详细内容（前10条）

1. ⭐ GSE320437 油菜素甾醇介导萼片伸长的适当协调[空间转录组学]

• ✍️ 作者：未知作者
• 🏷️ 关键词：spatial、spatial transcriptomics、transcriptomics
• 📝 描述：Contributors : Byron Rusank ; Lilijana Oliver ; Kyle Procopio ; Adrienne RoederSeries Type : OtherOrganism : Arabidopsis thalianaArabidopsis sepals must grow in a coordinated and robust fashion to a consistent size and shape to close and protect the developing flower bud. To understand how this robust coordination occurs, we use the loss of robustness mutant development related myb-like1 (drmy1), which exhibits variable sepal initiation and growth, causing failure of the sepals to close the flower bud. Specifically, drmy1 has overgrown outer (abaxial) sepals and undergrown inner (adaxial) sepals, leading to a large discrepancy in the sizes of different sepals within individual flower buds. Using single cell and spatial RNA-seq, we found changes in expression of key genes related to brassinosteroid (BR) signaling in drmy1, particularly in cell types important to young flower bud development such as epidermal cells, boundary cells, and meristematic cells. Confocal imaging of a BRI1-EMS-SUPPRESSOR1 (BES1) ratiometric reporter confirms that BR signaling is upregulated and more variable in young drmy1 sepals. Subsequently, we found that altering BR signaling in drmy1 by crossing with BR mutants or adding brassinolide (a potent brassinosteroid) or brassinazole (a brassinosteroid biosynthesis inhibitor) can partially rescue this elongation defect by differentially altering the relative growth of the inner and outer sepals. Increasing BR signaling rescues by increasing the growth of the inner sepal but not the outer sepal, while decreasing BR signaling rescues by decreasing the growth of the outer sepal but not the inner sepal. These results suggest that brassinosteroids mediate the robust coordination of the growth rates between inner and outer sepals during early development, ensuring proper flower bud closure.
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2. ⭐ GSE320380 共生原生生物之间的竞争塑造小鼠肠道黏膜免疫

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunity、gut、regex:gut(-?microbiome)?
• 📝 描述：Contributors : Marienela Y Heredia ; Paul A Kuehnert ; Kylie March ; Laura J Knoll ; Claire E O’LearySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusIntestinal protists are emerging as key modulators of host immunity and microbial ecology, yet their roles remain poorly defined. Here, we investigated the role of two distinct protists, the amoeba Entamoeba muris, and the parabasalid, Tritrichomonas, to determine how they shape gut immunity in vivo individually and together. Unlike the well-characterized inducer of type 2 immunity, Tritrichomonas, which activates the tuft cell–IL-25–ILC2 circuit in the small intestine, E. muris failed to elicit robust immune responses in the intestine or colon. However, introduction of E. muris into mice naturally colonized by Tritrichomonas spp., or co-infection with E. muris and Tritrichomonas spp. suppressed the Tritrichomonas-induced type-2 response in the small intestine. Fecal and cecal qPCR suggest that E. muris may outcompete Tritrichomonas spp., with reduced protist loads in the cecum and possibly diminished succinate-driven tuft cell activation. We also identified sex-specific differences in the intestinal response to primary Tritrichomonas spp. colonization which have not previously been described. These findings reveal that E. muris can dampen existing type-2 immune circuits without triggering overt inflammation, underscoring its role as an immunomodulatory agent. This work provides a framework for understanding how commensal protists interact within the gut ecosystem and shape mucosal immunity in the absence of pathogenicity.
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3. ⭐ GSE312957 用于靶向癌症化疗免疫疗法的先进双有效载荷抗体药物偶联物（DualADCs）

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、antibody、regex:immuno(logy|therapy|suppression)
• 📝 描述：Series Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAntibody–drug conjugates (ADCs) are a powerful class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. In this study, we developed novel dual-payload ADC (DualADC) platforms that enable co-delivery of a chemotherapeutic agent for direct tumor cell killing and a toll-like receptor agonist to stimulate antitumor immunity. Using triple-negative breast cancer (TNBC) as a model, we established advanced cysteine/lysine co-conjugation strategies optimized for antibody–drug ratio (ADR) and drug–drug ratio (DDR). These refinements minimized hydrophobicity-induced precipitation, enhanced conjugation efficiency, and improved formulation stability. In vivo evaluations in two xenograft mouse models demonstrated strong antitumor efficacy, highlighting the therapeutic potential of DualADCs as a next-generation approach for synergistic chemo-immunotherapy.
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4. ⭐ GSE309163 吉瑞替尼和维奈托克抑制P300/CBP靶向表观遗传突变型AML中的白血病干细胞[ChIP-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：leukemia、ChIP-seq、epigenetic
• 📝 描述：Contributors : Melanie L Goetz ; Jennifer S Romer-Seibert ; Amanda M Versace ; Scott Kogan ; Robert L Bowman ; Nigel Brooks ; Kis Frese ; Sara E MeyerSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusAcute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult AML patients and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (Inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and proliferation factors to effectively block leukemogenesis. This work identifies potential clinical utility of a novel, targeted, triplet combination therapy for treatment of AML.
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5. ⭐ GSE309162 吉瑞替尼和维奈托克抑制P300/CBP靶向表观遗传突变型AML中的白血病干细胞[RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：leukemia、RNA-seq、epigenetic
• 📝 描述：Contributors : Melanie L Goetz ; Jennifer S Romer-Seibert ; Amanda M Versace ; Scott Kogan ; Robert L Bowman ; Nigel Brooks ; Kis Frese ; Sara E MeyerSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAcute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult AML patients and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (Inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and proliferation factors to effectively block leukemogenesis. This work identifies potential clinical utility of a novel, targeted, triplet combination therapy for treatment of AML.
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6. ⭐ GSE293657 鸡体内 RAG1 非依赖性非典型 B 细胞发育：重新定义 RAG1 在禽类免疫学中的作用

• ✍️ 作者：未知作者
• 🏷️ 关键词：immunology、B cell、regex:immuno(logy|therapy|suppression)
• 📝 描述：Contributors : Seung Je Woo ; Kyung Youn Lee ; Jin Lee Kim ; Tae Hyun Kim ; Jin-Kyoo Kim ; Jae Yong HanSeries Type : Expression profiling by high throughput sequencingOrganism : Gallus gallusThe importance of RAG1 in avian B cell development has been a topic of significant debate, as chickens exhibit limited antibody diversity through RAG1-mediated V(D)J recombination compared to mammals. In chickens, antibody diversity is predominantly achieved through gene conversion in the bursa of Fabricius. However, the absence of RAG1 disrupts gene conversion and impairs B cell signaling pathways, underscoring its importance. In this study, we utilized a RAG1-deficient chicken model to uncover a classical RAG1-dependent and an alternative RAG1-independent B cell developmental pathway unique to avians. Unlike mammals, where RAG1-induced double-strand breaks (DSBs) activate ATM-dependent DNA damage responses (DDR) for B cell development, we found that ATR mediates this process in chickens. In RAG1-deficient chicken bursa, normal development of B cells is halted due to the absence of V(D)J recombination and reduced ATR-mediated B cell development signals. Although the absence of RAG1 significantly reduced B cell numbers, a small number of B cell subset was still observed. These atypical B cells (ABCs), which developed in the bursa, exhibited reduced ATR-mediated signaling but elevated expression of inflammatory and migration-related genes, allowing them to migrate into the bursa. ABCs were also specifically observed in peripheral organ (spleen) of RAG1-deficient chicken and expressed IgM with only harboring J and C segments. Additionally, ABCs displayed autoimmune-like phenotypes, including lysosome, TLR signaling activation, autophagy, and inflammation. This study highlights avian-specific alternative RAG1-independent B cell development and provides insights into autoantibody-independent mechanisms of autoimmune diseases, contributing to comparative immunology and therapeutic development.
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7. GSE316643 利用 GeoMx DSP 对 mRNA 疫苗相关心肌炎病例的人类心脏组织进行空间转录组分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：vaccine、spatial
• 📝 描述：Contributor : Atsushi KawaguchiSeries Type : OtherOrganism : Homo sapiensSpatial transcriptomic analysis was performed using the NanoString GeoMx Digital Spatial Profiler to characterize region-specific gene expression patterns in heart tissue sample obtained from mRNA vaccine-associated myocarditis cases.
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8. GSE313815 内皮脂肪4调控肿瘤血管生成和肿瘤免疫

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity
• 📝 描述：Contributors : Kyunghee Choi ; Yoojung KwonSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe atypical cadherin FAT4 has mainly been studied as a tumor suppressor, but a pan-cancer analysis of its expression in human tumors suggests this view is likely oversimplified. Here, we identify that across multiple cancer types, FAT4 expression was enriched in cancer patients with high angiogenic activity and low T-cell immunity signatures and was predominantly observed in tumor endothelial cells. Consistently, endothelial Fat4 is required for both retinal and tumor angiogenesis in preclinical mouse models. Mechanistically, FAT4 governs endothelial planar cell polarity (PCP), which is essential for coordinated sprouting and vessel patterning. Strikingly, loss of endothelial FAT4 normalizes tumor vessels, enhances tumor immunity and responsiveness to immune checkpoint blockade, suggesting that targeting FAT4 can overcome endothelial cell anergy and restore anti-tumor immunity. These findings reposition FAT4 as a regulator that links angiogenesis to tumor immunity and extend its function beyond a tumor-cell-intrinsic suppressor. Targeting this pathway may offer an opportunity to normalize tumor vasculature and enhance immunotherapy, but its clinical success will hinge on recognizing the distinct and context-dependent roles of FAT4 in tumor cells and within the tumor microenvironment.
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9. GSE310401 沉默的BASP1基因的重新激活抑制了人结直肠癌细胞中的致癌WNT信号通路

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、regex:onco(logy|logist|gene|genic)
• 📝 描述：Contributors : Weber Leonie ; Hartl MarkusSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensStarting from human colon cancer cells showing aberrant WNT/β-catenin/TCF4 signaling, hyperactivated MYC and silenced BASP1, we generated stable cell lines overexpressing BASP1, either ectopically, or by reactivating the dormant BASP1 promoter using a lentiviral CRISPR-based system. BASP1 encodes a neuronal signaling protein and transcriptional co-repressor, from which a tumor-suppressive function has been described in avian cell systems and in multiple human cancer cell types. Proteome and transcriptome analyses revealed activation of several tumor and metastasis suppressors in BASP1-expressing cells, which also show strong repression of the transformed phenotype in terms of contact inhibition, anchorage-independent growth, and tumorigenesis. Cells with reactivated BASP1 display a flat and differentiated morphology with enhanced migratory potential, accompanied by expression of multiple genes implicated in actin polymerization, focal adhesion, and neuronal migration. Furthermore, MYC protein expression is substantially repressed due to BASP1-mediated transcriptional MYC downregulation involving BASP1 interaction with β-catenin and binding to the MYC promoter. Upon BASP1 activation, multiple key proteins of the canonical WNT signaling pathway become suppressed. One of these BASP1 targets is the protein kinase TNIK catalyzing phosphorylation of TCF4, the latter required for transcriptional MYC activation. Results obtained with a preclinical TNIK inhibitor in human colorectal cancer cells show efficient abrogation of MYC expression and consequently impaired dimerization with its interaction partner MAX. The antagonistic BASP1 effect on MYC and the MYC dependency on TNIK could enhance the development of strategies to interfere with oncogenic functions of the cancer driver MYC.
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10. GSE292449 NOC4L通过调控核糖体生物合成相关过程来协调神经元和咽弓的发育。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Neuronal
• 📝 描述：Series Type : Expression profiling by high throughput sequencing ; OtherOrganism : Danio rerioBowen-Conradi syndrome (BCS) is an autosomal-recessive disease marked by lethality and characterized by neurodevelopmental delays, microcephaly, and craniofacial abnormalities, yet remains mechanistically underexplored due to the absence of robust biological models. To address this gap, we generated the first vertebrate model of BCS through CRISPR-Cas9-mediated noc4l knockout in zebrafish. Our model recapitulates key clinical features observed in BCS patients, including microcephaly, micrognathia, and developmental delay. Histopathology revealed diminished cell proliferation and elevated apoptosis within cephalic and pharyngeal arch regions of mutants. Molecular characterization revealed that rRNA processing defects impaired ribosome biogenesis, reducing 40S and 80S subunits and polysomes, ultimately leading to suppression of protein synthesis. Mechanistically, translatomic profiling identified PPARγ signaling as a significantly downregulated pathway in noc4l mutants. Rosiglitazone-induced PPARγ activation partially rescued cranial and pharyngeal cartilage defects, while also alleviating neurodevelopmental deficits. This work establishes impaired translational machinery as the pathogenic core of BCS and highlights PPARγ agonism as a viable therapeutic strategy, with rosiglitazone demonstrating preclinical efficacy in rescuing disease-relevant phenotypes. Our findings provide both a pathophysiological framework for BCS and a platform for testing translation-targeted interventions.
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1. 超越淀粉样斑块：人工智能揭示阿尔茨海默病大脑中隐藏的化学变化

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Scientists at Rice University have produced the first full, dye-free molecular atlas of an Alzheimer’s brain. By combining laser-based imaging with machine learning, they uncovered chemical changes that spread unevenly across the brain and extend beyond amyloid plaques. Key memory regions showed major shifts in cholesterol and energy-related molecules. The findings hint that Alzheimer’s is a whole-brain metabolic disruption—not just a protein problem.
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2. 新型铁纳米材料可在不损伤健康组织的情况下清除癌细胞

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer
• 📝 描述：Scientists at Oregon State University have engineered a powerful new nanomaterial that zeroes in on cancer cells and destroys them from the inside out. Designed to exploit cancer’s unique chemistry—its acidity and high hydrogen peroxide levels—the tiny iron-based structure sparks not one but two intense chemical reactions, flooding tumors with cell-damaging oxygen molecules. This dual attack overwhelms cancer cells with oxidative stress while sparing healthy tissue.
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• GSE320445 USP18 抑制巨噬细胞中的保护性免疫反应和结核分枝杆菌的细胞内控制。
• GSE316692 基因语法定义了超螺旋介导的转录反馈 [RNA-seq]
• GSE303814 用于骨质疏松骨修复中表观遗传和免疫代谢重编程的生物正交纳米浓缩体系统
• GSE290785 RNA-seq 分析溶组织内阿米巴 KERP2 敲低株
• GSE290101 野生型和阿尔茨海默病小鼠的皮质星形胶质细胞形成由内在信号级联定义的功能亚群
• GSE288106 额颞叶变性中单细胞转录组水平和hnRNP蛋白细胞定位的改变
• GSE228508 心肌细胞βII谱蛋白通过调节线粒体呼吸功能在维持心脏功能中发挥关键作用