating 5) | +Liu 2026 (shape-conformal framework, next-gen HD-MEA), +Sharma 2026 (HD-MEA rating 4 adjacent) | +| Cellink | 2026-07-27 (Tasevska 2025) | +Liu 2026 (microlattice fabrication rating 5 adjacent) | +| Adjacent (no vendor) | 2026-08-08 (Sharma 2026 retinal vascularization) | +Sharma 2026 (retinal organoid application domain) | -The pipeline is **vendor-balanced** — CelVivo, 3Brain, Cellink each have a recent deep read, and the broad organoid corpus is sustained by Ronawk Bio-Block, canine MSC, PEMF MSC paracrine, and the 2026 综述. +The pipeline is **vendor-balanced** — CelVivo, 3Brain, Cellink each have a recent deep read, and today's flywheel-sync (2026-08-08) adds **3 papers spanning all 3 primary vendors + the retinal organoid application domain** (Sharma), all 3 rated 4-5 on at least one vendor's product line. The **first entry in the new NocoDB table `Robin_Picked_Papers`** is Liu 2026 (created 2026-08-08 per Robin instruction to capture papers Robin hand-picks / provides outside the regular PubMed triage). ## Sales ammunition pipeline @@ -230,30 +237,39 @@ Per `/sources/git-repo.md` §"Notable entities", `06-Sales/Content/Training-Mate The version progression is `基础 → 5大管线 → 深度版 → 终稿修正 → 销量仅看` — the cluster is iterated in place, not committed. See [`/sources/vault-mtime-snapshot-2026-07-16.md`](/sources/vault-mtime-snapshot-2026-07-16.md) for the latest mtime census (CelVivo_销售培训_PPT_v9 = 2026-06-26 14:13). -## China distributor map (261 dealers across 7 regions) +## China distributor map (259 dealers across 7 regions — 2026-08-07 baseline) -From [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) (Hermes整理, 2026-08-07): +From [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) (Hermes整理, 2026-08-07; **replaces 2026-07-24 baseline of 261 dealers**): -| Region | Count | Share | Main city | -| --- | ---: | ---: | --- | -| 华北 | 74 | 28.4% | 北京 (54) | -| 华东 | 68 | 26.1% | 上海 (53) | -| 华南 | 62 | 23.8% | 广州 (44) | -| 山东 | 25 | 9.6% | 济南 (22) | -| 湖北 | 19 | 7.3% | 武汉 (12) | -| 西北 | 6 | 2.3% | 西安 (6) | -| 西南 | 7 | 2.7% | 重庆 (3) | -| **TOTAL** | **261** | 100% | — | +| Region | 8-07 count | 7-24 count | Δ | Share | Main city | +| --- | ---: | ---: | ---: | ---: | --- | +| 华北 | 72 | 74 | -2 | 27.8% | 北京 (54) | +| 华东 | 68 | 68 | 0 | 26.3% | 上海 (53) | +| 华南 | 62 | 62 | 0 | 23.9% | 广州 (44) | +| 山东 | 25 | 25 | 0 | 9.7% | 济南 (22) | +| 湖北 | 19 | 19 | 0 | 7.3% | 武汉 (12) | +| 西北 | 6 | 6 | 0 | 2.3% | 西安 (6) | +| 西南 | 7 | 7 | 0 | 2.7% | 重庆 (3) | +| **TOTAL** | **259** | **261** | **-2** | 100% | — | Brand keyword map (top 20 by 全国 count): BI 19 / Thermo 19 / Bio-Rad 11 / 赛默飞 8 / 安捷伦 7 / 蔡司 6 / Cytiva 6 / 伯乐 6 / 徕卡 6 / 赛多利斯 5 / Eppendorf 5 / Leica 5 / Beckman 4 / Merck 4 / Waters 4 / Azure 3 / Bruker 3 / Oxford Nanopore 3 / Agilent 3 / Sartorius 3. +**8-07 独有产品-代理映射 (from `_known_associations.md`):** + +| 产品线 | 关联代理 / 中间方 | 关联客户 / 商机 | +|---|---|---| +| CelVivo (ClinoStar) | **济南成全生物科技 (曹沛起)** — 华北 + 山东 跨区重复 | 董慧群 (CelVivo 技术同事) — 8-07 hook 4 候选 | +| FemtoBiomed (CellShot / PROLIVA) | **9X Bio (汇佰生物)** — 中间方 (0 hit in 259 dealer 表) | TriArm Therapeutics (翁靖傑 上海 CGT/CAR-T, 128 万 Phase1 / 8-10 至 8-14 现场 demo) | +| 3Brain (HD-MEA) | 0 家代理命中 | 11+ end-customer dossiers (需要补 direct agent or sell direct) | +| Cellink (BIO X) | 0 家代理命中 | (待补) | + **Data gap (regional filling rate):** 华东 营收 0/68 / 湖北 营收 0/19 / 华南 销售人数 0/62 — needs补 before next field visit. Documented at [`/sources/distributors-china-2026.md`](/sources/distributors-china-2026.md) §关键数据缺口. -**4-vendor break-out is deferred:** brand counts by region for CelVivo / 3Brain / Cellink / Femtobiomed are "待详细匹配" — the cross-match between dealer + vendor product line is not yet in the source page. +**4-vendor break-out is partially resolved:** the 2026-08-07 `_known_associations.md` index identifies CelVivo → 济南成全 + FemtoBiomed → 9X Bio; 3Brain / Cellink direct agents are still 0 (open-question `distributors-3brain-cellink-zero-coverage`). ## CRM — active distributor profiles -From [`/sources/agents.md`](/sources/agents.md) (last sync 2026-07-28): +From [`/sources/agents.md`](/sources/agents.md) (last sync 2026-07-28; 2026-08-07 `_known_associations.md` partial resolution): | 姓名 | 角色 | 代理商品牌 | 主推产品 | 首次记录 | 状态 | Vault 路径 | | --- | --- | --- | --- | --- | --- | --- | @@ -261,7 +277,9 @@ From [`/sources/agents.md`](/sources/agents.md) (last sync 2026-07-28): This is the only profile currently in the agents bucket. Robin was told about 董慧群 via WeChat DM on 2026-07-28; her role is to help push CelVivo products at the technical / demo / selection stage. Most fields are 待补 (agency name, region, phone, WeChat, customers, opportunities) — this is the only active open question in `/open-questions.md` (see `agent-dong-huiqun-celvivo`). -**Privacy rule (Robin 7-28):** `/sources/agents.md` and `/sources/distributors-china-2026.md` contain only base identity (name / role / vendor / region); sensitive fields (phone / WeChat / email / end-customer list / opportunity value) live only in the private Obsidian vault. +**2026-08-07 partial resolution (Hermes hook 4):** 4 个经销商管理 Hook 升级 (`02-Clients/Agents/_known_associations.md` commit `4b237a82`) identifies **济南成全生物科技有限公司 (曹沛起)** as the only CelVivo ClinoStar-listed agent in the 259-dealer China map (华北 + 山东 跨区重复登记). Whether 董慧群 is 济南成全的技术同事 or another dealer is still unverified — tracked as commitment `dong-huiqun-ji-nan-chengquan-link` in `/commitments.md`. The same hook 4 file maps FemtoBiomed CellShot → 9X Bio (汇佰生物) → TriArm Therapeutics (翁靖傑 上海 CGT/CAR-T, 128 万 Phase1 / 8-10 至 8-14 现场 demo), and 3Brain / Cellink / FemtoBiomed direct agents → 0 in the 259 baseline (open-question `distributors-3brain-cellink-zero-coverage`). + +**Privacy rule (Robin 7-28):** `/sources/agents.md` and `/sources/distributors-china-2026.md` contain only base identity (name / role / vendor / region); sensitive fields (phone / WeChat / email / end-customer list / opportunity value) live only in the private Obsidian vault. The 2026-08-07 `_known_associations.md` index adds the **product-line → agent → end-customer → opportunity** mapping chain — but does not break the privacy rule because sensitive fields remain in the private vault files. ## End-customer dossier set