{"title":"Unidirectional self-pumping esterified Poria cocos polysaccharides Janus nanofibrous membrane for facilitating wound repair.","authors":"Qiang Ding, Xuyang Wu, Qing Zhou, Yihan Rui, Hang Li, Zongbao Zhou","doi":"10.1016/j.ijbiomac.2025.148211","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.148211","url":null,"abstract":"<p><p>Although unidirectional self-pumping materials are widely utilized in wound repair, their fabrication using pure natural polysaccharides remains uncommon. In this study, we modulated the hydrophilic/hydrophobic properties of Poria cocos polysaccharides (PCP) by controlling the length of the lipid chains. Unidirectional self-pumping Janus nanofibrous membranes with distinct thickness gradients were fabricated using hydrophilic acetylated PCP and hydrophobic butyrylated PCP. At an optimal hydrophilic-to-hydrophobic layer thickness ratio of 3:1, the resulting membrane (JPCPM3) demonstrated outstanding physicochemical properties, superior hemostatic performance, efficient unidirectional self-pumping capability, and excellent biocompatibility. Furthermore, ELISA analysis revealed that JPCPM3 enhanced the expression and release of the pro-inflammatory mediators TNF-α and IL-6 in macrophages. In vivo studies further validated the efficacy of JPCPM3 in accelerating hemostasis, as well as promoting epithelial regeneration and collagen deposition in rat wound models. These results suggest that the bioactive JPCPM3 holds promising potential for clinical wound management applications.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"148211"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuqiong Yang, Jinyi Yang, Xiaona Su, Ruyu Fang, Zhenlin Xu, Yudong Shen, Wenbao Qi, Zhili Xiao, Hong Wang
{"title":"Nanobody-based epitope mapping and establishment of a blocking ELISA for S protein of porcine epidemic diarrhea virus.","authors":"Xuqiong Yang, Jinyi Yang, Xiaona Su, Ruyu Fang, Zhenlin Xu, Yudong Shen, Wenbao Qi, Zhili Xiao, Hong Wang","doi":"10.1016/j.ijbiomac.2025.148110","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.148110","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets. Nanobody (Nb) has the advantages of easy expression, short experimental cycles, stability, and small structural domains. It can recognize antigen epitopes that are difficult for traditional antibodies to recognize and has been widely used in the development of diagnostic methods and research on antigen epitopes. In this study, we used a naive library to screen Nbs for recombinant PEDV S protein and generated ten specific Nbs. A blocking ELISA (bELISA) assay for the detection of PEDV antibodies based on Nb C4 was developed and assessed. The cut-off value for bELISA was 53.61 %. A total of 219 clinical serum samples were tested, and the relative coincidence rate with a commercial ELISA kit was 94 %. 110 clinical serum samples immunized with the PEDV vaccine were tested, and the bELISA and serum neutralization test (SNT) showed a higher coincidence rate (86 %) than the commercial ELISA kit and SNT (81 %), demonstrating the good clinical application effects of the method. Then, the new linear neutralizing epitope recognized based on Nb H2 was mapped to 63STWYCAGQHPTA74. Homology analysis with 26 prevalent strains of PEDV showed that this epitope was highly conserved. These results offer a deeper understanding of the structure of the PEDV S protein, which is of great value for vaccine design and lays the foundation for further improving the diagnostic technology system of PEDV and the prevention and control of the disease.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"148110"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Zhang , Xin-Yi Wang , Ting-Fei Sun , Yue-Jin Peng , Ben-Jie Gao , Ming-Guang Feng , Sheng-Hua Ying
{"title":"Urate oxidase mediates the catabolism of uric acid critical for cellular physiology and pathobiology in filamentous entomopathogenic fungus Beauveria bassiana","authors":"Hao Zhang , Xin-Yi Wang , Ting-Fei Sun , Yue-Jin Peng , Ben-Jie Gao , Ming-Guang Feng , Sheng-Hua Ying","doi":"10.1016/j.ijbiomac.2025.148148","DOIUrl":"10.1016/j.ijbiomac.2025.148148","url":null,"abstract":"<div><div>Urate oxidase (Uox) catalyzes the degradation of uric acid in purine metabolism and has been implicated in various fungal physiologies. In this study, Uox was functionally characterized in the insect pathogenic fungus <em>Beauveria bassiana</em> and the fungus-host interaction. Firstly, the catalytic properties of BbUox were biochemically characterized, and the optimal reaction temperature and pH of this enzyme were 25 °C and 9.0, respectively. In addition, BbUox was extremely sensitive to copper ions. In <em>B. bassiana</em>, disruption of <em>BbUOX</em> resulted in a significant increase in intracellular uric acid level. Phenotypic evaluation indicated that BbUox contributed to fungal thigmotropism, development, stress response, and virulence of <em>B. bassiana</em>. Comparative transcriptomic analyses indicated that BbUox mediated a plethora of metabolic pathways and physiological responses to oxidative stress. Significantly, BbUox was required for stable localization of a mechanosensor, BbMid2, on the cytomembrane which played similar roles to BbUox in fungal physiologies. These results highlight that the entomopathogenic fungus deploys the thigmotropic mechanism for infection initiation, and the uric acid metabolism is essential for global expression and cellular morphogenesis in filamentous fungi.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"330 ","pages":"Article 148148"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhou Li , Jia Zeng , Min Wang , Die Gao , Deng Li , Yingxi Zhu , Jiahao Lin , Zhiyu Chen , Famin Ke , Lixian Li , Dandan Wang
{"title":"Enhanced specificity in molecular imprinting: A dual-role chitosan-bentonite substrate coupled with hierarchical monomers for ultrasensitive diclofenac potassium and metabolite enrichment","authors":"Zhou Li , Jia Zeng , Min Wang , Die Gao , Deng Li , Yingxi Zhu , Jiahao Lin , Zhiyu Chen , Famin Ke , Lixian Li , Dandan Wang","doi":"10.1016/j.ijbiomac.2025.148144","DOIUrl":"10.1016/j.ijbiomac.2025.148144","url":null,"abstract":"<div><div>Diclofenac potassium (DCF-K) is a widely used nonsteroidal anti-inflammatory drug with enhanced therapeutic effects mediated by its bioactive metabolites, particularly 4′-hydroxydiclofenac (4′-OH-DCF) and 5-hydroxydiclofenac (5-OH-DCF). However, the accurate detection of DCF-K and its metabolites in complex biological matrices remains challenging due to trace concentrations and matrix interference. To address this challenge, a chitosan-bentonite molecularly imprinted polymer (CB-MIP) was developed using a dual-role strategy, where chitosan-bentonite (CB) serves as both substrate and functional monomer, combined with a hierarchical functional monomer system (acrylamide as an auxiliary monomer) to enhance binding affinity and selectivity for the specific capture of DCF-K and its metabolites. Comprehensive characterization confirmed the successful synthesis of CB-MIP, revealing improved stability, hydrophilicity, and a mesoporous structure. CB-MIP exhibited good adsorption capacity for DCF-K (17.2× higher than CB), with Langmuir isotherm and pseudo-second-order kinetics indicating monolayer chemisorption. Selectivity studies demonstrated good recognition capability for DCF-K, achieving a selectivity factor up to 77.3 against structural analogs and co-administered drugs. Furthermore, cluster analysis revealed the CB-MIP sensitivity to DCF-K concentration variations as low as 0.3 μg·mL<sup>−1</sup> in complex matrices. Mechanistic studies identified electrostatic and hydrogen bonding interactions as the primary binding forces, validated by electrostatic potential simulations, hydrogen-bond modeling, and spectroscopic analyses. Practical application in mouse plasma and liver samples confirmed efficient enrichment and detection of DCF-K and metabolites (4′-OH-DCF, 5-OH-DCF, diclofenac acyl glucuronide) using CB-MIP coupled with HPLC/UPLC-MS/MS, achieving high sensitivity (limit of detection: 0.231 μg·mL<sup>−1</sup> in liver) and reproducibility (relative standard deviation: 1.22 %–5.81 %). This work establishes CB-MIP as a robust pretreatment material for targeted drug/metabolite analysis in complex biological systems.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"330 ","pages":"Article 148144"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dual-state responsive gelatin colloid coating: Dynamically switching lubrication-adhesion for Ti-6Al-4V alloy.","authors":"Xinyu Du, Yalong Zhang, Chenchen Wang, Jiao Wang, Sheng Zhang, Gangqiang Zhang","doi":"10.1016/j.ijbiomac.2025.148208","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.148208","url":null,"abstract":"<p><p>As a key metallic biomaterial in orthopedic implants, the clinical efficacy of titanium alloys is constrained by the colloid-based lubrication-adhesion imbalance at the bone-integration interface. In this study, leveraging the principles of colloid interface engineering, we innovatively developed an acrylic acid N-hydroxysuccinimide ester (AA-NHS) cross-linked gelatin/acrylic acid-surface functionalized nano-hydroxyapatite (nHAP) composite colloidal system. Through controlled self-assembly technology, an intelligent dual-state responsive interface coating was successfully fabricated. Coating characterization revealed that the 15 % gelatin component within the colloid network formed an ordered boundary lubrication layer under dehydrated conditions, reducing the friction coefficient by 77 %. In contrast, under hydrated conditions, the colloid-induced interfacial reconstruction triggered viscoelastic phase transitions, enhancing adhesion by 33 %, leading to a wear rate reduction of over 60 %. This colloid interface engineering strategy, through synergistic regulation of dry and wet state properties, established a dynamically adaptive smart lubrication-adhesion conversion mechanism tailored for physiological microenvironments, offering a theoretical framework for the development of next-generation biomedical interface materials.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"148208"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artemisia ciniformis-enhanced multifunctional hydrogel with ionic conductivity and anti-freezing properties for wearable strain sensors.","authors":"Maedeh Mohammadi Firouz, Mahsa Baghban Salehi, Mona Baniasadi, Babak Mokhtarani","doi":"10.1016/j.ijbiomac.2025.147892","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.147892","url":null,"abstract":"<p><p>This study investigates the formulation of a multifunctional hydrogel for wearable sensor applications using polyvinyl alcohol (PVA), Chitosan (CS), sophorolipid (SL), and Artemisia ciniformis extract (ATC). It was characterized via FTIR, ICP, TGA, DSC, SEM, ESEM, swelling, adhesion, tensile, rheology, conductivity tests, and MTT assays. FTIR spectroscopy confirmed the presence of specific chemical functional groups and the physical structure of the hydrogel, while ICP analysis verified the presence of ions within the ATC extract. SEM results indicated that SL altered the hydrogel structure from a layered to a porous morphology, with the pore size in the swollen sample of PCAS (PVA-CS-ATC-SL) being 5.1 times larger than in the dry state. TGA and DSC studies demonstrated the hydrogel's thermal stability and antifreeze properties, remaining effective at temperatures as low as -43.3 °C. Rheological tests revealed that adding SL enhanced thixotropy and extended the linear viscoelastic range (up to 62.1 % strain), with a mechanical strength of 484.0 Pa. ATC contributed an ionic conductivity of 4.0 × 10<sup>-2</sup> S/m, enabling effective motion sensing. Adhesion tests (ASTM-F2255) on hen skin showed strong bonding (17.2 kPa). The biocompatible hydrogel showed >90 % cell viability (MTT) and enhanced adhesion, mechanical/electrical properties, and antifreeze performance, ideal for wearable biosensors.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"147892"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Highly water- and oil-resistant cellulose paper fabricated through partial dissolution and regeneration based on different coagulation bath.","authors":"Ruotong Yao, Lijiaqi Zhang, Chao Wang, Min Wu","doi":"10.1016/j.ijbiomac.2025.148160","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.148160","url":null,"abstract":"<p><p>Developing renewable and biodegradable paper packaging materials as alternatives to traditional plastic packaging materials has been a hot topic in contemporary society. However, the primary disadvantage of paper in comparison to plastic is its poor barrier properties and low wet strength, causing a propensity for tearing when exposed to moisture. In this research, a facile and cost-effective deep eutectic solvent (DES, ZnCl<sub>2</sub>/H<sub>2</sub>O/HCOOH) system was employed to partially dissolve the ready-made paper at ambient temperature, followed by a regeneration process in seven different coagulation baths to produce partially regenerated cellulose paper. The barrier properties of the regenerated paper were tailored by the deliberate modulation of coagulation-bath polarity. The type of coagulation medium was found to significantly influence the morphology and crystallinity of the regenerated cellulose, thereby affecting the internal structure and properties of the partially regenerated paper. Remarkably, the paper regenerated in ethylene glycol showed a light transmittance of 60 %, high dry and wet strength of 56 MPa and 22 MPa, respectively, a low water vapor transmission rate of 62 g·m<sup>-2</sup>d<sup>-1</sup>, and superior oil repellency with a kit value of 12/12. The excellent water- and oil-resistant performance makes it an ideal material for food packaging. In a word, this work presents a simple approach and novel idea for fabricating water- and oil-proof and environmentally-friendly paper packaging.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"148160"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang Wang, Yanjie Yang, Lulu Wang, Haohao Wang, Wendi Wang, Shuhong Yang, Mingjun Yang, Chun Zhang, Yonggang Wang
{"title":"Purified C. pilosula polysaccharides attenuate streptozotocin-induced oxidative stress and restore gut microbiota in T2DM mice.","authors":"Fang Wang, Yanjie Yang, Lulu Wang, Haohao Wang, Wendi Wang, Shuhong Yang, Mingjun Yang, Chun Zhang, Yonggang Wang","doi":"10.1016/j.ijbiomac.2025.148217","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.148217","url":null,"abstract":"<p><p>As the primary bioactive component of the traditional Chinese medicinal herb Codonopsis pilosula (C. pilosula), C. pilosula polysaccharides (CPPs) have garnered considerable attention due to their diverse biological activities. This study investigated the physicochemical properties and structural characteristics of CPPs, as well as their effects on hypoglycemia, oxidative stress, and gut microbiota in diabetic mice induced by high-sugar/high-fat (HS/HF) feeding combined with streptozotocin (STZ) administration. The ameliorative effects of CPPs on type 2 diabetes mellitus (T2DM) were evaluated by measuring mouse blood glucose and other relevant indicators. Gavage administration of medium- and low-dose CPPs exerted beneficial effects in T2DM mice, as evidenced by reduced body weight, decreased blood glucose and lipid levels, restored blood biochemical parameters, lowered organ indices, and ameliorated oxidative stress in the liver, kidneys, and pancreas. Hematoxylin-eosin (HE) and Masson's trichrome staining revealed improved pathological changes in the liver and kidneys, characterized by neatly arranged organ cells with enlarged, oval nuclei. 16S rRNA gene sequencing demonstrated that CPP gavage modulated the abundance and diversity of gut microbiota in mice. Collectively, these findings indicate that CPPs-an active component of the medicinal plant C. pilosula-not only regulate gut microbiota but also hold potential as a supplementary agent for T2DM management.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"148217"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zheng Li , Jie Li , Jing Guo , Fucheng Guan , Xin Zhang , Qiang Yang , Da Bao , Xinbin Ji , Yihang Zhang , Minghan Li , Jiahao He , Yi Xu
{"title":"Fabrication of multi-network aerogels based on sesbania gum/nanocellulose and its application in oil recovery (from oily wastewater)","authors":"Zheng Li , Jie Li , Jing Guo , Fucheng Guan , Xin Zhang , Qiang Yang , Da Bao , Xinbin Ji , Yihang Zhang , Minghan Li , Jiahao He , Yi Xu","doi":"10.1016/j.ijbiomac.2025.148226","DOIUrl":"10.1016/j.ijbiomac.2025.148226","url":null,"abstract":"<div><div>Bio-based aerogels possess high porosity, low density, biodegradability, and environmental friendliness, offering significant potential in the field of oil-water separation. In this study, we developed a hydrophobic porous aerogel with a triple cross-linked network consisting of polysaccharide sesbania gum (SG) and nanocellulose (CNF). The aerogel was cross-linked with polyamide epoxy chloropropane resin (PAE) and methyltrimethoxysilane (MTMS), followed by MTMS hydrolysis for silane hydrophobic modification. The hydrophobic SG/CNF aerogel (SCA) was prepared through freeze-drying and annealing processes. SCA exhibits excellent properties, including low density (11.83–26.18 mg/cm<sup>3</sup>), high porosity (98.95–97.8 %), high adsorption capacity (39.4–72.9 g/g), and rapid adsorption. Additionally, the oil adsorbed by SCA can be easily desorbed using centrifugal method. Even after 10 adsorption-desorption cycles, the adsorption capacity remains at 81.8 % of the initial value. Therefore, SCA provides a simple, low-cost, efficient, and recyclable solution for the removal of organic pollutants, offering a sustainable approach for industrial wastewater treatment.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"330 ","pages":"Article 148226"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaopei Peng , Zhenhu He , Dandan Yuan , Jiong Li , Yaning Zhu , Xuan Zhang , Huaping Liu , Mengtian Ma , Juan Wang , Zhenguo Liu , Xiaolong Qi , Pengfei Rong
{"title":"The role of solute carrier family 16 member 3 protein in hepatocellular carcinoma and sorafenib resistance","authors":"Xiaopei Peng , Zhenhu He , Dandan Yuan , Jiong Li , Yaning Zhu , Xuan Zhang , Huaping Liu , Mengtian Ma , Juan Wang , Zhenguo Liu , Xiaolong Qi , Pengfei Rong","doi":"10.1016/j.ijbiomac.2025.148223","DOIUrl":"10.1016/j.ijbiomac.2025.148223","url":null,"abstract":"<div><div>Solute carrier family 16 member 3 (SLC16A3), a key protein mediating lactic acid efflux, promotes immune evasion and angiogenesis in tumour, correlating with poor prognosis and potentially impairing anti-angiogenic therapies like sorafenib. To elucidate SLC16A3's role and mechanism in hepatocellular carcinoma (HCC), particularly concerning sorafenib, we analysed public datasets and employed molecular biology techniques, animal experiments, and transcriptome sequencing. Our findings revealed that elevated SLC16A3 protein expression correlates with poor prognosis, reduced sorafenib response, and an altered tumour immune microenvironment (TIME), characterized by suppressed macrophage polarization. Mechanistically, sorafenib itself upregulates SLC16A3 protein expression by enhancing glycolysis, increasing lactate secretion which fosters an immunosuppressive TIME. Conversely, SLC16A3 inhibition promoted M1 macrophage polarization and CD8<sup>+</sup> T cell infiltration, thereby enhancing sorafenib efficacy. Transcriptomic analysis demonstrated that SLC16A3 overexpression selectively downregulates cytokine signalling (reducing CCL5, CCL9, CXCL10) while upregulating CCL8, revealing how this protein contributes to immunosuppression. These findings broaden our understanding of SLC16A3 protein's role in HCC prognosis and sorafenib resistance, indicating that combining SLC16A3 inhibition with sorafenib represents a promising therapeutic strategy.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"330 ","pages":"Article 148223"},"PeriodicalIF":8.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}