Reviews
Artificial intelligence and anti-cancer drugs' response
Xinrui Long, Kai Sun, Sicen Lai, Yuancheng Liu, ... Kai Huang
Acta Pharm Sin B 2025;15:3355-3371.
中南大学湘雅医院皮肤科团队聚焦癌症耐药难题，全面综述了利用人工智能算法分析多组学数据以预测癌症药物耐药性的研究进展，详细阐述数据处理和模型构建的过程，探讨该领域当前面临的挑战及未来发展方向，以期更好地推动精准医学的发展。
Trends in intestinal aging: From underlying mechanisms to therapeutic strategies
Yajun Wang, Xueni Zhang, Mengli Qing, Wen Dang, ... Ning Li
Acta Pharm Sin B 2025;15:3372-3403.
沈阳药科大学李宁教授团队概述了肠道衰老机制与治疗策略研究进展，总结了肠上皮更新失调、菌群紊乱两大病理特征，提出了靶向肠黏膜修复、菌群调节及天然产物干预等策略，为老年健康管理及延缓肠道衰老提供新思路。
Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis
Yufei Hui, Xue Jiao, Li Yang, Dejin Lu, ... Minjie Wei
Acta Pharm Sin B 2025;15:3404-3418.
中国医科大学魏敏杰团队概述了IDO介导MSCs免疫调节可塑性的作用机制，阐述了IDO表达变化对免疫细胞的影响，汇总了IDO表达对MSCs治疗多种疾病的相关研究及临床进展，并讨论了靶向IDO进行MSCs改造以增强其治疗效果的策略。
Immune organoid for cancer immunotherapy
Xiao-He Wang, Wu-Yin Wang, Zhi-Jun Sun
Acta Pharm Sin B 2025;15:3419-3435.
武汉大学口腔医院孙志军教授团队概述了免疫活性类器官的三维培养方法，深入探讨了类器官在肿瘤微环境中与免疫细胞的相互作用机制，并全面阐述了其在癌症免疫治疗、药物筛选和临床试验中的应用前景,为肿瘤免疫治疗研究提供了新的思路和方向。
Unraveling the therapeutic landscape of approved non-peptide macrocycles
Zhonghua Li, Zhenqiang Zhang, Bin Yu
Acta Pharm Sin B 2025;15:3436-3459.
Extracellular vesicles as biomarkers and drug delivery systems for tumor
Xue Wang, Wenjing Chen, Wei Zeng, Kuanhan Feng, ... Ruoning Wang
Acta Pharm Sin B 2025;15:3460-3486.
Nanomedicine-induced pyroptosis for anti-tumor immunotherapy: Mechanism analysis and application prospects
Yuelin Huang, Chunting Wang, Yanhong Chen, Dengbin Wang, Defan Yao
Acta Pharm Sin B 2025;15:3487-3510.
Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury
Wenya Chi, Yingying He, Shuisheng Chen, Lingyi Guo, ... Yuan Yu
Acta Pharm Sin B 2025;15:3511-3544.
海军军医大学药学系药剂教研室俞媛副教授，海军军医大学长征医院神经外科徐涛副主任医师，及同济大学材料科学与工程学院杜建忠教授团队合作综述了基于生物材料和干细胞/外泌体策略的创伤性脑损伤治疗研究进展、前景和挑战。
Original articles
Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells
Yuquan Tao, Yinuo Ma, Limei Gu, Ye Zhang, ... Haibo Cheng
Acta Pharm Sin B 2025;15:3545-3560.
南京中医药大学程海波团队联合南京大学孙洋团队建立“单细胞测序-液质联合-分子互作”三位一体的中医药机制解析策略，揭示了参白解毒方通过调节TMEM131–TNF信号通路介导的免疫抑制性树突状细胞的分化进而延缓结直肠腺瘤癌变的新机制。
Enzyme-independent functions of HDAC3 in the adult heart
Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, ... Zheng Sun
Acta Pharm Sin B 2025;15:3561-3574.
贝勒医学院孙正和沈英教授团队探究组蛋白去乙酰化酶3（HDAC3）在心肌中的作用，发现HDAC3调控心肌脂肪酸氧化和心脏收缩功能并非通过其酶活性，为理解组蛋白去乙酰化酶抑制剂（HDACi）治疗心脏疾病的机制提供了新思路。
Antisense oligonucleotides targeting IRF4 alleviate psoriasis
Yanxia Yu, Yirui Wang, Weiwei Chen, Chang Zhang, ... Liangdan Sun
Acta Pharm Sin B 2025;15:3575-3590.
安徽医科大学孙良丹教授团队阐述了干扰素调节因子4在银屑病中的研究进展，总结了IRF4在咪喹莫特诱导的银屑病皮损CD4+T中，通过结合EP300的启动子启动下游转录从而加重炎症的过程，并提出基于靶标IRF4的反义寡核苷酸可以减轻这种炎症，为银屑病治疗提供了新的思路。
Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1
Xiaohui Zhang, Xinyu Tang, Ting Gao, Yuanfang Guo, ... Junlian Gu
Acta Pharm Sin B 2025;15:3591-3610.
山东大学顾俊莲教授团队揭示了睡眠碎片化引发睾丸损伤的分子机制，提出褪黑激素受体1a通过FGFR1抑制TAB1/TAK1复合物，缓解T2DM患者睾丸损伤的新疗法，为精准干预T2DM相关生殖障碍提供了新思路。
RXRαmodulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ–AMPKαaxis
Lijun Cai, Meimei Yin, Shuangzhou Peng, Fen Lin, ... Xiao-Kun Zhang
Acta Pharm Sin B 2025;15:3611-3631.
厦门大学药学院张晓坤课题组发现，核受体RXRα调控肝星状细胞激活和肝纤维化进程。K-80003通过与RXRα结合，激活CaMKKβ/AMPKα通路，促进线粒体自噬，从而抑制肝星状细胞的活化、增殖和迁移，有效减少肝纤维化。
Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma
Dongyuan Su, Biao Hong, Shixue Yang, Jixing Zhao, ... Chunsheng Kang
Acta Pharm Sin B 2025;15:3632-3645.
天津医科大学总医院康春生教授团队发现GBM细胞长时间暴露于细胞质磷脂酶A2抑制剂AACOCF3后耐药关键蛋白二肽基肽酶-4（DPP4），并揭示DPP4与EGFR之间的正反馈调节环路。Linagliptin阻断DPP4和EGFR新机制的阐明和应用，为GBM的治疗提供新策略。
Discovery ofYersiniaLcrV as a novel biased agonist of formyl peptide receptor 1 to bi-directionally modulate intracellular kinases in triple-negative breast cancer
Yunjun Ge, Huiwen Guan, Ting Li, Jie Wang, ... Guosheng Wu
Acta Pharm Sin B 2025;15:3646-3662.
江南大学无锡医学院葛运军、吴国胜等研究者关注TNBC细胞上表达的一种GPCR-甲酰肽受体1（FPR1），发现耶尔森菌的LcrV蛋白能偏向激动FPR1并调控肿瘤细胞表型。
Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection
Xiu Liu, Li Zhao, Deshen Liu, Lingna Zhao, ... Shaoyi Zheng
Acta Pharm Sin B 2025;15:3663-3684.
南方医科大学南方医院郑少忆教授团队通过构建VSMC-NFATc3条件性敲除和过表达的小鼠模型，结合多种AAD动物模型，系统探讨了NFATc3在AAD发生中的功能及分子机制。
Design, synthesis, and antitumor activity of novel thioheterocyclic nucleoside derivatives by suppressing the c-MYC pathway
Xian-Jia Li, Ke-Xin Huang, Ke-Xin Wang, Ru Liu, ... Hai-Ming Guo
Acta Pharm Sin B 2025;15:3685-3707.
CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury
Yong Chen, Xue Yuan, Wei Yan, Yurong Zou, ... Lijuan Chen
Acta Pharm Sin B 2025;15:3708-3724.
四川大学华西医院陈永和陈俐娟团队提出CMD-OPT分子优化模型，成功筛选出RIPK2高选择性抑制剂RP20，并首次验证其在APAP诱导的急性肝损伤中的治疗潜力，开辟了RIPK2靶向治疗ALI的新路径。
Anacyphrethines A and B as potent analgesics: Multiple ion channel inhibitors with an unprecedented chemical architecture
Hui Chen, Hanqi Zhang, Chao Niu, Bianlin Wang, ... Haji Akber Aisa
Acta Pharm Sin B 2025;15:3725-3737.
新疆理化技术研究所阿吉艾克拜尔·艾萨团队与华中科技大学姚广民团队在维药阿纳其根的非阿片类多靶点强效镇痛成分的研究中取得进展，其中，Anacyphrethines A (1)是一类高度共轭的多甲基化的6/6/6/6/5/7/5-八环四氮生物碱，通过靶向TRPM8、Kv1.2、Kv1.3、Cav2.1和TRPC6等多个离子通道发挥强效镇痛作用。
Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy
Ting Wen, Yanping Fu, Xiangting Yi, Ying Sun, ... Guilan Quan
Acta Pharm Sin B 2025;15:3738-3755.
Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy
Jian Zhao, Xinyan Lv, Qi Lu, Kaiyuan Wang, ... Jin Sun
Acta Pharm Sin B 2025;15:3756-3766.
A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers
Jialing Cheng, Zhiyang Chen, Demin Lin, Yanfang Yang, ... Yuling Liu
Acta Pharm Sin B 2025;15:3767-3787.
High intensity forced ultrasound-driven ferroptosis as a strategy for anti-tumor immune priming
Xuejing Li, Jiayi Wu, Ruizhe Xu, Xifeng Qin, ... Zhiqing Pang
Acta Pharm Sin B 2025;15:3788-3804.
Polymer-assisted PD-L1 degradation and targeted photodynamic therapy synergize to suppress immunodeficient tumors
Changyong Guo, Shipeng He, Huaxing Shen, Wei Cong, ... Honggang Hu
Acta Pharm Sin B 2025;15:3805-3818.
Letter to the editor
Non-blocking anti-PD-L1 nanobody conjugated to TLR7 agonist mediates macrophage/NK cell-associated antitumor effects
Chao Hu, Chen Chen, Xiaolu Yu, Zhiying Li, ... Likun Gong
Acta Pharm Sin B 2025;15:3819-3823.
中国科学院上海药物研究所宫丽崑研究员和龙益如博士团队开发了一种新型ISAC药物并系统研究了抗体和激动剂各自的作用和组合效果。该药物由非阻断型PD-L1纳米抗体偶联TLR7激动剂形成，其通过巨噬细胞-NK细胞轴介导显著的抗肿瘤效应。
Highlights
Reshaping antivenom therapy: A triple-synergy strategy featuring broadly neutralizing antibodies and a small-molecule PLA2 inhibitor
Yangyihua Zhou, Ning Shi, Xiang Gao, Longlong Luo
Acta Pharm Sin B 2025;15:3824-3826.
Sympathetic nerve activity in obesity-associated insulin resistance
Shuchou Xia, Huili Wu, Jianping Ye
Acta Pharm Sin B 2025;15:3827-3828.
Editorials
Traditional Chinese medicine in the early prevention of colorectal cancer from the perspective of tumor microenvironment
Huan Tang, Jigang Wang
Acta Pharm Sin B 2025;15:3829-3830.
A transformer-based strategy to develop RP20 as a potent RIPK2 inhibitor for acetaminophen-induced acute liver injury
Liang Ouyang
Acta Pharm Sin B 2025;15:3831-3832.