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1. ⭐ GSE310443 单细胞空间转录组学揭示Fontan相关肝病中肝细胞代谢重编程

• ✍️ 作者：未知作者
• 🏷️ 关键词：metabolic、single-cell、spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Brandon M Lehrich ; Jordann N Lewis ; Vik Meadows ; Lori Schmitt ; Mylarappa B Ningappa ; Jia-Jun Liu ; Silvia Liu ; Catherine Gestrich ; Victor O Morell ; Rakesh Sindhi ; Satdarshan P Monga ; Anita SarafSeries Type : OtherOrganism : Homo sapiensBackground: Fontan-associated liver disease (FALD) is a common sequelae of single-ventricle patients palliated with the Fontan operation. FALD severity can impact clinical decisions; however, the pathophysiology of FALD progression is unknown. Methods: Single-cell spatial transcriptomics (ST) was performed on liver explant tissue sections from FALD patients with early and advanced fibrosis using CosMxTM Spatial Molecular Imaging with in-situ hybridization of 6000 genes (n=2). Immunofluorescence for hepatic zonation and cellular stress markers was used to confirm protein expression based on ST analysis in biopsy and explant FALD tissues (n=17). Results: Unbiased clustering yielded 12 liver cell types, comprising five subtypes of hepatocytes. FALD with advanced fibrosis demonstrated the expansion of mid-zonal hepatocytes, accompanied by the loss of metabolic markers associated with canonical pericentral and periportal hepatocytes. Advanced FALD hepatocytes uniquely demonstrated increased cellular stress and a redundant metabolic phenotype. Advanced FALD hepatocytes changed into a senescent-like state, which we have termed hepatocyte metabolic exhaustion. Protein expression analysis confirmed metabolic exhaustion within hepatocytes and upregulation of cellular stress markers in advanced FALD tissue specimens. Immunofluorescence staining of FALD samples demonstrated a disruption of zonation and a significant increase in heat shock protein 70 (HSP70). HSP70 expression strongly correlated with the congestive hepatic fibrosis (CHF) score. Conclusions: Single-cell ST has identified a population of hepatocytes with features of metabolic exhaustion and cellular stress unique to advanced FALD.
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2. ⭐ GSE313657 预康复作为一种生物活性干预措施，可重塑胰腺肿瘤免疫微环境，从而增强抗肿瘤免疫力

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immune、immunity
• 📝 描述：Contributors : Hong Zhao ; Renee StubbinsSeries Type : OtherOrganism : Homo sapiens ; synthetic constructThis dataset contains NanoString GeoMx Digital Spatial Profiling data generated from surgically resected pancreatic ductal adenocarcinoma (PDAC) specimens collected from patients who underwent a multimodal prehabilitation program and matched untreated controls. Spatial transcriptomic profiling was performed across immune (CD45 positive), tumor (PanCK positive), and stromal regions of interest to investigate the biological effects of prehabilitation on the PDAC tumor microenvironment. Differential expression, pathway enrichment, and immune deconvolution analyses were used to evaluate transcriptional changes associated with cytotoxic immune activation, stromal remodeling, and oncogenic signaling. The goal of this exploratory dataset is to provide an initial resource for investigating how prehabilitation may influence immune–tumor interactions in PDAC and to support future studies integrating biological and clinical endpoints.
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3. ⭐ GSE288874 结直肠癌起始细胞的整合基因组学和功能免疫学分析，以调节干性特性和对免疫反应的敏感性 [RNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune、RNA-seq
• 📝 描述：Contributors : Cristina Maccalli ; Alex Tout ; Salim BougarnSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWe conducted a Total RNAseq profiling of primary CICs-CRC and differentiated tumor cell lines-CRC (FBS), including autologous pairs. A differential gene expression profile was detected in CICs vs. FBS tumor cells. Overall, N=1187 were detected out of a total of 15,913 genes with measured expression as differentially expressed with p<0.05. Through applying the threshold of p<0.01and LogFC of 1.5, N=132 genes resulted as significantly differentially expressed in CICs as compared to FBS tumor cells. In summary, 33 pathways were found to be significantly impacted highlighting the hub function of differentially expressed genes (DEGs) (N=40) and significant pathways (N=26) (p<0.05). The differentially expressed genes include genes related to cancer development and progression, e.g., the unfolded protein response component CHAC1 as well as the hexokinase domain component 1, HKDC1 which promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression. Moreover, aldolase, fructose-bisphosphate C (ALDOC), that is associated with tumor cell spheroids formation, was 2.5-fold upregulated in CICs compared to FBS tumor cells while LCK kinase, implicated in various oncogenic processes, particularly in colorectal cancer was 5-fold upregulated in CICs. On the other hand, JUNB, a direct target of TGF-β-Smad signaling, which can act as tumor suppressor or oncogene depending on the cancer entity was found to be downmodulated in CRC-CICs vs. -FBS tumor cell lines.
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4. GSE318294 肺癌富集的 p53 突变体占据经典的 p53 靶基因，但并不激活转录，揭示了一种独特的失功能行为 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq
• 📝 描述：Contributors : Mason A Tracewell ; Hailey N Shankle ; Samantha M Barnada ; Khushali S Vyas ; Kevin M Kim ; Theodhora Qyshkollari ; Jonathan E Karlin ; Julie A Barta ; Steven B McMahonSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensLung cancer is the most common cause of cancer-related death in the U.S. and globally. Cigarette smoking remains the leading risk factor for lung cancer, in part by inducing loss-of-function mutations in tumor suppressor genes, including TP53. While most cancers share a set of common “hotspot” mutations in p53, lung cancer exhibits an additional, distinct cluster of hotspot mutations. This cluster is typified by the missense mutations TP53:p.V157F and TP53:p.R158L. While canonical hotspot mutations cause broad misfolding of p53 or eliminate specific DNA contact residues, mechanistic studies of the lung cancer mutants reported here demonstrate that they retain the ability to bind the same genomic sites as wild-type p53. Despite actively binding to traditional p53 target genes, the lung cancer mutants are defective in activating transcription. To our knowledge, this represents the first demonstration of functional inactivation of the p53 tumor suppressor at a point after DNA binding, but prior to target gene activation. Relevant to the sequential inactivation of each p53 allele during cancer progression, the lung cancer mutants block the activity of a wild-type p53 allele when co-expressed in a dominant negative manner. Identification of this loss-of-function mechanism has key implications for therapeutic strategies aimed at restoring p53 function in lung cancer.
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5. GSE318292 肺癌富集的 p53 突变体占据经典的 p53 靶基因而不激活转录，揭示了一种独特的失功能行为 [ChIP-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、ChIP-seq
• 📝 描述：Contributors : Mason A Tracewell ; Hailey N Shankle ; Samantha M Barnada ; Khushali S Vyas ; Kevin M Kim ; Theodhora Qyshkollari ; Jonathan E Karlin ; Julie A Barta ; Steven B McMahonSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensLung cancer is the most common cause of cancer-related death in the U.S. and globally. Cigarette smoking remains the leading risk factor for lung cancer, in part by inducing loss-of-function mutations in tumor suppressor genes, including TP53. While most cancers share a set of common “hotspot” mutations in p53, lung cancer exhibits an additional, distinct cluster of hotspot mutations. This cluster is typified by the missense mutations TP53:p.V157F and TP53:p.R158L. While canonical hotspot mutations cause broad misfolding of p53 or eliminate specific DNA contact residues, mechanistic studies of the lung cancer mutants reported here demonstrate that they retain the ability to bind the same genomic sites as wild-type p53. Despite actively binding to traditional p53 target genes, the lung cancer mutants are defective in activating transcription. To our knowledge, this represents the first demonstration of functional inactivation of the p53 tumor suppressor at a point after DNA binding, but prior to target gene activation. Relevant to the sequential inactivation of each p53 allele during cancer progression, the lung cancer mutants block the activity of a wild-type p53 allele when co-expressed in a dominant negative manner. Identification of this loss-of-function mechanism has key implications for therapeutic strategies aimed at restoring p53 function in lung cancer.
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6. GSE316796 IPMN 的空间分析定义了具有恶性特征的矛盾的 KRT17 阳性低级别上皮细胞群 [scRNA-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：scRNA、spatial
• 📝 描述：Contributor : Eileen S CarpenterSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBackground & Aims:Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that represent one of the few radiologically identifiable precursors to pancreatic ductal adenocarcinoma (PDAC). Though the IPMN-bearing patient population represents a unique opportunity for early detection and interception, current guidelines provide insufficient accuracy in determining which patients should undergo resection versus surveillance, resulting in a sizable fraction of resected IPMNs only harboring low-grade dysplasia, suggesting that there may be overtreatment of this clinical entity.Methods:To investigate the transcriptional changes that occur during IPMN progression, we performed spatial transcriptomics using the Nanostring GeoMx on patient samples containing the entire spectrum of IPMN disease including low-grade dysplasia, high-grade dysplasia, and IPMN-derived carcinoma. Single cell RNA sequencing was performed on side branch and main duct IPMN biospecimens.Results:We identified a subpopulation of histologically low-grade IPMN epithelial cells that express malignant transcriptional features including KRT17, S100A10 and CEACAM5, markers that are enriched in PDAC. We validated this high-risk gene signature in both single-cell RNA sequenced samples and an external ST dataset containing a larger number of IPMN samples including non-tumor bearing IPMN (i.e. low-grade IPMN in isolation). Immunofluorescence staining of a large cohort of patient tissues confirmed the presence of KRT17-positive cells, which were found to comprise a small subset of epithelial cells within histologically low-grade IPMN in a patchy distribution.Conclusions:Our study demonstrates that KRT17 marks a distinct transcriptional signature in a subpopulation of epithelial cells within histologically low-grade IPMN. This population of cells likely represents a transitional state of histologically low-grade epithelial cells undergoing progression to a higher grade of dysplasia and thus may represent a higher risk of progression to carcinoma.
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7. GSE318214 整合蛋白质组学鉴定出阿尔茨海默病中保守的Aβ淀粉样蛋白反应体、新型斑块蛋白和病理修饰因子

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer、proteomics
• 📝 描述：Contributors : Karen N McFarland ; Yona Levites ; Todd E GoldeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAlzheimer’s disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid b (Ab)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Ab amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Ab in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.
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8. GSE314373 singIST：一种用于比较疾病模型和人类单细胞转录组学的整合方法

• ✍️ 作者：未知作者
• 🏷️ 关键词：single-cell、transcriptomics
• 📝 描述：Contributors : Johann E Gudjonsson ; Lam C TsoiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDisease models are fundamental tools in drug discovery and early-stage drug development, but they only approximate human disease, and selecting a suitable model is challenging. Quantitative computational methods exist to assess molecular resemblance to human conditions, but approaching that work at single-cell resolution, and doing so in an explainable and generalizable way, remain very limited. We present singIST, a computational method for comparative single-cell transcriptomics analysis between disease models and human conditions. singIST provides explainable quantitative measures on disease model similarity to the human reference at the pathway, cell type and gene levels. These measures jointly account for gene orthology, cell type presence in the model, cell type and gene importance in the human condition, and gene level fold changes in the model, within a unifying framework that controls for the intrinsic complexities of single-cell data. We first test singIST in three well-characterized murine models against moderate-to-severe Atopic Dermatitis, showing that it recapitulates established biology while generating new hypotheses. We then apply it to Hidradenitis Suppurativa, comparing in vivo human lesions with ex vivo skin explants with and without CD3/CD28 stimulation, and show that stimulation selectively improves pathways that already recapitulate the human signal. Finally, we perform simulation studies that: (i) unit-test the implementation and behaviour of the algorithm under controlled scenarios and (ii) compare singIST against a na¨ıve baseline based on overlapping differentially expressed genes.
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9. GSE312914 基于DNA甲基化的儿童甲状腺癌侵袭性分层

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、methylation
• 📝 描述：Series Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below.
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10. GSE312587 基于DNA甲基化的儿童甲状腺癌侵袭性分层[第二批]

• ✍️ 作者：未知作者
• 🏷️ 关键词：carcinoma、methylation
• 📝 描述：Contributors : Jenny Z Li ; Julio R Filho ; Andrew J Bauer ; Aime T Franco ; Wanding ZhouSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensAccurate triage of pediatric thyroid carcinomas requires reliable biomarkers of tumor invasiveness. DNA methylation, a proven molecular analyte for cancer classification, offers potential for stratifying thyroid carcinoma behavior. In a cohort of 88 patients, we identified distinct methylation profiles associated with both tumor invasiveness and driver mutations, such as BRAF p.V600E, Ras-like, kinase fusions, and DICER1 mutations. Differentially methylated regions implicate immune infiltration and disrupted thyroid tissue development and function, implicating nuclear receptor, Hippo, and AP1 signaling pathways. Using these features, we developed accurate classifiers for tumor invasiveness and driver mutation groups. Our findings highlight the clinical utility of DNA methylation profiling for risk stratification and prognostic assessment in pediatric thyroid cancers.
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1. 转发：OpenAI Codex App：Vibe - 使用 plan+execute 将我的旧 qqman R 包更新为 ggplot2。

• ✍️ 作者：未知作者
• 🏷️ 关键词：R package
• 📝 描述：Reposted from the original at https://blog.stephenturner.us/p/openai-codex-app-qqman.Earlier this week I reposted a Bluesky post from Ethan Mollick. I’m on the same page here — there are problems for sure, but these tools have irreversibly changed th… Continue reading: Repost: OpenAI Codex App: Vibe-updating my old qqman R package to ggplot2 with plan+execute.
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1. ADAM-tRNA-seq——一种用于直接tRNA测序中解复用和增强层级映射的优化方法

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：An optimized RNA sequencing workflow improves direct Nanopore analysis of transfer RNAs, enabling accurate demultiplexing and hierarchical mapping to better quantify tRNA abundance and diversity…
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• GSE300358 TGFβ信号通路通过SOX4转录调控促进乳腺癌细胞的细胞周期进程和对CDK4/6抑制剂帕博西尼的耐药性
• GSE296440 基于DNA甲基化的儿童甲状腺癌侵袭性分层[第一批]
• GSE314660 鉴定东亚肺腺癌风险的表达和 DNA 甲基化生物标志物 [RNA-seq]
• GSE318278 三个 CBX2 分子的自聚集驱动 PRC2 促进 Polycomb 靶基因的兼性异染色质化 [RNA-Seq]
• GSE318277 三个 CBX2 分子的自聚集驱动 PRC2 促进 Polycomb 靶基因的兼性异染色质化 [Hi-C]
• GSE305695 IRE1α 通过 NR1D1 mRNA 降解和溶酶体生物合成调节免疫性血小板减少症中的巨噬细胞吞噬作用
• GSE237065 mTOR信号通路调控果蝇幼虫中有效细胞免疫反应所需的需求适应性造血和代谢重编程
• GSE317790 先导细胞的阶段特异性转录组学揭示了驱动集体入侵的细胞机制
• GSE316928 表征大脑中小胶质细胞、星形胶质细胞和神经元在健康、衰老和疾病状态下的代谢组
• GSE316003 IPMN空间分析揭示了一种矛盾的KRT17阳性低级别上皮细胞群，该细胞群具有恶性特征。
• GSE308455 基因组编辑胆管癌类器官中BAP1突变的功能表征：在细胞死亡和药物反应中的作用
• GSE303857 热休克后通读转录过程中 CPSF73 激活和 3’ Pol II 暂停消失 [ChIP-seq]
• GSE303856 热休克后通读转录过程中 CPSF73 激活和 3’ Pol II 暂停消失 [RNA-seq]
• GSE299895 转录能力决定了分离的MSR拷贝的异染色质成核潜力。[RNA-Seq]
• GSE318420 在索拉非尼联合纳武利尤单抗的 II 期临床试验中，肝功能障碍的肝细胞癌患者体内免疫抑制性单核细胞富集
• GSE318268 CMS亚型与直肠癌新辅助Galunisertib联合放化疗试验中的完全缓解相关
• GSE318059 环境诱导的表观遗传跨代遗传成人发病疾病的世代稳定性
• GSE317068 骨骼疾病细胞和遗传决定因素的多尺度分析和功能验证 [人类单细胞RNA测序]
• GSE316715 IAP 逆转录转座子促进小鼠胎盘的转录多样性 [RNA-Seq]
• GSE316711 IAP 逆转录转座子促进小鼠胎盘的转录多样性 [ATAC-Seq]
• GSE315592 大脂肪细胞增加囊泡介导的脂质释放并促进乳腺癌恶性转化
• GSE311545 阿尔茨海默病相关 circPDE4B 与 GEMIN5 相互作用以调节翻译
• GSE302937 阿尔茨海默病患者的人类鼻内嗅觉活检分析
• GSE294059 脓毒症患者和非脓毒症对照组外周血单核细胞的RNA测序
• GSE293190 木犀草素抑制类风湿关节炎中 Th17 细胞分化和脊髓浸润 [RNA-seq]
• GSE290684：全面的单细胞分析揭示了TPPU在缓解脓毒症相关急性肝损伤中的免疫调节机制
• GSE290455 激活的 CD8+ T 细胞（有或无谷氨酰胺合成酶）的 RNA 测序
• GSE285954 RNA-seq 分析了 RAW264.7 中 Dpep2 敲低的情况。
• GSE278461 独立的转录和剪接基因网络通过 pRb-E2F 通路相互连接和协调
• GSE212817 骨骼疾病细胞和遗传决定因素的多尺度分析和功能验证 [小鼠单细胞RNA测序]
• GSE314841 鉴定东亚肺腺癌风险的表达和DNA甲基化生物标志物[DNA甲基化芯片]
• GSE313764 线粒体转移至粒细胞髓系来源的抑制细胞可增强免疫抑制活性 [scRNA-seq]
• GSE318441 斑点定位激酶TAOK2对核RNA加工的协调作用
• GSE318347 小分子导向的浸没培养人鼻气道上皮分化用于呼吸系统疾病建模 [scRNA-seq]
• GSE318298 利用 CUT-taq 检测野生型 C57BL/6J 骨髓来源巨噬细胞中 EGR1 全基因组染色质占位情况
• GSE318286 SAGA/ATAC复合物维持异常染色质调控并促进弥漫性中线胶质瘤的肿瘤发生[CUT&Run]
• GSE318284 Acsl1 介导的 FA 合成损害 I 型糖尿病的骨整合 [ATAC-Seq]
• GSE318279 三个 CBX2 分子的自聚集驱动 PRC2 促进 Polycomb 靶基因的兼性异染色质化
• GSE318276 三个 CBX2 分子的自聚集驱动 PRC2 促进 Polycomb 靶基因的兼性异染色质化 [Cut & Run, Cut & Tag]
• GSE318243 缺氧诱导的lncRNA在肝细胞癌铁死亡调控中的作用和机制
• GSE317049 海藻酸钠通过 PPAR 通路激活皮下脂肪分化
• GSE316931 拟南芥 sqtl1 突变体的转录组分析
• GSE311093 Zeb2os 通过抑制 ZEB2 再激活和心肌细胞去分化来阻碍心脏愈合[2]
• GSE311091 Zeb2os 通过抑制 ZEB2 再激活和心肌细胞去分化来阻碍心脏愈合
• GSE294009 化脓性汗腺炎早期和晚期的空间转录组分析
• GSE288782 LACTB 通过促进 Hsc70 介导的 ERBB3 降解来抑制脂质合成，从而抑制胶质瘤生长