Life sciences最新文献

{"title":"Neuronal PAC1 deletion impairs structural plasticity","authors":"Margo I. Jansen ,&nbsp;Haley Hrncir ,&nbsp;Allan MacKenzie-Graham ,&nbsp;James A. Waschek ,&nbsp;Judith Brinkman ,&nbsp;Laura A. Bradfield ,&nbsp;Minduli Withana ,&nbsp;Giuseppe Musumeci ,&nbsp;Velia D'Agata ,&nbsp;Alessandro Castorina","doi":"10.1016/j.lfs.2025.123843","DOIUrl":"10.1016/j.lfs.2025.123843","url":null,"abstract":"<div><h3>Aims</h3><div><u>P</u>ituitary <u>A</u>denylate <u>C</u>yclase-<u>A</u>ctivating <u>P</u>olypeptide (PACAP) is an endogenous neuropeptide of the central nervous system (CNS), whose biological activities are mediated via three G protein-coupled receptors PAC1, VPAC1, and VPAC2. While its neuroprotective functions are well-characterised, the role of PAC1 receptor-specific signalling in neuronal plasticity remains insufficiently understood. This study aimed to define the contribution of PAC1 signalling in excitatory pyramidal neurons across brain regions critical for cognitive and motor functions.</div></div><div><h3>Materials and methods</h3><div>We employed a tamoxifen-inducible, conditional knockout mouse model to delete the PAC1 receptor gene (<em>Adcyap1r1</em>) specifically in Camk2a-expressing excitatory neurons. The model was crossed with <em>Thy1-YFP</em> and <em>Thy1-mitoCFP</em> reporter lines to enable high-resolution imaging of neuronal structures and mitochondria in the cortex and hippocampus. Behavioural assessments, molecular analyses, and confocal imaging were conducted to evaluate structural, functional, and biochemical consequences of PAC1 deletion.</div></div><div><h3>Key findings</h3><div>Loss of PAC1 in Camk2a⁺ neurons resulted in spatial memory deficits and locomotor impairments. These were associated with elevated expression of neuronal nitric oxide synthase (nNOS) and GAD65/67, reduced CREB phosphorylation at Ser133, diminished dendritic spine density, and decreased mitochondrial content. The most pronounced effects were observed in the CA1 region of the hippocampus.</div></div><div><h3>Significance</h3><div>Our findings establish PAC1 as a key modulator of synaptic integrity, neuronal plasticity, and energy homeostasis in excitatory neurons. These insights underscore PAC1's potential as a therapeutic target in neurological disorders characterised by cognitive decline and synaptic dysfunction.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123843"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From AKI to CKD: Role of miRNAs in disease progression","authors":"Marcela Sorelli Carneiro-Ramos ,&nbsp;Raquel Silva Neres-Santos ,&nbsp;Jéssica Verônica da Silva ,&nbsp;Beatriz Favero Bedin ,&nbsp;Aline Cristina Parletta ,&nbsp;Lara Mei Honda ,&nbsp;Carolina Victoria Cruz Junho","doi":"10.1016/j.lfs.2025.123836","DOIUrl":"10.1016/j.lfs.2025.123836","url":null,"abstract":"<div><div>Acute kidney injury (AKI) and chronic kidney disease (CKD) are closely linked, with AKI often accelerating CKD development through sustained inflammation, fibrosis, and tubular damage. Identifying biomarkers that track this transition is essential for early diagnosis and intervention. Recent research highlights microRNAs (miRNAs) as key regulators of AKI-to-CKD progression, with distinct expression patterns across experimental models and clinical samples. Given this context, this review consolidates recent advances in miRNA research related to the AKI-to-CKD transition. Animal studies demonstrate that miRNAs such as miR-101, miR-196a-5p, miR-874-3p, and miR-486-5p contribute to fibrosis, inflammatory signaling, and tubular cell injury-hallmarks of CKD progression. In vitro models further reveal that miRNAs drive pathological processes like epithelial-mesenchymal transition (EMT) and apoptosis, underscoring their role in kidney dysfunction at the cellular level. Clinically, miR-21 has emerged as a particularly promising biomarker, with elevated levels in urine and blood correlating with AKI severity and CKD advancement, suggesting its potential for early detection and disease monitoring. Despite growing evidence of miRNA involvement in AKI-to-CKD progression, research remains limited, particularly in translating findings into predictive diagnostic tools. Future studies should focus on validating miRNA signatures in large patient cohorts and uncovering their precise molecular mechanisms to refine therapeutic strategies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123836"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon monoxide poisoning triggers intestinal injury, inflammation, and microbiota dysbiosis that drive metabolic perturbations","authors":"Tzu-Hao Chen ,&nbsp;Chien-Chin Hsu ,&nbsp;Hung-Jung Lin ,&nbsp;Chung-Han Ho ,&nbsp;Ching-Ping Chang ,&nbsp;Chien-Cheng Huang ,&nbsp;Ying-Jan Wang","doi":"10.1016/j.lfs.2025.123839","DOIUrl":"10.1016/j.lfs.2025.123839","url":null,"abstract":"<div><h3>Aims</h3><div>To determine whether carbon monoxide poisoning (COP) increases the long-term risk of intestinal diseases and to elucidate the underlying mechanisms through translational investigation using both population data and animal experiments.</div></div><div><h3>Materials and methods</h3><div>An epidemiological study using the Taiwan National Health Insurance Research Database identified 11,025 COP patients and matched controls to assess long-term intestinal disease risk. A rat COP model was used to evaluate intestinal injury, permeability, and tight junction integrity. Systemic inflammation and immune cell populations were assessed. Gastrointestinal and stress/metabolic hormones and metabolic markers were measured. Gut microbiota was analyzed by 16S rRNA sequencing, with functional prediction using Tax4Fun and KEGG.</div></div><div><h3>Key findings</h3><div>COP increased long-term intestinal disease risk in humans. Rats showed duodenal and jejunal injury with elevated permeability and barrier disruption. Systemic inflammation (increased CX3CL1, CXCL7, IL1-α/β, CXCL5, CCL20, TIMP-1, CD54) and immune activation (increased CD86⁺ macrophages, neutrophils, CD4⁺ T cells) were observed. Hormones (decreased cholecystokinin and insulin; increased glucagon-like peptide-1, ghrelin, glucose-dependent insulinotropic polypeptide, cortisol) and metabolism were altered (increased glucose and lipids). Microbiota alterations, including increased <em>Mycoplasma</em>, <em>Streptococcus</em>, and <em>Desulfovibrio</em>, were associated not only with proinflammatory cytokine responses but also with metabolic dysregulation, including lipid imbalance and pathways linked to type II diabetes mellitus.</div></div><div><h3>Significance</h3><div>This study provides the first integrated clinical and experimental evidence linking COP to intestinal and metabolic dysfunction. A pathogenic axis involving gut barrier disruption, microbiota dysbiosis, and metabolic-immune imbalance may underlie COP-related chronic diseases. These findings suggest targets for early monitoring and intervention.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123839"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of 0839 – A tool compound for pre-clinical mode-of-action studies of amylin analogues such as cagrilintide","authors":"Sanaz Gabery ,&nbsp;Tine Glendorf ,&nbsp;Borja Ballarin-Gonzalez ,&nbsp;Kent Pedersen ,&nbsp;Thomas Kruse ,&nbsp;Kirsten Raun ,&nbsp;Rune Ehrenreich Kuhre","doi":"10.1016/j.lfs.2025.123845","DOIUrl":"10.1016/j.lfs.2025.123845","url":null,"abstract":"<div><div>Cagrilintide (also known as 0833) is an amylin and calcitonin receptor agonist in clinical development for weight management and type-2-diabetes in a fixed-dose combination with semaglutide. Here, we introduce 0174-0839 (0839) as a tool compound for mouse and rat in vivo and in vitro studies of amylin analogues such as cagrilintide. Structurally, 0839 shares 95 % sequence homology with 0833 and contains an identical acylation sidechain. Acute administration of 0839 and 0833 to normal weight rats' dose-dependently reduced food intake to a similar degree. Sub-chronically, 0839 and 0833 had comparable small and transient reducing effects on food intake and body weight in DIO mice, with similar additional add-on effects on top of semaglutide. In DIO rats, sub-chronic administration of 0833 and 0839 profoundly reduced food intake and body weight, and both potentiated semaglutide's effects on food intake and body weight to an equal extended. Both compounds mainly reduced body weight by fat mass reduction and equally improved metabolic parameters. Notably, 0839 is available through Novo Nordisk Compound Sharing, enabling advancement of mode-of-action studies in mice and rats whilst usage of cagrilintide and other amylin analogues in clinical development are restricted due to pharmacovigilance rules.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123845"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microgravity modulates keratinocyte, fibroblast, and endothelial cell communication during wound healing","authors":"Mengya Zhao ,&nbsp;Xiaofeng Ma ,&nbsp;Zhuo Zuo ,&nbsp;Yaxing Wang ,&nbsp;Yanwei Fang ,&nbsp;Yulong Sun","doi":"10.1016/j.lfs.2025.123842","DOIUrl":"10.1016/j.lfs.2025.123842","url":null,"abstract":"<div><div>In microgravity, skin tissue is particularly susceptible to damage from collisions, increasing the risk of injury for astronauts. This environment often delays wound healing, raising the potential for infections and adversely affecting astronaut health. The interplay between wound healing stages and cytokines in simulated microgravity remains poorly understood despite its importance. Microgravity exposure impacts key cell types in skin healing, including keratinocytes, fibroblasts, and endothelial cells. Noteworthy changes include enhanced keratinocyte migration, reduced fibroblast proliferation, and alterations in endothelial cell morphology and gene expression. These changes can hinder extracellular matrix remodeling and disrupt cell-to-cell adhesion during healing. Furthermore, advanced techniques like single-cell transcriptomics provide valuable insights into the mechanisms of skin wound healing in microgravity. This review highlights new perspectives on the dynamics of skin wound healing under these unique conditions.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123842"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation-induced gut microbiota dysbiosis and Treg cells dysfunction: Mechanistic insights and clinical implications - A review","authors":"Zhuo Wang ,&nbsp;Meichen Gu ,&nbsp;Shurui Zhang ,&nbsp;Fuxue Huang ,&nbsp;Ying Li ,&nbsp;Pengyu Chang","doi":"10.1016/j.lfs.2025.123844","DOIUrl":"10.1016/j.lfs.2025.123844","url":null,"abstract":"<div><div>Regulatory T cells (T_regs) play a crucial role in maintaining immune balance. These cells primarily reside in the gut and exhibit properties of gut homing and polarization. The intestinal microenvironment, influenced by cytokines such as IL-1β, TGF-β and IL-10, significantly affects T_reg function. Intestinal T_regs regulate the function and renewal of intestinal epithelial cells while suppressing excessive immune responses. However, T_regs are plastic cells; during inflammatory conditions, although they accumulate in the gut, they may lose their suppressive capacity (termed ‘T_reg wannabes’) and potentially transform into pro-inflammatory cells. Dysbiosis of the gut microbiota is a significant driver of this phenomenon. Ionizing radiation not only creates an inflammatory microenvironment characterized by a cytokine storm but also induces dysbiosis of the gut microbiota. Through these mechanisms, T_regs can facilitate recovery from inflammation in the irradiated intestine by modulating the gut microbiota. This review examines the development of T_regs in the intestine, their proliferation in response to radiation, the loss of their suppressive ability, and the progression of radiation-induced intestinal injury (RIII) following dysbiosis treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123844"},"PeriodicalIF":5.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Exploring the therapeutic promise of targeting HMGB1 in rheumatoid arthritis” [Life Sci. 258 (2020) 118164]","authors":"Ishnoor Kaur ,&nbsp;Tapan Behl ,&nbsp;Simona Bungau ,&nbsp;Arun Kumar ,&nbsp;Vineet Mehta ,&nbsp;Dhruv Setia ,&nbsp;Md Sahab Uddin ,&nbsp;Gokhan Zengin ,&nbsp;Lotfi Aleya ,&nbsp;Sandeep Arora","doi":"10.1016/j.lfs.2025.123838","DOIUrl":"10.1016/j.lfs.2025.123838","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123838"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifelong impact of BPA: Steroidogenic reprogramming in aged gerbil adrenal glands following developmental exposure","authors":"Luiz Henrique Alves Guerra ,&nbsp;Simone Jacovaci Colleta ,&nbsp;Vitor Grigio ,&nbsp;Salmo Azambuja de Oliveira ,&nbsp;Silvana Gisele Pegorin Campos ,&nbsp;Estela Sasso-Cerri ,&nbsp;Patrícia Simone Leite Vilamaior ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.lfs.2025.123825","DOIUrl":"10.1016/j.lfs.2025.123825","url":null,"abstract":"<div><div>Endocrine-disrupting chemicals, particularly bisphenol A (BPA), are ubiquitous environmental contaminants that can profoundly affect hormonal systems and human health. The effects are variable and are contingent upon the developmental stage at which exposure occurs. This study aimed to investigate the effects of intrauterine and lactational BPA exposure on the adrenal glands of aged Mongolian gerbils (<em>Meriones unguiculatus</em>). In a controlled experimental set-up, pregnant gerbils were assigned to control or BPA-exposed groups, with the BPA group receiving a high dose during critical periods of development to assess the subsequent effects on adrenal gland function in their offspring at senile age. Biometric and hormonal assessments (estradiol, cortisol and testosterone) were conducted. Immunohistochemical and immunofluorescence analysis assessed steroidogenic activity related to testosterone production (StAR, CYP17, 3βHSD, 17βHSD, testosterone, 5α-reductase and CYP19), expression of hormone receptors (AR, ERα, ERβ, GRP30) and evaluation of epigenetic markers (EZH2). The results revealed that gerbils exposed to BPA exhibited increased body weight, alongside significant alterations in serum hormone profiles, including decreased cortisol and elevated estradiol levels. Furthermore, there was an upregulation of steroidogenic enzymes, indicating BPA's disruptive effects on adrenal hormone production and regulation. Notably, intracellular testosterone levels were elevated despite the typical age-related declines observed in control groups. Additionally, increased expression of androgen receptors and GPR30 was noted, underscoring BPA's complex impact on steroidogenic pathways. These findings emphasize the potential for intrauterine BPA exposure to induce enduring endocrine disturbances.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123825"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placenta hIGF1 nanoparticle treatment in guinea pigs mitigates fetal sex dependent FGR-associated effects on kidney structure and blood pressure-related signaling pathways","authors":"Baylea N. Davenport ,&nbsp;Alyssa Williams ,&nbsp;Timothy R.H. Regnault ,&nbsp;Helen N. Jones ,&nbsp;Rebecca L. Wilson","doi":"10.1016/j.lfs.2025.123847","DOIUrl":"10.1016/j.lfs.2025.123847","url":null,"abstract":"<div><div>Fetal development in an adverse <em>in utero</em> environment significantly increases the risk of hypertension and cardiovascular disease. The kidneys play a pivotal role in the regulation of blood pressure and cardiovascular function, and perturbations in kidney structure and molecular profile are often demonstrated in offspring born fetal growth restricted (FGR). The aim of this study was to determine whether improving the <em>in utero</em> fetal growth environment with a placental nanoparticle gene therapy would ameliorate FGR-associated dysregulation of fetal kidney development which is correlated with altered function and ultimately elevated blood pressure in postnatal life. Using the guinea pig maternal nutrient restriction (MNR) model, we improved placenta efficiency and fetal weight following three placental administrations of a non-viral polymer-based human insulin-like growth factor 1 (<em>hIGF1</em>) nanoparticle gene therapy from mid-pregnancy (gestational day 35) until gestational day 52. Fetal kidney tissue was collected near-term at gestational day 60. Fetal sex-dependent differences in kidney structure, glomeruli size and gene expression of extracellular matrix (ECM) remodeling and blood pressure regulation-related factors were demonstrated in sham-treated FGR fetuses but not observed in FGR fetuses who received placental <em>hIGF1</em> nanoparticle treatment. We speculate that improving placental function creates a favorable environment for fetal kidney development, mitigating FGR-associated changes in kidney architecture and molecular profiles which might confer protection against increased susceptibility to aberrant kidney physiology in later-life. Overall, this work opens avenues for future research to assess the long-term impact of the placental hIGF1 nanoparticle gene therapy on cardiovascular function in offspring.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123847"},"PeriodicalIF":5.2,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MPNN-CWExplainer: An enhanced deep learning framework for HIV drug bioactivity prediction with class-weighted loss and explainability","authors":"Aga Basit Iqbal ,&nbsp;Assif Assad ,&nbsp;Basharat Bhat ,&nbsp;Muzafar A. Macha ,&nbsp;Syed Zubair Ahmad Shah","doi":"10.1016/j.lfs.2025.123835","DOIUrl":"10.1016/j.lfs.2025.123835","url":null,"abstract":"<div><h3>Aims</h3><div>Human Immunodeficiency Virus (HIV) remains a critical global health concern due to its impact on the immune system and its progression to Acquired Immunodeficiency Syndrome (AIDS) if untreated. While antiretroviral therapy has advanced significantly, challenges such as drug resistance, adverse effects, and viral mutation necessitate the development of novel therapeutic strategies. This study aims to improve HIV bioactivity prediction and provide interpretable insights into molecular determinants influencing bioactivity.</div></div><div><h3>Materials and methods</h3><div>We propose MPNN-CWExplainer, a novel graph-based deep learning framework for molecular property prediction. The model integrates a Message Passing Neural Network (MPNN) with a class-weighted loss function to effectively address class imbalance in HIV datasets. Furthermore, GNNExplainer is incorporated to provide post-hoc interpretability by identifying key atom- and bond-level substructures contributing to model predictions. Model robustness is ensured through Bayesian hyperparameter optimization and multiple independent runs.</div></div><div><h3>Key findings</h3><div>MPNN-CWExplainer achieved state-of-the-art predictive performance on the HIV dataset, with an AUC-ROC of 87.631 % and AUC-PRC of 86.02 %, surpassing existing baseline models. The class-weighted approach enhanced minority class representation, and GNNExplainer successfully highlighted chemically meaningful substructures correlating with bioactivity.</div></div><div><h3>Significance</h3><div>The proposed framework not only improves prediction accuracy for HIV bioactivity but also enhances transparency and interpretability, crucial for medicinal chemists in understanding model behaviour. MPNN-CWExplainer serves as a robust and interpretable tool for computational drug discovery, supporting informed decision-making in lead optimization and molecular design.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123835"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}