Lidamycin

点击蓝字，关注我们 Volume 16· Issue 7 · July 2026 长按扫码 直接阅读 Review papers Deep learning for small-molecule drug discovery: From molecular design to clinical translation Rita I. Oliveira, Tiago O. Pereira, Maryam Abbasi, Jorge A.R. Salvador, Joel P. Arrais J. Pharm. Anal. 2026. 16(7) 101533 https://doi.org/10.1016/j.jpha.2025.101533 Highlights Overview of cutting-edge AI models for molecular design and property prediction. Presentation of key data sources, descriptors, and evaluation benchmarks. Description of the evolution of models for molecular property prediction. Enumeration of promising AI-generated small molecules progressing in clinical trials. Survey of the regulatory framework responses to AI-driven drug development tools. Recent advances in proteomic strategies for target identification of traditional Chinese medicine Xueyan Zhen, Jingwen Liu, Yan Ren J. Pharm. Anal. 2026. 16(7) 101516 https://doi.org/10.1016/j.jpha.2025.101516 中药凭借其多成分、多靶点的协同作用机制，在疾病治疗中展现出独特优势，但其靶点蛋白的鉴定因成分复杂而面临瓶颈。蛋白质组学技术为该难题提供了系统化解决方案。本文系统综述了基于质谱的多种蛋白质组学策略在中药靶点发现中的最新进展，重点涵盖三大类方法：抗蛋白酶水解法（如以肽段为中心的局部稳定性探测）、抗变性沉淀法（如热蛋白质组学分析）以及化学探针法（如活性基团蛋白质组分析）。文章深入比较了各技术的适用场景与局限，指出多技术整合能有效提升低丰度靶点的检出率和可靠性。此外，本文还展望了氢氘交换质谱、单细胞蛋白质组学及人工智能预测等新兴方向，强调未来研究应聚焦体内靶点验证和临床转化。本综述为中药现代化提供了系统的方法学框架，也为新药发现开拓了新视角。 Highlights Innovative proteomic techniques enhance drug-target identification in more sensitive ways. Recent advances in proteomics strategies for the identification of TCM targets were included. Integrating different approaches proves more conducive in unveiling potential targets of TCM and its active ingredients. Iontophoresis-assisted transdermal drug delivery for the treatment of inflammatory dermatoses: A review Zhixiong Wang, Xiumei Jiang, Changzhao Jiang, Xiaohua Tao, Jincui Ye J. Pharm. Anal. 2026. 16(7) 101512 https://doi.org/10.1016/j.jpha.2025.101512 炎症性皮肤病（如银屑病、特应性皮炎和痤疮等）发病率高且易复发，传统外用治疗常受限于皮肤角质层屏障，导致药物难以达到有效治疗浓度。本文系统综述了离子电渗辅助经皮给药技术在炎症性皮肤病治疗中的最新研究进展，重点介绍其电迁移与电渗流作用机制、影响给药效率的关键因素，以及与微针、超声促渗、化学促渗剂等联合应用的协同优势。同时，文章总结了离子电渗在银屑病、特应性皮炎及痤疮等疾病中的应用现状，并展望了可穿戴离子电渗设备、智能闭环给药及生物大分子递送等未来发展方向。该综述为突破皮肤屏障、提高局部治疗效果、推动精准经皮给药技术的临床转化提供了系统参考与研究思路。 Highlights Non-invasive technique: Uses mild electrical currents to drive charged/ionic drugs across the SC via electrorepulsion (ER) and electroosmosis (EO). Synergistic combinations: Iontophoresis combined with other techniques significantly boosts efficacy, e.g., chemical enhancers, sonophoresis, and microneedles. Innovative designs: Flexible, self-powered systems enable continuous, patient-friendly drug administration. Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy Yakai Song, Nannan Zheng, Xu Yang, Zhaofan Tao, Qinghui Wang, Zhiyue Cao, Yi Zhang, Mengmeng Li, Ruixin Mao, Yuhao Chen, Chen Zhao, Huanjie Yang, Bin Yang, Qiuyue Ma, Liangcan He, Shaoqin Liu, Kai Li J. Pharm. Anal. 2026. 16(7) 101510 https://doi.org/10.1016/j.jpha.2025.101510 肿瘤免疫治疗疗效常受实体瘤免疫抑制微环境制约，传统新药研发成本高、周期长，老药新用是高效可行的优化路径。本文系统综述了FDA获批成熟药物重塑肿瘤微环境、协同免疫治疗的研究进展，包括二甲双胍、阿司匹林、塞来昔布、双硫仑、普萘洛尔等多种常用药，从免疫细胞调控、肿瘤细胞干预、基质改造、代谢重编程、炎症及血管生成调控六大维度梳理了这些老药在解除免疫抑制、放大免疫疗法效果中的核心作用机制，并且全面汇总了临床前联合给药证据与多项在研临床试验数据。同时，文章针对老药新用的临床转化瓶颈，提出了借助类器官、空间多组学、创新试验设计等前沿手段的解决思路，为开发低成本、易普及的肿瘤联合免疫方案提供了参考。 Highlights Repurposed drugs reprogram the tumor microenvironment to enhance immunotherapy. Mechanisms by which repurposed drugs reverse immunosuppression are detailed. Preclinical and clinical data on combinations and future directions are summarized. Synovial microenvironment and fluorescence imaging for early rheumatoid arthritis diagnosis Hua Wang, Pan Zhou, Huixiang Chen, Jiachen Zheng, Linlin Wei, Jiabin Chen, Yu Lei J. Pharm. Anal. 2026. 16(7) 101509 https://doi.org/10.1016/j.jpha.2025.101509 类风湿关节炎（RA）是一种以慢性滑膜炎症和进行性关节破坏为特征的自身免疫性疾病，早期诊断对改善患者预后至关重要。然而，传统血清学检测（如类风湿因子、抗环瓜氨酸肽抗体）和常规影像学方法（X线、MRI、超声）在敏感性和分子特异性上存在不足，难以捕捉关节出现不可逆损伤前的分子病理变化。本文系统综述了RA早期诊断的前沿进展，重点聚焦于滑膜微环境中巨噬细胞、中性粒细胞和成纤维样滑膜细胞等新型细胞生物标志物，及其与疾病活动度和严重程度的关联。同时，文章介绍了人工智能（AI）辅助诊断技术在影像判读和多组学整合中的潜力，并特别强调了荧光成像（FOI）技术的革新价值——通过可见光及近红外-I/II区的功能性荧光探针，可实时、无创地定量检测滑膜微环境中的次氯酸、过氧亚硝酸盐、一氧化氮及髓过氧化物酶等活性分子，从而实现早期RA的分子水平可视化诊断。此外，该综述还总结了多种新型近红外II区探针和智能纳米平台在动物模型中的成像与治疗一体化应用，展现了FOI结合AI在推动RA精准早诊和个体化治疗中的广阔前景，为临床转化和多模态整合策略提供了新思路。 Highlights Fluorescence imaging accurately quantifies molecular markers for early RA diagnosis. AI-driven diagnostic tools enhance early detection and treatment of RA. Synovial tissue biomarkers correlate with RA disease activity and severity. Advanced serologic tests identify new autoantibodies in RA patients. Innovative imaging techniques provide detailed insights into RA pathology. Potential mechanisms of natural products in improving gouty arthritis: Focusing on NLRP3 inflammasome regulation Yunhao Yi, Yanling Chen, Wuchaonan Liu, Jingjing Yang, Le Yang, Jing Liu, Shengping Luo, Qianru Zeng, Tao Gao, Yihui Deng J. Pharm. Anal. 2026. 16(7) 101563 https://doi.org/10.1016/j.jpha.2026.101563 Highlights Multiple mechanisms contribute to NLRP3 inflammasome overactivation, which drives the pathogenesis of GA. Natural products regulate GA by modulating priming signals, post-translational modifications, and inflammasome activation. Natural products directly target inflammasome structural domains or protein-protein interactions, inhibiting assembly. Natural products offer multi-target synergy, but toxicity, low bioavailability, and poor targeted delivery remain challenges. Elucidating how natural products regulate the NLRP3 inflammasome in GA will advance translational research. Intelligence on the graph: Graph neural networks for mechanistic drug target discovery Jing Chen, Nini Fan, Yuqing Lu, Jianhua Yang, Wenchao Song, Haiyang Sheng, Yinfeng Yang, Shengxi Chen, Jinghui Wang J. Pharm. Anal. 2026. 16(7) 101508 https://doi.org/10.1016/j.jpha.2025.101508 药物研发面临成本高、周期长、流失率大等挑战，靶标识别仍是关键瓶颈。尽管人工智能潜力显著，图神经网络（GNN）在药物-靶标相互作用（DTI）与亲和力（DTA）预测中的系统应用尚待深入。本文对该领域最新进展进行结构化综述，剖析图卷积网络、图注意力网络和图自编码器的方法论基础，比较其在复杂分子与生物系统建模中的机制、优势及适用场景。进一步整合多模态数据融合、高阶图推理和动态GNN等前沿范式。主要贡献包括：建立比较框架以明确各架构的适用条件，整合既往综述鲜有涉及的前沿范式，并通过典型案例将算法创新与药物发现实际成果相衔接。本工作为高效、可解释的人工智能驱动药物发现提供理论指导和前瞻性参考。 Highlights We comprehensively summarize recent advances in Graph Neural Networks for drug–target interaction and affinity prediction. Analysis of GCNs, GATs and GAEs reveals their strengths in modeling molecular and biological network complexities. Emphasis on multimodal data fusion, high-order graph reasoning and dynamic learning enhances DTI/DTA predictive performance. Key challenges such as data sparsity, computational load and interpretability are discussed with proposed solutions. The paper advocates a paradigm shift toward mechanism-informed AI to advance precision medicine and rational drug design. Sweat as a diagnostic biofluid: Analytical advances and future directions Dayanne Mozaner Bordin, Janice Irene McCauley, Eduardo Geraldo de Campos, David Bishop, Bruno Spinosa De Martinis J. Pharm. Anal. 2026. 16(7) 101473 https://doi.org/10.1016/j.jpha.2025.101473 Could sweat be the next frontier in personalised medicine? This review explores the growing potential of sweat as a diagnostic and monitoring biofluid, from established forensic and clinical applications to its emerging role in real-time health tracking. Sweat offers clear practical advantages over blood and urine: it's easy to collect, minimally invasive, and contains fewer interfering substances that can complicate analysis. These qualities have long made it valuable in forensic toxicology and clinical drug testing, however recent advances in analytical chemistry have expanded what sweat can reveal, enabling the detection of complex metabolites and biomarkers with a level of sensitivity and precision that was previously out of reach. The review also examines how artificial intelligence is reshaping this field. Since 2023, improved pattern recognition and classification algorithms have enhanced the diagnostic and therapeutic accuracy of sweat-based analysis, opening new possibilities for precision health monitoring. Paired with rapid progress in miniaturised electronics, stretchable materials, wireless connectivity and battery life, these developments are converging to make wearable sweat-sensing devices increasingly viable for everyday use. Structured in three parts, the review first covers traditional sweat analysis methods in clinical and forensic settings, then surveys recent breakthroughs in biomarker detection, and finally evaluates sweat's promise for continuous, real-time physiological monitoring. For anyone interested in the future of non-invasive diagnostics, this review makes the case that sweat, long an underused biofluid, may be poised to play a central role in how we monitor health and disease going forward. Highlights Sweat is an accessible source of information for diagnostic & health monitoring. Advanced analytical techniques are expanding capabilities in biomarker discovery. A key challenge is the identification of biomarkers of clinical signification Improvements in AI are anticipated to enable advancements in diagnostic accuracy. Original articles Self-assembled multifunctional hairpin probe for ultrasensitive and mismatch-selective miRNA detection Baoqiang Chen, Yiping Fan, Qi Wang, Jianguo Xu, Yi Wang, Bingyong Lin, Lee Jia, Longhua Guo J. Pharm. Anal. 2026. 16(7) 101561 https://doi.org/10.1016/j.jpha.2026.101561 本文建立了一种基于组装型多功能发夹探针(A-MF-HP)的微小RNA（miRNA)）检测方法。该方法利用回文序列介导探针自组装，将靶标识别、信号放大和荧光报告整合在同一核酸结构中。检测时，miRNA-21与A-MF-HP结合后引发发夹结构打开，并在核酸聚合酶和切口酶作用下发生延伸、切口和链置换反应，产生单链中间产物，进一步推动级联放大，使荧光信号增强。实验结果表明，该方法可实现飞摩尔级miRNA-21检测，并能区分单碱基错配序列；同时，A-MF-HP具有较好的结构稳定性，可应用于肺癌患者和健康人血液样本分析。该工作为复杂生物样本中miRNA检测提供了一种稳定性较好的核酸探针设计和信号放大思路。 Highlights A palindromic hairpin probe self-assembles into a nuclease-resistant DNA nanostructure. The probe enables target recognition, signal amplification, and reporting in a single system. Cascade amplification achieves femtomolar-level sensitivity and discriminates single-base mismatches. The system performs reliably in clinical lung cancer samples, confirming diagnostic potential. How many medicinal slices should be used in an experiment of Chinese medicine extraction process? Jiale Xie, Bo Chen, Jingmi Liu, Xingchu Gong J. Pharm. Anal. 2026. 16(7) 101562 https://doi.org/10.1016/j.jpha.2026.101562 中药饮片的异质性是影响提取工艺小试研究结果重复性的关键因素。本研究首次提出“代表性饮片质量（RMMS）”的概念，将其定义为“在提取研究中，当取样饮片质量不低于RMMS时，提取结果的重复性可控制在可接受阈值以内”。研究以防己黄芪汤加减方（MFD）为对象，通过测定各味饮片的活性成分产率（AIY）和出膏率（DMY），发现防己和甘草饮片的变异系数最大。经分布拟合分析，所有指标均服从3参数Weibull分布。在此基础上，比较了蒙特卡洛模拟和中心极限定理两种RMMS计算方法，结果表明后者方法更简便、准确。最终确定防己饮片的RMMS为136.96g，甘草饮片的RMMS为22.85g，并通过实验进行了验证。本研究为中药提取小试实验中保证结果重复性提供了定量化的取样量确定依据，提供了宝贵参考。 Highlights A novel concept of RMMS was presented. Fangji and Gancao exhibited greatest variability in MFD, a 3‑parameter Weibull distribution characterized their indicators. A universal method for determining the appropriate medicinal material quantity in Chinese medicine extraction was provided. Classification of pulmonary inflammation stages and assessment of multicomponent drug intervention based on spatiotemporal imaging variations utilizing RhB-conjugated poly-L-lysine nanoparticles Man Zhang, Shanshan Zhai, He Gao, Tong Sun, Kaixin Liu, Wenshuang Wang, Yuanyuan Hou, Gang Bai J. Pharm. Anal. 2026. 16(7) 101582 https://doi.org/10.1016/j.jpha.2026.101582 急性肺炎常伴随免疫反应失衡和血管通透性升高，传统影像手段难以实时、精准评估病程进展。本研究构建了罗丹明B偶联聚赖氨酸（RhB-PLL）自组装纳米粒，具有线粒体靶向性并同步感知血管渗漏状态。基于动态时空成像，研究将模型中的急性肺炎进程划分为四个阶段，并筛选出6种阶段相关磷脂酰胆碱代谢物作为辅助标志物。进一步以扶正解毒方及其简化方为研究范例，发现小柴胡汤、三仁汤和麻杏石甘汤分别在不同炎症阶段发挥优势作用，总方扶正解毒方可在整体肺炎进程中发挥疗效。该研究为急性肺炎的分期可视化、疗效评价和多组分药物精准干预机制提供了新思路。 Highlights RhB-PLL nanoparticles enable real-time dual imaging of mitochondrial dysfunction and vascular permeability in pneumonia. RhB-PLL imaging stratifies acute pneumonia progression into four distinct stages. RhB-PLL nanoparticles enable TCM multicomponent drug intervention assessment in pneumonia. A nanotechnology-enhanced SERS platform integrated with isothermal amplification for ultrasensitive detection of urinary miR-21 in early acute kidney injury diagnosis Liangping Fan, Wenna Liu, Qian Li, Jixue Lu, Fengchi Jiang, Qi Yan, Xiaoyan Liu, Jie Wang J. Pharm. Anal. 2026. 16(7) 101585 https://doi.org/10.1016/j.jpha.2026.101585 针对急性肾损伤（AKI）早期诊断困难、尿液微小RNA-21（miR-21）检测灵敏度低且前处理繁琐等问题，本研究构建等温核酸扩增耦合表面增强拉曼光谱（SERS）的纳米生物传感平台。该平台基于三级信号放大体系，通过双酶协同等温循环、杂交链式反应（HCR）有序组装及聚A修饰基底特异性捕获，实现尿液样本免洗涤直接检测，有效克服基质干扰。经材料表征、核酸验证及性能评估，级联扩增通路稳定可控，特异性良好。平台检测线性范围为10fM~100nM，覆盖临床浓度区间，重复性与抗干扰能力优异。临床测试结果与qRT-PCR高度吻合，可有效区分健康人群与AKI患者，较传统标志物更早预警肾损伤。本技术无需复杂前处理与大型设备，兼顾灵敏度与便捷性，为AKI早期筛查及miRNA临床转化提供可靠方案。 Highlights A multiplex isothermal amplification-SERS platform achieves 8.4 fM sensitivity, replacing qRT-PCR. Enables direct miR-21 detection in unprocessed urine within 2 h, by passing RNA extraction. Detects miR-21 elevations 24–48 h earlier than SCr/BUN, with high specificity (RSD < 5.7%). Adaptable design for other miRNAs, expanding potential in disease diagnostics. h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors Dan-Dan Zhou, Zi-Hui Xie, Ai-Jun Duan, Shi-Yu Zhu, Ying Wang, Yong-Su Zhen, Rui-Juan Gao, Qing-Fang Miao J. Pharm. Anal. 2026. 16(7) 101550 https://doi.org/10.1016/j.jpha.2026.101550 抗体药物偶联物（ADC）依托抗体的靶向作用将细胞毒性载荷递送至肿瘤病灶，实现精准杀伤。间皮素（MSLN）在多种恶性肿瘤中异常高表达，是极具开发潜力的肿瘤靶点。力达霉素（LDM）是一种新型抗肿瘤抗生素，其作用机制不同于临床主流微管、拓扑异构酶抑制剂类ADC载荷。本研究筛选得到抗MSLN的新型抗体h3B7A，然后采用独创的基因工程与分子组装技术制备了h3B7A与LDM的ADC h3B7A-LDM。体外实验证实，该分子可特异性杀伤MSLN阳性肿瘤细胞，抑制细胞增殖迁移，诱导周期阻滞和凋亡；本研究首次发现其能诱导肿瘤细胞发生免疫原性细胞死亡（ICD），激活小鼠抗肿瘤免疫。h3B7A-LDM在多种荷瘤小鼠模型中均具有显著抑瘤作用，且安全性良好。综上，h3B7A-LDM可作为治疗MSLN阳性肿瘤的新型候选ADC药物。 Highlights A novel antibody-drug conjugate, h3B7A-LDM, was constructed by conjugating the anti-MSLN antibody h3B7A with the potent cytotoxin lidamycin. h3B7A-LDM shows potent efficacy against MSLN-overexpressing solid tumors. h3B7A-LDM inhibits tumor via anti-proliferation/migration, pro-apoptosis/cycle arrest, and immune activation. Lidamycin-based ADCs, along with lidamycin itself, can induce antitumor immunity in solid tumors. Lappaconitine hydrobromide prevents NLRP3-GSDMD-mediated pyroptosis to alleviate sepsis-induced acute lung injury by enhancing NR1H3 Yuejia Lan, Qingrui Zhong, Hongkai Huang, Xiao Deng, Lu Yang, Jiayi Sun, Mingyang Liu, Xianli Meng, Jiasi Wu J. Pharm. Anal. 2026. 16(7) 101631 https://doi.org/10.1016/j.jpha.2026.101631 本研究发现，氢溴酸高乌甲素（LAH）可通过激活核受体亚家族1组H成员3（NR1H3，亦称LXRα），有效缓解脓毒症诱导的急性肺损伤（SALI）。SALI是重症监护中一种高致死率的并发症，目前缺乏特异性治疗药物。研究团队利用脂多糖和盲肠浆液诱导的SALI小鼠模型，证实LAH可显著降低肺水肿、炎症细胞浸润和死亡率，同时抑制NLRP3炎症小体活化及下游焦亡效应蛋白GSDMD的切割。转录组学与生物信息学分析提示，LAH逆转的差异表达基因富集于IL-1β产生、炎症反应调控等通路，其中NR1H3为核心节点。体外机制研究表明，LAH直接与NR1H3结合，激活其转录活性，促进胆固醇外排相关蛋白表达，减少脂筏胆固醇含量，阻断Toll样受体4（TLR4）向脂筏的募集，进而抑制NF-κB p65核转位和NLRP3炎症小体启动及组装。通过NR1H3抑制剂GSK2033或小干扰RNA敲减NR1H3，LAH对NLRP3活化及焦亡的抑制作用被部分逆转，证实其依赖NR1H3通路。本研究首次揭示LAH作为新型NR1H3激动剂，通过干扰脂筏完整性、阻断TLR4信号，抑制NLRP3-GSDMD介导的细胞焦亡，为SALI治疗提供了新策略，也为NR1H3作为抗炎靶点提供了有力证据。 Highlights Lappaconitine hydrobromide (LAH) attenuates SALI via modulating NR1H3-NLRP3 axis. LAH potentiates NR1H3 to disrupt lipid rafts and inhibit the priming of NLRP3 inflammasome. LAH displayed a direct interaction with NR1H3. NR1H3 inhibition partially reversed the effects of LAH on suppressing NLRP3-mediated pyroptosis in vitro. Drug delivery system of curcumin to the lungs based on poly(3-alloxyloxy-1,2-propylene succinate)-sebacic acid copolymers Karolina Knap, Konrad Kwiecień, Jonasz Czajkowski, Rafał Szostecki, Daria Niewolik, Katarzyna Jaszcz, Peter Olinga, Katarzyna Reczyńska-Kolman, Elżbieta Pamuła J. Pharm. Anal. 2026. 16(7) 101434 https://doi.org/10.1016/j.jpha.2025.101434 Highlights Curcumin-loaded poly(ester-anhydride) microparticle formulation for inhalation. Formulation with appropriate size, degradation rate, and aerodynamic properties to be deposited in the lungs. Microparticles cytocompatible up to 100 μg/mL according to in vitro and ex vivo models. Quantifying protein residues in APIs: Bradford assay mechanism and limitations, outperformed by HILIC-MS/MS Yangrui Zhang, Yizhen Liu, Yangyang Chen, Chen Guo, Fengting Ou, Junhuan Lin, Hanmeng Guo, Tao Ke, Lushan Yu J. Pharm. Anal. 2026. 16(7) 101552 https://doi.org/10.1016/j.jpha.2026.101552 Highlights Accuracy of conventional protein assays varies with protein and peptide structure. Mechanistic insights into Bradford assay via machine learning and molecular modeling. Amino acids beyond known basic and aromatic residues affect Bradford assay response. HILIC-MS/MS was established to quantify total protein, validated with 30+ standards. Protein residues in 8 APIs vary by strain and supplier, ranging from 9.53 to 5570 ppm. Augmented therapeutic efficacy of Erianin through pH-responsive charge-reversal liposome integrated synergistic PTT and PDT in breast cancer Jingshuo Li, Xibin Zhou, Shoushi Liu, Alu Ouyang, Bo Su, Zixin Wang, Jiayu Lu, Xin Chen, Qiuju Huang, Ronghua Jin, Hongwei Guo J. Pharm. Anal. 2026. 16(7) 101555 https://doi.org/10.1016/j.jpha.2026.101555 为解决毛兰素溶解度差及单一化疗模式疗效不足的问题，本研究构建了一种共包载毛兰素与IR780的电荷反转脂质体递送系统。该脂质体在生理条件下维持表面负电荷，以延长体内循环时间；而在酸性肿瘤微环境（pH 6.5-6.8）中，可发生pH响应性电荷翻转为正电荷，从而增强肿瘤细胞的选择性摄取。该脂质体可实现线粒体靶向递送，其中IR780介导的活性氧生成及温和光热疗法可激活应激相关信号通路，诱发线粒体损伤，并最终触发免疫原性细胞死亡。同时，包载的毛兰素可有效抑制光热治疗(PTT)/光动力治疗(PDT)诱导的程序性细胞死亡配体1（PD-L1）上调。该脂质体不仅规避了传统化疗的固有缺陷，同时构建了集PTT、PDT与化疗于一体的协同治疗策略，通过逆转耐药机制并限制免疫检查点表达，展现出显著的抗肿瘤活性，为脂质体在肿瘤联合治疗中的应用提供了创新性思路。 Highlights A pH-responsive charge-reversal liposome was designed to prolong systemic circulation and enhance tumor-selective delivery. Mitochondria-targeted photothermal/photodynamic therapy (PTT/PDT) triggers immunogenic cell death via mitochondrial stress pathways. The co-delivery of erianin and IR780 enables a synergistic therapeutic modality integrating PTT, PDT, and chemotherapy. Flavonoid compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming Xiaohui Hu, Yingxia Tian, Qianping Chen, Yanan Guo, Pengfei Ji, Yixiao Tian, Shuangxi Qian, Guolin Chai, Fangdi Hu, Rong Shen, Degui Wang J. Pharm. Anal. 2026. 16(7) 101559 https://doi.org/10.1016/j.jpha.2026.101559 Highlights SRW delays cellular senescence by restoring mitochondrial function. SRW enhances complex I activity and oxidative phosphorylation via upregulating NDUFV2. SRW reduces lactate accumulation and mitochondrial damage by modulating LDHB expression. A dual-pathway metabolic reprogramming mechanism targeting both mitochondria and glycolysis is proposed. Myricetin, luteolin, and γ-mangostin are identified as potent anti-senescence compounds from SRW. Short communications Active peptides pursuit from complicated matrices via tracing ligand-protein complex with MS/MS: Chaperone screening for lysozyme as a pilot study Zihan Zhu, Jiahui Wen, Ting Li, Han Li, Wei Li, Ke Zhang, Pengfei Tu, Wenjing Liu, Yuelin Song J. Pharm. Anal. 2026. 16(7) 101586 https://doi.org/10.1016/j.jpha.2026.101586 天然肽在药物研发中至关重要，但常规方法难以直接捕获配体-蛋白质复合物，易产生假阳性。本文构建了整合离线二维液相色谱（2D-LC）分离、96孔板孵育和串联质谱（MS/MS）的策略，用于配体-蛋白质复合物的形成与检测。以溶菌酶（Lyz）的伴侣筛选为例，通过离线2D-LC将地衣芽孢杆菌发酵液分离为139个流分，各流分与Lyz平行孵育后，利用MS/MS追踪复合物信号，最终成功在13个流分中检出复合物，并鉴定出两种潜在配体——杆菌肽A（Bac A）和杆菌肽B。实验验证了Lyz与Bac A的相互作用，且Bac A显著增强了Lyz的抗菌活性。该流程为复杂基质中活性肽的高效筛选提供了新思路。 Highlights A refined workflow was designed for high-throughput screening of active peptides in complicated matrices. Confidence was enhanced by directly capturing peptide-protein complex in MS1, assisted by MS2. Lysozyme (Lyz) and Bacillus licheniformis fermentation broth were utilized for utility illustration and justification. Fifteen potential peptides were detected, of which bacitracins A and B3 (Bacs A and B3) were annotated. The interactions between Lyz and Bac A dramatically advanced the antibacterial performance of Lyz. Discovery of mitochondrial modulators using target-aggregated machine learning Lizhuo Wang, Peng Yang, Sirui Wu, Fanding Xu, Wu Su, Le Shi, Hui Guo, Li Cui, Jiankang Liu, Zhiwei Yang, Jiangang Long J. Pharm. Anal. 2026. 16(7) 101579 https://doi.org/10.1016/j.jpha.2026.101579 线粒体功能异常与神经退行性疾病、代谢综合征等重大疾病密切相关，但其靶点众多、活性数据稀疏，长期制约药物发现。本文提出"靶点聚合"机器学习框架，整合63个线粒体相关靶点数据，训练模型学习"线粒体调控剂"宏观表型特征。针对性地以活性阈值定义负样本，规避了真阴性数据缺失难题，并保留骨架相似而活性迥异的化合物对，以捕捉精细构效关系。经对比多种模型，XGBoost表现最优，ROC AUC达0.943。基于模型从14.7万分子中筛选出6个新颖候选化合物，经线粒体活性实验验证，均显示显著的线粒体激活或抑制效应。该研究提供了一套可迁移的计算框架，为线粒体靶向药物研发等数据稀疏、机制复杂领域的药物发现开辟了新路径。 Highlights A target-agnostic and data-integrated machine learning strategy was developed to overcome data scarcity and enable robust predictive modeling. Multiple machine learning and deep learning algorithms were systematically evaluated, with XGBoost achieving a top ROC AUC of 0.943. Virtual screening of a large chemical library identified six novel mitochondrial modulators, all experimentally validated in human cell assays. A scalable and target-independent framework was established for phenotypic drug discovery in complex biological systems. Multiple gastric cancer tissue proteomic identification predicts CLU as a biomarker for anti-PD-1 immunotherapy Yu Zhang, Hao-Yi Zhu, Cong-Cong Ma, Ning Wang, Yan Li, Guo-Liang Lu, Xing-Jie Dai, Bo Wang, MAA Mamun, Ying Li, Xiao-Ying Zhao, Jing-Ru Pang, Ning-Jie Guo, Feng-Yu Qi, Jian-Gang Sun, Hong-Min Liu, Feng-Wu Liu, Piet Herdewijn, Long-Fei Zhao, Yi-Chao Zheng J. Pharm. Anal. 2026. 16(7) 101615 https://doi.org/10.1016/j.jpha.2026.101615 本研究基于胃癌患者治疗前肿瘤组织蛋白质组学分析，筛选并鉴定出簇集蛋白（CLU）是预测抗程序性死亡受体1（PD-1）免疫治疗疗效的重要阴性生物标志物。研究发现，CLU在抗PD-1治疗非应答患者中显著高表达，且其预测疗效的能力优于程序性死亡配体1（PD-L1）等传统指标。进一步机制研究表明，CLU不仅促进胃癌细胞增殖，还可塑造免疫抑制性肿瘤微环境，降低CD8⁺ T细胞浸润及免疫活化，削弱T细胞介导的抗肿瘤作用，从而促进肿瘤免疫逃逸。动物模型和体外共培养实验进一步证实，敲除或抑制CLU能够增强抗PD-1治疗效果，并提高T细胞杀伤活性。该研究提示，CLU兼具疗效预测标志物和潜在治疗靶点双重价值，有望用于胃癌患者精准分层，并为联合免疫治疗策略的开发提供新的理论依据和干预方向。 Highlights Clusterin (CLU) is a new negative predictive biomarker for anti-PD-1 immunotherapy of gastric cancer (GC). CLU is a pivotal regulator of both tumor-intrinsic proliferation and immune evasion in GC. CLU abrogation in GC enhances the immune response, boosting T-cell killing ability activity and cytokine secretion. 近期阅读： JPA文章推荐 | 贵州医科大学钱星凯、马红红团队与上海中医药大学邹立伟团队综述——DPP-IV检测技术及其抑制剂筛选研究进展 上海中医药大学葛广波、王平团队与海南医科大学杨献文团队成果—新型非硝基儿茶酚类COMT抑制剂的发现、成药性优化及左旋多巴代谢调控研究 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