Yajing Li , Peng Di , Yinan Zou , Xiao Li , Ke Zhang , Jing Wang , Yun Wang , Shi Qiu , Jingfu Tan , Weixu Chen , Bo Li , Tingzhao Li , Lei Zhang , Ying Xiao , Wansheng Chen , Junfeng Chen
{"title":"The transcriptional regulatory network involved in periderm-specific tanshinones biosynthesis in Salvia miltiorrhiza root","authors":"Yajing Li , Peng Di , Yinan Zou , Xiao Li , Ke Zhang , Jing Wang , Yun Wang , Shi Qiu , Jingfu Tan , Weixu Chen , Bo Li , Tingzhao Li , Lei Zhang , Ying Xiao , Wansheng Chen , Junfeng Chen","doi":"10.1016/j.apsb.2025.12.018","DOIUrl":"10.1016/j.apsb.2025.12.018","url":null,"abstract":"<div><div>Tanshinones (TAs), well-known specialized diterpenoid metabolites in <em>Salvia</em> plants, exhibit distinct tissue-specific production in the root periderm. However, the mechanisms regulating this accumulation pattern remain unknown. Here, we employed a multi-omics analysis strategy to uncover the transcriptional regulatory network responsible for TA biosynthesis in <em>Salvia miltiorrhiza</em> roots. By integrating metabolic profiling, RNA-seq, and ATAC-seq, we profile the temporo-spatial dynamics of metabolic, transcriptional, and chromatin landscapes during early root development. Our results demonstrate that TAs biosynthesis and accumulation in <em>S. miltiorrhiza</em> roots display spatiotemporal patterns, marked by periderm-specific accumulation and initiation exclusively at specific developmental stages, tightly coordinated with dynamic changes in chromatin accessibility and transcriptional regulation. The constructed transcriptional regulatory network driving TA biosynthesis was found to be dominated by 211 key transcription factors (TFs). Experimental validations highlighted SmERF105 as a key positive regulator of TA, activating the transcription of <em>KSL1</em>, <em>CYP76AH3</em>, and the TA transporter <em>ABCG1</em> to modulate the TA production. Our study uncovers novel, high-confidence regulators and offers an effective strategy for dissecting the genetic basis of plant specialized metabolites, offering value for advancing TA metabolic engineering.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1568-1583"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chaoyan Yao , Lei Wang , Weidong Liu , Ning Shi , Ziling Liao , Yuxuan Fu , Jinhao Ouyang , Xuan Lei , Qianping Huang , Siyu Li , Yihua Zhouyang , Pinnan Zhao , Jie Wang , Hongjuan Xu , Wenhu Zhou , Xingjun Jiang , Xiang Gao , Caiping Ren , Longlong Luo
{"title":"A triple combination strategy for nasopharyngeal carcinoma: Aptamer-guided liposomal chemotherapy, engineered NK cells, and Fc-enhanced PD-L1 antibody therapy","authors":"Chaoyan Yao , Lei Wang , Weidong Liu , Ning Shi , Ziling Liao , Yuxuan Fu , Jinhao Ouyang , Xuan Lei , Qianping Huang , Siyu Li , Yihua Zhouyang , Pinnan Zhao , Jie Wang , Hongjuan Xu , Wenhu Zhou , Xingjun Jiang , Xiang Gao , Caiping Ren , Longlong Luo","doi":"10.1016/j.apsb.2025.10.007","DOIUrl":"10.1016/j.apsb.2025.10.007","url":null,"abstract":"<div><div>The effective treatment of nasopharyngeal carcinoma (NPC) is challenged by an immunosuppressive tumor microenvironment (TME) and insufficient immune effector cell activation. Herein, we design a synergistic tri-modal therapeutic strategy to overcome these barriers. This platform integrates: (1) a CD109-targeted liposomal doxorubicin (S3-Lip-DOX) for precise chemotherapy and induction of immunogenic cell death (ICD); (2) non-genetically engineered natural killer (NK) cells armed with dual aptamers (targeting CD109 and PD-L1) <em>via</em> bio-orthogonal chemistry for enhanced tumor recognition (S3-P-NK); and (3) an Fc-engineered anti-PD-L1 antibody (Atezolizumab/IgG1) that restores antibody-dependent cellular cytotoxicity (ADCC). Crucially, we uncovered a key mechanistic synergy: S3-Lip-DOX treatment, as a stress-adaptive response, upregulates PD-L1 expression on NPC cells. This finding provides a compelling rationale for the integration, turning a potential immune escape mechanism into a therapeutic vulnerability. The complete regimen, comprising S3-Lip-DOX, S3-P-NK, and Atezolizumab/IgG1, demonstrated potent synergistic antitumor effects <em>in vitro</em> and <em>in vivo</em>. This triple-combination therapy not only achieved significant tumor regression but also robustly reprogrammed the innate tumor microenvironment, evidenced by enhanced dendritic cell (DC) maturation and pro-inflammatory macrophage activation. This work establishes a mechanism-driven, modular therapeutic platform that effectively coordinates targeted chemotherapy with innate immunotherapy, holding significant translational potential for solid tumors.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1584-1604"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating Chinese medicine and intermittent fasting: A promising approach for treating diabetic vascular calcification","authors":"Zhixiu Lin","doi":"10.1016/j.apsb.2026.01.004","DOIUrl":"10.1016/j.apsb.2026.01.004","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1797-1799"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nanxuan Luo , Yijie Xiao , Yile Zhai , Jie Li , Lijie Lv , Houhua Yin , Fang Lin , Biwen Wan , Ke Zhang , Junchi Hu , Junyan Liu , Yongjun Dang , Yi He , Yahui Zhao , Zhe Zhang , Shenyou Nie , Hai-Xin Yuan
{"title":"Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3","authors":"Nanxuan Luo , Yijie Xiao , Yile Zhai , Jie Li , Lijie Lv , Houhua Yin , Fang Lin , Biwen Wan , Ke Zhang , Junchi Hu , Junyan Liu , Yongjun Dang , Yi He , Yahui Zhao , Zhe Zhang , Shenyou Nie , Hai-Xin Yuan","doi":"10.1016/j.apsb.2025.11.004","DOIUrl":"10.1016/j.apsb.2025.11.004","url":null,"abstract":"<div><div>In our screening campaign for novel ferroptosis inhibitors, we identified that vitamin A (VA) and its metabolite all-<em>trans</em> retinoic acid (ATRA) exhibited potent ferroptosis-suppressing activity. Notably, through a combination of biochemical and pharmacological assays, we demonstrated that the anti-ferroptotic effects of VA and ATRA are independent of both antioxidative mechanisms and the canonical RAR/RXR signaling pathway. This conclusion was corroborated by a series of newly synthesized VA analogues. Furthermore, VA and its structural derivatives significantly alleviated ferroptosis-associated pathological phenotypes in murine models. Intriguingly, we discovered a novel function of VA and its analogues, which directly target acyl-CoA synthetase long-chain family member 3 (ACSL3) and enhance its enzymatic activity. This ACSL3-dependent mechanism increases the MUFA/PUFA ratio in phospholipids, thereby preventing lipid peroxidation. Strikingly, we further demonstrated that VA and its analogue D3 [(2<em>E</em>,4<em>E</em>,6<em>E</em>,8<em>E</em>)-<em>N</em>,3,7-trimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide] extend the lifespan of <em>C. elegans</em> in a manner dependent on ACSL3, highlighting the physiological relevance of this pathway in aging. Collectively, our findings unveil a previously unrecognized role for VA and its analogues in modulating lipid metabolism, thereby providing a theoretical basis for their potential application in treating ferroptosis-related diseases and possibly enhancing longevity.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1510-1529"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phosphatases: An undervalued class of antitumor drug targets","authors":"Mei Wang , Peng Zhan , Yuning Song","doi":"10.1016/j.apsb.2025.11.021","DOIUrl":"10.1016/j.apsb.2025.11.021","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1786-1789"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xing Zhao, Xi Wu, Ranran Shang, Haitao Dou, Huachao Chen, Ninghua Tan
{"title":"Extracellular vesicles-derived hybrid biomimetic nanoplatforms camouflaged Golgi apparatus-targeted aggregation induced emission photosensitizer to elicit pyroptosis and immunogenic cell death for efficient antitumor photoimmunotherapy","authors":"Xing Zhao, Xi Wu, Ranran Shang, Haitao Dou, Huachao Chen, Ninghua Tan","doi":"10.1016/j.apsb.2025.11.010","DOIUrl":"10.1016/j.apsb.2025.11.010","url":null,"abstract":"<div><div>Pyroptosis is a unique programmed cell death pattern, and targeting it is an effective strategy against cancer therapy by overcoming apoptosis resistance. However, Golgi apparatus-targeted aggregation induced emission (AIE) photosensitizer as pyroptosis inducer for efficient antitumor treatment has not been reported. In this study, we successfully synthesized three new AIEgens, including TMN, TBN and TCN, by changing functional groups through a reasonable molecular design strategy, which targeted mitochondria, lysosome and Golgi apparatus (GA), respectively. <em>In vitro</em> experiments demonstrated that TCN exhibited the strongest reactive oxygen species (ROS) production ability and significant phototoxicity. Therefore, TCN as the GA-targeted AIE photosensitizer wore biomimetic hybrid extracellular vehicles (EVs) and M1-type macrophage membranes (denoted as EM@TCN) as pyroptosis inducer were rationally designed and engineered to trigger the production of GA cytotoxic ROS <em>in situ</em>. EM@TCN plus white light irradiation caused GA oxidative stress and induced pyroptosis synergistic photoimmunotherapeutic, which could rebuild tumor microenvironment and improve tumor immunogenicity. Combined with <em>α</em>PD-L1 (anti-mouse PD-L1 antibody), the biomimetic hybrid delivery system EM@TCN significantly inhibit the both primary and distant tumors, and effectively suppress the orthotopic breast tumor. This is the first report on a hybrid nanovesicle coated GA-targeted AIE photosensitizer to induce pyroptosis for combination with <em>α</em>PD-L1 to enhance antitumor photoimmunotherapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1696-1716"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yejiao Shi , Zelin Zheng , Yuting Li , Yirong Wang , Helena S. Azevedo , Xi Liu , Cuiping Zhang , Honggang Hu
{"title":"Bacterial extracellular vesicles as bioactive nanocarriers for wound treatment","authors":"Yejiao Shi , Zelin Zheng , Yuting Li , Yirong Wang , Helena S. Azevedo , Xi Liu , Cuiping Zhang , Honggang Hu","doi":"10.1016/j.apsb.2026.01.007","DOIUrl":"10.1016/j.apsb.2026.01.007","url":null,"abstract":"<div><div>Bacterial extracellular vesicles (BEVs) secreted by bacteria are considered as messengers for the crosstalk between gut microbiota and wounded skin <em>via</em> the “gut–skin axis”. The BEVs with the lipid bilayer nanostructures can deliver various bioactive molecules from their parent bacteria to the host cells, modulating the signal pathways related to wound repair and regeneration. Besides, the cutting-edge gene editing strategies and mature bacterial culture methods further endowed their more customizable and scalable manufacture compared to the most commonly used extracellular vesicles from mammalian cells. Therefore, more and more BEVs have been exploited directly as bioactive nanocarriers or engineered as delivery vehicles for wound treatment. Herein, the present review began with an overview of the gut–skin axis to better comprehend the bioactivates of BEVs towards wound healing. Their biogenesis, isolation, and uptake were then introduced. A summary of recent advancements in exploring BEVs for accelerated wound healing was followed, with a focus on their roles as nanocarriers for delivery. Diverse engineering approaches to functionalize BEVs were especially discussed for optimal wound management. Constructive insights regarding the new upsurge of BEVs for wound treatment were provided in the end to boost these innovative therapeutic modalities from bench to bedside.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1368-1387"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Jiang , Daixin Li , Guilin Wang , Nicole Hayes , Yazhou Shi , Huahai Qiu , Bengong Zhang , Tianshou Zhou , Guo-Wei Wei
{"title":"A review of recent advances in generative artificial intelligence models for biomolecular sciences","authors":"Jian Jiang , Daixin Li , Guilin Wang , Nicole Hayes , Yazhou Shi , Huahai Qiu , Bengong Zhang , Tianshou Zhou , Guo-Wei Wei","doi":"10.1016/j.apsb.2025.12.012","DOIUrl":"10.1016/j.apsb.2025.12.012","url":null,"abstract":"<div><div>Generative artificial intelligence (AI) models, a class of AI techniques that learn data distributions to synthesize novel samples, have emerged as impactful tools across scientific disciplines. In recent years, these models have found extensive applications in fields such as natural language processing and biomedical sciences. Despite their growing influence, comprehensive reviews on the application of generative models in biomolecular sciences remain limited. In this review, we provide a systematic overview of recent advances in generative models applied to biomolecular sciences. We discuss several prominent generative architectures, including variational autoencoders, generative adversarial networks, and diffusion models, highlighting their applications in molecular design and bioinformatics. Additionally, we examine how these models contribute to critical challenges such as molecular property prediction and molecular generation. Finally, we discuss key challenges that remain in this field, including model interpretability, scalability, and the need for high-quality molecular datasets. We highlight emerging research directions that aim to overcome these limitations and propose strategies for improving the reliability and applicability of generative models in biomolecular problems. Through this review, our objective is to provide researchers with a comprehensive understanding of the current landscape of generative modeling in biomolecular sciences and to inspire further advancements in this interdisciplinary area.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1201-1218"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}