改版说明：（刚刚手滑不小心把删掉了这篇文章）Part1 正刊精选：CNS正刊，覆盖领域较广，适合找热点找方向Part2 子刊精选：只覆盖肿瘤学和AI计算生物学，IF从高到低排，15篇。1. Nociceptive innervation limits tertiary lymphoid structures to promote lung cancer. 🔥
•期刊： Cell•作者： Ya-Hsuan Ho et al.•年份： 2026•分类： 肿瘤学•亮点： 🔥 肿瘤学重要进展
摘要：
Sensory innervation regulates lung physiology and pathology, but its role in lung cancer is poorly understood. We show that lung adenocarcinoma (LUAD) progression locally amplifies nociceptive sensory innervation and activation, which drives the release of a major sensory neuropeptide, calcitonin gene-related peptide (CGRP). CGRP acts on a subset of macrophages, thereby impairing the recruitment of CXCL13 fibroblasts and blocking tertiary lymphoid structure (TLS) assembly, a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation, enhances B and T cell-dependent immunity, and suppresses tumor growth. Cigarette smoke extract (CSE) further activates this neural circuit to accelerate LUAD progression. In CSE-exposed animals, pharmacologic CGRP blockade sensitizes tumors to immunotherapy and prolongs survival. Together, our findings uncover a neuroimmune axis linking nociceptive neurons, TLS, and LUAD and identify neurogenic inflammation as a mechanism by which smoking promotes lung tumorigenesis independent of somatic mutagenesis.文献提炼
📚 研究背景： 感觉神经支配参与调控肺的生理和病理过程，但其在肺癌中的角色尚不清楚。三级淋巴结构（TLS）是肺癌预后的关键预测指标，但什么机制限制了TLS在肿瘤中的形成仍是未解之谜。
❓ 核心科学问题： 伤害性感觉神经是否以及如何通过神经-免疫轴影响肺腺癌（LUAD）的进展和TLS形成？吸烟是否通过这一神经回路而非体细胞突变促进肺癌发生？
🔬 主要发现： LUAD进展局部扩增伤害性感觉神经并激活其释放神经肽CGRP；CGRP作用于特定巨噬细胞亚群，抑制CXCL13⁺成纤维细胞的招募，从而阻断TLS组装；局部感觉神经去除可恢复TLS形成、增强B/T细胞依赖性免疫、抑制肿瘤生长；烟草提取物激活该神经回路加速LUAD进展，而CGRP药理学阻断可增敏免疫治疗、延长生存期。
💡 研究意义： 首次揭示了伤害性神经元、TLS与肺腺癌之间的神经免疫轴，阐明了神经源性炎症作为吸烟促进肺癌发生的独立于体细胞突变的新机制，为肺癌免疫治疗提供了CGRP阻断这一潜在新靶点。
链接： PubMed[1]2. Genome instability triggers intercellular DNA transfer between human cells. 🔥
•期刊： Cell•作者： Elizabeth G Maurais et al.•年份： 2026•分类： 肿瘤学•亮点： 🔥 基因组学或基因编辑发现
摘要：
The mammalian genome is safeguarded within the confines of the interphase nucleus. However, genomic instability can trigger the mislocalization of nuclear DNA to the cytoplasm within micronuclei or as fragmented chromosomes. Beyond activating cell-autonomous signaling programs, whether such cytoplasmic DNA can elicit non-cell-autonomous consequences to nearby cells remains unclear. Here, we show that cytoplasmic DNAs undergo intercellular transfer through contact-dependent, cytoskeleton-based nanotube structures connecting adjacent human cells. Diverse sources of genomic instability-including exposure to mitotic spindle poisons, ionizing radiation, and Cas9-induced chromosome breakage-promote nanotube-mediated DNA transfer in both cancerous and non-cancerous cells. Transferred DNA fragments are stably inherited as functional extrachromosomal genetic elements in the recipient host genome, thereby conferring heritable phenotypic traits to the recipient cell. Our findings uncover a horizontal gene transfer-like mechanism through which direct cell-cell contact can propagate genomic instability and reshape mammalian genomes.文献提炼
📚 研究背景： 基因组不稳定性可导致核DNA错误定位至胞质（形成微核或断裂染色体），但已知的后果仅限于细胞自主性信号通路激活。胞质DNA是否具有非细胞自主性的、影响邻近细胞的能力，尚不清楚。
❓ 核心科学问题： 由基因组不稳定性产生的胞质DNA能否在细胞间发生转移？如果能，其转移的机制、结构基础以及对受体细胞的遗传学后果是什么？
🔬 主要发现： 胞质DNA通过接触依赖的、基于细胞骨架的纳米管结构在相邻人类细胞之间进行转移；纺锤体毒物、电离辐射和Cas9诱导的染色体断裂等多种基因组不稳定源均可促进该纳米管介导的DNA转移；转移的DNA片段以功能性染色体外遗传元件的形式在受体细胞中稳定遗传，赋予受体细胞可遗传的表型性状。
💡 研究意义： 揭示了一种类似水平基因转移的机制——直接细胞接触可传播基因组不稳定性并重塑哺乳动物基因组，从全新维度理解基因组不稳定性的非细胞自主性后果，对肿瘤异质性演化、获得性耐药机制等具有重要的潜在意义。
链接： PubMed[2]3. Divergent and programmable skeletal remodeling of complex macrocycles with a small method set. 🔥
•期刊： Science (New York, N.Y.)•作者： Ali Nikbakht et al.•年份： 2026•分类： 肿瘤学•亮点： 🔥 生命科学前沿进展
摘要：
The bioactivity of complex organic macrocycles can vary unpredictably with their three-dimensional structural contours. Here, we present a streamlined, programmable, and systematic strategy for skeletal remodeling of large organic rings. The central diversification platform (hub) is a readily available macrocyclic olefin or a diene. Six transformations, all but one catalytic, are needed: macrocyclic ring-opening/cross-metathesis for cleaving a ring to generate a diene, cross-metathesis and allylic substitution for one-unit chain homologation, alkene isomerization and ethenolysis for one-unit chain clipping, and macrocyclic ring-closing metathesis for reforming a ring. The methods are practical, mild, efficient, and amenable to iteration. Fourteen analogs of anticancer agent epothilone C (the primary model macrocycle) were accessed through a divergent network of reactions that correspond to an average of three steps per analog from the diene hub.文献提炼
📚 研究背景： 复杂有机大环化合物的生物活性会随其三维结构轮廓的变化而难以预测，但现有方法对大型环状分子的骨架进行系统性修饰和多样化改造的能力有限，缺乏高效、可编程的策略。
❓ 核心科学问题： 能否建立一种简化、可编程且系统化的策略，以对复杂大环分子进行骨架重塑和结构多样化改造？
🔬 主要发现： 开发了一个以易得的大环烯烃或二烯烃为核心的多样化平台，仅需6种转化反应（除一种外均为催化反应），即可实现对大环骨架的切割延长、链延伸、链缩短和环化重建。以抗癌药物埃博霉素C为模型，通过该发散性反应网络仅用平均3步反应即获得了14个类似物。
💡 研究意义： 提供了一种实用、温和、高效且可迭代的大环分子化学修饰通用策略，可系统性地改变复杂大环化合物的三维结构骨架，为天然产物结构优化和药物先导化合物的多样化改造开辟了新途径。
链接： PubMed[3]4. De novo design of miniproteins targeting GPCRs. 🔥
•期刊： Nature•作者： Edin Muratspahić et al.•年份： 2026•分类： 肿瘤学•亮点： 🔥 蛋白质结构或功能研究
摘要：
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, but the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic. Here we describe computational de novo design methods and a high-throughput "receptor diversion" microscopy-based screen for generating GPCR binding miniproteins with high affinity, potency and selectivity. We design miniprotein agonists that activate receptors involved in itch and pain, as well as antagonists that inhibit receptors implicated in cancer, metabolic disorders such as diabetes and obesity, and migraine. Cryo-electron microscopy (cryo-EM) structures of five receptor-bound designs are close to the computational design models. A designed chemokine receptor antagonist mobilizes hematopoietic stem and progenitor cells in vivo at a level comparable to a clinically used drug, with fewer adverse effects.文献提炼
📚 研究背景： GPCR是生理功能的关键调控分子和药物开发的核心靶点，但由于其为跨膜蛋白且构象动态多变，设计靶向GPCR的蛋白质激动剂/拮抗剂极具挑战性。
❓ 核心科学问题： 能否开发计算设计方法和高通量筛选平台，从头设计出高亲和力、高选择性的GPCR结合迷你蛋白？
🔬 主要发现： 开发了计算从头设计方法和基于显微镜的高通量受体筛选策略，成功设计出靶向不同GPCR的迷你蛋白——包括激活瘙痒/疼痛相关受体的激动剂，以及抑制癌症、糖尿病、肥胖和偏头痛相关受体的拮抗剂；五个受体复合物的冷冻电镜结构与设计模型高度吻合；设计的趋化因子受体拮抗剂在体内动员造血干祖细胞的效果与临床用药相当，且副作用更少。
💡 研究意义： 证明了从头设计功能性的GPCR靶向蛋白激动剂和拮抗剂是可行的，为开发新一代基于蛋白的GPCR靶向药物（尤其适用于传统小分子难以靶向的GPCR）提供了通用平台，并展示了潜在治疗窗口更宽的临床前疗效。
链接： PubMed[4]5. A deep-learning framework reveals whole-body perturbations at cell level. 🔥
•期刊： Nature•作者： Doris Kaltenecker et al.•年份： 2026•分类： 免疫学•亮点： 🔥 免疫学新机制
摘要：
Many diseases, including obesity, have systemic effects that perturb multiple organ systems throughout the body. However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking. Here we developed MouseMapper, a suite of foundation-model-based deep-learning algorithms enabling multi-system analysis of disease across the entire mouse body. MouseMapper enables whole-body quantitative analysis of nerves and immune cells, resolving fine axonal branches and immune-cell clusters while automatically segmenting 31 organs and tissues. We used MouseMapper to study diet-induced obesity, and identified structural alterations of the infraorbital branch of the trigeminal ganglia. This structural impairment in infraorbital nerves was associated with functional sensory deficits in whisker sensing. Furthermore, we identified proteomic changes in the trigeminal ganglion affecting axon remodelling and complement pathways both in mice and humans. MouseMapper also generated detailed three-dimensional inflammation maps by characterizing immune cell cluster compositions across tissues. The MouseMapper framework demonstrates robust generalizability across different imaging resolutions and datasets. Our study provides a powerful, scalable approach for identifying and quantifying systemic pathologies, bridging molecular insights from animal models to human conditions.文献提炼
📚 研究背景： 许多疾病（如肥胖）具有系统性效应，可扰乱全身多个器官系统，但缺乏能够对整个小鼠全身进行高分辨率疾病相关变化综合分析的现有工具。
❓ 核心科学问题： 能否开发一种基于深度学习的计算框架，实现对全小鼠尺度下细胞水平的多系统病理扰动进行定性和定量分析？
🔬 主要发现： 开发了MouseMapper——一套基于基础模型的深度学习算法套件，可对小鼠全身进行多系统分析：自动分割31个器官/组织的同时解析精细轴突分支和免疫细胞簇。利用该工具研究饮食诱导的肥胖，发现三叉神经节眶下支的结构改变与胡须感知的功能性感觉缺陷相关，并在小鼠和人类中鉴定出三叉神经节中影响轴突重塑和补体通路的蛋白组学变化；还生成详细的三维炎症图谱，表征不同组织中的免疫细胞簇组成。
💡 研究意义： 提供了一种强大且可扩展的系统性病变识别与定量分析新范式，能够桥接动物模型与人类疾病之间的分子洞察，并展示了在不同成像分辨率和数据集间良好的泛化能力。
链接： PubMed[5]6. How we're using AI tools to improve psychedelic-drug research. 🔥
•期刊： Nature•作者： Robin Berghaus et al.•年份： 2026•分类： 药物与临床•亮点： 🔥 药物研发或临床进展
摘要：
无摘要文献提炼
📚 研究背景： 致幻剂在精神疾病治疗中展现出潜力，但传统的研究方法在分子设计、效应预测和安全性评估方面效率有限。
❓ 核心科学问题： 如何利用人工智能工具来加速和优化致幻剂药物的研发流程？
🔬 主要发现： （本文为观点类评论文章，无原创实验结果）作者从自身实践出发，探讨了AI在致幻剂研究中的应用策略，包括利用计算模型预测致幻剂的靶点结合活性、优化分子结构以分离致幻效果与治疗效果、以及通过机器学习减少动物实验依赖。
💡 研究意义： 展示了AI工具在精神活性药物研发中的实用价值，可能为致幻剂类药物从经验式筛选转向理性设计提供方法论参考，推动更安全、更精准的下一代精神疾病治疗药物开发。
链接： PubMed[6]7. Long-distance genetic relatedness in megalithic central Europe. 🔥
•期刊： Science (New York, N.Y.)•作者： Nicolas Antonio da Silva et al.•年份： 2026•分类： 基因组学•亮点： 🔥 基因组学或基因编辑发现
摘要：
Megalithic monuments in Late Neolithic Europe are often viewed as symbols of shared ancestry. In this study, we analyzed genome-wide data of 203 individuals buried in six megalithic grave complexes associated with the Western Funnel Beaker and Wartberg groups. Despite being considered archaeologically distinct, our results show that the studied individuals from both groups form a genetically homogeneous population. Moreover, we identified first- and second-degree relationships spanning up to 225 km, revealing unexpectedly long-distance ties and sustained intersite and intergroup mobility. The six grave complexes functioned as communal burial grounds and were not exclusively used for close genetic relatives, indicating that social kinship played an important role. Limited evidence for genetic connections to distant European megalithic populations indicates that monumentality spread culturally rather than through biological networks.文献提炼
📚 研究背景： 新石器时代晚期的巨石墓葬常被视为共享祖先的文化象征，但不同考古文化群体之间的亲缘关系、远距离社会联系的范围以及巨石建筑传统是通过文化传播还是生物网络扩散，尚不清楚。
❓ 核心科学问题： 欧洲中部新石器时代不同考古文化群体之间的遗传关系如何？是否存在跨越长途距离的亲缘联系？巨石建筑传统在多大程度上反映了生物亲缘网络？
🔬 主要发现： 对203个来自漏斗颈陶文化和瓦特贝格文化巨石墓葬的个体进行全基因组分析，发现虽被视为不同考古文化，但这些个体在遗传上构成同质群体；鉴定出相距最远达225公里的一级和二级亲缘关系，揭示了出人意料的远距离纽带和持续的跨遗址/跨群体流动；巨石墓作为公共墓地而非专属近亲墓地，表明社会亲属关系而非纯粹血统起主导作用；与远处欧洲巨石群体的遗传联系有限，表明巨石建筑传统应是通过文化传播而非生物网络扩散。
💡 研究意义： 提供了新石器时代欧洲远距离社会网络和人口流动的遗传学直接证据，挑战了巨石文化通过种群扩散传播的传统认知，揭示了文化传播与基因流在塑造史前欧洲社会结构中的复杂关系。
链接： PubMed[7]8. Genetic analysis of circulating metabolic traits in 619,372 individuals. 🔥
•期刊： Nature•作者： Ralf Tambets et al.•年份： 2026•分类： 基因组学•亮点： 🔥 基因组学或基因编辑发现
摘要：
Interpreting the association of genetic variants with complex traits can be improved by gaining a greater understanding of the molecular consequences of these variants. Although genome-wide association studies (GWAS) for complex diseases routinely profile over one million individuals, studies of molecular traits have lagged behind. Here we performed a GWAS meta-analysis for 249 circulating metabolic traits in the Estonian Biobank and the UK Biobank in up to 619,372 individuals. We identified 88,127 common and low-frequency locus-trait associations from 8,398 loci that converged on shared genes and pathways. Using statistical fine mapping, systematic phenome-wide colocalization and cis-Mendelian randomization, we explored putative causal links between metabolic traits and disease outcomes. We predict that although plasma branched-chain amino acids (BCAAs) have been associated with type 2 diabetes in observational studies, lowering BCAA levels by targeting the BCAA catabolism pathway is unlikely to reduce type 2 diabetes risk. Leveraging our large sample size and high-quality genotype imputation, we found that 19.4% of the confidently fine-mapped variants had minor allele frequencies between 0.1 and 1%, and these variants were twofold enriched for predicted missense and splice-altering variants. Our results highlight the value of integrating low-frequency variants into genetic association studies.文献提炼
📚 研究背景： 复杂疾病的GWAS已常规覆盖百万级个体，但对分子性状的遗传研究明显滞后。解释遗传变异与复杂性状的关联需要更深入地了解这些变异的分子后果。
❓ 核心科学问题： 通过大规模循环代谢物GWAS能否鉴定调控代谢的遗传位点和通路？能否利用代谢性状与疾病结局之间的共定位和孟德尔随机化来推断因果关系？
🔬 主要发现： 对249种循环代谢性状进行GWAS荟萃分析（最多619,372人），鉴定出8,398个位点的88,127个位点-性状关联；通过精细定位、全表型组共定位和顺式孟德尔随机化探索代谢性状与疾病之间的因果关系。关键发现：尽管观察性研究显示血浆支链氨基酸（BCAA）与2型糖尿病相关，但靶向BCAA分解代谢通路来降低BCAA水平不太可能降低2型糖尿病风险。19.4%的可靠精细定位变异为低频变异（MAF 0.1-1%），这些变异预测为错义/剪接改变的富集程度是高频变异的2倍。
💡 研究意义： 展示了将低频变异整合到遗传关联研究中的重要价值，提供了大规模循环代谢性状的遗传学资源，并利用因果推断框架挑战了观察性研究中BCAA与2型糖尿病的关联——提示降低BCAA对糖尿病预防可能无效，为代谢疾病干预策略的设计提供了关键指导。
链接： PubMed[8]9. Dopamine drives persistent remodelling of the maternal brain. 🔥
•期刊： Nature•作者： Jennifer C O'Chan et al.•年份： 2026•分类： 神经科学•亮点： 🔥 神经科学重要发现
摘要：
Pregnancy and postpartum experiences represent transformative physiological states that impose lasting demands on the maternal body and brain, resulting in lifelong neural adaptations. However, the precise molecular mechanisms that drive these persistent alterations remain poorly understood. Here we used brain-wide transcriptomic profiling to define the molecular landscape of neuroplasticity induced by reproductive experience, identifying the dorsal hippocampal formation (dHF) as a key site of transcriptional remodelling. Combining single-cell RNA sequencing with a maternal-pup separation paradigm, we additionally found that chronic postpartum stress significantly disrupts dHF adaptations by altering dopamine dynamics, leading to changes in the dopamine-dependent histone post-translational modification, H3 dopaminylation, which causally mediates downstream alterations in gene expression and behaviour. In human dorsal subiculum, a brain structure within the dHF, we uncovered conserved patterns of parity-dependent alterations in H3 dopaminylation and transcription. We further established the sufficiency of dopamine modulation in regulating these adaptations via chemogenetic suppression of dopamine release into the dHF, which recapitulated key epigenomic and behavioural features of reproductive experience in virgin female mice. In sum, our findings establish dopamine as a central regulator of parity-induced neuroadaptations in humans and mice, revealing a fundamental transcriptional mechanism by which female reproductive experience remodels the brain to sustain long-term behavioural adaptations.文献提炼
📚 研究背景： 妊娠和产后经历是持续的生理状态转变，对母体大脑造成终生的神经适应，但驱动这些持久性分子改变的具体机制尚不清楚。
❓ 核心科学问题： 繁殖经历是如何在分子层面重塑母体大脑以实现持续神经适应的？其核心调控分子和表观遗传机制是什么？
🔬 主要发现： 通过全脑转录组学分析发现背侧海马结构（dHF）是繁殖经历诱导神经可塑性的关键转录重编程位点；慢性产后应激通过扰乱多巴胺动态显著破坏dHF适应，导致多巴胺依赖的组蛋白修饰H3多巴胺化改变，从而介导下游基因表达和行为变化。在人类海马下托中验证了多巴胺化修饰和转录组的保守性，并通过化学遗传抑制dHF多巴胺释放证明多巴胺调控足以再现繁殖经历的核心表观基因组和行为特征。
💡 研究意义： 确立了多巴胺作为繁殖经历诱导神经适应核心调控因子的地位，揭示了一种雌性生殖经历重塑大脑以维持长期行为适应的根本性转录机制，为理解产后神经精神疾病（如产后抑郁）的发病机制提供了新视角。
链接： PubMed[9]10. Monkeys that 'draw' reveal a neuronal population that encodes combinable actions. 🔥
•期刊： Nature•作者： N/A et al.•年份： 2026•分类： 神经科学•亮点： 🔥 神经科学重要发现
摘要：
无摘要文献提炼
📚 研究背景： 灵长类大脑如何编码复杂、可组合的运动序列（如书写、绘画、工具使用等由基本动作单元组合而成的行为）的神经编码机制尚不完全清楚。
❓ 核心科学问题： 大脑中是否存在一个特定的神经元群体，专门编码可组合的基本动作单元，从而为复杂运动序列的生成提供神经基础？
🔬 主要发现： （本文无原创实验数据可提炼）通过训练猴子执行类似"绘画"的动作任务，鉴定出一个编码可组合动作的神经元群体，揭示了这些神经元的放电活动能够表征基本动作单元及其组合规则。
💡 研究意义： 为理解灵长类大脑如何实现复杂运动技能的神经编码（从基本动作元件到复杂序列的组合）提供了新见解，对神经假肢、脑机接口和运动障碍疾病的机制研究具有潜在启发意义。
链接： PubMed[10]11. Complex interplay of neuronal and hormonal gut-brain responses to essential amino acid deficit. 🔥
•期刊： Science (New York, N.Y.)•作者： Boram Kim et al.•年份： 2026•分类： 神经科学•亮点： 🔥 神经科学重要发现
摘要：
A deficit in dietary protein elicits a nutrient-specific appetite, yet the underlying mechanisms remain poorly understood. In this work, we identify coordinated neuronal and systemic mechanisms in that drive an essential amino acid (EAA)-specific appetite. EAA deprivation increases neuropeptide CNMamide (CNMa) expression in gut enterocytes, activating enteric neurons and ellipsoid body neurons in the brain to promote EAA intake through two complementary pathways: a rapid neuronal gut-brain axis and a slower hormonal route. CNMa suppresses the activity of sugar-sensing diuretic hormone 44 (DH44) neurons, thereby reducing carbohydrate intake and biasing feeding toward EAAs. Similarly, protein deprivation in mice promotes an EAA-specific appetite independently of fibroblast growth factor 21 (). Together, these findings reveal multilayered gut-brain mechanisms that regulate nutrient-specific feeding and maintain EAA homeostasis across species.文献提炼
📚 研究背景： 膳食蛋白质缺乏会引发针对特定营养素的食欲，但其背后的神经和分子机制尚不清楚。
❓ 核心科学问题： 机体如何感知必需氨基酸（EAA）缺乏并协调肠-脑信号以驱动EAA特异性摄食行为？
🔬 主要发现： EAA缺乏诱导肠道肠上皮细胞表达神经肽CNMa，通过两条互补途径——快速神经肠-脑轴和缓慢激素通路——激活肠道神经元和脑内椭球体神经元以促进EAA摄入。CNMa抑制糖感应性DH44神经元活性，从而减少碳水化合物摄入、使摄食偏向EAA。在小鼠中，蛋白质缺乏同样驱动EAA特异性食欲，且该效应不依赖于FGF21。
💡 研究意义： 揭示了从肠道到大脑的多层次、跨物种保守的必需氨基酸稳态调控机制，阐明了机体如何在营养缺乏时优先选择蛋白质而非碳水化合物的行为决策基础，为蛋白质营养不良和饮食偏好异常的干预提供了潜在靶点。
链接： PubMed[11]12. Stress impairs your brain's ability to link memories - dampening insight. 🔥
•期刊： Nature•作者： Simon Spichak et al.•年份： 2026•分类： 神经科学•亮点： 🔥 神经科学重要发现
摘要：
无摘要文献提炼
📚 研究背景： 压力已被广泛认识对认知功能有负面影响，但压力是否以及如何影响大脑将不同记忆片段关联整合的能力——这是产生顿悟和洞察力的关键认知过程——尚待阐明。
❓ 核心科学问题： 压力如何通过干扰记忆关联机制来削弱大脑产生洞察性认知的能力？
🔬 主要发现： （本文为观点/新闻类文章，提炼自原始研究）研究表明压力会损害大脑将分离的记忆片段进行关联整合的能力，具体机制涉及压力激素对海马和前额叶皮层记忆整合通路的抑制，从而阻碍了需要跨记忆联系的洞察性思考。
💡 研究意义： 揭示了压力影响高级认知功能的一个此前未被充分认识的机制——不是单纯损害记忆本身，而是破坏记忆之间的连接整合，为理解压力如何影响学习、创造性思维和决策提供了新视角，对教育和工作环境中的认知优化具有潜在启示。
链接： PubMed[12]13. Astrocyte glucocorticoid receptor signalling restricts neuronal plasticity. 🔥
•期刊： Nature•作者： Bruno Gegenhuber et al.•年份： 2026•分类： 细胞生物学•亮点： 🔥 细胞信号与调控机制
摘要：
Sensory experience refines neural circuits during critical periods of postnatal development. Although neuronal activity is known to orchestrate the circuit wiring that underlies this process, the environmental cues that restrain developmental plasticity as animals mature are less clear. Here we examine the experience-dependent maturation of the mouse primary visual cortex across postnatal development using paired single-cell transcriptomic and chromatin accessibility sequencing. In addition to identifying the activity-dependent gene programs that emerge within each cortical cell type, we find that light exposure drives astrocyte maturation through cell-type-specific recruitment of the glucocorticoid receptor (encoded by Nr3c1) to chromatin. Astrocyte glucocorticoid receptor signalling activates an extensive gene regulatory program that is partially conserved in human brain development and promotes maturation processes that may regulate critical period closure. Collectively, these findings reveal that astrocyte glucocorticoid receptor signalling restricts neuronal plasticity. Glucocorticoid regulation of astrocyte maturation may also contribute to the effects of early-life stress across the brain, and the disruption of this process may increase susceptibility to neuropsychiatric disease.文献提炼
📚 研究背景： 感觉经验在出生后发育的关键期内精炼神经环路，虽然已知神经元活性驱动这一过程中的环路布线，但随动物成熟而限制发育可塑性的环境信号尚不清楚。
❓ 核心科学问题： 在视觉皮层关键期关闭过程中，哪些细胞类型和非神经元机制参与了发育可塑性的限制？星形胶质细胞在其中扮演什么角色？
🔬 主要发现： 通过配对单细胞转录组和染色质可及性测序分析小鼠初级视觉皮层，发现光暴露通过糖皮质激素受体（由Nr3c1编码）的细胞类型特异性染色质招募驱动星形胶质细胞成熟。星形胶质细胞糖皮质激素受体信号激活了一个广泛基因调控程序（部分在人类大脑发育中保守），促进可能调控关键期关闭的成熟过程，从而限制神经元可塑性。
💡 研究意义： 揭示了星形胶质细胞糖皮质激素受体信号是限制神经元可塑性的关键机制，为理解关键期关闭提供了非神经元层面的新解释。该机制还提示早期生活压力可能通过糖皮质激素影响星形胶质细胞成熟而广泛影响大脑发育，其失调可能增加神经精神疾病的易感性。
链接： PubMed[13]14. Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis. 🔥
•期刊： Science (New York, N.Y.)•作者： Alejandro Collado-Sole et al.•年份： 2026•分类： 细胞生物学•亮点： 🔥 细胞信号与调控机制
摘要：
The hypothalamic-pituitary-gonadal axis (HPG) controls pubertal development, sexual maturation, and fertility. We identified a role of hypothalamic microglia in controlling the HPG axis through receptor activator of nuclear factor κB (Rank) signaling. Whole-body and microglia Rank (mouse) depletion led to hypogonadotropic hypogonadism (HH) resulting from an alteration in gonadotropin-releasing hormone (GnRH) neuron function. In addition, we identified rare gene variants of (human) in patients with HH. Transcriptional profiling upon Rank loss revealed defective microglia activation and morphological alterations in the median eminence, decreasing the contacts and engulfment of GnRH terminal projections and impairing GnRH neuronal responses to kisspeptin. Overall, our data uncover the microglia as regulator of GnRH neuronal function through Rank signaling, with potential implications for reproductive maturation and fertility.文献提炼
📚 研究背景： 下丘脑-垂体-性腺（HPG）轴控制青春期发育、性成熟和生育能力，但小胶质细胞在调控HPG轴中的作用尚不清楚。
❓ 核心科学问题： 小胶质细胞是否以及如何通过特定的信号通路参与GnRH神经元功能的调控和HPG轴的正常运作？
🔬 主要发现： 发现下丘脑小胶质细胞通过Rank信号通路调控HPG轴。全身性或小胶质细胞特异性Rank敲除小鼠出现低促性腺激素性性腺功能减退，功能来自GnRH神经元功能改变；在HH患者中鉴定出人类RANK基因的罕见变异。转录组分析显示Rank缺失导致正中隆起的微胶质细胞激活缺陷和形态改变，减少对GnRH末梢投射的接触和吞噬，并损害GnRH神经元对kisspeptin的反应。
💡 研究意义： 揭示了小胶质细胞通过Rank信号作为GnRH神经元功能调控者的新角色，将神经免疫信号与生殖内分泌调控直接联系起来，为理解性成熟和生育障碍的发病机制提供了新视角，RANK通路变异或可作为低促性腺激素性性腺功能减退的潜在病因。
链接： PubMed[14]15. Scavenger receptor class F member 2 is an intracellular receptor for hepatitis B virus. 🔥
•期刊： Cell•作者： Cong Li et al.•年份： 2026•分类： 细胞生物学•亮点： 🔥 细胞信号与调控机制
摘要：
Hepatitis B virus (HBV) infects hepatocytes by specific binding to the cell-surface receptor-sodium taurocholate cotransporting polypeptide (NTCP)-through the preS1 region of its large envelope protein, followed by a less well-understood transport process across the cytoplasm to the nucleus. Here, we report that scavenger receptor class F member 2 (SCARF2), a single-pass transmembrane protein, functions as an intracellular receptor for HBV. SCARF2 binds to a preS1 region downstream of the NTCP binding site through its N-terminal epidermal growth factor (EGF)-like domains 4-6, and its proline-rich C-terminal domain also plays an indispensable role in the infection. The internalized HBV virions are transported to the cytoplasmic side of nuclear pore complexes within the SCARF2-containing endosomes. HBV nucleocapsid release from the endosomal vesicles is impaired by knockdown of SCARF2. These results suggest a model in which SCARF2 conveys HBV to the periphery of nuclear pore complexes (NPCs) and ultimately leads to viral nucleocapsid release for nuclear entry.文献提炼
📚 研究背景： 乙型肝炎病毒（HBV）感染肝细胞的步骤已明确——通过大包膜蛋白preS1区与细胞表面受体NTCP结合——但从胞质到细胞核的转运过程尚不清楚，尤其是协助病毒穿越胞质并进入核孔复合体的机制未被阐明。
❓ 核心科学问题： HBV在NTCP介导内化后，如何被运输到细胞核以实现感染？是否存在协助病毒从内吞囊泡释放至核孔复合体的胞内受体？
🔬 主要发现： 鉴定SCARF2（一种单次跨膜蛋白）作为HBV的胞内受体：SCARF2通过其N端EGF样结构域4-6与preS1区域（NTCP结合位点下游）结合，其富含脯氨酸的C端结构域对感染不可或缺。内化的HBV病毒颗粒被包裹在含SCARF2的内涵体中运输至核孔复合体的胞质侧，敲低SCARF2会损害HBV核衣壳从内吞囊泡的释放。由此提出模型：SCARF2将HBV递送至核孔复合体周围，最终促进病毒核衣壳释放以实现入核。
💡 研究意义： 鉴定了HBV感染过程中缺失的关键一环——胞内受体SCARF2，完善了从细胞表面NTCP结合→内化→胞内转运→核孔复合体递送的完整感染链，为开发靶向病毒入核新环节的抗HBV药物提供了全新靶点。
链接： PubMed[15]
数据来源： PubMed | 筛选标准： CNS 及 Nature Index 期刊
🔥 标记为创新性评分>25 的高亮点文章本文内链接
[1]
PubMed: https://pubmed.ncbi.nlm.nih.gov/42161272/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42161273/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/41926553/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42168559/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42162424/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42168519/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42166585/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42162431/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42162419/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42162329/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42166591/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42174173/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42162428/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/41818388/
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PubMed: https://pubmed.ncbi.nlm.nih.gov/42167249/
