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1. ⭐ GSE237820：经工程化癌细胞膜修饰的纳米药物靶向CDK，激活PD-L1抗体免疫疗法，对抗免疫沙漠结肠癌肝转移

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune、antibody、regex:immuno(logy|therapy|suppression)
• 📝 描述：Contributors : Dongbing Ding ; Rongpu Liang ; Tan Li ; Tianyun LanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusImmunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the MSS/pMMR subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Thus, turning the tumor microenvironment immunologically hot is critical for activating a potent immunotherapy through immune checkpoint blockade (ICB) in this unique subtype accounting for 85% cases of total colon cancer. Here, a multifunctional nanodrug (NP-D@MP) carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody to boost the ICB-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modified the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. The nanodrug boosted the immunogenicity of tumor microenvironment, thus improving response rate of PD-L1 antibody treatment. First, CDK inhibitor (CDKi) delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells (TAMCs) sensitizing ICB therapy in CCLM of murine CT26 cell. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft (PDX) model and the patient-derived organoid (PDO) model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the TIME, and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.
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2. GSE297077 表观突变率的遗传修饰因子定位鉴定出 VIM2/4 是 CG 甲基化维持的剂量敏感负调控因子 [ATAC-seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：ATAC-seq、methylation
• 📝 描述：Contributors : Zhilin Zhang ; Wilma Wanney ; Robert J Schmitz ; Frank JohannesSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Arabidopsis thalianaSpontaneous epimutations—stochastic changes in cytosine methylation—can persist across generations in plants and are thought to contribute to phenotypic variation. Although epimutations are increasingly studied for their potential long-term effects, it remains unclear why their accumulation varies across genotypes. Here, we tracked DNA methylation across nine generations in ~400 mutation accumulation lineages derived from ~70 Arabidopsis Ler × Cvi recombinant inbred lines. Treating epimutation rates as quantitative molecular traits, we mapped a major QTL to a Cvi-derived deletion near VIM2 and VIM4, two genes involved in CG methylation (mCG) maintenance. We show that this deletion rapidly reduces genome-wide methylation to a lower steady-state and compromises mCG maintenance fidelity across generations, resulting in a ~1.5-fold increase in epimutation rates. Genotypes with elevated rates exhibited accelerated epigenetic drift and phenotypic divergence. Our findings support a punctuated-equilibrium model of mCG evolution, in which sudden disruptions to methylation homeostasis can destabilize epigenetic inheritance over longer time-scales.
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3. GSE333206 表观突变率的遗传修饰因子定位鉴定出 VIM2/4 是 CG 甲基化维持的剂量敏感负调控因子 [RNAseq_VIM2/4]

• ✍️ 作者：未知作者
• 🏷️ 关键词：methylation
• 📝 描述：Contributors : Zhilin Zhang ; Wilma Wanney ; Frank Johannes ; Yangyang Xu ; Robert J SchmitzSeries Type : Expression profiling by high throughput sequencingOrganism : Arabidopsis thalianaSpontaneous epimutations are stochastic gains and losses of cytosine methylation that arise from imperfect maintenance across cell divisions. At CG sites, such epimutations can be inherited across generations in plants and constitute a major source of CG methylation (mCG) diversity. However, why the fidelity of mCG inheritance varies among genotypes, and how this variation relates to steady-state mCG levels, remain poorly understood. Here we tracked DNA methylation over ten generations in ~400 mutation-accumulation lines derived from ~70 Arabidopsis thaliana Ler × Cvi recombinant inbred founders. By treating methylation gain and loss rates as quantitative molecular traits, we mapped a major-effect locus to a Cvi-derived deletion between VIM2 and VIM4, two components of the MET1-dependent mCG maintenance pathway. Lines carrying this deletion showed elevated VIM2/4 expression, a rapid shift of genome-wide mCG toward a lower steady state, and reduced fidelity of methylation inheritance across generations. Complementary overexpression and loss-of-function experiments identify VIM2 and VIM4 as dosage-sensitive negative regulators of mCG maintenance, in contrast to the canonical positive role of VIM-family proteins in CG methylation. Together, our results support a punctuated-equilibrium model of DNA methylome evolution, in which naturally segregating modifiers of mCG homeostasis can produce abrupt shifts in methylation state and alter the rate at which heritable epigenetic variation accumulates in plant genomes.
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4. GSE333205 表观突变率的遗传修饰因子定位鉴定出 VIM2/4 是 CG 甲基化维持的剂量敏感负调控因子 [WGBS_VIM2/4]

• ✍️ 作者：未知作者
• 🏷️ 关键词：methylation
• 📝 描述：Contributors : Zhilin Zhang ; Wilma Wanney ; Frank JohannesSeries Type : Methylation profiling by high throughput sequencingOrganism : Arabidopsis thalianaSpontaneous epimutations are stochastic gains and losses of cytosine methylation that arise from imperfect maintenance across cell divisions. At CG sites, such epimutations can be inherited across generations in plants and constitute a major source of CG methylation (mCG) diversity. However, why the fidelity of mCG inheritance varies among genotypes, and how this variation relates to steady-state mCG levels, remain poorly understood. Here we tracked DNA methylation over ten generations in ~400 mutation-accumulation lines derived from ~70 Arabidopsis thaliana Ler × Cvi recombinant inbred founders. By treating methylation gain and loss rates as quantitative molecular traits, we mapped a major-effect locus to a Cvi-derived deletion between VIM2 and VIM4, two components of the MET1-dependent mCG maintenance pathway. Lines carrying this deletion showed elevated VIM2/4 expression, a rapid shift of genome-wide mCG toward a lower steady state, and reduced fidelity of methylation inheritance across generations. Complementary overexpression and loss-of-function experiments identify VIM2 and VIM4 as dosage-sensitive negative regulators of mCG maintenance, in contrast to the canonical positive role of VIM-family proteins in CG methylation. Together, our results support a punctuated-equilibrium model of DNA methylome evolution, in which naturally segregating modifiers of mCG homeostasis can produce abrupt shifts in methylation state and alter the rate at which heritable epigenetic variation accumulates in plant genomes.
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5. GSE297108 通过绘制表观突变率的遗传修饰因子图谱，发现 VIM2/4 是 CG 甲基化维持的剂量敏感型负调控因子。

• ✍️ 作者：未知作者
• 🏷️ 关键词：methylation
• 📝 描述：Series Type : Methylation profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Arabidopsis thalianaThis SuperSeries is composed of the SubSeries listed below.
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6. GSE296957 表观突变率的遗传修饰因子定位鉴定出 VIM2/4 是 CG 甲基化维持的剂量敏感负调控因子 [WGBS]

• ✍️ 作者：未知作者
• 🏷️ 关键词：methylation
• 📝 描述：Contributors : Zhilin Zhang ; Robert J Schmitz ; Frank JohannesSeries Type : Methylation profiling by high throughput sequencingOrganism : Arabidopsis thalianaSpontaneous epimutations—stochastic changes in cytosine methylation—can persist across generations in plants and are thought to contribute to phenotypic variation. Although epimutations are increasingly studied for their potential long-term effects, it remains unclear why their accumulation varies across genotypes. Here, we tracked DNA methylation across nine generations in ~400 mutation accumulation lineages derived from ~70 Arabidopsis Ler × Cvi recombinant inbred lines. Treating epimutation rates as quantitative molecular traits, we mapped a major QTL to a Cvi-derived deletion near VIM2 and VIM4, two genes involved in CG methylation (mCG) maintenance. We show that this deletion rapidly reduces genome-wide methylation to a lower steady-state and compromises mCG maintenance fidelity across generations, resulting in a ~1.5-fold increase in epimutation rates. Genotypes with elevated rates exhibited accelerated epigenetic drift and phenotypic divergence. Our findings support a punctuated-equilibrium model of mCG evolution, in which sudden disruptions to methylation homeostasis can destabilize epigenetic inheritance over longer time-scales.
• 🔗 查看原文

7. GSE324132 对染色质复合物依赖性的系统性多元分析揭示了 Set1C/COMPASS 是黑色素瘤中富集的表观遗传脆弱性

• ✍️ 作者：未知作者
• 🏷️ 关键词：epigenetic
• 📝 描述：Contributors : Luisa Q Camacho ; Mohammad Fallahi-SichaniSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMelanoma exhibits lineage-specific transcriptional programs that may create selective epigenetic vulnerabilities. To identify melanoma-enriched chromatin dependencies, we analyzed large-scale CRISPR gene-dependency data from cancer cell lines together with curated epigenetic complex annotations. This analysis identified the H3K4 methyltransferase complex Set1C/COMPASS as a melanoma-enriched dependency, with CXXC1 emerging as a selectively required subunit in a subset of melanoma cell lines. Functional validation using iterative indirect immunofluorescence imaging (4i) and quantitative single-cell analysis showed that siRNA-mediated depletion of CXXC1 reduced global H3K4me3 levels and impaired proliferation in CXXC1-dependent melanoma cell lines. To define the transcriptional consequences of Set1C/COMPASS perturbation, we performed bulk RNA sequencing (RNA-seq) following siRNA-mediated depletion of CXXC1. Four melanoma cell lines (UACC62, LOXIMVI, MALME3M, and SKMEL28) were transfected with siCXXC1 or a non-targeting control (siNTC), with three independent biological replicates per condition. RNA was harvested 96 hours post-transfection and sequenced to quantify genome-wide expression changes associated with CXXC1 depletion. Transcriptomic analysis revealed suppression of proliferation-associated gene expression programs, including MYC and E2F target signatures, in CXXC1-dependent melanoma cell lines.
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8. GSE338646：对患有和未患有多囊卵巢综合征的女性胎盘组织进行RNA测序分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：sequencing
• 📝 描述：Contributor : Jie YuanSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensThis study performed bulk RNA sequencing of term placental tissues collected from women with polycystic ovary syndrome and control pregnancies. The placental transcriptomic analysis was conducted to explore potential molecular alterations associated with the amniotic fluid metabolic changes identified in the accompanying study
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9. GSE338539 基因表达调控的新机制 [RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Series Type : Expression profiling by high throughput sequencingOrganism : Arabidopsis thalianaThis study describes a novel mechanism by which histones and transcription factors coordinately regulate gene expression in plants.
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10. GSE303253 蓝斑核通过交感神经介导肺部特异性免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune
• 📝 描述：Contributors : Xiaoyu Sun ; Wanbing Dai ; Qiang Wang ; Sihan ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusIn this study, single-cell RNA sequencing (scRNA-seq) was conducted on lung tissues from adult C57BL/6J male mice under various experimental conditions. The mice were divided into control, LPS-treated, and SLC-Gq activation + LPS groups. Lung tissues were collected three days after intratracheal administration of PBS or LPS. Single-cell suspensions were prepared and processed using the BD Rhapsody system for scRNA-seq. Our objective was to investigate cell type-specific responses and transcriptional profiles in the lung microenvironment following LPS challenge, with or without SLC activation. The results provide a comprehensive single-cell atlas of mouse lung immune responses and potential targets for future interventions.
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1. 饮用水中的微小塑料可能正在增强危险细菌的活性。

• ✍️ 作者：未知作者
• 🏷️ 关键词：bacteria、regex:bacter(ia|ial|ium)
• 📝 描述：Tiny plastic particles in drinking water may be doing more than contaminating the environment. New research suggests nanoplastics can actually help harmful bacteria survive by strengthening the slimy biofilms they form inside water systems. These tougher biofilms become more resistant to disinfectants, making them harder to remove and potentially increasing public health risks.
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2. 流行的糖替代品与大脑加速衰老有关

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging
• 📝 描述：Several popular sugar substitutes may not be as harmless as they seem. Adults who consumed the most artificial sweeteners showed substantially faster declines in memory and thinking, especially if they were under 60 or had diabetes. The highest intake was linked to cognitive aging roughly 1.6 years faster than the lowest intake. Researchers stressed that more studies are needed before concluding that sweeteners are the cause.
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3. 咖啡或许通过一种隐藏的细胞开关帮助身体对抗压力和衰老。

• ✍️ 作者：未知作者
• 🏷️ 关键词：aging
• 📝 描述：Scientists may have uncovered one reason coffee is repeatedly associated with healthier aging and lower disease risk. Compounds in coffee appear to activate NR4A1, a receptor that helps protect cells from stress, inflammation, and damage. These protective effects disappeared when the receptor was removed, strengthening the connection. Surprisingly, plant-based compounds such as caffeic acid seemed far more active than caffeine itself.
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• GSE303038 小鼠海马体衰老和记忆形成过程中的单细胞多组学分析