近期，深圳湾实验室取得了多项研究突破，快来和湾豆一起回顾2024年7月至9月的科研成果吧！以下成果据各课题组、实验室官网整理。
深圳湾实验室系统与物理生物学研究所李磊与复旦大学倪挺团队在Science Advances 杂志发表题为“Pan-cancer transcriptome analysis reveals widespread regulation through alternative tandem transcription initiation”的研究论文。该研究开发了首个可以从转录组识别基因可变串联转录起始的新方法，并利用该方法系统解析了人类癌症中可变串联转录起始介导信使RNA的5′ UTR长度变化规律，并探究了其介导的基因表达调控在癌症发生发展过程中的作用，为理解癌症发生机制提供新角度。
张勃课题组报道孤独症相关分子Nlgn3在星形胶质细胞中的作用机制
深圳湾实验室神经疾病研究所张勃课题组在Molecular Psychiatry 杂志发表了题为Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number的研究论文，提出在中枢神经系统中，星形胶质细胞中孤独症相关的细胞粘附分子Nlgn3影响基因表达和动物行为但不影响突触数量。
病毒传染病课题组/太万博课题组与合作者发现基于感染模型的系统性“大脑-肌肉”信号轴
病毒传染病课题组/太万博课题组与合作者在国际学术期刊Science Immunology《科学·免疫》在线发表了“Infection and chronic disease activate a systemic brain-muscle signaling axis”《感染和慢性疾病激活系统性大脑-肌肉信号轴》的研究论文。在该研究中，合作者基于感染及慢性疾病模型发现了首个独立于神经连接体（Connectome），由中枢神经系统的分泌性因子对肌肉生理功能的的直接调控机制。该研究为治疗神经系统疾病并发性肌无力，提供了重要潜在靶点，具有高度的科学意义和临床转化价值。
张泽民团队通过泛癌种单细胞整合分析揭示表型各异的肿瘤浸润B细胞亚类
北京大学生物医学前沿创新中心（BIOPIC）/深圳湾实验室张泽民课题组在Cell发表了题为“Pan-cancer single-cell dissection reveals phenotypically distinct B cell subtypes”的研究论文。该研究整合了来自19种癌症类型患者的大规模单细胞转录组测序数据，描绘了肿瘤浸润B细胞在泛癌种水平上丰度和构成的异质性，发现了能够与CD4 T细胞进行互作并具有预后潜力的肿瘤相关非典型B细胞（tumor-associated atypical B cell, TAAB）。
黄湧/陈杰安课题组发展可见光催化取代烯烃的氧化还原中性裂解新策略
香港科技大学黄湧教授和深圳湾实验室陈杰安研究员团队一直致力于开发可见光催化的碳-碳键裂解新策略，先后实现了无张力脂肪醇和烷基芳烃的Csp3−Csp3选择性裂解反应（Cell Rep. Phys. Sci. 2022, 3, 100763; J. Am. Chem. Soc. 2023, 145, 12284）。近日，合作团队报道了一种可见光催化芳基烯烃裂解的新策略。与常规氧化裂解反应相比，该方法在无外源氧化剂的条件下实现了碳氢化合物Csp2=Csp2键的歧化裂解，同时生成还原性（Csp3）及氧化性（Csp2=O）产物片段。相关成果在线发表于《自然通讯》（Nat. Commun. 2024, 15, 6227）。
大湾区老年脑健康计划——揭示阿尔茨海默病生物标记物和神经影像的时序演变规律及早期诊疗策略
AD是造成老年痴呆症的最主要原因，占所有病例的70%左右。为促进粤港澳大湾区在AD早期诊断和干预治疗领域的发展，以深圳湾实验室郭腾飞博士为代表的研究人员联合多家单位，于2021年5月份启动了《大湾区老年脑健康计划（GHABS）》AD社区队列，旨在通过生物标记物和多模态成像研究AD的发病特点及演变规律研究，支持我国AD早期诊断和干预治疗研究。
2024年7月4日，深圳湾实验室郭腾飞课题组基于GHABS社区队列的分子影像数据在核医学与分子影像领域知名期刊European Journal of Nuclear Medicine and Molecular Imaging杂志发表“[18F]-D3FSP β-amyloid PET imaging in older adults and Alzheimer’s disease”研究论文，在我国老年人群中完成了Aβ PET新探针[18F]-D3FSP 的临床验证和诊断价值评估。
2024年7月30日，深圳湾实验室郭腾飞课题组进一步基于GHABS社区队列数据在神经退行性疾病领域内高水平期刊Molecular Neurodegeneration杂志上发表“Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer’s disease”研究论文。该研究基于GHABS队列中的血浆生物标记物和神经影像数据建立了适用于我国社区老年人群的血浆Aβ42/Aβ40及p-Tau181生物标记物的检测阈值，并结合神经影像证实了该阈值检测AD病理变化的有效性，为基于血浆Aβ42/Aβ40及p-Tau181在我国社区人群中筛查AD高风险人群提供了依据。
传染病研究所与中国科学院微生物研究所合作揭示调控银屑病样炎症的关键因子
深圳湾实验室传染病研究所刘文军团队和中国科学院微生物研究所合作在Journal of Autoimmunity上发表了题为“The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation”的研究论文。该研究发现，胞外cyclophilin A (eCypA)是调控银屑病样炎症的关键因子，并证明eCypA是治疗银屑病的潜在靶点。
葛韵/饶浪团队发展糖基化纳米抗体工程化细胞囊泡用于癌症免疫治疗
深圳湾实验室葛韵团队和饶浪团队合作在Angewandte Chemie International Edition《德国应用化学》上发表题为“Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy”的研究论文。该研究提供了一种全新的、通用的、具有展示单一高甘露糖型修饰的纳米抗体细胞囊泡的方法，不仅有效地阻断了CD47/SIRPα轴，携带高甘露糖修饰还能够激活MBL补体途径，同时凭借细胞囊泡长半衰期和高肿瘤靶向的优势，最终增强抗肿瘤免疫效应。
张泽民团队通过跨组织单细胞多组学揭示肌成纤维细胞的多样化免疫调节特征
深圳湾实验室/北京大学生物医学前沿创新中心（BIOPIC）张泽民课题组在Cancer Cell上发表一篇题为Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation的研究。该研究基于健康、纤维化、炎症以及癌症等多种疾病状态下的11种组织的单细胞数据，构建了涵盖517个人类样本、269,899个成纤维细胞的图谱，并鉴定出20种成纤维细胞亚型，揭示了成纤维细胞未被充分认识的转录异质性，其中发现了4类具有独特表型的肌成纤维细胞亚型。通过整合空间转录组、多重免疫组化和体外实验，该研究进一步揭示了肌成纤维细胞在肿瘤微环境中的独特免疫调控功能，为开发肿瘤微环境特异性靶向治疗策略提供了新的思路。
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