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点击蓝字，关注我们 Volume 16· Issue 6 · June 2026 长按扫码 直接阅读 Review papers Raman spectroscopy combined with multiple technologies for label-free identification of immune cells: An overview Chengshun Jiang, Jie Deng, Wanwan Gan, Jiaqi Zou, Tongkai Cai, Hao Yin, Yongbing Cao J. Pharm. Anal. 2026. 16(6) 101468 https://doi.org/10.1016/j.jpha.2025.101468 传统流式、免疫磁珠分选依赖荧光抗体标记，易损伤免疫细胞活性并干扰其生理状态。拉曼光谱（RS）作为一种无标记分子指纹检测技术，可基于细胞内源生化组分精准识别免疫细胞亚型。本文系统梳理了髓系、淋巴系免疫细胞分类体系，对比分析了各类传统与无标记免疫细胞检测技术的优劣；详解了共聚焦拉曼、表面增强拉曼等多种拉曼技术原理，重点剖析RS分别结合化学计量学、微流控芯片及机器学习/深度学习的集成策略与应用效果，并探讨模型可解释性、联邦学习等前沿优化思路。此外，无抗体污染的高纯度“洁净”免疫细胞难以获取，仍是当前领域的核心瓶颈。这套集成检测体系有望成为肿瘤免疫、自身免疫病诊疗及个体化免疫监测的重要工具。 Highlights Raman spectroscopy enables label-free immune cell identification with high precision. Integration with AI, microfluidics, and chemometrics enhances classification accuracy. Deep learning extracts spectral features, improving accuracy and efficiency. Microfluidic-Raman platforms enable high-throughput single-cell immune profiling. Future trends include federated learning and enhanced multimodal data integration. Recent advances and expanding applications of organoid models in unveiling drug ADME profiles Guolei Zhang, Ruifan Zhang, Zihang Shu, Jing Zhao, Lei Yin, Meiyun Shi, Yanshuo Han J. Pharm. Anal. 2026. 16(6) 101676 https://doi.org/10.1016/j.jpha.2026.101676 类器官是干细胞自组织的三维体外模型，能高度模拟人体器官结构与功能。本综述聚焦肝、肠等类器官在药物吸收、分布、代谢与排泄（ADME）研究中的最新进展。相比传统模型，类器官在预测口服生物利用度、评估药物相互作用及揭示个体药代差异方面具有显著优势。其中，肝类器官可稳定表达CYP450酶系，肠类器官保留外排转运体功能，而肾、胎盘等模型为排泄与胎儿暴露评估提供人源化平台。尽管目前面临功能成熟度不足、标准化缺失等挑战，但器官芯片、共培养、血管化及人工智能的融合正逐步突破瓶颈。类器官已从基础研究迈向临床试验，助力个体化药代分析与精准用药，有望成为药物研发与精准医学的核心工具。 Highlights Organoids enhance drug ADME prediction, surpassing traditional models. Patient-derived organoids reveal PK variability for personalized therapy. Integrating organoids with organ-on-a-chip and AI boosts drug development. Innovative diabetes mellitus treatment strategies: Mesenchymal stem cell-based therapy and its impact on pro- and anti-inflammatory cytokines modulation Amin Ullah, Yutao Wu, Rajeev K. Singla, Weidong Tian, Bairong Shen J. Pharm. Anal. 2026. 16(6) 101497 https://doi.org/10.1016/j.jpha.2025.101497 糖尿病（DM）是一种严重的代谢性疾病，其并发症包括视网膜病变、神经病变、心肌病和肾病等。炎症反应和细胞因子失衡是糖尿病发生发展的关键因素。间充质干细胞（MSCs）因其具有免疫调节和组织修复能力，已成为治疗糖尿病的新策略。本研究系统综述了MSCs疗法通过调控促炎与抗炎细胞因子网络，改善糖尿病微环境及促进组织再生的作用机制。研究发现，MSCs能够显著降低白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和IL-6等促炎因子水平，同时上调IL-10、转化生长因子-β（TGF-β）和IL-4等抗炎因子，从而重塑免疫稳态。此外，本研究还探讨了关键细胞因子在炎症与修复中的双重功能，为理解MSCs治疗的复杂机制提供了新视角。本文为基于MSCs的DM治疗策略提供了理论依据，有助于推动该领域的临床转化。 Highlights MSCs treat DM via immune modulation and tissue repair using mADSC-EVs, ADSC-Exos, BM-MSCs, and hUMSCs. MSCs heal wounds and reduce inflammation by lowering TNF-α/IL-6 and raising TGF-β/IL-10. MSC therapy's potential and challenges arise from the dual roles of cytokines like TGF-β and IL-6. Combination MSC therapy with gels/compounds enhances DM management through cytokine regulation. Immunocyte senescence: A new perspective on the remodeling of the ovarian cancer microenvironment and therapeutic intervention Xiang Li, Xian Li, Sha Ni, Xiaohui Zhang, Bingnan Liu J. Pharm. Anal. 2026. 16(6) 101492 https://doi.org/10.1016/j.jpha.2025.101492 Highlights The senescence phenotypes of immunocyts are mapped for revealing their collective role in fostering an immune-evasive niche. Chemotherapy and chronic inflammation as exogenous accelerators of immunosenescence. Single-cell multi-omics and senescence-focused therapeutic windows are critical for personalized anti-TME strategies. Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways Chenyu Zhou, Murni Nazira Sarian, Xiaohui Tong, Rongchun Han, Theebaa Anasamy, Hamizah Shahirah Hamezah J. Pharm. Anal. 2026. 16(6) 101538 https://doi.org/10.1016/j.jpha.2025.101538 Highlights SAR analysis reveals that halogen substitutions improve molecular stability and selectivity of anthraquinone derivatives. Halogenated anthraquinones exhibit anti-angiogenic activity by modulating VEGF signaling axis, especially in TNBC. ROS induced by anthraquinone derivatives triggers cancer cell apoptosis or promotes host toxicity depending on the dosage. Principles and strategies in cold/hot property studies of traditional Chinese medicine: An evolution from traditional theory to modern elucidation Min Zhang, Xin Zhang, Rui Wei, Yi-nuo Li, Ying Hu, Ya-dan Zou, Xue Li, Yue-fei Wang, Wen-zhi Yang, De-an Guo J. Pharm. Anal. 2026. 16(6) 101455 https://doi.org/10.1016/j.jpha.2025.101455 Highlights Research methods on the cold and hot properties of TCM are summarized. It focuses on the principles, characteristics, and typical applications. Overall physical tests to material basis-based modern analyses are included. It has demonstrated the important research ideas and key achievements. Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy Li Zhou, Xin-Lei Shen, Qing-Ru Zhu, Wen-Kai Yu, Hang-Chao Li, Gang Cao, Yi-Ni Bao J. Pharm. Anal. 2026. 16(6) 101558 https://doi.org/10.1016/j.jpha.2026.101558 氧化应激相关的蛋白翻译后修饰（PTMs）在糖尿病肾病（DN）的发生与发展中发挥重要作用。DN是糖尿病常见的微血管并发症，可进展为终末期肾病。氧化应激是驱动DN进展的核心机制之一，过量活性氧（ROS）的生成可诱发炎症、细胞凋亡、线粒体损伤及纤维化等病理过程。本文重点阐述乙酰化、泛素化、小泛素样修饰蛋白修饰、糖基化及乳酸化等主要PTMs类型如何通过调控核因子E2相关因子2/Kelch样ECH关联蛋白1（Nrf2/Keap1）等信号通路，影响ROS的生成与清除效率，进而参与DN的病理进程。此外，靶向PTMs相关调控酶或应用小分子化合物进行干预，可通过恢复肾组织氧化还原稳态、减轻肾脏损伤，为DN的防治提供新的理论依据与潜在治疗策略。 Highlights Oxidative stress damages lipids, proteins, and DNA, driving inflammation, ECM accumulation, and fibrosis in DN. PTMs regulate oxidative stress in DN by modulating signaling pathways that control cellular responses to oxidative injury. Modulating PTMs offers a promising strategy to reduce oxidative damage and protect renal function in DN. Targeting angiogenesis in diabetic wound healing: New insight from chemical architecture to functional outcomes Junren Chen, Siqi Qin, Ziwei Xing, Cheng Peng, Dan Li J. Pharm. Anal. 2026. 16(6) 101475 https://doi.org/10.1016/j.jpha.2025.101475 糖尿病足溃疡（DFU）是糖尿病最常见的严重并发症之一,直接威胁糖尿病患者的生存预后。血管生成受损是DFU的核心病理特征，该过程与创面微环境中内皮细胞、角质形成细胞及巨噬细胞功能异常密切相关，并涉及氧化应激损伤、慢性炎症反应、细胞外基质重塑障碍等病理进程。天然产物具有多种生物活性，其化学结构的异同在一定程度上决定了其调控糖尿病创面血管新生的效能与分子机制。本文系统梳理了糖尿病创面愈合（DWH）过程中血管新生调控相关分子机制及靶向血管新生的天然产物在DWH中的潜在作用机制，并深入剖析了天然产物促血管新生活性的构效关联，以期筛选靶向血管新生的天然活性小分子化合物，为研发安全有效的DFU创新候选药物提供理论依据与研究思路。 Highlights Natural products exhibit powerful effect in diabetic wound healing by targeting angiogenesis. Chemical architecture of natural products drives specific biological activity on angiogenesis. Structural features of natural products guide development of angiogenesis-targeting agents. Original articles Label-free detection of microRNA by polymerization and isomerization cyclic amplification coupled with G/Hemin DNAzyme Xinlan Zhu, Ziyan Zhang, Ruiyang Ma, Huachu Chen, Yi Zheng, Su Zeng, Zheyong Li, Sheng Cai J. Pharm. Anal. 2026. 16(6) 101536 https://doi.org/10.1016/j.jpha.2025.101536 研究团队基于靶标置换、聚合和异构化循环扩增（PICA），以G/Hemin DNAzyme作为信号输出，开发了一种用于miRNA无标记检测技术（PICA-G）。所设计的发夹探针在Bst DNA聚合酶催化下，通过聚合与异构化的循环交替，实现靶标置换循环及单链DNA（ssDNA）连续自延伸，从而产生大量可与Hemin结合的G-四链体序列，最终通过催化反应实现miRNA的无标记检测。该miRNA检测技术的关键优势包括：引物自延伸机制有效避免非特异性扩增；一步等温设计简化了操作流程，增强了系统稳健性，可适配多种检测场景；无标记检测策略大幅降低了成本。因此，该技术有望成为临床miRNA分析的可靠工具，为肿瘤生物标志物的早期诊断、治疗及预后评估提供潜在指导。 Highlights A miRNA detection was developed based on target recycling, polymerization and isomerization cyclic amplification (PICA). G/Hemin DNAzyme was used as signal output. This label-free method would be a reliable tool for clinical miRNA analysis. SERS detection of osteoarthritis-linked microRNA-204 via a DNAzyme-catalyzed self-amplifying circuit Zhe Ni, Xingshi Yuan, Zhengliang Luo, Xiaoqi Zhang, Min Chen, Lee Jia, Jie Wang, Xifu Shang J. Pharm. Anal. 2026. 16(6) 101518 https://doi.org/10.1016/j.jpha.2025.101518 骨关节炎（OA）是全球高发的退行性关节疾病，早期诊断对延缓病程至关重要。微小RNA-204（miR-204）作为OA的关键调控因子，其表达水平与疾病进展密切相关，但由于其在临床样本中含量极低，实现高灵敏、特异性检测仍具挑战。本研究开发了一种新型表面增强拉曼散射（SERS）生物传感器，用于miR-204的超灵敏检测。该平台的核心是一条精心设计的含悬垂结构的发夹探针（O-HP），它同时承担靶标识别与扩增启动功能。当miR-204与O-HP结合后，触发聚合酶介导的链延伸反应，生成富G序列并折叠为G-四链体；该结构结合血红素形成类过氧化物酶DNAzyme，催化产生活性氧，进而刻蚀金纳米星/银壳SERS探针，导致拉曼信号显著降低，实现“信号关闭”式定量检测。该传感器检测限低至8.13 fM，动态范围跨越5个数量级（10 fM～150 nM），并能有效区分单碱基变异。在临床软骨组织样本中，检测结果与RT-qPCR高度一致，验证了其实用可靠性。此外，通过简单替换O-HP序列，该平台可灵活适配miR-21等其他核酸标志物的检测，展现出良好的通用性。本研究为OA早期诊断及精准医疗提供了一种简便、灵敏且通用的新型检测工具。 Highlights Single O-HP probe integrates recognition and amplification, simplifying detection. DNAzyme catalysis achieves highly specific and reproducible Raman signal readout. Platform validated in cartilage tissue shows strong diagnostic reliability. Platform adapts to various nucleic acid markers by simply adjusting the O-HP sequence. M1-NP1 interfering-peptide inhibits cancer cell proliferation and migration by targeting the transcription factor FOXM1 Chaozhu Pei, Ziwu Xu, Min Ouyang, Huitong Bu, Zhenyu Zou, Yuting Ma, Zhengqing Zhu, Yan Chen, Li Yu, Mingmin Huang, Yongjun Tan J. Pharm. Anal. 2026. 16(6) 101493 https://doi.org/10.1016/j.jpha.2025.101493 转录因子叉头框蛋白M1（FOXM1）在多种肿瘤细胞中过表达，并可促进肿瘤的发生和发展。因此，FOXM1已经被认为是开发抗肿瘤药物的有效靶点。本研究以FOXM1为靶点旨在开发抗肿瘤多肽药物。使用酵母双杂交技术筛选到靶向FOXM1的抗肿瘤肽M1-NP1,通过偶联细胞穿膜肽的策略实现多肽的细胞内传递。M1-NP1进入到肿瘤细胞内与FOXM1结合，阻滞其进入细胞核内发挥功能，其次干扰了FOXM1与细胞周期相关激酶（PLK1）及转录共激活因子（CBP）的互作，还阻断了高转录活性FOXM1同源二聚体的形成，进而抑制了FOXM1的转录活性。使用M1-NP1对小鼠进行治疗，发现M1-NP1可显著抑制小鼠皮下移植瘤的生长以及肿瘤细胞向肺部的转移。且治疗期间M1-NP1无明显毒副作用，这为M1-NP1的抗肿瘤临床试验奠定了基础。 Highlights The interfering-peptide M1-NP1 is obtained by yeast-two-hybrid screening to inhibit the functions of transcription factor FOXM1. M1-NP1 disrupts the interactions between FOXM1 and cell cycle-related kinase PLK1, transcriptional co-activator CBP in cancer cells. M1-NP1 prevents the proliferation and migration of cancer cells in vitro and in vivo. M1-NP1 shows no obvious toxic and side effects, providing a foundation to apply clinical trials of its anti-cancer effects. HIF-1α in CD4+ T cells drives gout pathogenesis via metabolic reprogramming and Th17 differentiation Siyue Song, Jiatao Li, Fusen Chen, Kaiyue Shi, Yu Lou, Anyi Xu, Yun Zhang, Chengping Wen, Tiejuan Shao J. Pharm. Anal. 2026. 16(6) 101494 https://doi.org/10.1016/j.jpha.2025.101494 痛风是一种以高尿酸血症和反复炎症发作为特征的代谢性疾病，其免疫代谢调控机制尚未完全阐明。本研究发现，缺氧诱导因子-1α（HIF-1α）在痛风患者及尿酸氧化酶敲除（Uox-KO）小鼠CD4+ T细胞中显著升高，并与疾病严重程度密切相关。进一步研究表明，HIF-1α通过促进糖酵解代谢重编程，驱动辅助性T细胞17（Th17）分化及白细胞介素-17（IL-17）的产生，从而加重炎症反应。药物抑制或CD4+ T细胞特异性敲除HIF-1α，均可显著改善痛风表型。机制研究显示，天然活性成分薯蓣皂苷（DIO）可直接结合并抑制HIF-1α，进而降低糖酵解水平和Th17介导的炎症反应，缓解痛风进展。本研究揭示了“HIF-1α-糖酵解-Th17”免疫代谢轴在痛风发病中的关键作用，并为痛风防治提供新的潜在靶点和天然药物候选。 Highlights HIF-1α in CD4+ T cells is a pivotal factor in gout progression. HIF-1α overexpression exacerbates Th17 cells differentiation. Glycolysis is the metabolic bridge between HIF-1α and Th17 polarization. Dioscin is a promising therapeutic agent for gout by suppressing HIF-1α expression. Menaquinone-7 alleviates mitochondrial dysfunction and senescence in senile osteoporosis by targeting the PINK1-mediated mitophagy via PXR/ERK/CREB signaling pathway Yu Xu, Wencan Zhang, Wenpeng Xu, Shangzhi Li, Dingxin Zhang, Xiangyu Lin, Jincheng Liu, Qingyang Fu, Peijie Hu, Haipeng Si J. Pharm. Anal. 2026. 16(6) 101432 https://doi.org/10.1016/j.jpha.2025.101432 本研究针对老年骨质疏松低骨转换的病理特征与现有治疗的局限性，系统揭示了维生素K2亚型甲基萘醌-7（MK-7）通过靶向线粒体稳态发挥骨保护作用的完整机制。研究证实，MK-7可有效改善老年小鼠骨量丢失与骨微结构退化，逆转衰老骨髓间充质干细胞的成骨-成脂分化失衡，并抑制细胞衰老表型与衰老相关分泌表型。机制上，MK-7通过直接结合核受体PXR的F285位点以稳定蛋白表达，激活ERK1/2/CREB信号通路上调关键介质Ccn2，进而增强PINK1介导的线粒体自噬，清除受损线粒体、降低氧化应激，恢复线粒体能量代谢。本研究提出“抗衰+代谢调控”双靶点干预新策略，为MK-7用于老年骨质疏松的临床转化提供了坚实理论依据。 Highlights MK-7 targets PXR to activate ERK/CREB-Ccn2 axis, restoring mitophagy in senile osteoporosis. MK-7 binds PXR at F285 residue, validated by DARTS, CETSA, and molecular docking. Dual action: MK-7 mitigates senescence and metabolic dysfunction in aged BMSCs. Ccn2-driven mitophagy reduces mtDNA damage and SASP, reversing bone loss. MK-7 offers a safe strategy for geriatric bone health via mitochondrial quality control. β-Caryophyllene confers protection against type 2 diabetic osteoporosis by blocking ferroptosis via the AMPK/Nrf2 pathway Lai-lai Fan, Chun-hui Chen, Wen-hao Zheng, Li-jiang Han, Yi-tian Yu, Yi-yun Lv, Wen-lai Fang, Ling-ling Lin J. Pharm. Anal. 2026. 16(6) 101522 https://doi.org/10.1016/j.jpha.2025.101522 2型糖尿病性骨质疏松症（T2DOP）是一种以骨折风险增加为特征的慢性骨骼疾病，高糖高脂微环境可加剧其病理进程。铁死亡，一种由脂质过氧化引起的铁依赖性程序性细胞死亡，在糖脂毒性导致的骨髓间充质干细胞（BMSCs）死亡中发挥关键作用。本研究发现，天然双环倍半萜类化合物β-石竹烯（BCP）能有效减轻高糖高脂（HGHF）诱导的铁死亡和骨丢失。体外实验表明，BCP可降低线粒体活性氧、脂质过氧化和丙二醛水平，同时增加谷胱甘肽含量；体内实验显示，BCP可增加T2DOP小鼠股骨远端的骨量，并上调p-AMPK、GPX4及成骨标志物的表达。机制上，BCP通过激活AMPK/Nrf2信号通路发挥作用，而敲低AMPK可消除其在HGHF处理的BMSCs中的保护效应。网络药理学分析、分子对接和细胞热位移分析进一步验证了BCP与AMPK/Nrf2的相互作用。本研究揭示了BCP通过AMPK/Nrf2通路抑制铁死亡从而改善T2DOP的新机制，为BCP作为潜在治疗药物提供了实验依据。 Highlights This is the first investigation of β-Caryophyllene in type 2 diabetic osteoporosis. Network pharmacology and experiments confirm β-Caryophyllene's targets and pathways against type 2 diabetic osteoporosis. β-Caryophyllene might be a breakthrough type 2 diabetic osteoporosis treatment. TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications Jing Liu, Mingxia Deng, Xiaoying He, Jing Ma, Li Zhang, Xi Yang, Jinyao Dai, Shaohua Dong, Yichun Zhang, Zhijuan Zhang, Shuaibing Ying, Haoyang Hu, Lushun Jiang, Yujing Wang, Yunqing Qiu, Yan Lou J. Pharm. Anal. 2026. 16(6) 101540 https://doi.org/10.1016/j.jpha.2025.101540 药物性肝损伤是伏立康唑临床应用中的重要限制因素，但其早期预警指标与关键致病机制尚不明确。本研究围绕髓系细胞触发受体1（TREM1）展开，发现伏立康唑可直接结合TREM1并促进其与TLR4形成复合物，进一步激活PI3K/AKT、NF-κB及NLRP3炎性小体通路，诱导巨噬细胞释放IL-1β，最终通过ROS-SREBP1轴驱动肝细胞脂质沉积和脂肪变性。研究同时证实，可溶性TREM1（sTREM1）在动物模型和患者血清中均显著升高，且早于传统肝损伤指标ALT出现，显示出良好的早期诊断潜力。进一步研究证实，遗传敲除或药物抑制TREM1均可显著减轻肝脏炎症和脂肪变，提示TREM1兼具生物标志物和治疗靶点双重价值。本研究为理解伏立康唑肝毒性的免疫代谢机制及其精准防治提供了新思路。 Highlights sTREM1 serves as a potential early-warning biomarker for VCZ-induced liver injury. Voriconazole structurally binds to TREM1, which assembles with TLR4 to activate PI3K/AKT–NF-κB signaling. TREM1-dependent NLRP3–IL-1β activation induces hepatocyte steatosis via ROS–SREBP1 axis. TREM1 inhibitor LR12 reduces inflammation and steatosis, showing therapeutic potential efficacy. Macrophage TREM1 integrates inflammatory-metabolic crosstalk in VCZ-induced liver injury. Cuproptosis tracker: Visualizing organelle dynamics with a dual-targeted fluorescent probe Furao Li, Chunyan Liang, Xifeng Mo, Xiaohuan Xu, Yongbiao Wei, Chunyan Zhou, Ting Meng, Hui Zhang, Fan Yang J. Pharm. Anal. 2026. 16(6) 101500 https://doi.org/10.1016/j.jpha.2025.101500 铜死亡是一种铜依赖性程序性细胞死亡，与线粒体功能障碍及脂滴代谢紊乱密切相关，但两者在铜死亡过程中的动态交互仍缺乏有效的研究工具。针对这一空白，本研究设计了一种线粒体-脂滴双靶向荧光探针MLR，通过实时监测细胞内二氧化硫（SO₂）的波动，首次实现了铜死亡过程中两种细胞器互作的可视化追踪。MLR采用香豆素-苯并吡喃杂化结构，合成简便，对SO₂响应迅速（<10秒）、灵敏度高（检出限0.34μM），并能随SO₂浓度变化发生从红色到橙色的比率型荧光转变。活细胞成像显示，在铜死亡诱导剂作用下，MLR从线粒体易位至脂滴，直观反映了细胞器间的通讯动态；斑马鱼模型进一步验证了其体内成像能力。此外，基于MLR的试纸条和水凝胶可实现快速现场检测。该探针克服了单靶点工具的局限，为解析铜死亡中细胞器时空动力学及氧化还原调控机制提供了变革性平台，有望推动相关诊断策略的发展。 Highlights Dual-organelle tracking enabling SO2-mediated fluorescence tracing during cuproptosis with low LOD and rapid response. Achieving SO2 specific detection with dual channel ratio imaging to reveal SO2 metabolic law in cuproptosis. Rapid on-site SO2 detection, extending to real-time tracking of copper toxicity in zebrafish. Discovery and optimization of a novel non-nitrocatechol COMT inhibitor for modulating levodopa metabolism Rong Zhu, Pu Wang, Sheng-Lan Qi, Yu Zhang, Chun-Lan Xie, Ya Yang, Cong Hu, Zi-Qiong Zhou, Dong-Fang Zhao, Chao Yang, Jie Sun, Xian-Wen Yang, Guang-Bo Ge, Ping Wang J. Pharm. Anal. 2026. 16(6) 101520 https://doi.org/10.1016/j.jpha.2025.101520 通过抑制儿茶酚-氧-甲基转移酶（COMT），从而改善左旋多巴代谢是治疗帕金森病的重要策略。目前临床使用的COMT抑制剂主要为硝基儿茶酚类化合物，存在一定安全性风险。本研究基于自主构建的荧光可视化筛选体系，从天然黄酮类化合物中发现黄芩素（BA）具有良好的COMT抑制活性，并针对其成药性缺陷开展多维属性结构优化，获得新型非硝基儿茶酚类COMT抑制剂BA24。与BA相比，BA24的细胞水平COMT抑制活性提高26倍，代谢稳定性、膜通透性和口服生物利用度均提升约10倍，具有良好的安全性，并显著改善左旋多巴体内代谢。本研究系统阐明了黄酮类COMT抑制剂的构效关系，为新一代COMT抑制剂的研发及天然先导化合物成药性的优化提供了重要依据和研究思路。 Highlights A fluorescence method was established to visualize and evaluate COMT inhibition in vitro and in living cells BA24 showed 26-fold stronger cellular COMT inhibition than baicalein and 10-fold better stability, permeability and absorption, respectively. BA24 competitively inhibited COMT by binding to the catechol pocket, with a Kᵢ of 89.28nM and an IC₅₀ of 72.6nM. BA24 exhibited favorable safety profiles and significantly modulated levodopa metabolism in rats. Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets Xiangwei Li, Ting Xu, Shaochuang Wang, Long Ma, Xiangyou Yu, Yi Wang, Linlin Bai, Jun Cao, Zuyi Zhao, Meiting Du, Hao Wen, Kun Wu J. Pharm. Anal. 2026. 16(6) 101542 https://doi.org/10.1016/j.jpha.2025.101542 Highlights Unveiling ACAT1 and TFEB roles in HIRI pathogenesis. ACAT1 emerges as a pivotal hepatoprotective factor. TFEB-mediated mitophagy counteracts cellular stress. ACAT1's modulation of ferroptosis key in HIRI resilience. Therapeutic potential highlighted for hepatic damage in surgery and transplantation. Short communications GSH-triggered release of anabasine in mitochondria for synergistic chemotherapy assisted by OATP transportation Miao Zhang, Ling-Li Wang, Si-Ling Chen, Yan-Ping Liu, Ming-Hua Zheng, Jing-Yi Jin J. Pharm. Anal. 2026. 16(6) 101565 https://doi.org/10.1016/j.jpha.2026.101565 将抗肿瘤药物精准递送到肿瘤细胞的细胞器内部，是第三代精准化疗发展过程中亟待解决的关键性问题之一。不同于纳米药物平台，分子基药物递送平台具有明确的化学组成，但其相对复杂的结构限制了其发展。本研究在派洛宁9位引入母体药物毒藜碱（Ana），所得到的9-亚胺基派洛宁衍生物（APY）是一种结构简洁的分子基平台。通过肿瘤细胞表面高表达的有机阴离子转运多肽的介导，APY能够选择性进入肿瘤细胞内部。在线粒体谷胱甘肽的作用下，APY原位释放Ana，协同诱导铁自噬和凋亡。在活体实验中，APY表现出良好的化疗效果。本研究不仅提供了细胞器靶向递送药物的分子基平台的设计思路，也拓展了非抗肿瘤药物在化疗方面的应用前景。 Highlights A GSH-triggered prodrug targets tumor cell mitochondria via OATP-mediated uptake. APY releases a parent drug through an GSH-triggered SNAr mechanism. A nicotinic acetylcholine receptor is translated to an antitumor drug. Anabasine in mitochondria can induce a synergistic ferritinophagy and apoptosis. Pharmacomultiomics suggests new off-targets for targeted anti-cancer agents Xuan Linh Mai, Chae-Young Lee, Eunbyul Cho, Sunghyouk Park, Hyuk Nam Kwon J. Pharm. Anal. 2026. 16(6) 101580 https://doi.org/10.1016/j.jpha.2026.101580 Highlights Multi-omics of more than 900 cell lines links drug sensitivity to 6 omics layers. EGFR-TKIs show novel epigenetic and metabolic off-target effects. Butyrylcarnitine serves as a potential biomarker for ibrutinib sensitivity. KPT-9274 disrupts CoA metabolism in addition to NAMPT/PAK4 inhibition. NAMPT upregulation contributes to KPT-9274 resistance. 近期阅读： 中国科学院宁波材料技术与工程研究所郭明全研究员科研团队成果/综述——纳米材料赋能光学生物传感技术在生物医学诊断与制药领域创新应用 JPA文章推荐 | 四川大学华西基础医学与法医学院王魁教授科研团队综述——用于肿瘤免疫治疗的纳米药物靶向递送系统 期刊简介 Journal of Pharmaceutical Analysis（JPA,《药物分析学报（英文）》）创刊于2011年，由教育部主管，西安交通大学主办，是国内第一本有关药物分析的专业英文学术期刊，JPA 始终秉承服务国家重大战略需求、建设世界一流科技期刊的办刊宗旨，重点报道药物发现与药品全生命周期质量控制的新理论、新技术、新方法，临床精准用药，以及药物与生物、人工智能等交叉领域的技术方法方面的最新研究成果，为全球药物研发和药品质量控制提供高水平的国际学术交流平台，持续推动药物分析学科以及药学领域的快速发展。 JPA目前已组建一支以主编贺浪冲教授为核心的国际化的学术团队和专业的编辑出版团队，已实现编委国际化、稿源国际化、同行评议国际化、读者国际化和出版国际化。已被SCIE、PubMed、Scopus、DOAJ、中国科学引文数据库（CSCD）及中国科技论文与引文数据库（中国科技核心期刊）等多种重要国际和国内数据库和评价体系定为刊源。JPA连续8年入选“中国最具国际影响力学术期刊”。2019年入选“中国科技期刊卓越行动计划”重点期刊，2024年入选“中国科技期刊卓越行动计划二期”英文领军期刊。2025年影响因子 11.2，位于全球药理学和药学类学术期刊第15位（15/356），继续稳居于Q1区前列。2026年新锐期刊分区表1区，Top期刊。 收稿范围 药物分析新技术、新方法，分析药理学，药物代谢与递送，中药与天然药物，生物传感，可视化分析，生物功能分析，生物技术药物，药物分析装备，人工智能应用 收稿栏目 原创论文、综述、快报、展望、观点、新闻、社评等 期刊官网 https://www.journals.elsevier.com/journal-of-pharmaceutical-analysis 投稿网址 https://www.editorialmanager.com/jpa/Default.aspx  编辑 | 李   蕾  校对 | 朱丹丹 审核 | 王梦杰、马维娜 阅读原文 了解更多