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1. ⭐ GSE316054 研究发现，靶向 ADAR1 p150 亚型可触发肿瘤生长抑制和抗肿瘤免疫，从而克服免疫治疗耐药性。

• ✍️ 作者：未知作者
• 🏷️ 关键词：tumor、immunity、regex:immuno(logy|therapy|suppression)、resistance
• 📝 描述：Contributors : Zhichao Ai ; Yuying Bian ; Gang LiSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusCancer immunotherapy efficacy is often limited by primary and acquired resistance. The RNA- editing enzyme ADAR1 has emerged as a key regulator of tumor immune evasion, yet therapeutic targeting is challenged by the essential physiological roles of its constitutively expressed p110 isoform. Here, we identify the interferon-inducible p150 isoform and its Zα domain as a critical therapeutic vulnerability. We demonstrate that ADAR1 p150 is frequently overexpressed in human cancers and correlates with an immunosuppressive tumor microenvironment. Genetic ablation of ADAR1 p150 intrinsically inhibits tumor proliferation and extrinsically triggers a robust type I interferon response and profound remodeling of the tumor immune landscape, converting immunologically “cold” tumors to “hot.” Furthermore, we establish that myeloid-specific ADAR1 deletion synergizes with anti-PD-1 therapy by enhancing antigen presentation and fostering a pro-inflammatory microenvironment. Crucially, we delineate the Zα domain as the essential structural determinant for dsRNA editing selectivity. Targeted disruption of this domain alone, without affecting the catalytic deaminase domain, is sufficient to recapitulate the potent antitumor effects of complete ADAR1 ablation, leading to accumulation of immunogenic dsRNA, activation of cytosolic sensors (MDA5/PKR), and potent anti-tumor immunity. Our work provides a compelling rationale for selectively targeting the ADAR1 p150-Zα axis to reverse malignant RNA editing and overcome resistance to immunotherapy, offering a refined strategy with a potentially superior therapeutic index.
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2. GSE310210 浆果衍生的金纳米颗粒诱导4T1三阴性癌细胞发生整合的氧化应激介导的细胞凋亡、免疫调节和转录组重塑

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、immune
• 📝 描述：Contributors : Oladapo Fagbohun ; Adewale Oladipo ; Chengyu Gao ; Babatunde Olawoye ; Rachel Berry ; Jaylah Captain ; Olive Iragena ; Xavier McDougle ; Randy Harris ; Amanda Rollins ; Jitcy Joseph ; Olatomide Fadare ; Russell KincaidSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusComprehensive molecular and phenotypic characterization of tumor models is still needed for robust understanding of breast cancer mechanisms and therapies. Here, we explore genome, transcriptome, and proteome of treated and untreated 4T1 triple-negative breast cancer cells. Nanoencapsulation (AuNPs) of berry-derived polyphenolic compounds was influenced by limited clinical use due to poor stability and bioavailability. Several physicochemical characterizations employed include TEM, FTIR, and targeted UPLC/MS-QQQ assays. We identified significant mutations to breast cancer-related tumor suppressor genes (Trp53, Brca2, Bard1, Cdh1, Nf1, and Chek2) and deciphered the function consequences leveraging on the higher throughput Illumina NovaSeq X and NextSeq 1000 sequencers and highly accurate predicting power of AlphaFold. We found ~5700000 single nucleotide variations (SNVs) and 329448 indels achieving an important upgrade over previous literature data. Key findings from differentially expressed gene enrichment analyses (GSEA) revealed positive gene enrichments of DNA repair regulators and TGF-β signaling while having negative enrichments of cell adhesion, cadherin and MAPK signaling via PI3K/AKT/MAPK/Wnt pathways, potentially influencing apoptosis and immune evasion intrinsic to cancer. Notably, decreased expression of PIK3CG, PALLD, PTPRZ1, and CDH8 and increased expression of SEMA6C, WWOX, NHEJ1, and MAML3 suggested suppression of epithelial-to-mesenchymal transition (EMT) and metastatic potential. Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles can modulate oncogenic transcription factors and induce caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1Thr212 dephosphorylation, downregulation of pPI3Kp85αγ(Tyr467/199)/pAKT1Thr450/mTOR signaling, and modulation of pJAK3Tyr785/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells. Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in…
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3. GSE301480 对从肺、肠和膀胱中分离的非血管平滑肌细胞 (NVSMC) 进行 RNA-seq 分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq、regex:intestin(e|al)
• 📝 描述：Contributors : Lei Wang ; Guenther Stefan ; Kuenne Carsten ; Andre SchneiderSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNone of the currently available Cre recombinase-expressing mouse lines allows for exclusive and specific manipulation of non-vascular smooth muscle cells (NVSMCs). To address this, we focused on the Chrm2 gene, which encodes the M2 muscarinic acetylcholine receptor (M2R), a G protein-coupled receptor (GPCR) previously reported to be expressed selectively in NVSMCs and also in CD45-positive immune cells. In contrast, Acta2 is broadly and strongly expressed in all smooth muscle cells (SMCs), including both vascular and non-vascular populations. To achieve specific labeling of NVSMCs, we generated NVSMC-effector mice by combining Chrm2-Dre with Acta2-Rox-CreER and R26-LoxP-GFP alleles. Following tamoxifen administration, we observed robust GFP fluorescence specifically in NVSMCs of the lung, stomach, and intestine. Notably, GFP labeling was virtually absent in vascular SMCs across multiple organs, confirming the specificity of this genetic strategy.
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4. GSE301477 对从肺、心脏、主动脉、胃、肠、肾和膀胱中分离的动脉平滑肌细胞 (ASMC) 进行 RNA-seq 分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq、regex:intestin(e|al)
• 📝 描述：Contributors : Lei Wang ; Guenther Stefan ; Kuenne Carsten ; Andre SchneiderSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusNone of the currently available Cre recombinase-expressing mouse lines allows exclusive and specific manipulation of arterial smooth muscle cells (ASMCs). To enable targeted manipulation of ASMCs, we generated two knock-in mouse lines: one carrying a Dre recombinase cassette inserted into the Cspg4 locus (Cspg4-Dre) and another carrying a Rox-Stop-Rox-CreER cassette inserted into the Acta2 locus (Acta2-Rox-CreER). These two lines (hereafter referred to as ASMC-effector mice) were crossed with R26-LoxP-GFP reporter animals, and the offspring were treated with three doses of tamoxifen to induce recombination. This strategy resulted in robust and specific labeling of ASMCs in virtually all arteries examined.To further enhance specificity, we generated an additional line in which a tamoxifen-inducible DreERT cassette was inserted into the Cspg4 locus. This Cspg4-DreERT line also enabled specific labeling of ASMCs in distinct organs.
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5. GSE314521 靶向ADAR1 p150亚型以克服免疫疗法耐药性

• ✍️ 作者：未知作者
• 🏷️ 关键词：regex:immuno(logy|therapy|suppression)、resistance
• 📝 描述：Contributor : Zhichao AiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCancer immunotherapy efficacy is often limited by primary and acquired resistance. The RNA-editing enzyme ADAR1 has emerged as a key regulator of tumor immune evasion, yet therapeutic targeting is challenged by the essential physiological roles of its constitutively expressed p110 isoform. Here, we identify the interferon-inducible p150 isoform and its Zα domain as a precise therapeutic vulnerability. We demonstrate that ADAR1 p150 is frequently overexpressed in human cancers and correlates with an immunosuppressive tumor microenvironment. Genetic ablation of ADAR1 p150 intrinsically inhibits tumor proliferation and extrinsically triggers a robust type I interferon response and profound remodeling of the tumor immune landscape, converting immunologically “cold” tumors to “hot.” Furthermore, we establish that myeloid-specific ADAR1 deletion synergizes with anti-PD-1 therapy by enhancing antigen presentation and fostering a pro-inflammatory microenvironment. Crucially, we delineate the Zα domain as the essential structural determinant for dsRNA editing fidelity. Targeted disruption of this domain alone, without affecting the catalytic deaminase domain, is sufficient to recapitulate the potent antitumor effects of complete ADAR1 ablation, leading to accumulation of immunogenic dsRNA, activation of cytosolic sensors (MDA5/PKR), and potent anti-tumor immunity. Our work provides a compelling preclinical rationale for selectively targeting the ADAR1 p150-Zα axis to reverse malignant RNA editing and overcome resistance to immunotherapy, offering a refined strategy with a potentially superior therapeutic index.
• 🔗 查看原文

6. GSE312828 整合应激反应的谱系可塑性是肺癌演化的标志。[RNA-Seq]

• ✍️ 作者：未知作者
• 🏷️ 关键词：cancer、RNA-seq
• 📝 描述：Contributors : Shiqi Diao ; Jia Zou ; Antonis E KoromilasSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusLung adenocarcinoma (LUAD) progresses from a single alveolar type 2 (AT2) cell to a complex, malignant tissue through a multi-step process involving acquisition of high plasticity and stem cell-like traits in a subset of cancer cells. Oncogenic transformation and signals from the tumor microenvironment (TME) activate the integrated stress response (ISR), a key survival mechanism that allows tumor cells to adapt and thrive under stress. Using single-cell transcriptomics, we identified high stemness and plasticity cell clusters in mouse LUAD tumors expressing mutant KRAS and lacking TP53 (KP model), which displayed elevated ISR program expression. Disrupting ISR via the genetic loss of phosphorylated eIF2a (p-eIF2a) or the transcription factor ATF4 hindered LUAD growth and the emergence of high-plasticity, stemness-associated lineages, resulting in the formation of a distinct cell state characterized by mitochondrial dysfunction. Additionally, treatment with ISRIB - a small-molecule ISR inhibitor with low toxicity and cognitive benefits - led to an accumulation of AT2-like LUAD cells, blocking developmental progression and tumorigenesis. In human LUAD, the ISR program is similarly elevated in KRAS-mutant tumors with high plasticity and stemness features and correlates with poor patient outcomes. These findings suggest that ISR is a key driver of LUAD progression and targeting ISR could provide a promising approach to slow LUAD progression and improve lung cancer treatment outcomes.
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7. GSE325886 多微生物细胞外囊泡降低人囊性纤维化支气管上皮细胞的先天免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune
• 📝 描述：Contributors : Lily A Charpentier ; Bruce A StantonSeries Type : Non-coding RNA profiling by high throughput sequencingOrganism : Prevotella melaninogenica ATCC 25845 ; Pseudomonas aeruginosa PA14 ; Staphylococcus aureus subsp. aureus str. Newman ; Streptococcus sanguinis SK36Adults with cystic fibrosis (CF) have chronic antibiotic-resistant polymicrobial lung infections, the leading cause of death in CF. We developed a polymicrobial culture model containing four genera that represents a ‘pulmotype’ detected in ~34% of lung infections in people with CF (pwCF), and accounts for 27% of the variability in lung function. This community, comprised of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, is grown in synthetic CF media (SCFM2) under anoxic conditions that mimic the environment in mucus plugs in CF. We have shown that Pseudomonas in monoculture communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. We report herein that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. Trikafta, a highly effective drug, does not ameliorate the response or return it to WT levels. Bacterial EVs also inhibited Trikafta-stimulated CFTR Cl- currents by CF pHBEC. These studies provide insight into why Trikafta does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.
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8. GSE325885 多微生物细胞外囊泡降低人囊性纤维化支气管上皮细胞的先天免疫反应

• ✍️ 作者：未知作者
• 🏷️ 关键词：immune
• 📝 描述：Contributors : Lily A Charpentier ; Bruce A StantonSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAdults with cystic fibrosis (CF) have chronic antibiotic-resistant polymicrobial lung infections, the leading cause of death in CF. We developed a polymicrobial culture model containing four genera that represents a ‘pulmotype’ detected in ~34% of lung infections in people with CF (pwCF), and accounts for 27% of the variability in lung function. This community, comprised of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, is grown in synthetic CF media (SCFM2) under anoxic conditions that mimic the environment in mucus plugs in CF. We have shown that Pseudomonas in monoculture communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. We report herein that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. Trikafta, a highly effective drug, does not ameliorate the response or return it to WT levels. Bacterial EVs also inhibited Trikafta-stimulated CFTR Cl- currents by CF pHBEC. These studies provide insight into why Trikafta does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.
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9. GSE301479 RNA-seq 分析肺动脉高压 (PAH) 治疗后肺动脉平滑肌细胞 (PASMC) 和支气管平滑肌细胞 (BSMC)

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Contributors : Lei Wang ; Guenther Stefan ; Kuenne Carsten ; Andre Schneider ; Maximilian StapsSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusPrevious studies to determine transcriptional changes in PASMCs during PAH were affected by the inevitable contamination with BSMCs and venous SMCs. To specific target ASMCs, we generated an ASMC-effector mouse line by combining Cspg4/Acta2 intersectional genetics, enabling specific targeting of vascular SMCs, including PASMCs. To target non-vascular SMCs, including BSMCs, we generated the NVSMC-effector mouse line using Chrm2/Acta2 intersectional genetics. The development of ASMC-effector mice, excluding venous and BSMCs, enabled us to avoid such problems and determine PASMC-specific reactions after induction of PAH.
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10. GSE301478 肺动脉平滑肌细胞 (PASMCs)、支气管平滑肌细胞 (BSMCs) 和肺静脉平滑肌细胞的 RNA-seq 分析

• ✍️ 作者：未知作者
• 🏷️ 关键词：RNA-seq
• 📝 描述：Contributors : Lei Wang ; Guenther Stefan ; Kuenne Carsten ; Andre SchneiderSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusInformation about the differences among arterial, venous, and bronchial smooth muscle cells (SMCs) in the lung is particularly valuable, as these distinct SMC populations are differentially affected in pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary arterial hypertension (PAH). To directly compare these SMC subtypes, we employed a combination of genetic tools and fluorescence-activated cell sorting (FACS) isolation strategies.We generated an ASMC-effector mouse line by combining Cspg4/Acta2 intersectional genetics, enabling specific targeting of vascular SMCs, including pulmonary arterial SMCs (PASMCs). To target non-vascular SMCs, including bronchial SMCs (BSMCs), we generated the NVSMC-effector mouse line using Chrm2/Acta2 intersectional genetics. As no driver specific to venous vascular SMCs (VVSMCs) is currently available, we used the transgenic reporter line [Tg(Acta2-GFP)], which labels all pulmonary SMCs, including venous SMCs.
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1. 你的鼻子可能在阿尔茨海默病症状出现前数年就检测出来。

• ✍️ 作者：未知作者
• 🏷️ 关键词：Alzheimer
• 📝 描述：Losing your sense of smell might signal Alzheimer’s far earlier than expected. Scientists found that immune cells in the brain actively destroy smell-related nerve fibers after detecting abnormal signals on their surfaces. This damage begins in early stages of the disease, well before cognitive decline. The discovery could help identify at-risk patients sooner and improve treatment timing.
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2. 科学家终于破解了新冠疫苗罕见血栓之谜

• ✍️ 作者：未知作者
• 🏷️ 关键词：vaccine
• 📝 描述：Researchers have uncovered why a rare blood clotting disorder can occur after certain COVID-19 vaccines or adenovirus infections. The immune system can mistakenly target a normal blood protein (PF4) after confusing it with a viral protein. This triggers clotting in extremely rare cases. The breakthrough means vaccines can now be redesigned to avoid this reaction while staying effective.
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• GSE327684 RNA测序验证神经发育障碍相关基因敲除效率[RNA测序]
• GSE327269 体内 RNA 测序鉴定出 lncRNA ReLoV 在白色念珠菌 II 型的形态转变和毒力中起关键作用
• GSE327268 体内RNA测序鉴定出lncRNA ReLoV对白色念珠菌I型形态转变和毒力至关重要
• GSE327236：来自多因素基准研究的小鼠脑单核RNA测序整合数据集