生物学最新文献

{"title":"Enterovirus 2B protein: From viroporin to membrane stress sensor, mechanistic principles of multi-pathway regulation.","authors":"Zengjun Ji, Yikun Chen, Hongxing Shen","doi":"10.1080/21505594.2026.2739074","DOIUrl":"10.1080/21505594.2026.2739074","url":null,"abstract":"<p><p>Enterovirus 2B is a highly conserved, functionally versatile, nonstructural protein. The classic viroporin model, which restricts its role to ion channel formation, cannot account for its interactions with host factors such as Bcl-2-associated X protein, interleukin enhancer-binding factor 2, and karyopherin subunit alpha 1, nor its functional divergence among enteroviruses. We propose a novel, testable membrane stress sensor hypothesis: the transmembrane helices of 2B sense lipid composition and pH changes, and through conformational dynamics, spatiotemporally coordinate calcium signaling, cell death pathway selection, including apoptosis, pyroptosis, autophagy, and ferroptosis, and immune evasion. We elaborate on this framework across six dimensions: structure-function mapping, calcium signaling, cell death pathways, immune evasion, evolutionary footprint, and antiviral targeting, along with cross-virus comparisons. We highlight key evidence gaps and limitations, and propose several future research directions. This framework establishes a mechanistic foundation for understanding 2B function and guiding rational anti-enteroviral drug designs.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739074"},"PeriodicalIF":6.8,"publicationDate":"2027-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolic characteristics in PWHIV with metabolic dysfunction-associated steatotic liver disease (MASLD).","authors":"Huiting Liu, Tianzhen Xu, Yongzheng Guo, Xiaotang Zhou, Chunhui Yan, Biao Zhu, Yirui Xie","doi":"10.1080/21505594.2026.2739091","DOIUrl":"10.1080/21505594.2026.2739091","url":null,"abstract":"<p><p>The global prevalence of Metabolic dysfunction-associated steatotic liver disease (MASLD) among persons with HIV (PWHIV) is estimated at 34%. This study examined the influence of gut microbial and metabolic alterations in PWHIV with MASLD. We conducted 16S rRNA sequencing on 60 fecal samples (24 from HIV group and 36 from HIV-MASLD group) to assess microbial composition, and employed LC/MS-based metabolomics on both fecal and plasma samples to identify variations in metabolites. An exploratory analysis was performed to compare plasma cytokines and oxidative stress markers between the two groups. Sequencing in the HIV-MASLD group showed lower <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, and higher <i>Klebsiella</i>, <i>Escherichia</i>, and <i>Enterococcus</i>. Metabolomic analysis revealed a reduction in anti-inflammatory metabolites (Dodecanedioic acid, 5-Phenylvaleric acid, Kynurenic acid) and antioxidant metabolites, coupled with an increase in the pro-inflammatory metabolite Gamma-Glutamyl-L-Putrescine in the HIV-MASLD group. And plasma analysis indicated a decline in 20-carboxy arachidonic acid. Additionally, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> correlated positively with anti-inflammatory metabolites, while <i>Klebsiella</i>, <i>Enterobacter</i>, and <i>Citrobacter</i> correlated negatively. Furthermore, <i>Faecalibacterium</i> and <i>Anaerobutyricum</i> also showed a moderate negative correlation with MDA levels. A random forest model using plasma metabolites showed the optimal discriminative ability for HIV-MASLD (AUC = 0.819 ± 0.0059). Differences in gut microbiota and metabolites in PWHIV may affect MASLD progression by influencing inflammation and oxidative stress. Modulating gut microbiota, such as adding <i>Faecalibacterium</i> and <i>Anaerobutyricum</i>, could be a treatment strategy for HIV-MASLD. Plasma metabolites have potential as noninvasive markers.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"18 1","pages":"2739091"},"PeriodicalIF":6.8,"publicationDate":"2027-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentadecanoic acid as a potential endogenous mTOR modulator for age-related female infertility: Mechanistic insights, molecular docking evidence, and therapeutic perspectives.","authors":"Reni Kalfin, Sidharth Mehan, Rajaram Samant, Manoj Tongra, Harsh Patil, Rohit Kumar Singh","doi":"10.1016/j.jsbmb.2026.107100","DOIUrl":"10.1016/j.jsbmb.2026.107100","url":null,"abstract":"<p><p>Age-related female infertility is a major reproductive health challenge that accelerates sharply after the age of 34, primarily due to declining oocyte quality, increased chromosomal abnormalities, and impaired embryonic developmental competence. Emerging evidence identifies chronic hyperactivation of the mechanistic target of rapamycin (mTOR) signalling pathway as a central molecular driver of ovarian aging, promoting excessive ribosome biogenesis, impaired proteostasis, suppressed autophagy, mitochondrial dysfunction, and oxidative stress within oocytes and surrounding cumulus cells. Although rapamycin, the prototypical mTOR inhibitor, has demonstrated promising effects in improving ovarian function and in vitro fertilization outcomes, its teratogenic potential, immunosuppressive properties, metabolic side effects, and prolonged pre-conception washout requirements limit its clinical applicability in fertility management. This review synthesises current evidence on the role of mTOR in ovarian aging and is complemented by an original molecular docking analysis performed by the authors to evaluate the interaction between pentadecanoic acid and the mTOR kinase domain, an endogenous odd-chain saturated fatty acid, as a potential fertility-safe mTOR modulator. A comprehensive review of the literature was conducted using PubMed and related databases, encompassing pentadecanoic acid biochemistry, molecular mechanisms, mTOR signalling architecture, ovarian aging biology, rapamycin pharmacology, and molecular docking studies. Available evidence indicates that pentadecanoic acid activates AMP-activated protein kinase (AMPK), modulates PPAR-α/δ signalling, supports cellular antioxidant defence, and collectively attenuates anabolic mTOR activity while promoting autophagic recycling and metabolic homeostasis. Molecular docking analysis against the mTOR kinase domain (PDB ID: 4JSV) demonstrated that pentadecanoic acid binds within the active site with a binding energy of -4.4 kcal/mol through interactions with key hydrophobic residues, including Leu1936, Ile1939, Tyr2144, Val2227, and Gly2142, whereas rapamycin exhibited a stronger affinity (-10.1 kcal/mol). Unlike rapamycin, pentadecanoic acid is endogenously produced, compatible with pregnancy, and requires no washout period. Collectively, these findings position pentadecanoic acid as a promising endogenous mTOR modulator with potential therapeutic relevance for age-related female infertility, warranting further mechanistic investigations and well-designed human clinical trials.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107100"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human TBC1 domain-containing kinase is a class I multidomain pseudokinase.","authors":"Shiwangi Maurya, Lilly E Cheek, Anthony T Iavarone, Wen Zhu","doi":"10.1016/j.pep.2026.106989","DOIUrl":"10.1016/j.pep.2026.106989","url":null,"abstract":"<p><p>TBCK-related encephalopathy (TBCKE) is a neurodevelopmental disorder associated with biallelic mutations in TBCK. Despite the increasing number of reported cases worldwide, the biochemical and biophysical properties of TBCK remain unclear, hindering molecular understanding of its role in disease. Here, we report the successful expression and purification of full-length human TBCK using Spodoptera frugiperda cells. Biochemical and biophysical analyses reveal that the catalytically inactive pseudokinase domain of TBCK lacks nucleotide binding, consistent with the absence of the canonical VAIK, HRD, and DFG motifs required for catalysis. These findings support that TBCK is a class I pseudokinase and provide a foundation for future structural and functional studies to elucidate its biological role.</p>","PeriodicalId":20757,"journal":{"name":"Protein expression and purification","volume":" ","pages":"106989"},"PeriodicalIF":1.8,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the putative role of EGFR in prostate cancer: Interactions with androgen and estrogen receptors.","authors":"G M Gonçalves, D S Souza, C R M Costa, M E G Oliveira, C S Porto, C M Vicente","doi":"10.1016/j.jsbmb.2026.107101","DOIUrl":"10.1016/j.jsbmb.2026.107101","url":null,"abstract":"<p><p>The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a critical role in regulating cell proliferation, survival, and differentiation. Aberrant activation or overexpression of EGFR has been observed in several cancers, including prostate cancer (PCa), and is associated with aggressive tumor behavior and poor prognosis. The development and progression of PCa largely depend on the involvement of androgen receptor (AR) pathways, which are directly related to EGFR signaling. Research indicates that EGFR can affect AR activity, increasing transcriptional activity or promoting ligand-independent activation, which may lead to castration-resistant prostate cancer (CRPC). Furthermore, emerging evidence suggests that estrogen receptors (ERs) may also interact with EGFR signaling in prostate tissue. These may influence tumor growth, interactions with cellular plasticity, and therapy resistance, but their exact mechanisms require further investigation. Identifying and improving treatment strategies for advanced and treatment-resistant PCa requires understanding the interplay between the EGFR, AR, and ER pathways. However, clinical trials have shown limited success in targeting EGFR alone, possibly through compensatory mechanisms via steroid hormone receptors. Therefore, therapies that simultaneously target EGFR and AR/ER activity may be more effective. Continued research into the molecular interplay between these pathways will broaden our understanding of prostate cancer biology and support the development of more personalized and effective treatments. In this review will focus on EGFR/HER1 and its putative role in prostate cancer. Furthermore, we discuss the potential interaction between EGFR, androgen receptor (AR), and estrogen receptor (ER) signaling pathways.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107101"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-predominant estrogen metabolic remodeling in adenomyosis revealed by LC-MS/MS profiling.","authors":"Qing Wang, BoYang Liu, Lei Kuang, Lingke Wang, Yingying Chou, Bei Zhang, Guiping Wan, Tao Gui","doi":"10.1016/j.jsbmb.2026.107095","DOIUrl":"10.1016/j.jsbmb.2026.107095","url":null,"abstract":"<p><p>Adenomyosis (AM) is an estrogen-dependent gynecological disorder in which local steroid handling may contribute to clinical heterogeneity. To characterize estrogen metabolic features in AM, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify 13 estrogens and estrogen metabolites in endometrial tissue and serum. Tissue metabolite profiles showed marked increases in catechol estrogens, particularly 2-hydroxyestrone (2-OHE1) and 4-hydroxyestrone (4-OHE1), whereas serum changes were more limited, with 2-methoxyestrone (2-MeOE1) representing the main circulating difference. Pathway- and ratio-based analyses indicated enhanced hydroxylation in tissue without a proportionate increase in downstream methylation-related readouts. Correlation and regression analyses further showed that tissue 2-OHE1 and 4-OHE1 were independently associated with dysmenorrhea severity. In exploratory receiver operating characteristic analyses performed within the discovery cohort, tissue catechol estrogens showed stronger discriminatory ability than serum metabolites. These findings suggested that AM was associated with endometrial tissue-predominant remodeling of estrogen metabolism rather than with generalized elevation of parent estrogens. The present study identified candidate metabolic markers requiring further validation and provided a framework for future investigation of local steroid metabolism in AM.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"107095"},"PeriodicalIF":3.1,"publicationDate":"2027-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing nitazoxanide as a novel ferroptosis inducer for triple-negative breast cancer via dual disruption of iron homeostasis and the β-catenin/GPX4 axis.","authors":"Chenshan Zhang, Ting Yang, Yuxuan Meng, Yao Zou, Ying Lu, Wenjun Wang, Sakorn Pornprasert, Wuga Jiwa, Tao He, Yan Lin","doi":"10.1080/13510002.2026.2695689","DOIUrl":"https://doi.org/10.1080/13510002.2026.2695689","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis induction is a promising triple-negative breast cancer (TNBC) therapy, but current inducers are suboptimal. Nitazoxanide (NTZ), an FDA-approved antiparasitic with anticancer and redox activity, may be repurposed as a ferroptosis inducer, yet its effects and mechanisms in TNBC are unclear.</p><p><strong>Methods: </strong>Anti-TNBC effects of NTZ were assessed in MDA-MB-231 and Hs578T cells via viability, clonogenicity, migration/invasion, and zebrafish xenografts. Ferroptosis was evaluated by iron levels, lipid peroxidation, GSH/GSSG, MDA, ROS, and mitochondrial TEM. Mechanisms were studied by docking, western blot, qPCR, apoptosis assay, cycloheximide chase, and pharmacological rescue.</p><p><strong>Results: </strong>NTZ inhibited proliferation, migration, and invasion in vitro and tumor growth in vivo, and induced ferroptosis. Mechanistically, it disrupted iron homeostasis by upregulating TFR1 and downregulating FPN1, causing iron overload and lipid peroxidation, and promoted β-catenin degradation, which transcriptionally suppressed GPX4, weakening antioxidant defense. Both β-catenin stabilization and ferroptosis inhibition reversed these effects.</p><p><strong>Conclusion: </strong>NTZ is repurposed as a ferroptosis inducer for TNBC via dual disruption of iron homeostasis and β-catenin/GPX4 axis, providing a strong preclinical rationale for its therapeutic use.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2695689"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of starvation-driven diffusions and diverse interspecific competitions on species coexistence and fitness.","authors":"Youngseok Chang, Inkyung Ahn, Wonhyung Choi","doi":"10.1080/17513758.2026.2623563","DOIUrl":"10.1080/17513758.2026.2623563","url":null,"abstract":"<p><p>This study examines competition models based on the Lotka-Volterra form that incorporate starvation-driven diffusions (SDD). Such dispersal assumes that species disperse in response to resource abundance or scarcity in a heterogeneous habitat. The primary objective of this study is to examine how SDD, in combination with diverse interspecific interactions, affects species' fitness and coexistence states. To this end, the study introduces a refined classification for competing interactions based on a novel metric that quantifies the variability of resource heterogeneity across the environment. This approach contrasts with traditional models that assume uniform diffusion within homogeneous environments. This study investigates the local stability of two semitrivial steady states and establishes the existence and uniqueness of positive steady states by eigenvalue analysis and monotone dynamical systems theory. Through this analytical exploration, the study reveals that the interplay between species' dispersal strategies and the varying intensities of interspecific competition significantly impacts ecological outcomes.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2623563"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability and bifurcation analysis of a discrete plankton system with holling Type-II predation and toxin effects.","authors":"Abdou Al Zubaidi, Muhammad Rafaqat, Jihad Younis, Syed Tauseef Saeed","doi":"10.1080/17513758.2026.2619269","DOIUrl":"10.1080/17513758.2026.2619269","url":null,"abstract":"<p><p>This work examines the dynamics of a discrete-time plankton interaction model, in which phytoplankton generate toxins and are vulnerable to external contamination. The model includes a Holling Type-II predation response and uses a piecewise constant argument approach to break it up into smaller pieces. This keeps the ecological realism of the continuous system while making it possible to study complex discrete-time behaviors. Our focus is on the formation of Neimark-Sacker bifurcation, a phenomena associated with the initiation of quasi-periodic oscillations in population densities. We show how toxin buildup and outside contamination can make plankton populations unstable, which could cause blooms to happen in an irregular way, using stability analysis and numerical simulations. The results show how useful discrete-time models are for capturing rapid changes in ecosystems, such damaging algal blooms. They also give ideas for managing ecosystems and reducing blooms.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"20 1","pages":"2619269"},"PeriodicalIF":2.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/13510002.2026.2645268","DOIUrl":"10.1080/13510002.2026.2645268","url":null,"abstract":"","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2645268"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}