University of Michigan

Not intended for the UK Apecotrep (BI 764198) is a potential first-in-class, oral, selective TRPC6 inhibitor being investigated as a novel, targeted, non-immunosuppressive therapy in people with primary focal segmental glomerulosclerosis (FSGS). Primary FSGS is a rare kidney condition in which injury and loss of podocytes, the cells responsible for the kidney’s filtration system, lead to proteinuria and kidney failure over time. Phase II trial results, published in The Lancet, demonstrated a 40% reduction in proteinuria with apecotrep (20 mg dose group) compared to placebo after 12 weeks of treatment. The Phase III trial is open for recruiting adults and adolescents with primary FSGS. An additional Phase II trial in other proteinuric kidney diseases will start in the first quarter of this year. Boehringer Ingelheim today announced results from a 12-week Phase II clinical trial evaluating apecotrep (BI 764198), an oral, potential first-in-class, non-immunosuppressive TRPC6 inhibitor for people with primary focal segmental glomerulosclerosis (FSGS). Apecotrep reduced proteinuria, a key indicator associated with kidney damage, by 40% in the 20 mg dose group compared to placebo. 1 The results were published in The Lancet and presented at the 2025 American Society of Nephrology (ASN)’s Kidney Week. The Phase III trial ( NCT07220083 ) is open for recruiting adults and adolescents with primary FSGS. An additional Phase II trial ( NCT07355296 ) evaluating the safety and efficacy of apecotrep in other proteinuric kidney diseases will start in the first quarter of this year. Apecotrep demonstrates Boehringer’s commitment to addressing high unmet medical needs across a broad spectrum of kidney diseases. This includes primary kidney conditions where no approved disease-modifying therapies currently exist. “The results underscore Boehringer’s scientific leadership in kidney health and deep commitment to people living with cardiovascular, renal, and metabolic diseases, including rare kidney conditions like FSGS,” said Paola Casarosa, Head of Innovation Unit, Board of Managing Directors, Boehringer Ingelheim. “With the Phase III trial now underway, we are advancing apecotrep driven by the potential to deliver the first disease-modifying treatment for primary FSGS and redefine the standard of care for patients.” Primary FSGS is a rare, progressive kidney disease which can end in kidney failure. 2,3,4 Despite its severity and burden for patients, there are currently no approved targeted therapies. 5,6,7 There remains a significant unmet need for a targeted therapy that addresses the root cause of the disease. “Primary FSGS is a serious glomerular disease and an important cause of kidney failure in both children and adults. By targeting the underlying mechanism of primary FSGS, apecotrep reduced proteinuria by 40% compared to placebo, with a favorable tolerability pro adults,” said Howard Trachtman, Lead Investigator, University of Michigan. “These clinically relevant findings reinforce the importance of further investigation of its potential as a first-in-class targeted treatment for primary FSGS, where the unmet need remains high.” In primary FSGS, the protein Transient Receptor Potential Channel 6 (TRPC6) is hypothesized to be overactivated on podocytes, cells responsible for the kidney’s filtration system. 8 This allows excessive calcium to enter the cells, causing progressive podocyte injury and loss, and ultimately, proteinuria and kidney disease progression. Apecotrep intends to protect podocytes and slow down disease progression by decreasing proteinuria. 9 Highlighting its potential as a new treatment option for primary FSGS, apecotrep was granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China and Orphan Drug Designations by the European Medicines Agency (EMA) and the Japanese Ministry for Health, Labour and Welfare (MHLW). About apecotrep (BI 764198) and the Phase II trial Apecotrep is an investigational, potential first-in-class, oral, once daily, non-immunosuppressive TRPC6 inhibitor that is being developed as a potential treatment for people living with primary FSGS. 9 Its mechanism of action intends to counter the overactivation of TRPC6, a protein channel essential for the structure and function of podocytes, which are specialized cells responsible for the kidney’s filtration system. 9 The compound was discovered and developed by Boehringer Ingelheim, and is part of its Cardiovascular-Renal-Metabolic portfolio. In the Phase II trial, a response to treatment defined as greater than or equal to 25% reduction in urine protein-creatinine ratio (UPCR) was observed in 35% of participants receiving apecotrep across all dose groups after 12 weeks, compared to 1 out of 14 (7.1%) in the placebo arm. The greatest proportion of patients responding to apecotrep were in the 20mg dose (44.4%). Furthermore, a 40% (p=0.0024) reduction in UPCR compared to placebo was observed with 20 mg dose. 1 Finally, apecotrep was generally well-tolerated. About FSGS Focal segmental glomerulosclerosis (FSGS) is a type of podocytopathy in which podocyte injury and loss result in excess protein in the urine (proteinuria). Approximately, 50% of people with primary FSGS progress to end-stage kidney disease (ESKD) within 5-10 years. 10 FSGS is a leading cause of nephrotic syndrome in adults and is estimated to affect up to 0.8 per 100,000 population globally. 7 The condition is associated with scarring in the kidney’s filtering units called glomeruli and causes swelling of legs and other parts of the body, foamy urine, fatigue, weight gain, high blood pressure, and cholesterol increase. 11 Primary FSGS means that the disease occurs without a known cause, while secondary FSGS is caused by another known cause such as infection, diabetes or obesity. 11 Additionally, genetic FSGS results from mutations in podocyte or glomerular basement membrane proteins or specific susceptibility genes such as TRPC6 . 12,13 About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at . References 1 Trachtman H, et al. TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomized, placebo-controlled, phase 2 trial of BI 764198. Lancet. 2026;S0140-6736(25)02255-X. 2 Rosenberg AZ, Kopp JB. Focal segmental glomerulosclerosis. Clinical Journal of the American Society of Nephrology. 2017;12:502–517. 3 Munis MA, et al. Incidence and proportion of primary focal segmental glomerulosclerosis (FSGS) among a racially and ethnically diverse adult patient population between 2010 and 2021. Clinical Journal of the American Society of Nephrology. 2025;20(2):229-238. 4 Ossareh S, et al. Kidney outcome in primary focal segmental glomerulosclerosis (FSGS) by using a predictive model. Iranian Journal of Kidney Diseases. 2021;15(6):408-418. 5 Buttgereit F, et al. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet 2005;365:801–803. 6 Trachtman H. Emerging drugs for treatment of focal segmental glomerulosclerosis. Expert Opinion on Emerging Drugs. 2020;25(3):367-375. 7 McGrogan A, et al. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrology Dialysis Transplantation. 2011;26(2):414-30. 8 Kim EY, et al. Changes in podocyte TRPC channels evoked by plasma and sera from patients with recurrent FSGS and by putative glomerular permeability factors. Molecular Basis of Disease. 2017;1863(9):2342-2354. 9 Trachtman H, et al. TRPC6 inhibitor BI 764198 in focal segmental glomerulosclerosis: Phase 2 study design. Kidney International Reports. 2023;;8(12):2822-2825. 10 Bensink ME, et al. Kidney failure attributed to focal segmental glomerulosclerosis: a USRDS retrospective cohort study of epidemiology, treatment modalities, and economic burden. Kidney Medicine. 2023;6(2):100760. 11 Mayo Clinic. Focal segmental glomerulosclerosis (FSGS). Available at: . Accessed January 2026. 12 Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International. 2021;100:S1-S276. 13 Winn MP et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308(5729):1801-4.

单细胞组学 1. GATA1 N-terminus coordinates metabolic reprogramming in erythropoiesis. GATA1 N端协调红细胞生成过程中的代谢重编程。GATA1突变与多种血液肿瘤和贫血相关，但其N端区域的具体分子功能仍不明确。通过单细胞测序和PRO-seq发现，GATA1直接靶向并抑制糖酵解基因PKM，其缺失会导致组蛋白乳酸化增加及糖酵解通量异常。该研究揭示了GATA1在红细胞发育中调控糖酵解重编程的新机制，为相关血液病治疗提供了理论依据。 红细胞生成, 贫血 | GATA1, PKM, 糖酵解 | 单细胞RNA测序, PRO-seq Ling Te · … · Crispino John D · Blood · 2026/01/26 原文链接：https://doi.org/10.1182/blood.2025030464 2. Phf6 truncating mutation drives leukemogenesis via disrupted epigenetic regulation in mice. Phf6截短突变通过表观遗传失调驱动白血病发生。PHF6突变在血液恶性肿瘤中常见且预后差，但其截短蛋白的具体致病机制尚不明确。研究通过Phf6R274X转基因小鼠模型发现，该突变通过增强KAT6B乙酰转移酶活性改变H3K27ac修饰，驱动造血干细胞向髓系分化并诱发恶性肿瘤。该研究揭示了PHF6突变的功能获得性效应，并证实KAT6B是潜在的治疗靶点。 急性髓系白血病 | PHF6突变, KAT6B乙酰转移酶 | 转基因小鼠模型, 单细胞转录组测序 Guo Ying · … · Yang Feng-Chun · · 2026/01/26 该研究由德克萨斯大学圣安东尼奥分校血液学专家Feng-Chun Yang团队完成 Leukemia 原文链接：https://doi.org/10.1038/s41375-025-02828-8 3. Substantially Altered Local and Systemic Immunity in Ischemia-Free Versus Conventional Liver Transplantation. 无缺血肝移植显著改变局部与全身免疫反应。无缺血肝移植旨在减少缺血再灌注损伤，但其对免疫系统的影响尚不明确。研究通过单细胞测序发现，该技术通过抑制ANXA1-FPR1信号减少受体单核细胞浸润，并上调HMOX1发挥保护作用。该研究揭示了无缺血肝移植在减轻同种异体排斥反应中的关键免疫机制。 肝移植, 缺血再灌注损伤 | ANXA1-FPR1信号, HMOX1 | 单细胞RNA测序, 免疫细胞嵌合图谱 Luo Tao · … · Guo Zhiyong · · 2026/01/27 该研究由中山大学附属第一医院何晓顺教授团队完成，何教授是无缺血器官移植技术的开拓者 Advanced science (Weinheim, Baden-Wurttemberg, Germany) 原文链接：https://doi.org/10.1002/advs.202502854 4. RORγt+ dendritic cells are a distinct lymphoid-derived lineage. RORγt+树突状细胞是独特的淋巴来源谱系。建立耐受性树突状细胞谱系以防止对共生菌产生免疫反应的机制尚不明确。研究通过谱系追踪和单细胞转录组学发现，小鼠RORγt+ DCs起源于骨髓中的淋巴祖细胞，其发育依赖于特定的增强子和转录因子。该发现定义了维持肠道免疫稳态的关键淋巴来源DC谱系。 肠道免疫稳态 | RORγt+ DCs, 淋巴来源谱系 | 谱系追踪, 单细胞转录组学 Rodrigues Patrick Fernandes · … · Colonna Marco · · 2026/01/27 该研究由美国国家科学院院士、国际顶尖免疫学家Marco Colonna团队完成 Science immunology 原文链接：https://doi.org/10.1126/sciimmunol.aed7439 5. Targeting LRRC15 in Cancer-Associated Fibroblasts Modifies the Extracellular Matrix and Enhances Tumor Immune Responses to Suppress Lung Cancer Progression. 靶向LRRC15成纤维细胞增强肺癌免疫反应。肺癌中成纤维细胞（CAF）的异质性驱动了肿瘤进展，但有效的靶向策略仍然匮乏。研究识别出LRRC15+ CAF亚群，发现缺失LRRC15可通过减少细胞外基质产生来调节巨噬细胞极化并增强T细胞活性。该研究开发的双特异性抗体展示了良好的抗肿瘤潜力，为CAF导向的癌症治疗提供了新思路。 肺癌 | LRRC15, 肿瘤相关成纤维细胞(CAF), 免疫微环境 | 单细胞转录组学, 双特异性抗体 Qi Lu · … · Zhu Linnan · · 2026/01/27 该研究由北京大学张泽民（Zemin Zhang）教授团队合作完成，张教授是单细胞测序领域的知名专家。 Cancer research 原文链接：https://doi.org/10.1158/0008-5472.CAN-25-2871 6. Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids. 自噬激活剂改善人AD类器官的Tau蛋白稳态与突触损伤。阿尔茨海默病（AD）的早期分子机制尚不明确，且缺乏理想的人源化疾病模型。研究利用hiPSC衍生的脑类器官模型，发现自噬激活剂能有效清除病理性Tau蛋白并恢复神经元电生理功能。该研究不仅揭示了AD早期的细胞类型特异性异常，还为筛选潜在治疗药物提供了高效平台。 阿尔茨海默病(AD) | Tau蛋白, 自噬通路 | 人诱导多能干细胞(hiPSC), 脑类器官, 单细胞RNA测序 Labra Sergio R · … · Lipton Stuart A · · 2026/01/27 该研究由神经科学领域知名专家、美国斯克里普斯研究所Stuart A. Lipton教授团队完成。 Advanced science (Weinheim, Baden-Wurttemberg, Germany) 原文链接：https://doi.org/10.1002/advs.202514783 空间组学 1. A temporal and spatial atlas of adaptive immune responses in the lymph node following viral infection. AIR-SPACE技术构建了病毒感染后淋巴结自适应免疫反应的时空图谱。淋巴结内免疫细胞的空间组织对理解感染至关重要。研究开发了整合空间转录组与长读长受体测序的方法，描绘了生发中心的亚解剖结构及B细胞克隆的动态网络。该研究为深入探讨淋巴器官内的空间免疫动力学提供了强有力的工具。 病毒感染免疫反应 | 生发中心, B细胞克隆演化 | 空间转录组学, 长读长测序 Jiang Shaowen · … · De Vlaminck Iwijn · Proceedings of the National Academy of Sciences of the United States of America · 2026/01/26 原文链接：https://doi.org/10.1073/pnas.2504742123 2. Tissue and extracellular matrix remodeling of the subchondral bone during osteoarthritis of knee joints as revealed by spatial mass spectrometry imaging. 空间质谱成像揭示骨关节炎膝关节下骨及细胞外基质重塑。骨关节炎（OA）缺乏除关节置换外的有效疗法，主因是其分子驱动机制尚不明确。研究利用空间质谱成像技术绘制了人OA关节的蛋白质图谱，发现软骨下骨的重塑可能早于软骨的完全丧失。该研究鉴定了31个与疾病相关的基质肽标记物，为OA的早期检测和分级提供了潜在的生物标志物。 骨关节炎 | 软骨下骨重塑, 细胞外基质 | 空间质谱成像 Schurman Charles A · … · Schilling Birgit · Bone research · 2026/01/26 原文链接：https://doi.org/10.1038/s41413-025-00495-0 3. Spatially resolved molecular signatures of Lewy body dementia. 空间转录组学揭示路易体痴呆的层级特异性分子特征。SNCA和APOE4是路易体痴呆（LBD）的关键遗传风险因素，但其影响神经元脆弱性的机制不明。研究利用空间转录组学发现皮层第5层是易感区域，表现为SNCA高表达及代谢失调，且APOE4加剧了白质髓鞘损伤。该研究为LBD的区域特异性病理提供了分子图谱，助力开发精准治疗策略。 路易体痴呆 | SNCA基因, APOE4 | 空间转录组学, 单细胞核测序 Jin Yunjung · … · Zhao Na · Acta neuropathologica · 2026/01/26 原文链接：https://doi.org/10.1007/s00401-026-02981-z 基因组或者转录组学 1. Uncovering the genomic complexity of PAX5 intragenic tandem multiplication via long-read and short-read sequencing. 长读长测序揭示PAX5基因内串联重复的复杂性。PAX5基因重排在急性淋巴细胞白血病中常见，但其基因内串联重复（ITM）的精确结构难以通过短读长测序完全解析。研究整合长读长和短读长RNA测序，发现PAX5-ITM导致产生可能改变蛋白结构域的框内转录本。该研究提升了对白血病基因组复杂性的认识，为精准诊断和治疗提供了新依据。 急性淋巴细胞白血病 | PAX5基因, 基因重排 | 长读长测序, RNA-seq Liu Yanling · … · Ma Xiaotu · Blood · 2026/01/26 原文链接：https://doi.org/10.1182/blood.2025031289 2. Therapeutic Potential of HSP90 Inhibitor 17-DMAG in Regulating METTL3 for Kidney Fibrosis Treatment. HSP90抑制剂17-DMAG通过调节METTL3缓解肾纤维化。肾纤维化是慢性肾病的核心病理特征，METTL3介导的m6A甲基化在其中发挥关键促进作用。研究发现17-DMAG通过诱导HSP70表达并抑制JNK/c-Jun通路，从而下调METTL3水平，显著减轻了小鼠模型的肾脏胶原沉积。该研究揭示了17-DMAG在表观转录组水平的抗纤维化新机制，为慢性肾病治疗提供了新候选药物。 肾纤维化, 慢性肾病 | METTL3, HSP90, m6A甲基化 | MeRIP-Seq Lee Soo Min · … · Lee Jung Pyo · Journal of the American Society of Nephrology : JASN · 2026/01/26 原文链接：https://doi.org/10.1681/ASN.0000000975 3. Oncogenic SF3B1 mutations alter the splicing of mRNA noncoding regions to induce a novel therapeutic vulnerability. SF3B1突变通过改变非编码区剪接诱导肿瘤治疗新脆弱性。SF3B1突变在多种癌症中常见，以往研究多关注其对蛋白编码区的剪接影响。研究发现SF3B1突变能改变DCAF16等基因非编码区的剪接，导致蛋白水平升高，从而使突变细胞对利用DCAF16的新型降解剂更加敏感。该发现揭示了SF3B1突变导致的功能获得性新机制，为开发针对性蛋白降解疗法开辟了道路。 血液肿瘤, 慢性淋巴细胞白血病 | SF3B1突变, DCAF16, 异常剪接 | 蛋白降解剂(PROTAC) Sekrecki Michal · … · Lu Sydney X · Blood · 2026/01/26 原文链接：https://doi.org/10.1182/blood.2025029972 4. Evolution of AR and non-AR alterations in circulating tumor DNA of metastatic prostate cancer patients treated in the phase 3 Alliance A031201 trial. ctDNA动态监测揭示转移性前列腺癌的耐药演化。前列腺癌患者对雄激素受体通路抑制剂（ARPI）的耐药机制具有高度异质性。通过对327名患者的纵向ctDNA分析发现，AR基因增益和重排在耐药后显著增加，且AR与非AR改变的积累模式与疾病进展速度相关。该研究支持利用液体活检实时追踪耐药机制，为晚期前列腺癌的精准治疗提供指导。 前列腺癌, 耐药性 | 雄激素受体(AR) | ctDNA测序, 液体活检 Valentín López José C · … · Dehm Scott M · Clinical cancer research : an official journal of the American Association for Cancer Research · 2026/01/26 原文链接：https://doi.org/10.1158/1078-0432.CCR-25-2779 5. ctDNA dynamics and recurrence patterns after organ-sparing trimodality therapy for bladder cancer. ctDNA动态变化可预测膀胱癌三联疗法后的转移复发。三联疗法是肌层浸润性膀胱癌的保膀胱方案，但缺乏有效的生物标志物来预测复发风险。研究发现放化疗后ctDNA的可检测性与远处转移密切相关，但与单纯的局部复发无关。该研究表明ctDNA监测有助于识别高风险转移患者，从而优化膀胱癌的个体化随访和治疗策略。 膀胱癌 | 肿瘤复发, 转移预测 | ctDNA监测 Epstein Ilana B · … · Mouw Kent W · Clinical cancer research : an official journal of the American Association for Cancer Research · 2026/01/26 原文链接：https://doi.org/10.1158/1078-0432.CCR-25-3712 6. Role of ctDNA in predicting the outcome of patients with hormone receptor-positive, HER2-negative advanced breast cancer treated with first-line ribociclib and letrozole: BioItaLEE trial. ctDNA早期动态变化预测乳腺癌一线治疗疗效。HR+/HER2-晚期乳腺癌患者接受瑞波西利联合来曲唑治疗时，需要可靠的预后和预测标志物。BioItaLEE研究发现，基线ctDNA突变缺失及治疗早期突变清除与更好的无进展生存期显著相关。该研究证实了ctDNA作为乳腺癌治疗反应评估和预后预测工具的临床应用价值。 晚期乳腺癌 | PIK3CA, TP53 | ctDNA测序, 液体活检 Bianchini Giampaolo · … · De Laurentiis Michelino · Clinical cancer research : an official journal of the American Association for Cancer Research · 2026/01/26 原文链接：https://doi.org/10.1158/1078-0432.CCR-25-0650 7. De novo nucleotide biosynthesis and its dynamic regulation are crucial for systemic infection by extraintestinal Escherichia coli. 从头核苷酸生物合成及其动态调节对肠外致病性大肠杆菌的系统性感染至关重要。研究旨在阐明ExPEC如何适应血液环境并导致高死亡率的系统性感染。发现核苷酸合成基因受PurR调节，对细菌在血清中的增殖和巨噬细胞内存活必不可少。该研究揭示了克服营养免疫的致病机制，为开发抗感染疗法奠定了基础。 肠外致病性大肠杆菌感染 | 核苷酸生物合成, PurR调节 | 转录组分析, 转座子诱变 Zhang Chu · … · Huang Qi · PLoS pathogens · 2026/01/26 原文链接：https://doi.org/10.1371/journal.ppat.1013889 8. Ancestral and local adaptation contribute to dispersal out of the Qinghai-Tibet Plateau in a bumblebee. 祖先和局部适应共同促进了熊蜂走出青藏高原。青藏高原是熊蜂多样性的中心，但其演化扩散机制不明。研究发现染色体倒位变异与海拔适应密切相关，影响了熊蜂在不同温度下的飞行性能。该发现揭示了染色体倒位在促进局部适应和物种多样化中的关键作用。 物种演化与扩散 | 染色体倒位, 局部适应 | 基因组分析, 飞行性能测试 Jiang Chunyan · … · Chen Bing · Proceedings of the National Academy of Sciences of the United States of America · 2026/01/26 原文链接：https://doi.org/10.1073/pnas.2513080122 9. Three open questions in polygenic score portability. 多基因评分迁移性的三个核心问题。多基因评分（PGS）在不同遗传背景人群间的迁移性受限，阻碍了其广泛应用。研究发现，预测准确性的变化受社会经济因素影响显著，且在免疫相关性状中下降尤为剧烈。该研究强调，理解PGS迁移性需考虑性状进化、社会背景及构建方法等多元因素。 多基因评分 (PGS) 迁移性 | 遗传距离, 性状进化 | 全基因组关联分析 (GWAS), 预测准确性评估 Wang Joyce Y · … · Harpak Arbel · Nature communications · 2026/01/26 原文链接：https://doi.org/10.1038/s41467-026-68565-3 10. Repeatability of gene expression evolution in experimental environmental adaptation. 实验环境适应中基因表达进化的可重复性。评估进化中的偶然与必然是生物学关注的焦点。通过分析22个环境下的转录组数据，研究发现基因表达性状在重复群体间的变化具有高度一致性。结果表明，相对于基因型进化的不可预测性，表型进化在环境适应过程中是相当可重复且确定的。 环境适应进化 | 环境特异性选择, 转录因子控制 | 转录组测序, 实验室进化实验 Li Jiachen · Zhang Jianzhi · · 2026/01/26 该研究由密歇根大学张建之团队完成，张建之教授是进化遗传学领域的知名学者 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-68838-x 11. Origin of small chromosome A08 and genome evolution of Arachis species. 小染色体A08的起源与花生属基因组进化。野生花生属物种具有丰富的遗传多样性，但其基因组进化史尚不清晰。研究通过比较寡聚染色体涂染技术，确定了多个基因组的同源组，并揭示了小染色体A08的起源。该研究提出了花生属基因组进化模型，为花生改良提供了重要的遗传资源。 花生基因组进化 | 染色体倒位与收缩, 同源组鉴定 | T2T基因组组装, 比较寡聚染色体涂染 Du Pei · … · Zhang Xinyou · · 2026/01/26 该研究由河南省农业科学院张新友院士团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-68884-5 12. Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study. 基因组风险模型助力实现前列腺癌的精准筛查。传统筛查方法缺乏针对性，亟需结合个体遗传背景的精准预防策略。研究开发并验证了P-CARE模型，整合多基因评分与家族史，能有效识别转移性和致命性前列腺癌的高风险人群。该模型已应用于临床试验，展示了基因组学在提升癌症筛查效率方面的巨大潜力。 前列腺癌 | 多基因风险评分 | 基因组风险模型, 精准筛查 Vassy Jason L · … · Seibert Tyler M · Nature cancer · 2026/01/26 原文链接：https://doi.org/10.1038/s43018-025-01103-0 13. Genome-wide methylation detection and episignature analysis using PacBio long-read sequencing. PacBio长读长测序实现全基因组甲基化检测与表观特征分析。检测5-甲基胞嘧啶模式对诊断遗传病至关重要，传统短读长技术在某些区域存在局限。研究证实PacBio HiFi测序能可靠识别印记区域和罕见病的表观遗传特征，其准确性与传统方法相当且覆盖范围更广。该技术为临床诊断罕见病和解析意义不明变异提供了一种强有力的全基因组表观遗传分析工具。 罕见遗传病 | DNA甲基化, 表观遗传特征 | 长读长测序, PacBio HiFi Ivashchenko Véronique · … · Gilissen Christian · Genome medicine · 2026/01/26 原文链接：https://doi.org/10.1186/s13073-025-01506-9 14. Highly Secure In Vivo DNA Data Storage Driven by Genomic Dynamics. 基因组动力学驱动的高安全性活体DNA数据存储。DNA存储具有高密度和稳定性，但现有的活体存储方法存在数据泄露风险且缺乏有效的加密手段。研究提出ICBP范式，利用基因调控网络构建动态代码表，通过计算与生物逻辑结合实现海量密钥空间加密。该系统在活体微生物中实现了100%的数据恢复率，为构建高安全性的生物信息存储系统提供了变革性策略。 DNA数据存储, 信息安全 | 基因调控网络, 动态编码 | 合成生物学, 活体存储系统 Xu Jiaxin · … · Huang Xiaoluo · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/26 原文链接：https://doi.org/10.1002/advs.202514565 15. Tracing the recent evolution of Group A Streptococcus M1 serotype. A族链球菌M1血清型的近期演化追踪。21世纪全球范围内猩红热和侵袭性GAS感染激增，主要由高毒性M1UK谱系的出现驱动。该综述探讨了M1UK谱系在基因组和分子层面的驱动因素，及其在欧洲、澳洲等地的流行病学转变。研究强调了持续监测病原体多样性的重要性，以应对公共卫生挑战。 A族链球菌感染, 猩红热 | M1UK谱系, SpeA超抗原 | 基因组流行病学, 进化追踪 Bertolla Olivia M · … · Brouwer Stephan · Emerging microbes & infections · 2026/01/27 原文链接：https://doi.org/10.1080/22221751.2026.2623691 16. F-Box and Leucine-Rich Repeat Protein 4 (FBXL4) Maintains Sarcomere Integrity and Cardiac Function by Enhancing K48-Linked Ubiquitinated Degradation of Profilin-1 (PFN1). FBXL4通过增强PFN1的泛素化降解维持肌节完整性和心脏功能。病理性心脏肥大伴随严重的蛋白质周转失调。研究发现FBXL4在衰竭心脏中显著下调，其缺失会导致心脏功能减退和肌节紊乱。机制上，FBXL4作为E3泛素连接酶促进PFN1降解，从而保护心脏结构，为心脏肥大治疗提供了新靶点。 心脏肥大, 心力衰竭 | FBXL4, PFN1, 泛素化降解 | 转录组分析, AAV9递送 Li Xingda · … · Du Weijie · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/27 原文链接：https://doi.org/10.1002/advs.202516702 17. Efficient Mining for Structurally Diverse Fusicoccane-Type Diterpenoids as Novel Antithrombotic Agents and Their Divergent Mechanisms on Platelet Inhibition. 高效挖掘多样化二萜类化合物作为新型抗血栓药物。研究从哈茨木霉中发现首个5/8/5型二萜基因簇，并通过异源表达分离出33种化合物。其中化合物6和31分别通过拮抗GPVI通路和ROCK1通路抑制血小板活化。关键在于这些化合物能在不损害正常止血的情况下有效预防血栓，为安全抗栓治疗提供了新策略。 血栓形成 | GPVI通路, ROCK1通路 | 基因组挖掘, 异源表达 Bao Alan · … · Zhu Hucheng · Journal of medicinal chemistry · 2026/01/27 原文链接：https://doi.org/10.1021/acs.jmedchem.5c02817 18. Loss of JAK1 Function Causes G2/M Cell Cycle Defects Vulnerable to KIF18A Inhibition. JAK1缺失诱导G2/M期缺陷并增强放疗耐受。头颈鳞癌放疗耐受的生物学机制尚不完全清楚，限制了增效策略的开发。研究发现JAK1缺失通过增强G2/M期阻滞并减少有丝分裂灾难，导致肿瘤细胞产生放射抗性。该研究确立了抑制驱动蛋白KIF18A可作为克服JAK1缺失诱导的放疗耐受并增强疗效的新策略。 头颈鳞癌, 放疗耐受 | JAK1, KIF18A, G2/M细胞周期阻滞 | CRISPR-Cas9筛选, 活细胞成像 Kelley Vanessa M · … · Contessa Joseph N · Cancer research · 2026/01/27 原文链接：https://doi.org/10.1158/0008-5472.CAN-25-1423 19. FOSL1 Orchestrates Epigenetic Reprogramming of Anaplastic Thyroid Cancer and Suppresses Natural Killer Cell-Mediated Antitumor Immunity. FOSL1介导甲状腺未分化癌表观重塑与免疫逃逸。甲状腺未分化癌（ATC）极具侵袭性，且肿瘤微环境中自然杀伤（NK）细胞功能受损。研究发现超级增强子驱动的FOSL1通过重塑染色质结构，促进金属蛋白酶表达并诱导MICA脱落，从而抑制NK细胞的杀伤作用。该研究揭示了ATC恶性转化的表观遗传机制，为开发新型免疫治疗方案提供了靶点。 甲状腺未分化癌(ATC) | FOSL1, 超级增强子, NK细胞免疫逃逸 | 表观基因组测序, 染色质构象捕获 Huo Yanfei · … · Yang Ming · Cancer research · 2026/01/27 原文链接：https://doi.org/10.1158/0008-5472.CAN-25-2781 蛋白质组学 1. Ubiquitin D Promotes Lung Metastasis by Stabilizing MMP3 in Triple-Negative Breast Cancer. UBD通过稳定MMP3促进三阴性乳腺癌肺转移。三阴性乳腺癌具有高度侵袭性和转移倾向，其分子机制尚不完全明确。研究发现SPIB转录激活UBD表达，进而抑制MMP3的蛋白酶体降解，从而增强肿瘤细胞的侵袭和肺部定植能力。该发现为三阴性乳腺癌的预后评估和靶向治疗提供了新靶点。 三阴性乳腺癌, 肿瘤转移 | UBD, MMP3, SPIB | 蛋白质组学, 荧光素酶报告基因 Xu Rong · … · Du Wei · Research (Washington, D.C.) · 2026/01/23 原文链接：https://doi.org/10.34133/research.1065 2. Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β. 轴突线粒体分布通过eIF2β维持衰老过程中的神经元自噬。神经元衰老伴随蛋白质稳态失衡和线粒体转运受阻，但两者间的直接联系尚不明确。研究在果蝇模型中发现，轴突线粒体缺失通过上调eIF2β抑制自噬并导致蛋白异常聚集，而降低eIF2β水平可挽救神经功能。该研究揭示了线粒体-eIF2β轴在维持轴突稳态中的关键作用，为防治衰老相关神经退行性疾病提供了新思路。 神经元衰老 | eIF2β, 线粒体分布, 自噬 | 蛋白质组学, 果蝇遗传学 Shinno Kanako · … · Ando Kanae · eLife · 2026/01/26 原文链接：https://doi.org/10.7554/eLife.95576 3. Subcellular mass spectrometry reveals proteome remodeling in an asymmetrically dividing (frog) embryonic stem cell. 亚细胞质谱技术揭示了青蛙胚胎干细胞不对称分裂过程中的蛋白质组重塑。在单细胞水平实现深度亚细胞蛋白质组定量仍具挑战。研究改进了微探针毛细管电泳-质谱技术，在活体胚胎中定量了上千种蛋白质的空间分布。结果表明，早期的蛋白质组差异预示并可能偏向细胞的命运决定。 细胞命运决定 | 蛋白质组重塑, 不对称分裂 | 毛细管电泳-质谱(CE-MS) Shen Bowen · … · Nemes Peter · Proceedings of the National Academy of Sciences of the United States of America · 2026/01/26 原文链接：https://doi.org/10.1073/pnas.2518372123 4. Combined Immunohistochemical and Proteomic Description of Neutrophil Extracellular Trap (NET) Burden in Acute Ischemic Stroke Thrombi. 结合免疫组化与蛋白质组学描述急性缺血性卒中血栓中的NET负担。中性粒细胞胞外陷阱（NETs）参与病理性血栓形成，但其在卒中血栓中的分子特征尚不完全清楚。研究通过免疫染色与质谱分析相结合，验证了蛋白质组学评估血栓NET负担的可靠性，并发现高龄和房颤患者血栓中NET含量更高。该研究揭示了NET丰富型血栓的分子表型，为卒中治疗提供了潜在靶点。 急性缺血性卒中 | 中性粒细胞胞外陷阱, 蛋白质组学特征 | 质谱分析, 免疫组织化学 Sleasman Eric · … · Bender Matthew · Journal of thrombosis and haemostasis : JTH · 2026/01/24 原文链接：https://doi.org/10.1016/j.jtha.2025.12.027 5. Chloroplast Stress Signals Orchestrate Epidermis-Specific Remodeling of Mitochondria and ER Under High Light. 叶绿体应激信号协调强光下表皮特异性的线粒体与内质网重塑。环境压力要求细胞器间精确协调以维持稳态。研究发现强光触发叶绿体产生H2O2，进而激活钙信号和GTP酶MIRO1，驱动表皮细胞中线粒体和内质网的形态重塑。这一发现揭示了植物在环境界面处特有的细胞器通讯和应激适应机制。 植物应激适应 | 叶绿体信号, MIRO1 | 活细胞成像, 蛋白质组学 Angelos Evan R · … · Dehesh Katayoon · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/27 原文链接：https://doi.org/10.1002/advs.202514970 6. A Mussel-Inspired Bioadhesive Patch to Selectively Kill Glioblastoma Cells. 仿生粘附贴片通过诱导氧化应激选择性杀伤胶质母细胞瘤。胶质母细胞瘤术后极易复发，亟需开发能够局部清除残留癌细胞的新型疗法。研究开发了一种含儿茶素的仿生生物粘附膜，通过产生活性氧（ROS）特异性诱导肿瘤细胞凋亡并抑制其迁移。该研究展示了仿生支架在脑肿瘤局部治疗中的巨大潜力，为预防肿瘤复发提供了新方案。 胶质母细胞瘤 | 活性氧(ROS), 儿茶素 | 仿生粘附材料, 蛋白质组学 Bolaños-Cardet Jose · … · Yuste Victor J · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/27 原文链接：https://doi.org/10.1002/advs.202510658 代谢组学 1. Coordination of cell organelles to promote metabolon formation. 细胞器间的空间协调促进了代谢酶复合体的形成。细胞器如何调节代谢酶组装以维持效率是基础生物学问题。研究发现营养缺乏诱导线粒体和内质网形态改变，促进嘌呤体与其共定位以增强代谢通道。该发现揭示了细胞器形态动态调节代谢凝聚物功能的新机制。 代谢效率调节 | 嘌呤体, 细胞器互作 | 邻近标记, 超分辨率显微镜 Sha Zhou · … · Benkovic Stephen J · · 2026/01/26 该研究由美国国家科学院院士Stephen J. Benkovic团队完成 Proceedings of the National Academy of Sciences of the United States of America 原文链接：https://doi.org/10.1073/pnas.2532504123 多组学 1. Redefining Treatment Paradigms for Glioma in Adolescents and Young Adults: Population-Based Evidence for Molecular Classification. 分子分类重塑青少年及青年胶质瘤治疗范式。青少年及青年（AYA）胶质瘤的分子特征尚不明确，传统基于年龄的分层治疗存在局限。通过多组学分析发现，AYA胶质瘤包含成人型和儿童型，且具有显著的分子-解剖异质性，H3.3 K27M突变预后最差。该研究强调应根据分子分类而非年龄来制定AYA胶质瘤的治疗策略。 胶质瘤, 青少年肿瘤 | IDH突变, H3.3 K27M | 多组学分析, 分子分型 Qu Shanqiang · … · Huang Guanglong · Clinical cancer research : an official journal of the American Association for Cancer Research · 2026/01/26 原文链接：https://doi.org/10.1158/1078-0432.CCR-25-2496 2. The Japanese Archipelago sheltered cave lions, not tigers, during the Late Pleistocene. 晚更新世时期的日本群岛是洞穴狮而非老虎的避难所。日本长期被认为是老虎的避难所，但其大型猫科动物化石的身份一直存疑。研究通过对26件古代标本进行基因组和蛋白质组分析，证实其均为洞穴狮。这一发现挑战了传统观点，揭示了洞穴狮在东北亚的广泛分布及其迁徙历史。 生物地理分布 | 物种鉴定 | 古DNA测序, 古蛋白质组学 Sun Xin · … · Luo Shu-Jin · · 2026/01/26 该研究由北京大学猫科动物遗传学专家罗述金团队完成 Proceedings of the National Academy of Sciences of the United States of America 原文链接：https://doi.org/10.1073/pnas.2523901123 3. A proteogenomic atlas of 1032 brain metastases identifies molecular subtypes, immune landscapes, and therapeutic vulnerabilities. 1032例脑转移瘤的蛋白基因组图谱。脑转移瘤的高度分子异质性严重阻碍了有效疗法的开发。本研究构建了涵盖多组学、单细胞及空间分辨率的综合图谱，鉴定了四种具有独特生物学特征的分子亚型。该 atlas 为脑转移瘤的精准分类及亚型特异性治疗提供了重要参考。 脑转移瘤 | 分子亚型, mTOR信号, CDK4/6轴 | 蛋白基因组学, 单细胞测序, 空间转录组 Yang Zhenyu · … · Zhang Gao · · 2026/01/26 该研究由香港大学张高团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-68748-y 4. Priming versus propagating: distinct immune effects of alpha- versus beta-particle emitting radiopharmaceuticals when combined with immune checkpoint inhibition in mice. α与β放射性药物联合免疫治疗的差异。放射性药物疗法（RPT）与免疫检查点抑制剂（ICI）具有协同作用，但不同同位素的免疫调节机制尚不明确。研究发现β发射体主要扩增现有的适应性免疫，而α发射体则启动免疫启动。这一发现为针对不同免疫背景的肿瘤选择合适的同位素提供了依据。 肿瘤免疫治疗 | 免疫启动, 适应性免疫扩增 | 放射性药物疗法 (RPT), 单细胞RNA测序 Kerr Caroline P · … · Morris Zachary S · Nature communications · 2026/01/26 原文链接：https://doi.org/10.1038/s41467-026-68834-1 5. Periodontitis-associated salivary microbiota exacerbates systemic osteoclastogenesis via gut modulation and tryptophan metabolism suppression in ovariectomized mice. 唾液微生物通过肠道调节加剧系统性破骨。牙周炎与骨质疏松症的关联机制尚不明确。研究发现牙周炎患者唾液微生物通过口-肠轴改变肠道菌群，并抑制色氨酸代谢产物ILA的产生。补充ILA能有效抑制破骨细胞形成并缓解骨破坏，为牙周炎相关的系统性骨代谢疾病提供了新疗法。 牙周炎, 骨质疏松 | 口-肠轴, 色氨酸代谢, ILA | 16S rRNA测序, 代谢组学 Wang Nannan · … · Yan Fuhua · · 2026/01/27 该研究由南京大学医学院附属口腔医院闫福华团队完成 International journal of oral science 原文链接：https://doi.org/10.1038/s41368-025-00415-2 6. CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting. CXCR4诱导CAR-T细胞形成记忆以持久靶向白血病。CAR-T疗法在急性髓系白血病（AML）中的疗效受限于细胞耗竭。研究发现CXCR4能促进CAR-T细胞的记忆相关转录程序，减少耗竭并支持氧化代谢。在PDX模型中，协同表达CXCR4显著增强了CAR-T的持久性和抗白血病活性，为改善AML免疫治疗提供了新策略。 急性髓系白血病 (AML) | CXCR4, T细胞记忆, 氧化代谢 | CAR-T疗法, 单细胞分析 Itoh-Nakadai Ari · … · Ishikawa Fumihiko · · 2026/01/26 该研究由理化学研究所 (RIKEN) 石川文彦团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-025-67745-x 7. Olig2 acts as an inducible barrier to in vivo astrocyte-to-neuron conversion. Olig2作为体内星形胶质细胞向神经元转化的诱导屏障。体内重编程效率低受限于内在屏障。研究鉴定出转录因子Olig2在神经重编程因子诱导下显著上调，成为转化过程中的诱导屏障。敲低Olig2可显著提高转化效率，该发现揭示了神经元重编程的调控新机制。 神经再生, 细胞重编程 | Olig2, Ngn2, 诱导屏障 | 体内细胞转化, 多组学分析 Lai Chuying · … · Wu Zheng · · 2026/01/26 该研究由暨南大学吴政团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-68869-4 8. Modulation of gut microbiota and its metabolite Equol by Huaier granule suppresses hepatocellular carcinoma via the gut-liver axis. 槐耳颗粒通过调节肠道菌群及其代谢产物抑制肝癌。槐耳颗粒在临床上具有显著的抗肝癌效果，但机制尚不完全清楚。研究发现其通过调节肠道菌群产生代谢物Equol，进而修复肠道屏障并改善免疫微环境。该研究为槐耳颗粒的临床应用提供了科学依据，并确定Equol为潜在的治疗候选物。 肝细胞癌 (HCC) | 肠-肝轴, Equol, MAPK通路 | 16S rRNA测序, 代谢组学 Wei Xuejiao · … · Hu Zhongdong · · 2026/01/26 该研究由北京中医药大学胡仲冬团队完成 NPJ biofilms and microbiomes 原文链接：https://doi.org/10.1038/s41522-026-00919-7 9. Neuroprotective Effects of Time-Restricted Feeding Combined With Different Protein Sources in MPTP-Induced Parkinson's Disease Mice Model and Its Modulatory Impact on Gut Microbiota Metabolism. 限时进食结合大豆蛋白通过调节肠道菌群缓解帕金森病。饮食干预可缓解帕金森病进展，但限时进食（TRF）与不同膳食蛋白来源的交互作用尚不明确。研究发现TRF结合大豆蛋白能通过增加益生菌并调节代谢物，抑制神经炎症并保护多巴胺能神经元。该研究揭示了TRF的蛋白质依赖性神经保护作用，为帕金森病的临床饮食管理提供了极具前景的策略。 帕金森病, 肠道菌群失调 | 神经炎症, 多巴胺代谢 | 限时进食, 肠道微生物组学 Li Ting · … · Shen Yan-Qin · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/26 原文链接：https://doi.org/10.1002/advs.202516502 10. Microbial extracellular vesicles from min pigs remodel macrophage polarization via STING to sustain intestinal immune homeostasis. 民猪肠道菌群胞外囊泡通过STING调节巨噬细胞极化。特定肠道微生物能增强宿主免疫调节能力，但其跨物种作用机制及关键信号通路尚不明确。研究发现民猪源猪肠链球菌胞外囊泡能抑制STING通路过度激活，诱导巨噬细胞向M2型极化以维持肠道稳态。该发现揭示了宿主-微生物通讯的新路径，为炎症性肠病的治疗提供了具有转化潜力的微生物制剂策略。 炎症性肠病, 肠道免疫稳态 | STING信号通路, 巨噬细胞极化 | 胞外囊泡, 多组学整合分析 Sun Zhendong · … · Dong Na · Gut microbes · 2026/01/27 原文链接：https://doi.org/10.1080/19490976.2026.2620126 11. Intratumoral P. copri Reprograms MARCO+ Tumor-Associated Macrophages by Depleting Glycerophosphocholine to Drive Colorectal Cancer Progression. 肠道普氏菌通过耗竭GPC驱动结直肠癌进展。结直肠癌微环境受肠道微生物影响，但特定肿瘤内细菌的作用机制仍不明确。研究发现普氏菌（P. copri）通过耗竭甘油磷酸胆碱（GPC）将巨噬细胞重塑为促癌表型，从而加速肿瘤生长。该发现将普氏菌定位为潜在的诊断标志物，并提出GPC补充作为一种新型免疫代谢干预策略。 结直肠癌 | 普氏菌, 甘油磷酸胆碱(GPC), 肿瘤相关巨噬细胞 | 16S rRNA测序, 空间代谢组学 Yuan Qihang · … · Feng Yifei · Cancer research · 2026/01/27 原文链接：https://doi.org/10.1158/0008-5472.CAN-25-3400 12. FAP expression as a marker of malignant transformation enabling in vivo characterization in peripheral nerve sheath tumors: a multimodal and translational study. FAP表达可作为外周神经鞘瘤恶性转化的标志物。区分恶性外周神经鞘瘤（MPNST）与良性神经纤维瘤在临床上极具挑战性。研究通过整合单细胞和空间转录组学，证实FAP在MPNST中显著高表达，并成功利用FAP-PET成像实现了临床诊断。该研究确定了FAP作为恶性转化生物标志物的价值，支持其在神经肿瘤诊疗中的应用。 恶性外周神经鞘瘤(MPNST) | FAP(成纤维细胞激活蛋白) | 空间转录组学, 单细胞测序, PET/CT成像 Reitsam Nic G · … · Enke Johanna S · Acta neuropathologica · 2026/01/27 原文链接：https://doi.org/10.1007/s00401-026-02979-7 生物信息软件 1. Neuron Segment Connectivity Prediction with Multimodal Features for Connectomics. 融合多模态特征的深度学习方法提升了连接组学中神经元片段连接预测的准确性。从大规模电镜数据中重建复杂形态的神经元是连接组学的重大挑战。研究提出一种结合全局形态和局部图像特征的连接点检测网络，实现了全自动神经元校对流程。实验证明该方法在处理大规模神经元重建任务中具有极高的鲁棒性和效率。 神经元重建 | 神经连接组 | 深度学习, 多模态特征融合 Chen Qihua · … · Wu Feng · · 2026/01/26 该研究由IEEE Fellow、中国科学技术大学吴枫教授团队完成 IEEE transactions on medical imaging 原文链接：https://doi.org/10.1109/TMI.2026.3658169 2. Identifying variation in dinosaur footprints and classifying problematic specimens via unbiased unsupervised machine learning. 无监督机器学习技术实现了恐龙足迹变异的客观识别与分类。传统古生物学分类依赖主观标记，易产生偏差。研究利用变分自编码器网络分析了近两千个足迹，识别出八个关键形状特征，并支持了鸟类起源早于骨骼记录的观点。该研究提供了DinoTracker应用，为古生物形状变异研究提供了新工具。 物种演化 | 形状变异特征 | 无监督机器学习, 变分自编码器 Hartmann Gregor · … · Brusatte Stephen L · · 2026/01/26 该研究由著名古生物学家Stephen L. Brusatte团队完成 Proceedings of the National Academy of Sciences of the United States of America 原文链接：https://doi.org/10.1073/pnas.2527222122 3. Aligned cross-modal integration and regulatory heterogeneity characterization of single-cell multiomic data with deep contrastive learning. 深度对比学习助力单细胞多组学数据整合与异质性表征。单细胞多组学技术虽能揭示细胞功能，但跨模态数据的尺度差异和生物变异给整合分析带来巨大挑战。研究开发了基于对比学习的scMDCF模型，通过跨模态特征融合有效平衡数据异质性并提取关键调控元件。该工具在疫苗免疫反应及阿尔茨海默病生物标志物鉴定中表现卓越，为复杂生物过程提供了机械性见解。 阿尔茨海默病, 免疫调节 | 顺式调控元件, 细胞异质性 | 深度学习, 单细胞多组学整合 Cheng Yue · … · Li Xiangtao · Genome medicine · 2026/01/26 原文链接：https://doi.org/10.1186/s13073-025-01586-7 4. His-MMDM: Multi-Domain and Multi-Omics Translation of Histopathological Images with Diffusion Models. 扩散模型驱动病理图像跨域与跨组学翻译。计算病理学中的图像翻译模型通常局限于特定领域对，缺乏多领域扩展能力。研究提出His-MMDM框架，实现了冷冻切片转石蜡切片、虚拟染色及基因/转录组引导的病理图像编辑。该工具不仅能辅助病理医生识别驱动突变对组织的影响，还为生成式AI在精准医疗中的应用提供了多功能平台。 肿瘤病理诊断, 基因突变表型 | 跨模态翻译, 知识迁移 | 扩散模型, 计算病理学 Li Zhongxiao · … · Gao Xin · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/26 原文链接：https://doi.org/10.1002/advs.202518066 5. DualPG-DTA: A Large Language Model-Powered Graph Neural Network Framework for Enhanced Drug-Target Affinity Prediction and Discovery of Novel CDK9 Inhibitors Exhibiting in Vivo Anti-Leukemia Activity. 大语言模型驱动的图神经网络框架助力CDK9抑制剂发现。准确预测药物-靶点亲和力是药物研发的核心，但现有模型在处理复杂分子与蛋白质表征时存在局限。研究开发了DualPG-DTA框架，整合预训练语言模型与图神经网络，成功筛选出具有高效抗白血病活性的CDK9抑制剂C1。该研究不仅建立了精准的亲和力预测框架，还为克服急性髓系白血病耐药性提供了极具潜力的候选药物。 急性髓系白血病, 药物研发 | CDK9抑制剂, 药物-靶点亲和力 | 大语言模型, 图神经网络 Chen Yihao · … · Wang Ling · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026/01/27 原文链接：https://doi.org/10.1002/advs.202513099 6. Radiomics++: Review of Habitat Imaging Analysis for Decoding Tumor Heterogeneity. Radiomics++：利用生境影像分析解码肿瘤异质性。肿瘤的表型异质性与预后密切相关，传统影像学方法难以对其进行深度量化。本文综述了基于AI的生境影像分析（Radiomics++）在识别肿瘤内部异质性方面的最新进展、方法学及临床应用。该技术通过整合多模态影像与多组学数据，有望显著提升精准医疗的诊断与治疗水平。 肿瘤异质性 | 影像组学特征 | 人工智能(AI), 生境影像分析(Habitat Imaging) Wu Jiaojiao · … · Shen Dinggang · · 2026/01/27 该研究由医学影像AI领域国际知名专家、IEEE Fellow沈定刚教授团队完成。 Annual review of biomedical engineering 原文链接：https://doi.org/10.1146/annurev-bioeng-031825-040442 声明：本文使用了AI进行翻译和总结

MONTREAL--(BUSINESS WIRE)--Indero is pleased to announce a strategic collaboration with the World Scleroderma Foundation (WSF) to support WSF SHIELD platform trial, a randomized, double-blind, adaptive platform clinical trial designed to evaluate multiple investigational medicinal products (IMPs) for patients meeting VEDOSS criteria. This trial aims to intervene at the earliest stages of systemic sclerosis to improve long-term patient outcomes. This partnership brings together 2 leaders in their respective fields, Indero in clinical trial operations and WSF in Scleroderma research and advocacy, to create a powerful platform for innovation in rheumatology. The WSF SHIELD platform is led by Professor Francesco Del Galdo (Chair) and Professor Dinesh Khanna (Co-PI), with Professor Marco Matucci and Professor Yannick Allanore serving as WSF representatives on the steering committee. For pharmaceutical sponsors and biotech companies, this collaboration represents a unique opportunity to engage with a research initiative that is both scientifically rigorous and operationally agile. WSF SHIELD is designed to address one of the most pressing challenges in systemic sclerosis: identifying patients at the earliest stages of disease and intervene to modify scleroderma progression before irreversible organ damage occurs. By doing so, it opens the door to more efficient therapeutic development through improved trial design, with lower heterogeneity, higher responder potential, reduced screen-failure rates, and ultimately, better patient outcomes. “Very Early Intervention in Systemic Sclerosis is the best chance we have for a future without the pain and disability that Scleroderma brings to our patients,” said Prof. Del Galdo, who continued, “by intervening in the very early stages with the right drugs, we can transform the field and make Scleroderma as we know it today, a memory from the past. The knowledge on the early biology and the infrastructure are now there, this is the right time.” The WSF brings unparalleled scientific credibility and a global network of key opinion leaders, clinicians and patient advocates. Their involvement ensures that Project SHIELD is grounded in the latest research and aligned with the needs of the medical community. Professor Dinesh Khanna, Professor of Medicine and Director, University of Michigan Scleroderma Program, Co-Principal Investigator of SHIELD and experienced in platform trials adds: “This alliance offers the pharmaceutical partners access to a highly engaged ecosystem that actively supports Industry-Academia collaboration, encourages early-phase innovation, and increases visibility within the broader field of autoimmune research.” “WSF SHIELD is purpose-built to enable early intervention in VEDOSS,” said Juan Ovalles, Senior Director of Rheumatology at Indero. “By harmonizing capillaroscopy, pulmonary and imaging readouts, and longitudinal biomarkers, we aim to generate decision-grade evidence while keeping patient needs at the center.” Prof. Matucci, Chair of the WSF, said, “We are excited to partner with Indero on WSF SHIELD, which represents a critical step forward in our mission to improve the lives of people living with systemic sclerosis.” Prof Allanore, from the WSF board added: “By combining our scientific leadership with Indero’s operational capabilities, we are creating new opportunities for early intervention, patient-centered research, and industry engagement that can truly change the trajectory of this disease.” Indero complements this with deep operational expertise and a proven track record in managing complex clinical trials and Industry-Academia collaboration. The company’s infrastructure, digital platforms, and sponsor-facing services are designed to streamline study execution while maintaining the highest standards of quality and compliance. Visit www.inderocro.com to explore Indero’s services and expertise. About Indero Indero is a dual-focus CRO for dermatology and rheumatology, with over 25 years of experience in clinical research and trial delivery. Our full-service approach, which includes everything from protocol design and patient recruitment to trial monitoring and biometrics, provides biotech and pharmaceutical sponsors with the rigorous scientific foundation and tailored expertise their studies need to reach the finish line efficiently and effectively. With capabilities in North America, Europe, Latin America, and Asia-Pacific; vast, continuously growing relationships with investigators and patients; and a dedicated research clinic through which we design and execute our own studies, Indero is the ideal partner for clinical needs at a global scale. About World Scleroderma Foundation The World Scleroderma Foundation is a non-profit, non-governmental organization based in Switzerland, committed to advancing global research on scleroderma and improving the lives of those affected by the disease. WSF initiates and supports research in all aspects of scleroderma across all regions of the world, while also working to enhance the quality of life for patients and their families through advocacy, education, and collaboration.