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全部共 141 篇

合成生物学综述Microorganisms

Synthetic Biology and Systems Metabolic Engineering of Aminoglycoside Antibiotics: From Biosynthetic Pathways to Resistance-Evading and Low-Toxicity Design.

Shan Chu、Yuqing Chu、Mohan Huang 等DOI: 10.3390/microorganisms14102209

综述

0 次引用趋势数据不足

氨基糖苷类抗生素是临床治疗革兰阴性菌感染的重要药物，但耐药性传播及耳毒性、肾毒性等剂量限制性副作用严重制约其临床应用。合成生物学与系统代谢工程的发展为解析和改造其生物合成途径提供了有力手段。本文系统总结氨基糖苷类抗生素的保守生物合成逻辑，重点阐述2-脱氧链霉胺和链霉胍核心骨架的组装，以及糖基转移酶、磷酸吡哆醛依赖型氨基转移酶、S-腺苷-L-甲硫氨酸依赖型甲基转移酶和磷酸化/脱氨酶四类主要酶的催化特征与底物选择性。在此基础上，从基因线路设计、底盘细胞优化、无细胞合成、异源从头生物合成和系统生物学驱动的全局优化五个方面综述其合成生物学与系统代谢工程核心策略。以庆大霉素、卡那霉素、妥布霉素、阿普拉霉素、新霉素和链霉素为代表，分析各生物合成途径特点及合成生物学开发潜力，重点关注新型衍生物研发，包括普拉佐米星等规避耐药性衍生物、基于4-单取代阿普拉霉素结构的低毒性设计及组合生物合成杂合抗生素进展。最后探讨异源表达兼容性、产物产量瓶颈和构效关系认识不足等关键挑战及应对策略。

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完整作者

Shan Chu、Yuqing Chu、Mohan Huang、Haoran Lu、Zhiqiao Liu、Shuo Wang、Hongquan Zhao、Xiaotang Chen

作者机构

College of Medical Engineering, Jining Medical University, Jining 272067, China.

技术路线

暂未整理

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:24

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临床队列临床研究Nature

Sugar-rich foods exacerbate antibiotic-induced microbiome disruption.

Anqi Dai、Annamaria Ballweg、William Jogia 等DOI: 10.1038/s41586-026-11077-3

多组学风险模型队列研究

1 次引用趋势数据不足

一项研究通过精确追踪173名因造血细胞移植住院患者摄入的9 419餐饮食并分析随后微生物组变化，评估饮食与肠道微生物组动态的关系。对158名有配对纵向微生物组样本患者数据应用贝叶斯推断显示，抗生素暴露期间摄入甜食和糖类可预测微生物失调加重，表现为α多样性降低和致病共生菌肠球菌更大程度扩增。小鼠实验亦表明，补充蔗糖可增加并延长抗生素诱导的肠球菌扩增。研究提示，抗生素治疗期间避免富含单糖的饮食或可减轻微生物群破坏。

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编辑短评

评估了饮食（特别是甜食和糖类）与肠道微生物组动态的关系，抗生素治疗期间避免富含单糖的饮食或可减轻微生物群破坏。

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完整作者

Anqi Dai、Annamaria Ballweg、William Jogia、Madhumitha Rangesa、Peter A Adintori、Mirae Baichoo、Tyler Funnell、Teng Fei、Nicholas R Waters、Abrielle Swartz、Sukanya Sahu、Brianna Gipson、Sandeep S Raj、Eiko Hayase、Zoe Pierce、Kenton Wu、Natalie Smith、Justin Neuberger、Adam Warren、Marina Burgos da Silva、Oriana Miltiadous、Corrado Zuanelli Brambilla、Marissa Lubin Buchan、Tatanisha K Peets、Ana Gradissimo、Luigi A Amoretti、Caichen Duan、Chenzhen Zhang、Fanny Matheis、Alexis P Sullivan、John B Slingerland、Annelie G Clurman、Daniel G Brereton、Paul A Giardina、Antonio L C Gomes、Abigail J Johnson、Dan Knights、Robert R Jenq、Kate A Markey、Miguel-Angel Perales、Sergio A Giralt、Marcel R M van den Brink、Jonas Schluter、Jonathan U Peled

作者机构

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Institute for Systems Genetics, NYU Langone Health Grossman School of Medicine, New York, NY, USA.
Department of Microbiology, NYU Langone Health Grossman School of Medicine, New York, NY, USA.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Departments of Genomic Medicine and Stem Cell Transplantation Cellular Therapy, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Human Oncology & Pathogenesis Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Haematology Unit, Department of Cellular Therapy, Hematology and Laboratory Medicine, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.
Food and Nutrition Services, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Biomedical Engineering, NYU Tandon School of Engineering, New York, NY, USA.
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Riddet Institute, Massey University, Palmerston North, New Zealand.
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.
Biotechnology Institute, University of Minnesota, Saint Paul, MN, USA.
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Division of Medicine, University of Washington, Seattle, WA, USA.
Weill Cornell Medical College, New York, NY, USA.
City of Hope, Duarte, CA, USA. mvandenbrink@coh.org.
Institute for Systems Genetics, NYU Langone Health Grossman School of Medicine, New York, NY, USA. jonas.schluter@nyulangone.org.
Department of Microbiology, NYU Langone Health Grossman School of Medicine, New York, NY, USA. jonas.schluter@nyulangone.org.
Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA. jonas.schluter@nyulangone.org.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. peledj@mskcc.org.
Weill Cornell Medical College, New York, NY, USA. peledj@mskcc.org.

技术路线

数据/样本：173例造血干细胞移植住院患者的9,419餐饮食记录及纵向肠道菌群样本（其中158例有配对纵向菌群样本用于贝叶斯推断）；分析：贝叶斯推断评估饮食与菌群动态关系；验证：小鼠实验验证蔗糖补充对抗生素诱导肠球菌扩张的影响。

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:30

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临床队列方法学Nature methods

CytoVI: deep generative modeling of antibody-based single cell data.

Florian Ingelfinger、Nathan Levy、Can Ergen 等DOI: 10.1038/s41592-026-03224-5

单细胞队列研究方法学

0 次引用趋势数据不足

基于抗体的单细胞技术（如流式细胞术、质谱流式细胞术和CITE-seq）已广泛应用于临床诊断和基础研究，但其分析受到技术噪声、批次效应、平台差异和抗体组合受限等因素的影响。为此，研究提出CytoVI——一种概率生成模型，用于对基于抗体的单细胞数据进行统计严谨的统一分析。CytoVI可在单一概率模型中生成信息丰富的细胞嵌入、填补缺失测量值、进行差异蛋白表达检验并自动注释细胞。研究应用CytoVI构建了涵盖350种蛋白的B细胞成熟整合图谱，识别出与免疫球蛋白类别转换相关的蛋白；在经流式细胞术和CITE-seq分析的B细胞非霍奇金淋巴瘤患者队列中，CytoVI揭示了疾病相关的T细胞状态。CytoVI已作为开源软件发布于scvi-tools.org。

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完整作者

Florian Ingelfinger、Nathan Levy、Can Ergen、Artemy Bakulin、Alexander Becker、Pierre Boyeau、Martin Kim、Diana Ditz、Jan Dirks、Jonas Maaskola、Tobias Wertheimer、Robert Zeiser、Corinne C Widmer、Ido Amit、Nir Yosef

作者机构

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. florian.ingelfinger@uniklinik-freiburg.de.
Department of Internal Medicine I, Medical Center-University of Freiburg, Freiburg, Germany. florian.ingelfinger@uniklinik-freiburg.de.
German Cancer Consortium (DKTK) Partner Site Freiburg, a partnership between DKFZ and Medical Center-University of Freiburg, Heidelberg, Germany. florian.ingelfinger@uniklinik-freiburg.de.
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, USA.
Institute of Systems Immunology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Division of Hematology and Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
Department of Internal Medicine I, Medical Center-University of Freiburg, Freiburg, Germany.
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. ido.amit@weizmann.ac.il.
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. nir.yosef@weizmann.ac.il.
Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, USA. nir.yosef@weizmann.ac.il.

技术路线

抗体单细胞数据（流式细胞术、质谱流式、CITE-seq） → 统一概率生成模型分析（细胞嵌入生成、缺失测量插补、差异蛋白表达检验、自动细胞注释）

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:02

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临床队列临床研究Cell

Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort.

Lu Yang、Vaidhvi Singh、Brent J Gawey 等DOI: 10.1016/j.cell.2026.09.009

肿瘤与癌症多组学风险模型多中心队列研究

0 次引用趋势数据不足

一项真实世界混合癌症队列研究（Mayo Clinic Cancer Microbiome）纳入1,364例癌症患者和287名健康对照，采用可校正癌症、合并症及人口学和临床变量相关非特异性微生物组关联的分析框架，在五类癌症中鉴定出341种最可能参与癌症发病的癌症相关菌种。在癌种内部，早期乳腺癌患者粪便胆汁酸及C. scindens水平较低，早期结直肠癌患者乳酸和Veillonella parvula升高；携带二氢嘧啶脱氢酶的Anaerostipes hadrus对5-氟尿嘧啶所致腹泻具有保护作用。研究提示该队列可用于发现癌症特异性微生物组特征和预测性生物标志物。

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暂未整理

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完整作者

Lu Yang、Vaidhvi Singh、Brent J Gawey、Jason P Sinnwell、Stephen Johnson、Elle C Billings、Trena M Van Gorp、Jonathan J Harrington、Michael Q Slama、Lisa M Till、Manavjot Singh、Thoshik R Samineni、Mojun Zhu、Krishna R Kalari、Gianrico Farrugia、Jun Chen、Ruben A T Mars、Purna C Kashyap

作者机构

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA; The Benioff Center for Microbiome Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Division of Gastroenterology, Mount Sinai, New York, NY, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology, Mount Sinai, New York, NY, USA.
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: chen.jun2@mayo.edu.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: mars.ruben@mayo.edu.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. Electronic address: kashyap.purna@mayo.edu.

技术路线

真实世界混合癌症队列（1364例癌症患者和287例健康对照）的粪便微生物组数据 → 构建校正框架以排除与合并症、人口学和临床变量的非特异性关联，鉴定出五类癌症相关的341个菌种

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 12:53

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临床队列临床研究Nature medicine

Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial.

Timothy A Yap、Elisa Fontana、Natalie Cook 等DOI: 10.1038/s41591-026-04657-3

肿瘤与癌症风险模型成人队列研究

2 次引用趋势数据不足

一项正在进行的首次人体1期试验第1部分评估了WRN共价抑制剂RO7589831（VVD-133214）在88例微卫星不稳定（MSI）和/或DNA错配修复缺陷晚期实体瘤患者中的递增剂量。给药方案为每日一次150 mg、每日两次150~1,000 mg或每日三次200~600 mg，主要目标为安全性和耐受性及推荐2期剂量与方案（RP2D）。600 mg每日三次组发生1例剂量限制性2级恶心，但未确定最大耐受剂量。发生率≥10%的治疗中出现不良事件多为1~2级；≥30%者为恶心（54.5%）、腹泻（43.2%）、乏力（39.8%）、贫血（37.5%）和呕吐（30.7%）。导致停药的不良事件少见（3.4%），无5级事件。MSI可评估患者疾病控制率为74.2%（49/66），7例确认为部分缓解（客观缓解率10.6%），中位缓解持续时间10.2+个月；中位无进展生存期6.7个月，中位总生存期17.6个月。选择150 mg和600 mg每日两次作为RP2D。

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编辑短评

WRN共价抑制剂RO7589831（VVD-133214）的首次人体1期试验第1部分，评估了患者中的递增剂量。

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完整作者

Timothy A Yap、Elisa Fontana、Natalie Cook、Marwan Fakih、Oliver Bechter、Erica S Tsang、Emiliano Calvo、Kristoffer S Rohrberg、Javier Ros、Ignacio Matos、John H Strickler、Malaka Ameratunga、Meredith Pelster、Adam Sharp、Jaspreet Grewal、Susanna Ulahannan、Rajesh Belani、Matthew P Patricelli、Sophia M Blake、David Dejardin、Stephen Fowler、Christina Godfried Sie、Astrid Heller、Nina Henkel、Michael Hettich、Angelika Lahr、David Lamparter、Charlotte Lane、Ting Liu、Hélène Meistermann、Christophe Meille、Neil Parrott、Sotirios K Sotiriou、Denise Reeves、Barbara Romagnoli、Piergiorgio Pettazzoni、Daniel Waterkamp、Matthias Wittwer、Yali Fu、Sophie Postel-Vinay

作者机构

University of Texas MD Anderson Cancer Center, Houston, TX, USA. tyap@mdanderson.org.
Sarah Cannon Research Institute, London, UK.
The Christie NHS Foundation Trust and The University of Manchester, Manchester, UK.
City of Hope National Medical Center, Duarte, CA, USA.
Universitair Ziekenhuis (UZ) Leuven, Leuven, Belgium.
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.
Rigshospitalet, Copenhagen, Denmark.
Vall d´Hebron Institut d'Oncologia (VHIO), Barcelona, Spain.
Clinica Universidad de Navarra, Madrid, Spain.
Duke University, Durham, NC, USA.
The Alfred, Melbourne, Victoria, Australia.
Sarah Cannon Research Institute, Nashville, TN, USA.
Royal Marsden Hospital, London, Institute of Cancer Research, London, UK.
Norton Cancer Institute, Louisville, KY, USA.
University of Oklahoma, Norman, OK, USA.
Vividion Therapeutics, San Diego, CA, USA.
Roche Pharma Research and Early Development, Roche Innovation Center Munich, Munich, Germany.
Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
Roche Products Ltd., Welwyn Garden City, UK.
Roche Pharma Research and Early Development, Roche Innovation Center New York, New York, NY, USA.
Gustave Roussy, Villejuif and University College of London Cancer Institute, London, UK.

技术路线

88例MSI和/或dMMR晚期实体瘤患者→剂量递增（每日一次150 mg、每日两次150-1,000 mg、每日三次200-600 mg）→安全性/耐受性分析及RP2D确定→抗肿瘤活性分析（DCR、ORR、DOR、PFS、OS）→探索性ctDNA分子缓解和FDG-PET代谢缓解分析支持生物学活性（肿瘤组织直接靶点结合未能证实）

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:03

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合成生物学基础研究Medicines (Basel, Switzerland)

The Role of Zinc and Junctional Adhesion Molecule A Protein in Platelet Plug Formation.

Sai Harsha Nagidi、Jonah Stringham、Ethan Firth 等DOI: 10.3390/medicines13040028

0 次引用趋势数据不足

血小板血栓是血管损伤后由血小板快速形成的临时止血封堵物，血小板活化脱颗粒可释放ADP、5-羟色胺、纤维蛋白原和锌等物质，但锌的靶点尚不明确。本研究采用血小板聚集实验和重组蛋白技术，结合尺寸排阻色谱、表面等离子共振及透射电子显微镜，在1 mM锌和10 µM ADP条件下评估血小板聚集及相关蛋白作用。结果显示，锌的局部高浓度靶向连接黏附分子A（JAM-A）；JAM-A在无需凝血时保持无活性状态，抑制细胞黏附和细胞骨架动态，使血小板以单一单位随血流移动，而锌激活JAM-A后促使血小板聚集。采用合成生物学小肽淬灭锌作用进一步验证了该过程。结论认为，JAM-A与锌相互作用促进血小板血栓形成，并激活JAM-A的细胞黏附和细胞骨架动态功能。

为什么值得关注

AI 辅助短评，基于标题和摘要整理

摘要聚焦锌与JAM-A在血小板栓形成中的作用，技术路线涵盖聚集实验、SEC、SPR、TEM及小肽淬灭验证，逻辑较完整。但未说明样本来源、分组与统计学方法，机制结论主要基于体外实验，缺乏体内验证。标题与摘要一致，表述克制，未夸大。建议补充样本量、对照设置及JAM-A激活的直接证据，以增强结论可靠性。

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完整作者

Sai Harsha Nagidi、Jonah Stringham、Ethan Firth、Brent Lisonbee、Chris Hart、Dario Mizrachi

作者机构

Arizona College of Osteopathic Medicine (AZCOM), Midwestern University, Glendale, AZ 85308, USA.
Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84604, USA.
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA.

技术路线

['血小板样本与重组蛋白（1 mM锌、10 µM ADP处理）', '血小板聚集实验评估聚集行为', '体积排阻色谱（SEC）分析蛋白', '表面等离子共振（SPR）评估靶蛋白在血小板表面的亲和力', '透射电子显微镜（TEM）观察', '合成生物学小肽淬灭锌效应验证']

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/29 11:45

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临床队列临床研究Cell

Opposing functions of gut immunomodulatory metabolites on CAR-T therapy.

Markus Perl、Severin Guetter、Dhyani Shah 等DOI: 10.1016/j.cell.2026.09.004

肿瘤与癌症多组学风险模型队列研究

0 次引用趋势数据不足

一项研究纳入德国三个中心的129例患者，采用鸟枪法宏基因组学和靶向质谱分析发现，CAR-T细胞治疗前短链脂肪酸（尤其是戊酸）水平降低与疾病进展风险增加相关；而吲哚类代谢物（包括吲哚-3-甲醛和吲哚-3-乙酸）及支链脂肪酸异戊酸水平升高与不良结局相关。在人源和小鼠CAR-T细胞模型中的功能验证表明，补充戊酸可增强CAR-T细胞疗效，而吲哚-3-甲醛和异戊酸则损害其疗效。研究揭示了免疫调节代谢物对CAR-T细胞治疗的对立作用，对设计代谢物引导的微生物组治疗策略具有重要意义。

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完整作者

Markus Perl、Severin Guetter、Dhyani Shah、Simon Holzinger、Luisa Becker、Misbah Tariq、Philipp Menauer、Simon Delahais、Gloria Lutzny-Geier、Julian N Scherer、Sascha Göttert、Konstantin Herfeld、Paul Heinrich、Klaus Georg Kreitmeier、Claudia Gebhard、Wolfgang Herr、Marcel P Trefny、Janina Doerr、Saba Sameri、Dennis C Harrer、Kai Ziegler-Martin、Sarah Staudt、Leo Hansmann、Matthias Edinger、Daniel Wolff、Daniela Weber、Elisabeth Meedt、Alexander Denk、Andre Gessner、Ernst Holler、Tobias Wertheimer、Klaus Neuhaus、Tingting Zheng、David M Cordas Dos Santos、Sebastian Theurich、Melanie Schirmer、Karin Kleigrewe、Jonas Schluter、Marcel van den Brink、Michael Schmitt、Markus Feuerer、Christoph Heuser-Loy、Jeremy Baldwin、Luca Gattinoni、Michael Rehli、Michael Hudecek、Camille Bigenwald、Laurence Zitvogel、Marion Subklewe、Viktoria Blumenberg、Maria-Luisa Schubert、Christoph Stein-Thoeringer、Maik Luu、Sebastian Kobold、Matthias A Fante、Erik Thiele Orberg、Hendrik Poeck

作者机构

Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany. Electronic address: markus.perl.ukr@gmail.com.
Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany.
Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany.
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.
Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany.
Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
Division of Hematology and Oncology, Department of Medicine, Freiburg University, Freising, Germany.
Core Facility Microbiome, ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany.
Translational Microbiome Data Integration, School of Life Sciences, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany.
Gene Center and Department of Biochemistry, LMU Munich, Munich, Germany.
Department of Medicine III, Hematology/Oncology, LMU University Hospital and Gene Center, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ and BZKF at the University Hospital of the LMU, Germany.
Translational Microbiome Data Integration, School of Life Sciences, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany; Center for Organoid Systems, Technical University Munich, Garching, Germany.
Bavarian Center for Biomolecular Mass Spectrometry, TUM School of Life Sciences, Technical University Munich, Freising, Germany.
Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA; Institute for Systems Genetics, NYU Langone Health Grossman School of Medicine, New York, NY, USA.
Beckman Research Institute, City of Hope, Duarte, CA, USA.
Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany; Department of Internal Medicine III, Haematology and Oncology, University Hospital Bonn, Bonn, Germany.
Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany; Branch Cellular Immunotherapy, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Würzburg, Germany.
Gustave Roussy Cancer Campus, Villejuif, France.
Department of Medicine III, Hematology/Oncology, LMU University Hospital and Gene Center, LMU Munich, Munich, Germany; Laboratory for Translational Cancer Immunology, Gene Center LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany.
Department of Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany; Laboratory for Translational Cancer Immunology, Gene Center LMU Munich, Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany; German Center for Lung Research (DZL), Partner Site Munich, Munich, Germany.
Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany. Electronic address: erik.orberg@ukr.de.
Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany; Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany. Electronic address: hendrik.poeck@ukr.de.

技术路线

粪便宏基因组与靶向质谱（129例三中心队列）→代谢物与疾病进展关联分析→人及小鼠CAR-T细胞模型功能验证

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不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:03

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公共数据库临床研究Nucleic acids research

circRNADisease v3.0: an updated resource for high-quality, experimentally supported circRNA-disease associations.

Chang-Lin Yang、Rui Yang、Wen-Lu Tan 等DOI: 10.1093/nar/gkag927

TCGA 肿瘤与癌症多组学队列研究

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环状RNA（circRNA）与疾病关联的系统整合对阐明其在疾病发生中的作用及评估其生物标志物和治疗靶点潜力具有重要意义。circRNADisease v3.0是一个经过人工审编、实验支持的circRNA-疾病关联数据库的扩展升级版本，共收录15 390条circRNA-疾病条目，涉及9 168个circRNA、656个MONDO标准化疾病术语和66个物种，数据量较v2.0增加两倍以上。每条记录依据支持证据的强度和多样性赋予置信评分，证据类型包括临床证据、环状转录本身份验证、表达检测、功能实验、分子机制验证和生物信息学分析。该版本还整合了基因组坐标、亚细胞定位、实验验证方法、临床意义、数据与代码可用性及多疾病术语交叉引用。新增Circ2CNV模块（含33个TCGA癌症队列中2 962 504条circRNA-癌症队列拷贝数变异记录）和Circ2Celltype模块（含29种细胞类型的2 025条细胞类型解析证据记录），与原有Circ2Mut模块共同将文献审编的circRNA-疾病关联与基因组改变和细胞背景相连接。该数据库为circRNA研究提供了全面且以证据为导向的平台，可通过http://cgga.org.cn/circRNADisease/免费获取。

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Chang-Lin Yang、Rui Yang、Wen-Lu Tan、Han-Xiao Zhou、Ling-Xiang Wu、Ji Shi、Fan Wu、Li-Jie Huang、Zhi-Yan Sun、Tao Jiang、Zheng Zhao

作者机构

Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China.
Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Chinese Glioma Genome Atlas (CGGA) Network and Asian Glioma Genome Atlas (AGGA) Network, Beijing 100070, China.
Chinese Neuro-Oncology Genome Atlas (CGGA-CNS) Network, Beijing 100070, China.

技术路线

数据/样本：文献人工审编的circRNA-疾病关联，v3.0含15,390条条目（9,168个circRNA、656个MONDO标准化疾病术语、66个物种），并整合TCGA 33个癌症队列的2,962,504条circRNA-癌症队列记录（Circ2CNV模块）和2,025条细胞类型分辨证据（29种细胞类型，Circ2Celltype模块）；分析：依据临床证据、circular-transcript身份验证、表达检测、功能实验、分子机制验证和生物信息学分析等支持证据的强度与多样性，为每条记录赋予置信度评分，并整合基因组坐标、亚细胞定位、实验验证方法、临床意义、数据与代码可及性及多疾病术语交叉引用；验证：原文未报告独立的实验或计算验证。

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数据来源：openalex更新时间：2026/10/29 12:36

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AI 靶点发现综述Frontiers in oncology

Colorectal cancer organoids: a developmental trajectory from Matrigel embedding to AI-empowered precision medicine.

作者信息暂未整理DOI: 10.3389/fonc.2026.1901112

肿瘤与癌症综述

0 次引用趋势数据不足

结直肠癌的高度异质性与复杂微环境是治疗耐药和临床转化失败的关键瓶颈，类器官技术的迭代发展为精准肿瘤学提供重要驱动力。本文系统梳理结直肠癌类器官技术的四阶段发展轨迹，并指出各阶段并非严格依次替代，而是长期共存、互补。第一代Matrigel包埋法奠定三维培养基础，但微环境模拟不足；第二代通过优化培养基和共培养体系实现初步肿瘤-基质相互作用；第三代整合微流控芯片和生物打印等工程技术，突破专用平台在高通量标准化和动态调控方面的瓶颈；第四代借助人工智能，在智能表型分析、药物反应预测及数字孪生系统初步探索方面取得实质进展。通过比较四代技术在异质性保留、通量、临床潜力和成本效益方面的差异，强调其在个体化用药指导和新靶点发现中的核心临床价值。尽管仍面临微环境模拟不足、人工智能可解释性差和缺乏标准化等挑战，现有证据表明，跨学科整合与智能平台开发可推动类器官技术成为连接基础研究与临床实践的关键枢纽。建议加快建立标准化类器官生物样本库，将人工智能驱动的预测模型嵌入临床工作流程，并制定监管框架，以促进结直肠癌类器官精准医学转化。

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最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:05

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公共数据库基础研究Cell

CD4 T cells convert transient responses to KRAS inhibition to durable remissions in pancreatic cancer.

Li Qiang、Megan T Hoffman、Jung-Ho Chun 等DOI: 10.1016/j.cell.2026.08.045

MIMIC 肿瘤与癌症方法学

1 次引用趋势数据不足

胰腺导管腺癌对多数疗法（包括免疫治疗）耐受，单纯通过免疫检查点阻断重振CD8 T细胞不足以诱导长期持久缓解。KRAS抑制剂虽显示临床前景，但获得性耐药常见。研究在小鼠中建模KRAS抑制剂应答与复发，发现IL-21细胞因子模拟物21h10可诱导长期持久缓解，而化疗或联合检查点阻断无此效果。其疗效依赖Th1极化的CD4 T细胞，不依赖CD8 T细胞或肿瘤细胞MHC I类分子表达。经2型经典树突状细胞（cDC2）致敏的CD4 T细胞产生IFN-γ，促进巨噬细胞介导的肿瘤细胞吞噬。人PDAC标本体外经21h10处理可诱导浸润T细胞产生IFN-γ。表明IL-21激发的CD4 T细胞在小鼠及可能在人中发挥抗肿瘤活性，将KRAS抑制的短暂应答转化为持久缓解。

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编辑短评

该研究在小鼠模型中系统揭示IL-21模拟物21h10可将KRAS抑制剂短暂响应转化为持久缓解，机制上依赖cDC2启动的Th1样CD4 T细胞分泌IFN-γ并促进巨噬细胞吞噬，而非CD8 T细胞或肿瘤MHC I类分子。人PDAC离体实验仅显示IFN-γ诱导，样本量与临床验证有限，向人体转化仍需体内试验支持。

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完整作者

Li Qiang、Megan T Hoffman、Jung-Ho Chun、Brendan Parent、Felix Hambitzer、Frank Peprah、Courtney T S Kureshi、Birkley S Lim、Eugena Chang、Michael J Walsh、Julissa G Tello、Tavus Atajanova、Hojeong Shin、Corey Perkins、Rakeeb Kureshi、Yaniris Molina-Aponte、James M Dougan、Chong Zuo、Lauren Brais、Thomas E Clancy、James M Cleary、Jason L Hornick、Brandon M Huffman、Joseph D Mancias、George Molina、Mark Fairweather、Jonathan A Nowak、Kimberly J Perez、Douglas A Rubinson、Sarah Slater、Ritchell van Dams、Jiping Wang、Brian M Wolpin、Kwok-Kin Wong、Harshabad Singh、Andrew J Aguirre、David Baker、Michael Dougan、Stephanie K Dougan

作者机构

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Radiation Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA.
Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: stephanie_dougan@dfci.harvard.edu.

技术路线

小鼠KRASi响应/复发模型 → 与化疗或检查点阻断联合方案对比分析

最近 5 个完整年度引用趋势

不含 2026 年，仅展示最近 5 个完整年度。

数据来源：openalex更新时间：2026/10/30 06:04

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