Biomolecules最新文献

{"title":"Proton Radiation-Induced Cognitive Impairment via Disruption of Hippocampal Neuronal Mitophagic Homeostasis.","authors":"Longzhen Zhang, Pu Chen, Nan Xu, Junli Chen, Yishu Yin, Wei Liu, Liang Li, Yingying Yu, Weihong Lu, Peng Zang","doi":"10.3390/biom16091342","DOIUrl":"10.3390/biom16091342","url":null,"abstract":"<p><p><b>Background:</b> Proton radiation is both a core component of the space radiation environment and a pivotal modality for precision clinical tumor radiotherapy. Proton exposure can impair cognitive, learning and memory functions, representing a common concern in the fields of deep space aerospace medicine and clinical radiotherapy. Nevertheless, the cellular and molecular regulatory mechanisms underlying proton-induced cognitive impairment remain incompletely elucidated. <b>Methods:</b> In vivo and in vitro injury models were established via 100 MeV proton radiation. Specifically, an in vivo model of proton radiation-induced cognitive injury was constructed using C57BL/6J mice (male), and an in vitro radiation injury model was established with HT22 hippocampal neuronal cells to systematically investigate the molecular mechanism of cognitive impairment caused by proton radiation. <b>Results:</b> Proton radiation induced a persistent decline in learning and memory capacity in mice, triggered systemic oxidative stress, caused metabolic disturbances of multiple neurotransmitters in the hippocampus, and induced structural mitochondrial damage and decreased mitochondrial membrane potential in hippocampal neurons, suggesting that mitochondria are the key subcellular target of its neurotoxicity. Proton radiation induced oxidative stress in hippocampal neurons. Hyperactivation of mTORC1 inhibited the kinase activity of ULK1 by phosphorylating its Ser757 residue and downregulated ULK1 protein levels, resulting in mitophagy dysfunction and mitophagic flux blockade. Persistent severe oxidative stress prevented damaged mitochondria from being cleared via mitophagy and activated the apoptotic cascade, ultimately leading to hippocampal neuronal death and cognitive impairment. <b>Conclusions:</b> This study reveals the molecular mechanism by which proton radiation induces mitophagy dysfunction and hippocampal neuronal apoptosis and subsequently triggers cognitive impairment, providing a new theoretical basis and potential intervention targets for the prevention and treatment of neurocognitive complications associated with space radiation exposure and clinical radiotherapy.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058240","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}

{"title":"The Flexible Peripheral Segments Modulate the Catalytic Activity of the FAD-Containing Monooxygenase EthA from <i>Mycobacterium tuberculosis</i>.","authors":"Dafeng Liu, Xieping Sun, Feng Yu, Hongying Song, Wenshuang Yao, Huashui Deng, Daoqi Song","doi":"10.3390/biom16091333","DOIUrl":"10.3390/biom16091333","url":null,"abstract":"<p><p>Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), remains a major global health concern, particularly due to the emergence of drug-resistant strains. FAD-containing monooxygenase EthA activates the antitubercular prodrug ethionamide (ETH) in <i>Mtb</i>. However, the structural and functional mechanisms of <i>Mtb</i> EthA are not fully understood. Here, we report an AlphaFold2-predicted structural model of <i>Mtb</i> EthA, validated using Ramachandran analysis (91.7% residues in favored regions) and a ProSA Z-score of -10.96. Based on the results of molecular docking, site-directed mutagenesis was conducted. We found that R207 is required for EthA activity. Alanine substitutions at T186, S208, and T210 resulted in 5.8- to 7.2-fold reductions in activity. Conversely, deletion of three peripheral segments (residues 137-176, 315-336, and 419-460) enhanced activity by 1.9-, 1.5-, and 1.2-fold, respectively. These results provide a structural framework for EthA function and suggest that flexible peripheral regions may constrain catalytic activity, offering insights into ETH activation and potential mechanisms of drug resistance.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058376","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}

{"title":"Early-Life Stress Programs a Vulnerable Renal Phenotype Under Metabolic Challenge in a Murine Model.","authors":"Jhonatan Duque-Colorado, Bélgica Vásquez","doi":"10.3390/biom16091332","DOIUrl":"10.3390/biom16091332","url":null,"abstract":"<p><p>Early-life stress and post-weaning exposure to a high-fat diet (HFD) have been independently associated with renal abnormalities; however, little is known about how these stressors interact to increase renal susceptibility to subsequent metabolic challenges. Therefore, this study evaluated the effects of early-life stress induced by maternal separation (MS) and post-weaning HFD on renal structure and function in male C57BL/6 mice. Animals were subjected to MS or remained unmanipulated (UM) and were subsequently fed a control diet (CD) or HFD until postnatal day 133, generating four experimental groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Renal structure was assessed by renal mass, histological analysis of the renal corpuscle, stereological quantification of glomerular numerical density (Nv) and individual glomerular volume (IGV), whereas renal function was evaluated by diuresis. MS and HFD independently increased renal mass, altered diuresis, reduced glomerular Nv, and promoted glomerular hypertrophy. Histological analysis revealed mesangial expansion, narrowing of the capsular space, focal capillary obliteration, and glomeruloparietal synechiae, which were pronounced in the MS-HFD group. Two-way ANOVA showed independent effects on Nv and a significant interaction for IGV. Reduced Nv correlated with increased IGV and diuresis. These findings indicate that early-life stress and post-weaning HFD promote complementary mechanisms of glomerular remodeling, increasing susceptibility to metabolically induced renal injury.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058070","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}

{"title":"Integrated Multi-Omic Analyses Reveal Gender-Specific Molecular Mechanisms Regulating Growth and Muscle Development in Zhongshan Partridge Ducks.","authors":"Tong Ouyang, Xiaohuan Chao, Yingshan Yin, Congliang Ji, Xuerong Ma, Youcheng He, Tianxi Cui, Haoqi Zhong, Zhou Wu, Qingbin Luo","doi":"10.3390/biom16091335","DOIUrl":"10.3390/biom16091335","url":null,"abstract":"<p><p>Zhongshan Partridge duck is a unique indigenous dual-purpose waterfowl native to China's Pearl River Delta. This once endangered breed has been restored through conserved breeding. Its slow growth and low breast muscle yield limit industrial application, and obvious sexual dimorphism in pectoral muscle growth and metabolism lacks systematic molecular explanation. Herein, we combined GWAS, pectoral RNA-seq and untargeted metabolome to dissect regulatory networks of growth and carcass traits using 365 standardized ducks. Ten growth and carcass phenotypes were collected, and the Gompertz model fitted growth trajectories with mean R² > 0.98. Critical trait-related genes, including <i>FTO</i>, <i>ACVR2B</i> and <i>IGFBP3</i>, were identified by GWAS. We detected 313 differentially expressed genes (DEGs) showed differentially expressed pattern between high- and low-breast-weight groups in males and 309 DEGs in females. Distinct sex-specific metabolic patterns were observed: males depended on pentose phosphate and glycine-serine-threonine pathways for muscle protein deposition, whereas females utilized fatty acid β-oxidation for energy and lipid control. Lipid gene <i>ECHS1</i> and growth factor <i>PRDM16</i> were identified as candidate regulators mediating sexually dimorphic breast muscle development. Joint enrichment of DEGs and differentially expressed metabolites (DEMs) pinpointed key pathways for myogenesis. This study elucidates multi-level sexual dimorphism in duck pectoral development, supplies molecular markers for indigenous duck conservation and breeding, and advances our understanding of poultry growth regulation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058119","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}

{"title":"Lipid Metabolic Reprogramming in Periodontitis-Associated Alveolar Bone Remodeling: Mechanisms, Signaling Pathways, and Therapeutic Implications.","authors":"Jinping Wang, Xiaorui Zhang, Yuxiao Zhang, Xiangyao Wang, Bowen Yang, Xiaojie Hu, Jing Mao, Zhixing Zhang, Haosen Li","doi":"10.3390/biom16091334","DOIUrl":"10.3390/biom16091334","url":null,"abstract":"<p><p>Periodontitis-associated alveolar bone loss reflects not only persistent inflammation but also profound metabolic remodeling within the periodontal microenvironment. This review synthesizes current evidence on how lipid metabolic reprogramming regulates periodontal bone remodeling and its therapeutic significance. Under physiological conditions, fatty acid uptake and β-oxidation, lipid droplet turnover, and lipid-derived signaling support osteoblast bioenergetics, stem-cell osteogenesis, and balanced bone remodeling. In contrast, dyslipidemia and chronic inflammatory stress promote the accumulation of free fatty acids, oxidized lipoproteins, cholesterol derivatives, and sphingolipid metabolites, thereby enhancing reactive oxygen species production, lipid peroxidation, inflammasome activation, and pro-inflammatory immune polarization. These changes suppress osteogenic differentiation, stimulate osteoclastogenesis, and impair periodontal regeneration. We further integrate major regulatory networks, including PPARγ-Wnt/β-catenin, AMPK-mTOR, NF-κB/NLRP3, and GSK3β-NRF2/ferroptosis signaling. Therapeutic strategies targeting these lipid-redox-immune circuits include specialized pro-resolving lipid mediators, n-3 polyunsaturated fatty acids, statins, metabolic modulators, and local biomaterial- or nanocarrier-based delivery systems. Accordingly, lipid metabolic reprogramming may provide a framework for developing metabolism-oriented adjunctive and regenerative strategies for periodontitis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058094","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}

{"title":"Beyond Exosomes: Biological Properties, Isolation Challenges, and Functional Redefinition of Non-Vesicular Extracellular Nanoparticles (NVEPs).","authors":"Hengxiang Liu, Zishuai Chen, Hai He, Jiaxue Yuan, Xiaoyong Chen, Heqiang Yang, Sijing Yang, Zifan Wang, Zhiqiang Li","doi":"10.3390/biom16091330","DOIUrl":"10.3390/biom16091330","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have dominated research on intercellular communication for decades. However, the discovery of exomeres in 2018 revealed that conventional exosome preparations contain large quantities of long-overlooked non-membranous nanoparticles. Additional non-vesicular extracellular nanoparticles (NVEPs), including supermeres and SECmeres, have since been reported. Most of these particles are smaller than 50 nm in diameter, yet they carry protein and RNA cargo that was previously thought to be delivered exclusively by exosomes. Consequently, certain functions once attributed to exosomes now require reassignment. This review summarizes the classification, cargo composition, and structural features of NVEPs. It then compares the respective limitations of differential ultracentrifugation, density gradient centrifugation, size-exclusion chromatography, and flow field-flow fractionation for NVEP isolation, together with strategies for their combined use. Furthermore, the functional mechanisms that distinguish NVEPs from vesicular EVs are discussed at three levels: the extracellular stability of non-vesicular extracellular RNA (nv-RNA), cellular uptake pathways, and downstream effects. Current evidence indicates that NVEPs are enriched for disease-associated cargo in cancer and neurodegenerative diseases and show potential for liquid biopsy and drug delivery. Nevertheless, ambiguous definitional boundaries, the absence of reference materials, and insufficient in vivo evidence jointly hinder quantification and clinical translation in this field. Because these limitations arise largely from the absence of unified technical criteria, establishing internationally recognized standards for isolation and characterization is a prerequisite for the maturation of NVEP research.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058257","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}

{"title":"The Hierarchical Organization of the Layered Fibrous Shell of <i>Chamelea gallina</i> Guides Fracture Pathways.","authors":"Devis Montroni, Emilio Catelli, Silvia Prati, Arianna Mancuso, Stefano Goffredo, Giuseppe Falini","doi":"10.3390/biom16091331","DOIUrl":"10.3390/biom16091331","url":null,"abstract":"<p><p>Molluscan shells combine mineralized layers with distinct microstructures that can influence crack propagation. Here, we provide a through-thickness, multiscale characterization of the all-aragonitic shell of the striped venus clam <i>Chamelea gallina</i> and relate its hierarchical textural organization to observed fracture-surface trajectories. Optical microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and spatially resolved Fourier-transform infrared spectroscopy and X-ray diffraction resolve an outer region comprising (i) convergent and divergent fibrous sublayers separated by a preferred fracture plane, (ii) a porous transition layer with inverse-tulip microstructures, and (iii) a structurally distinct homogeneous inner layer whose crossed-lamellar organization becomes visible after etching. The key advance is the resolution of this outer architecture from nanogranule alignment to curved fibrous layers and a porous transition region, together with the identification of recurring changes in fracture-surface direction at its interfaces. FTIR and XRD reveal through-thickness variations in vibrational-band ratios and crystallographic parameters. As the fracture analysis is based on post-fracture morphology, crack steering and damage localization are discussed as plausible structure-related mechanisms supported by the observed features. The architecture suggests transferable design principles, including graded orientation, interface-guided deflection, and localized porosity, for mechanically robust bioinspired composites and provides a structural framework for future studies of shell evolution and function.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058450","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}

{"title":"Controlling Epileptic Activity by Modulating Putrescine Metabolism.","authors":"Saif Qahtan, Zsolt Kovács, Enikő Rauch, Pál Szabó, László Héja","doi":"10.3390/biom16091329","DOIUrl":"10.3390/biom16091329","url":null,"abstract":"<p><p>Glial mechanisms regulate neuronal excitability through multiple mechanisms, including the control of extracellular inhibitory signaling. One such mechanism is the Glu/GABA exchange process, in which glutamate uptake is coupled to GABA release, with GABA being synthesized from the polyamine putrescine, placing putrescine at a central position in metabolic pathways that may influence epileptiform activity. Here, we examined how pharmacological manipulation of key enzymes of putrescine metabolism affects seizure-like activity in the low-[Mg²⁺] in vitro model of frontotemporal epilepsy, complemented by in vivo recordings in the non-convulsive absence epilepsy model Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Increasing putrescine availability by inhibiting spermidine synthase with trans-4-methylcyclohexylamine significantly reduced both the duration and appearance of seizure-like events. Strikingly, simultaneous inhibition of monoamine oxidase B (MAO-B) and diamine oxidase (DAO) with deprenyl and aminoguanidine almost completely abolished seizure-like events in vitro and markedly suppressed spike-wave discharges in WAG/Rij rats. This effect was largely reversed by blockade of GAT-2/3 transporters with SNAP-5114, suggesting the presence and significant anti-epileptic potential of a MAO-B- and DAO-independent putrescine-GABA synthesis pathway. Together, these findings indicate that the anticonvulsant effects of putrescine metabolism arise from the coordinated engagement of multiple parallel pathways rather than from a single dominant enzymatic route. Putrescine thus appears to function as a metabolic hub whose increased availability can be channeled into several anticonvulsant processes, suggesting that therapeutic strategies enhancing putrescine-dependent inhibitory pathways at the network level may offer promising avenues for the modulation of epileptiform activity.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058116","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}

{"title":"Mechanism of Synergistic Action of Isochlorogenic Acid C and Ciprofloxacin Against Drug-Resistant <i>Escherichia coli</i>.","authors":"Yubin Bai, Xu Chen, Rongbin Hu, Xun Gao, Xiaojuan Wei, Zixuan Shang, Jiyu Zhang, Zhen Zhu, Mingze Cao, Bing Li","doi":"10.3390/biom16091328","DOIUrl":"10.3390/biom16091328","url":null,"abstract":"<p><strong>Background: </strong>The rapid emergence of antibiotic resistance in <i>E. coli</i> has outpaced the development of new drugs, creating an urgent demand for novel therapeutic strategies.</p><p><strong>Methods: </strong>We screened ten antibiotics in combination with isochlorogenic acid C (ICAC) against multidrug-resistant (MDR) <i>E. coli</i>. Synergistic effects of antibiotics and ICAC were evaluated by measuring the leakage of alkaline phosphatase (AKP), potassium ions (K⁺), as well as changes in total protein, and ATP levels. The integrity of bacterial membrane and cell wall was visualized by SEM and CLSM. The underlying mechanisms were elucidated via proteomic analysis and molecular docking. Finally, the protective effect of ICAC in vivo was evaluated using an intraperitoneal infection model in SPF female BALB/c mice.</p><p><strong>Results: </strong>ICAC exerted a specific synergistic effect with ciprofloxacin, significantly enhancing its efficacy. The combination disrupted bacterial membrane and cell wall integrity, increased permeability, and inhibited ATP synthesis. Mechanistically, ICAC may target OmpF and inhibit fatty acid biosynthesis. This interference reduced β-oxidation and the influx of acetyl-CoA into the TCA cycle, thereby impairing bacterial energy metabolism and destabilizing the membrane. In vivo validation using a mouse peritonitis model confirmed that the combination treatment effectively alleviated systemic <i>E. coli</i> infection.</p><p><strong>Conclusion: </strong>ICAC may potentiate the antibacterial activity of ciprofloxacin through targeting of OmpF, which disrupts bacterial membrane integrity and energy metabolism, providing a promising candidate strategy for combating infections caused by the tested antibiotic-resistant <i>E. coli</i>.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058241","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}

{"title":"<i>Styela clava</i>-Derived Peptide Cla-H Is a Promising Green Biofungicide for Crop Protection.","authors":"Yuliang Xu, Lang Su, Yating Zhang, Changfu Li, Yansheng Zhang","doi":"10.3390/biom16091326","DOIUrl":"10.3390/biom16091326","url":null,"abstract":"<p><p><b>Background</b>: Crop fungal diseases cause huge yield losses globally, and the abuse of chemical fungicides has led to severe resistance and environmental risks. Antimicrobial peptides (AMPs) represent ideal green alternatives, but poor salt tolerance and high production costs limit their field application. <b>Results</b>: In this study, we developed a His-tag engineering strategy to enhance salt tolerance of antifungal peptides, and identified a novel peptide Cla-H derived from <i>Styela clava</i>. Cla-H was efficiently expressed via secretory fermentation in <i>Pichia pastoris</i>, and its crude fermentation supernatant could be directly applied to plants. Cla-H exhibited strong and rapid fungicidal activity against <i>Fusarium graminearum</i> and <i>Botrytis cinerea</i>, accompanied by irreversible inhibition of spore germination and observable membrane permeabilization phenotypes. While SYTOX green and PI staining indicated membrane-damaging events, adequate control experiments are still required to firmly establish membrane permeabilization as its primary mode of action. Meanwhile, it showed outstanding thermal and storage stability. Most importantly, His-tag modification significantly improved its salt tolerance, enabling stable activity under high-salt conditions that completely inactivated the parental peptide. In planta assays demonstrated that crude Cla-H fermentation supernatant effectively controlled wheat scab and tomato gray mold. <b>Conclusions</b>: This study provides a promising salt-tolerant antifungal peptide for crop protection and establishes a simple and low-cost technical route for developing next-generation green biofungicides.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058144","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}