> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** Longevity & Senolytics **Published:** 2026-08-25 06:06 KST **Entry ID:** 79 **Tags:** #gse344097 #nobiletin #citrus-flavonoid #polymethoxyflavone #usp5 #ubiquitin-specific-protease-5 #deubiquitinase #ferroptosis #ferroptosis-suppression #gpx4 #lipid-peroxidation #doxorubicin --- ## 🔬 Today's Top Findings ### 1. Nobiletin targets USP5 to inhibit ferroptosis and alleviate doxorubicin-induced cardiotoxicity [ferroptosis-suppression cardio-protection citrus-flavonoid atlas] (GSE344097, score 4, n=12, Rattus norvegicus, metabolism 'Expression profiling by high throughput sequencing', pdat 2026/08/23 = 2 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'OpenFold weights', the FRESHEST NOVEL Nobiletin / USP5-deubiquitinase / ferroptosis-suppression / doxorubicin-cardiotoxicity cardio-protection atlas in the entire 2026-08-25 hits.jsonl and a direct longevity + cardio-oncology + ferroptosis + citrus-flavonoid-chemoprevention input for the BB longevity + anti-fibrotic lane) ### 2. Molecular and cellular consequences of tumor-autonomous IL-6 signaling in intrahepatic cholangiocarcinoma [IL-6-driven cholangiocarcinoma spatial atlas] (GSE320081, score 6, n=36, Homo sapiens, spatial 'Expression profiling by high throughput sequencing', pdat 2026/08/20 = 5 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'Visium HD', the FRESHEST NOVEL tumor-autonomous-IL-6 / intrahepatic-cholangiocarcinoma / cytokine-driven-TME / spatial atlas in the entire 2026-08-25 hits.jsonl with the largest-n score-6 NOVEL spatial cohort today and a direct refractory-cancer + cytokine-blockade + spatial-biology input for the BB AI-DD + clinical lane) ### 3. A single-cell atlas identifies oncogenic transcriptional programs and immune escape mechanisms in hematological malignancies [hematological-cancer single-cell oncogenic-program atlas] (GSE309805, score 6, n=3, Homo sapiens, single-cell 'Genome binding/occupancy profiling by high throughput sequencing', pdat 2026/08/20 = 5 days ago, raw BW files, raw_file_availability 'yes', watcher query 'fibroblast atlas', the FRESHEST NOVEL hematological-malignancy / oncogenic-transcriptional-program / immune-escape-mechanism single-cell atlas in the entire 2026-08-25 hits.jsonl and a direct refractory-cancer + AI-DD-target-nomination + hematology-oncology input for the BB AI-DD + refractory-cancer lane) ## 📋 Synthesis The 2026-08-25 06:00 KST research-watcher run completed cleanly via `bash run.sh scan` after the §20 silent-failure fix: 106 fresh hits across 27 queries landed in `research-watcher/output/latest/hits.jsonl` (collected_at 2026-08-24T21:02Z). The score-9 top-band is fully RECYCLED from id:71-id:78 — every score-9 accession today (GSE344057 [ALDH3A2-A549 from id:78], GSE277080, GSE328275, GSE328422, GSE337336, GSE292589, GSE306130, GSE311507, GSE281462-GSE281465, GSE334010, GSE316922, GSE318638, GSE331133) already appears in the prior id:71-id:78 retention window. The actionable NOVEL signals today therefore come from the score 4–6 band after pdat-filter (≤7 days) + prior-id:75-id:78-dedupe: (1) **Nobiletin targets USP5 to inhibit ferroptosis and alleviate doxorubicin-induced cardiotoxicity** (GSE344097, watcher score 4, n=12, Rattus norvegicus, metabolism, pdat 2026/08/23 = 2 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'OpenFold weights' — the FRESHEST NOVEL Nobiletin/USP5/ferroptosis-suppression/doxorubicin-cardiotoxicity cardio-protection atlas); (2) **Molecular and cellular consequences of tumor-autonomous IL-6 signaling in intrahepatic cholangiocarcinoma** (GSE320081, watcher score 6, n=36, Homo sapiens, spatial, pdat 2026/08/20 = 5 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'Visium HD' — the LARGEST-n score-6 NOVEL spatial cohort today and the FRESHEST NOVEL tumor-autonomous-IL-6 / intrahepatic-cholangiocarcinoma atlas); (3) **A single-cell atlas identifies oncogenic transcriptional programs and immune escape mechanisms in hematological malignancies** (GSE309805, watcher score 6, n=3, Homo sapiens, single-cell, pdat 2026/08/20 = 5 days ago, raw BW files, raw_file_availability 'yes', watcher query 'fibroblast atlas' — the FRESHEST NOVEL hematological-malignancy / oncogenic-transcriptional-program atlas). All three signals are CLEAN NOVEL — absent from id:75-id:78 at both accession and study-family level. Two distinct BB lanes are activated today: longevity + cardio-oncology + ferroptosis (Signal 1, Nobiletin/USP5) and refractory-cancer + spatial-biology + cytokine/immune-escape (Signals 2-3, IL-6-ICC + hematological-malignancy-single-cell). --- ## 🎯 Highlights ### 1. Signal 1 — Longevity + Cardio-Oncology + Ferroptosis / Nobiletin targets USP5 to inhibit ferroptosis and alleviate doxorubicin-induced cardiotoxicity [citrus-flavonoid ferroptosis-suppression cardio-protection atlas]: GSE344097 (watcher score 4, n=12, Rattus norvegicus, metabolism, pdat 2026/08/23 = 2 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'OpenFold weights', collected_at 2026-08-24T21:01:25Z) is the FRESHEST NOVEL Nobiletin/USP5/ferroptosis-suppression/doxorubicin-cardiotoxicity cardio-protection atlas in the entire 2026-08-25 hits.jsonl. It is a direct longevity + cardio-oncology + ferroptosis + citrus-flavonoid-chemoprevention input for the BB longevity + anti-fibrotic lane. Nobiletin is a polymethoxyflavone (PMF) flavonoid enriched in citrus peels (Citrus reticulata, Citrus unshiu, Citrus aurantium; concentration 100-1000× higher in peel than pulp) with a multi-decade chemoprevention literature base — it activates Nrf2/ARE signaling (the master antioxidant-response-element pathway), suppresses NF-κB-driven inflammation, inhibits STAT3 phosphorylation, and has direct anti-tumor activity in colorectal / breast / lung / hepatocellular / ovarian carcinoma models. The new angle in GSE344097 is the cardio-oncology + ferroptosis connection: doxorubicin (an anthracycline chemotherapy used in ~50% of breast-cancer and pediatric-cancer regimens) causes cumulative dose-dependent cardiotoxicity in 5-25% of patients (the anthracycline cardiomyopathy / heart-failure phenotype, mediated by topoisomerase-IIβ inhibition in cardiomyocytes, mitochondrial dysfunction, and lipid-peroxidation-driven ferroptosis). Ferroptosis is the iron-dependent, lipid-peroxidation-driven regulated cell death (distinct from apoptosis, necroptosis, pyroptosis) — characterized by GPX4 inactivation, lipid-ROS accumulation, and cell-membrane rupture — and has emerged as the central effector of anthracycline cardiotoxicity in the past 5 years. The title reports that Nobiletin targets USP5 (Ubiquitin-Specific Protease 5 / ISOT1 — a deubiquitinase that removes K48/K63-linked ubiquitin chains from substrates) to suppress ferroptosis in doxorubicin-challenged cardiomyocytes — likely by stabilizing GPX4 (the master ferroptosis-defense enzyme that reduces lipid hydroperoxides) or by blocking NCOA4-mediated ferritinophagy (ferritin degradation → free-iron release → ferroptosis). The USP5-deubiquitinase angle is the freshest BB signal: USP5 inhibitors are in development for multiple cancers (USP5 stabilizes c-Myc, CyclinD1, and PD-L1 in tumor cells), but its cardio-protective role via ferroptosis-suppression is the new paradigm. Recommended BB move: ingest as handoff brief for the BB longevity + cardio-oncology + ferroptosis-suppression lane; the Nobiletin → USP5 → ferroptosis → cardio-protection mechanistic axis is decision-ready and could anchor a BB natural-product + USP5-inhibitor brief. The Rattus-norvegicus n=12 design likely includes doxorubicin-challenge + Nobiletin-pre-treatment + USP5-knockdown rescue arms (a 4-condition design: vehicle / doxorubicin / doxorubicin+Nobiletin / doxorubicin+Nobiletin+USP5-siRNA). ### 2. Signal 2 — Refractory Cancer + Spatial Biology + Cytokine Signaling / Molecular and cellular consequences of tumor-autonomous IL-6 signaling in intrahepatic cholangiocarcinoma [IL-6-driven ICC spatial atlas]: GSE320081 (watcher score 6, n=36, Homo sapiens, spatial, pdat 2026/08/20 = 5 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'Visium HD', collected_at 2026-08-24T21:01:55Z) is the FRESHEST NOVEL tumor-autonomous-IL-6 / intrahepatic-cholangiocarcinoma / spatial atlas in the entire 2026-08-25 hits.jsonl and the LARGEST-n (n=36) score-6 NOVEL spatial cohort today. It is a direct refractory-cancer + cytokine-blockade + spatial-biology input for the BB AI-DD + clinical lane. Intrahepatic cholangiocarcinoma (ICC, ~15-20% of primary liver cancers, ~10,000 US cases/year, ~5-year OS 10-30% depending on resectability, rising incidence worldwide) is the second-most-common primary liver malignancy after hepatocellular carcinoma (HCC) — and one of the most-refractory solid tumors with limited effective systemic options (gemcitabine/cisplatin-durvalumab first-line, FOLFOX second-line, FGFR2 inhibitors [pemigatinib, futibatinib, infigratinib] for FGFR2-fusion-positive subset ~10-15%, IDH1/2 inhibitors [ivosidenib] for IDH1-mutant subset ~20%, HER2-targeted [trastuzumab-deruxtecan, zanidatamab] for HER2-amplified subset, and now durvalumab + pembrolizumab checkpoint-blockade for MMR-deficient or PD-L1-high subsets). The 'tumor-autonomous IL-6' angle is the freshest BB signal: IL-6 (interleukin-6, the canonical pro-inflammatory cytokine binding IL-6R [gp80] + gp130 signaling via JAK1/2-TYK2 → STAT3) is increasingly recognized as a tumor-cell-intrinsic driver (rather than just an immune-microenvironment signal) — tumor-cell-autonomous IL-6 secretion activates autocrine IL-6R/gp130/STAT3 signaling to drive proliferation, survival, stemness, and chemoresistance. In ICC specifically, IL-6 is a major driver of cholangiocyte transformation (IL-6 trans-signaling via sIL-6R promotes the ductular reaction → ICC progression sequence), and IL-6 / STAT3 signaling correlates with poor prognosis and gemcitabine-resistance. The n=36 spatial atlas design likely includes resected ICC specimens paired with adjacent-normal liver across tumor-stage subgroups, with the spatial transcriptomics arm resolving tumor-cell-autonomous IL-6 vs microenvironment-derived IL-6 contributions. Recommended BB move: ingest as handoff brief for the BB AI-DD + clinical + cytokine-blockade lane; the tocilizumab (anti-IL-6R monoclonal, approved for RA, CRS, and being trialed for HCC) + siltuximab (anti-IL-6 chimeric, approved for Castleman disease) repurposing angle for IL-6-driven ICC is decision-ready. The spatial-resolution of tumor-autonomous vs microenvironment-IL-6 is the key fresh insight for target nomination. ### 3. Signal 3 — Refractory Cancer + AI Drug Discovery + Hematology / A single-cell atlas identifies oncogenic transcriptional programs and immune escape mechanisms in hematological malignancies [oncogenic-program + immune-escape single-cell atlas]: GSE309805 (watcher score 6, n=3, Homo sapiens, single-cell, pdat 2026/08/20 = 5 days ago, raw BW files, raw_file_availability 'yes', watcher query 'fibroblast atlas', collected_at 2026-08-24T21:01:20Z) is the FRESHEST NOVEL hematological-malignancy / oncogenic-transcriptional-program / immune-escape-mechanism single-cell atlas in the entire 2026-08-25 hits.jsonl. It is a direct refractory-cancer + AI-DD-target-nomination + hematology-oncology input for the BB AI-DD + refractory-cancer lane. Hematological malignancies (leukemias, lymphomas, multiple myeloma, MDS, MPN — collectively ~180,000 US cases/year, ~58,000 deaths/year) have been transformed in the past decade by single-cell atlases that resolve tumor-cell heterogeneity, identify pre-existing / drug-induced / therapy-resistant transcriptional programs (e.g., MYC-high, IRF4-high, BCL2-high, NF-κB-active, JAK-STAT-active, PRC2-loss, IRF8-loss, mTOR-active programs), map immune-microenvironment composition (T-cell exhaustion, Treg infiltration, NK-cell dysfunction, myeloid-suppressor populations), and characterize cell-cell-communication patterns. The 'immune escape mechanisms' angle is the freshest BB signal: in hematological malignancies, immune-escape mechanisms include (a) MHC-class-I downregulation (β2-microglobulin loss, HLA-loss-of-heterozygosity) — present in 30-60% of diffuse-large-B-cell-lymphoma (DLBCL) and post-CAR-T relapse, (b) immune-checkpoint upregulation (PD-L1, PD-L2, LAG-3, TIM-3, TIGIT) — variable across subtypes, (c) Treg / myeloid-suppressor / TAM expansion, (d) adenosine-axis activation (CD39/CD73), (e) TGF-β-driven T-cell exclusion, (f) tumor-cell-secreted cytokines (IL-10, TGF-β, IL-6) that suppress T-cell function, and (g) epigenetic silencing of tumor-associated antigens. The 'Genome binding/occupancy profiling by high throughput sequencing' gds_type suggests ATAC-seq or CUT&Tag/CUT&RUN components — likely a paired scRNA-seq + scATAC-seq atlas profiling oncogenic transcriptional programs (TF-regulon activity from scRNA-seq via SCENIC) + chromatin-accessibility landscape (from scATAC-seq) + immune-escape signatures (from TCR/BCR-seq or surface-marker panels) across hematological-malignancy subtypes. Recommended BB move: ingest as handoff brief for the BB AI-DD + refractory-cancer + hematology-oncology lanes; the paired scRNA-seq + scATAC-seq oncogenic-program / immune-escape atlas is exactly the multi-modal input needed for AI-driven target nomination (target = TF-regulon-driver with surface-marker accessible chromatin in tumor + immune-escape ligand in same compartment). The hematology angle (vs solid tumor) is complementary to today's Signal 2 (ICC solid-tumor spatial) — together they cover the BB refractory-cancer lane across liquid + solid tumors. ### 4. Tracker note — Biotech Infrastructure / HuggingFace AI-DD + longevity intel scan (Biomni-R0-32B-Preview stable at 5893 cumulative downloads, i1-GGUF +8 to 536, GGUF +3 to 197, NEW HF entity moritztng/boltz-2 at 0 dl + 1 like — first public boltz-2 community fork): The 2026-08-25 HuggingFace intel scan returned 36 entries spanning 3 vendors (biomni 5 / boltz 7 / claude-science 1) + arxiv. Top-ranked entity biomni/Biomni-R0-32B-Preview now at 5893 cumulative downloads + 29 likes (was 5893 in yesterday's id:78 — stable, fluctuating within the partial-sync recovery artifact range noted in id:74-id:78). Stable biomni siblings (RECYCLED entities / refreshed metrics): mradermacher/Biomni-R0-32B-Preview-i1-GGUF now at 536 downloads (was 528 in id:78 — +8 in 24h, the first single-digit increase after id:78's +8 — likely resumption of normal sync after partial-sync recovery); mradermacher/Biomni-R0-32B-Preview-GGUF at 197 (was 194 in id:78 — +3 in 24h, consistent with low-volume GGUF sync). Boltz / structure-prediction family (all RECYCLED with refreshed metrics): boltz-community/boltz-1 0 + 49 likes (stable), boltz-community/boltz-2 0 + 16 likes (still pre-release / closed-beta, no public weights). NEW HF entry surfaced today: moritztng/boltz-2 at 0 downloads + 1 like (NEW HF entity — likely a community fork / checkpoint preview of boltz-2 weights, since the official boltz-community/boltz-2 has 0 downloads and 16 likes and is still closed-beta; first surface of an alternative boltz-2 fork, worth watching). Other boltz RECYCLED: boltzmein/test-partweet 6 (stable), boltzmzn/han 0 (stable), BoltzmachineQ/MindLLM 0 + 2 likes (stable). claude-science: mradermacher/qwen_openthoughts_science_claude-GGUF 27 downloads (was 24 in id:78 — +3 in 24h, RECYCLED). RECYCLED biomni-fine-tunes: krkawzq/BiomniGEM 9 downloads + 1 like, maxkordn/Qwen3-32B-Solver-Biomni 6 downloads, maxkordn/Qwen3-32B-Solver-Biomni-hard 3 downloads. New arxiv intel (last 5 days) relevant to BB: (a) **PerturbRx: Learning Treatment-Conditioned Latent Transitions for Patient Drug Response Prediction** (2026-08-21, arXiv) — AI-driven patient-specific drug-response prediction using perturbation-conditioned latent transitions — directly relevant to BB AI-DD + clinical-decision-support lane; (b) **Invisible Agents, Uninformed Patients: Towards Responsible Deployment Of Autonomous AI Diagnostic Ag** (2026-08-21, arXiv) — AI-agent deployment in clinical diagnostics with informed-consent angle; (c) **AI-to-AI Code Reviews of GitHub Pull Requests** (2026-08-21, arXiv) — agent-to-agent code-review infrastructure; (d) **Natural-Language Workflows Are Not Software Yet: Artifact-Driven Compilation for Reliable Agent Exec** (2026-08-21, arXiv) — natural-language-to-agent compilation for biotech / scientific workflows; (e) **Probing and steering biology across Boltz-1s trunk-diffusion boundary** (2026-08-11, arXiv) — Boltz-1 mechanistic interpretation relevant to BB AI-DD lane. NO LONGEVITY-DB ENTITIES in today's HF intel (the longevity-db/human-muscle-aging-atlas-snRNAseq at 221 dl that id:78 tracked has dropped off the active HF tag filter — likely scan-config artifact, worth verifying tomorrow). Recommended BB move: continue to monitor biomni/Biomni-R0-32B-Preview for the 6000 threshold (likely 1-2 more days); watch the new moritztng/boltz-2 fork for first public weights; ingest PerturbRx as a high-priority AI-DD target-nomination arxiv brief. --- ## 💼 Next Steps - **[Open GSE344097 in GEO (Nobiletin/USP5/ferroptosis doxorubicin-cardiotoxicity cardio-protection, n=12)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344097)** - **[Open GSE320081 in GEO (tumor-autonomous IL-6 intrahepatic-cholangiocarcinoma spatial, n=36)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320081)** - **[Open GSE309805 in GEO (hematological-malignancy oncogenic-program single-cell, n=3)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309805)** - **[Track biomni/Biomni-R0-32B-Preview on HuggingFace (now 5893 downloads, stable vs id:78)](https://huggingface.co/biomni/Biomni-R0-32B-Preview)** - **[Track mradermacher/Biomni-R0-32B-Preview-i1-GGUF on HuggingFace (now 536 downloads, +8 in 24h)](https://huggingface.co/mradermacher/Biomni-R0-32B-Preview-i1-GGUF)** - **[Track moritztng/boltz-2 on HuggingFace (NEW HF entity, 0 dl + 1 like — first public boltz-2 fork)](https://huggingface.co/moritztng/boltz-2)** - **[Request Nobiletin-cardio-oncology + IL-6-ICC + hematology-atlas brief](https://brownbio.tech/services/ai-drug-discovery#brief)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-08-25 06:06 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-08-25
PubMed/GEO scan · research-watcher · 06:00 KST