{"title":"AIE-active dual-channel fluorescent probe for simultaneous viscosity and HClO detection in ferroptosis, acute liver injury and hepatocellular carcinoma models.","authors":"Jiakang Sun, Lidong Cao, Yumeng Liu, Yun Wang, Yong Zhan","doi":"10.1016/j.jpha.2025.101489","DOIUrl":"10.1016/j.jpha.2025.101489","url":null,"abstract":"<p><p>This study addresses the technical challenge of simultaneously detecting viscosity and hypochlorous acid (HClO) within the liver disease microenvironment by developing a novel near-infrared (NIR) dual-channel fluorescence probe, BCz-DCN-TPA, based on the aggregation-induced emission (AIE) mechanism. The probe exhibits pronounced fluorescence enhancement at 675 nm (viscosity-responsive) and 465 nm (HClO-responsive), attributed to the restriction of intramolecular motion (RIM) effect and HClO-specific oxidation reactions, respectively. It also possesses high sensitivity, excellent selectivity (toward 15 types of interferents), superior photostability (for more than 300 min), and a low limit of detection (LOD), as low as 0.233 nM, for HClO. Theoretical calculations revealed the ground state and excited state reaction pathways underlying the reaction between HClO and BCz-DCN-TPA. <i>In vitro</i> experiments validated its ability to monitor real-time changes in viscosity and oxidative stress levels during ferroptosis, which aids in elucidating ferroptosis mechanisms. In acetaminophen (APAP)-induced acute liver injury (ALI) and hepatocellular carcinoma models, the probe tracked dual parameters abnormal viscosity and HClO levels in liver injury regions and tumor microenvironments <i>in vivo</i>, with live imaging clearly delineating lesion areas. Notably, BCz-DCN-TPA enabled deep tissue photoacoustic imaging (PAI) in a hepatocellular carcinoma model. This multimodal probe provides a versatile platform for studying liver disease pathology and advancing precision diagnosis and treatment strategies.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101489"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing HIV drug resistance testing: A leap forward with DNA-based genotyping.","authors":"Yan Jiang","doi":"10.1016/j.jpha.2026.101636","DOIUrl":"10.1016/j.jpha.2026.101636","url":null,"abstract":"","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101636"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Xu, Zhulin Gu, Li Wang, Xinghan Liu, Hao Wu, Zhenzhou Jiang, Jinfang Song, Changjiang Ying, Tan Li, Tao Wang, Na Xie, Xiaoxing Yin, Tingting Yang
{"title":"Predictive serum metabolic markers in GDM patients: A targeted metabolomics study combined with machine learning of sex steroid hormones.","authors":"Yi Xu, Zhulin Gu, Li Wang, Xinghan Liu, Hao Wu, Zhenzhou Jiang, Jinfang Song, Changjiang Ying, Tan Li, Tao Wang, Na Xie, Xiaoxing Yin, Tingting Yang","doi":"10.1016/j.jpha.2025.101530","DOIUrl":"10.1016/j.jpha.2025.101530","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101530"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyo Gi Jung, Yeon Ho Kim, Junho Bang, Dongsung Park, Jae Won Jang, Yonghwan Kim, Hyunji Kim, Kyo Seon Hwang, Jeong Hoon Lee, Dongtak Lee, Dae Sung Yoon
{"title":"Citric acid disassembles α-synuclein fibrils and reduces their cytotoxicity.","authors":"Hyo Gi Jung, Yeon Ho Kim, Junho Bang, Dongsung Park, Jae Won Jang, Yonghwan Kim, Hyunji Kim, Kyo Seon Hwang, Jeong Hoon Lee, Dongtak Lee, Dae Sung Yoon","doi":"10.1016/j.jpha.2025.101404","DOIUrl":"10.1016/j.jpha.2025.101404","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101404"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ACAA1 mediates arachidonic acid dysregulation and membrane phospholipid remodeling to promote crystal-cell adhesion and ferroptosis susceptibility in calcium oxalate kidney stone.","authors":"Qinhong Jiang, Yanqi Xie, Chao Song, Caitao Dong, Wenbiao Liao, Qianlin Song, Xiaozhe Su, Heng Xiang, Yunhan Wang, Bobo Cheng, Ziqi He, Sixing Yang","doi":"10.1016/j.jpha.2025.101470","DOIUrl":"10.1016/j.jpha.2025.101470","url":null,"abstract":"<p><p>Crystal adhesion is a key process in the formation of kidney stones, playing a synergistic role at every crystallization stage. Damage to the renal tubular epithelial cell (RTEC) membrane provides essential sites for crystal adhesion. During the terminal phase of ferroptosis, accumulated polyunsaturated phospholipids integrate into the cell membrane, leading to membrane damage and deformation, which may be an important mechanism in calcium oxalate (CaOx) crystallization. In this study, targeted peroxidomics analysis revealed a significant increase in arachidonic acid (AA) levels in a CaOx kidney stone model. Meanwhile, transcriptomic analysis indicated that the key enzyme in fatty acid metabolism, acetyl-coenzyme A (CoA) acyltransferase 1 (ACAA1), was significantly downregulated in the CaOx kidney stone model. Besides, overexpression of ACAA1 (OE-ACAA1) alleviated AA accumulation and reduced oxalate (Ox)-induced RTEC ferroptosis. Notably, the OE-ACAA1 alleviated the accumulation of AA-containing polyunsaturated phospholipids without regulating acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, thereby reducing membrane peroxidative damage and crystal adhesion. Furthermore, transcription factor array analysis identified the downregulation of activating transcription factor 1 (ATF1), an upstream transcriptional regulator of ACAA1, which might be involved in the transcriptional repression of ACAA1. Finally, OE-ATF1 partially alleviated Ox-induced RTEC membrane peroxidative damage and crystal adhesion. These findings demonstrated that ferroptosis participates in the early crystallization process by mediating RTEC membrane peroxidative damage and provided a novel approach to influencing downstream lipid peroxidation by regulating fatty acid activation substrates rather than ACSL4. Therefore, this study offers potential therapeutic targets for the prevention and treatment of CaOx kidney stones.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101470"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Distinct types of regulated cell death in atherosclerosis.","authors":"Danyi Cao, Han Han, Deyong Yue, Guojun Shi, Yun Chen, Jiahai Shi, Guoliang Meng","doi":"10.1016/j.jpha.2025.101431","DOIUrl":"10.1016/j.jpha.2025.101431","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disorder with high morbidity and mortality, leading to serious complications like myocardial infarction and strokes. Key cell types involved in atherosclerotic lesions include vascular endothelial cells (VEC), vascular smooth muscle cells (VSMC) and macrophages. Types of regulated cell death (RCD) are significant in the development and progression of AS, including apoptosis, autophagy, necroptosis, efferocytosis, ferroptosis, pyroptosis, parthanatos, cuproptosis, lysosome-dependent cell death (LDCD), NETotic cell death, paraptosis, alkaliptosis, oxeiptosis, entotic cell death and PANoptosis. The regulatory mechanisms and the crosstalk between different types of cells during AS are complex, and the exact molecular basis remains obscure. Currently, numerous drugs and compounds have been found to attenuate AS by targeting RCD. The review aims to provide an overview of RCD types related to VEC, VSMC, and macrophages in AS, providing a reliable theoretical basis of the cellular mechanisms and exploring potential therapeutic strategies.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101431"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic difference of potentially toxic components from Psoraleae Fructus and Euodiae Fructus in Sishen formula by different compatibilities and physiologies.","authors":"Lili Hong, Yijin Yang, Lianxing Wang, Yiqing Yao, Yadan Zou, Hongda Wang, Xue Li, Yuan Li, Lingli Ma, Xiaoying Wang, Xiumei Gao, Wenzhi Yang","doi":"10.1016/j.jpha.2025.101467","DOIUrl":"10.1016/j.jpha.2025.101467","url":null,"abstract":"<p><p>Compatibility attenuation is an effective strategy to ensure the safety of traditional Chinese medicine (TCM). Mechanistic elucidation is essential, however, no consensus reaches on the scientific connotation of compatibility attenuation in Sishen formula (SSF). Given TCM metabolism is closely associated with its toxicological consequences, this study was designed to systematically decipher and compare the holistic metabolic differences of potential toxicants derived from Psoraleae Fructus (PF) and Euodiae Fructus (EF) within SSF. In total, 23 potential toxicants from PF and EF were identified through a comprehensive literature review. Using ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry and ultra-high performance liquid chromatography/triple quadrupole-linear ion trap mass spectrometry, the metabolic difference of target components among differentiated compatibility and physiological state was elucidated by integrating serum metabolomics and poly-pharmacokinetics analyses. Holistically, the compatibility could suppress the transformation of potential toxicants, whereas irritable bowel syndrome (IBS) state exhibited a promoting effect. Myristicae Semen (MyS) or Schisandrae Chinensis Fructus (SCF) increased the exposure of toxicants from PF, while EF demonstrated an opposing effect. SCF promoted the exposure of toxicants from EF, which could be mitigated by Ershen formula. The IBS mice exhibited greater exposure to potential toxicants and their metabolites from PF (compared to the sham operation group), yet SSF alleviated this effect. Furthermore, potential toxicants in the SSF group tended to exhibit reduced metabolic transformation, decreased exposure, enhanced tissue distribution, and facilitated excretion. Collectively, these findings provide novel insights into the metabolic mechanisms underlying SSF detoxification and offer valuable safety recommendation in clinical use.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101467"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A comprehensive review of intelligent question-answering systems in traditional Chinese medicine based on LLMs.","authors":"Qilan Xu, Tong Wu, Yiwen Wang, Xingyu Li, Heshui Yu, Shixin Cen, Zheng Li","doi":"10.1016/j.jpha.2025.101406","DOIUrl":"10.1016/j.jpha.2025.101406","url":null,"abstract":"<p><p>Large language models (LLMs) are advanced deep learning models with billions or even trillions of parameters, enabling powerful natural language processing and knowledge reasoning capabilities. Their applications in the medical domain have been rapidly expanding, spanning medical research, clinical diagnosis, drug development, and patient management. As a cornerstone of China's healthcare system, traditional Chinese medicine (TCM) faces significant challenges, including difficulties in knowledge extraction, and lack of standardization. The emergence of TCM-focused LLMs presents a transformative opportunity, offering a novel technological framework to process vast amounts of TCM data, uncover hidden theoretical insights, and enhance both research and clinical applications. Despite the growing interest in artificial intelligence (AI)-driven medical solutions, systematic research on LLMs in the TCM domain remains limited. This article provides a comprehensive review of LLM development, detailing their underlying mechanisms, training methodologies, and key technological advancements. It further explores the unique characteristics and diverse application scenarios of existing TCM-LLMs. Additionally, this study also conducts a horizontal comparison of the differences between intelligent question-answering (QA) systems on general LLMs and QA systems on TCM-LLMs, discusses challenges and potential risks, and offers strategic recommendations for future development. By synthesizing current advancements and addressing critical gaps, this work aims to support the continued modernization and intelligent evolution of TCM, fostering its integration into contemporary healthcare systems.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101406"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan Xu, Fanhe Meng, Binglun Zhang, Xing Yang, Haibo Wang, Fan Yang
{"title":"Polysaccharides self-healing hydrogel for skin regeneration.","authors":"Nan Xu, Fanhe Meng, Binglun Zhang, Xing Yang, Haibo Wang, Fan Yang","doi":"10.1016/j.jpha.2025.101447","DOIUrl":"10.1016/j.jpha.2025.101447","url":null,"abstract":"<p><p>Damaged skin is prone to infection and impaired healing, making efficient wound care materials critical. Polysaccharide-based self-healing hydrogels have demonstrated significant potential in skin regeneration due to their biocompatibility, biodegradability, and ability to mimic the extracellular matrix (ECM). This review summarizes the fabrication techniques, core polysaccharide materials, and challenges of these hydrogels. Hydrogel preparation primarily involves chemical cross-linking, physical cross-linking, and three-dimensional (3D) bioprinting. Chemical cross-linking confers high mechanical strength but limited self-healing capacity, while physical cross-linking enables rapid self-healing via dynamic non-covalent interactions, responsive to stimuli like pH and temperature. 3D bioprinting allows customizable tissue-like structures with precise control over cell distribution and bioactive molecule release. Key polysaccharides include alginate, chitosan, hyaluronic acid (HA), cellulose, and dextran. Alginate forms reversible networks via calcium ion cross-linking, suitable for wound dressings and tissue engineering. Chitosan, with amino and hydroxyl groups, exhibits antibacterial activity and promotes cell proliferation, widely used in infected wounds. HA achieves self-healing through dynamic covalent bonds, accelerating collagen deposition and angiogenesis. Cellulose derivatives employ boronic ester or Schiff base linkages for self-healing systems in injectable formulations. Dextran utilizes Diels-Alder reactions for self-healing under physiological conditions, ideal for drug delivery. Commercial products like HyStem® and Chitogel® have entered clinical use, integrating growth factors or antimicrobials to enhance wound healing. However, challenges persist, including insufficient mechanical strength, mismatched degradation rates with healing processes, long-term safety concerns, and scalability. Future directions focus on \"smart\" hydrogels, combined with clustered regularly interspaced short palindromic repeats (CRISPR) gene editing or artificial intelligence (AI)-optimized design, to enhance functionality and clinical translation.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101447"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen-Kai Yu, Qing-Ru Zhu, Li Zhou, Xin-Lei Shen, Tian-Yang Cheng, Yi-Ni Bao, Gang Cao
{"title":"Small molecules targeting regulated cell death for chronic kidney disease therapy.","authors":"Wen-Kai Yu, Qing-Ru Zhu, Li Zhou, Xin-Lei Shen, Tian-Yang Cheng, Yi-Ni Bao, Gang Cao","doi":"10.1016/j.jpha.2025.101427","DOIUrl":"10.1016/j.jpha.2025.101427","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a significant contributor to the global morbidity of non-communicable diseases and is predicted to become the fifth leading cause of death worldwide. However, effective treatments that directly target the underlying causes of CKD remain limited due to its complicated pathogenesis. Recent research has increasingly focused on elucidating the molecular mechanisms and identifying new therapeutic targets of CKD. In recent years, regulated cell death (RCD) has been highlighted as a central mechanism in the development and progression of CKD, suggesting that targeting specific RCD signaling pathways may offer effective strategies for CKD. Emerging research reveals that small molecules can effectively target different types of RCD in the context of CKD, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis, and necroptosis. In this review, we summarize current understanding of the mechanism of RCD in CKD. Importantly, we emphasize the regulatory mechanism of small molecules on disturbed RCD to alleviate CKD. Taken together, this review enhances the comprehension of small molecules as modulators of RCD against CKD, which will provide new insights and potential avenues for CKD therapy.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"16 4","pages":"101427"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}