Although Semaphorin 5B (SEMA5B) has been reported to be involved in tumor progression, the underlying mechanisms in esophageal squamous cell carcinoma (ESCC) are still largely unknown. In this study, we found that SEMA5B gene was significantly upregulated in both ESCC samples and cell lines. Knockdown of SEMA5B suppressed cell proliferation, migration, and invasion in ESCC cells, whereas its overexpression produced the opposite effects. Notably, SEMA5B depletion markedly reduced glucose consumption and lactate production, and downregulated the expressions of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), phosphofructokinase, muscle-type (PFKM), and lactate dehydrogenase A (LDHA). Conversely, SEMA5B overexpression enhanced glycolytic activity. Mechanistically, SEMA5B interacted with voltage-dependent anion channel 2 (VDAC2) in ESCC cells and stabilized VDAC2 protein by suppressing the expression of the E3 ubiquitin ligase neural precursor cell expressed, developmentally down-regulated protein 4 (NEDD4). VDAC2 was overexpressed in ESCC samples compared to normal controls, and its knockdown dramatically inhibited the expressions of glycolytic proteins. Importantly, the pro-glycolytic effect of SEMA5B was attenuated by VDAC2 silencing, while VDAC2 overexpression partially rescued the glycolytic suppression caused by SEMA5B knockdown.. In conclusion, our current data suggest that SEMA5B promotes glycolysis by upregulating VDAC2 in ESCC cells, and thus targeting SEMA5B-VDAC2 signal axis may be a novel therapeutic strategy for ESCC patients.
{"title":"SEMA5B depletion suppresses cell proliferation and glycolysis by downregulating VDAC2 expression in esophageal squamous cell carcinoma.","authors":"Caifeng Zhang, Lanfang Zhang, Xiaoling Zhang, Lijun Meng, Yuyu Wang, Chaoqun Zhang, Ke Li, Tianli Fan, Hongtao Liu, Tingmin Chang","doi":"10.1016/j.ijbiomac.2025.149690","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.149690","url":null,"abstract":"<p><p>Although Semaphorin 5B (SEMA5B) has been reported to be involved in tumor progression, the underlying mechanisms in esophageal squamous cell carcinoma (ESCC) are still largely unknown. In this study, we found that SEMA5B gene was significantly upregulated in both ESCC samples and cell lines. Knockdown of SEMA5B suppressed cell proliferation, migration, and invasion in ESCC cells, whereas its overexpression produced the opposite effects. Notably, SEMA5B depletion markedly reduced glucose consumption and lactate production, and downregulated the expressions of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), phosphofructokinase, muscle-type (PFKM), and lactate dehydrogenase A (LDHA). Conversely, SEMA5B overexpression enhanced glycolytic activity. Mechanistically, SEMA5B interacted with voltage-dependent anion channel 2 (VDAC2) in ESCC cells and stabilized VDAC2 protein by suppressing the expression of the E3 ubiquitin ligase neural precursor cell expressed, developmentally down-regulated protein 4 (NEDD4). VDAC2 was overexpressed in ESCC samples compared to normal controls, and its knockdown dramatically inhibited the expressions of glycolytic proteins. Importantly, the pro-glycolytic effect of SEMA5B was attenuated by VDAC2 silencing, while VDAC2 overexpression partially rescued the glycolytic suppression caused by SEMA5B knockdown.. In conclusion, our current data suggest that SEMA5B promotes glycolysis by upregulating VDAC2 in ESCC cells, and thus targeting SEMA5B-VDAC2 signal axis may be a novel therapeutic strategy for ESCC patients.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"149690"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773188","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}
Asthma is a common respiratory disease characterized by chronic inflammation and airway obstruction, with airway epithelial damage playing a pivotal role in pathogenesis. Existing treatments regulate inflammation without addressing epithelial barrier repair, indicating the need for therapeutic agents that target damaged epithelial cells. This study evaluates the effects of bacterial cellulose (BC), a biocompatible polymer with anti-inflammatory and pro-regenerative properties, as a promising therapeutic candidate for asthma. In a mouse model of house dust mite (HDM)-induced allergic asthma, intranasal BC administration markedly reduces both airway inflammation and mucus hypersecretion while also improving epithelial barrier integrity. Bronchoalveolar lavage fluid (BALF) metabolomics and single-cell RNA sequencing of human asthmatic epithelium samples reveal that BC downregulates epithelial CDP-diacyl glycerol synthase 1 (CDS1), resulting in decreased synthesis of phosphatidylinositol (PI) and PI 4,5- bisphosphate (PI(4,5)P₂) and suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling. CDS1 overexpression reverses the effect of BC on asthma in vivo, confirming that CDS1 is a key target. BC administration alleviates asthma by repairing the epithelial barrier and inhibiting PI3K/AKT signaling via CDS1-dependent PI reprogramming. Thus, treatment with BC represents a promising therapeutic strategy for asthma, with dual actions in repairing epithelial barrier dysfunction and mitigating inflammation.
{"title":"Bacterial cellulose repairs asthmatic epithelial injury by reprogramming CDS1-mediated phosphatidylinositol metabolism to inhibit PI3K/AKT signaling.","authors":"Qi Yu, Liping Huang, Zhuman Wu, Jinzhong Zhuo, Haohua Huang, Yixin Cheng, Mingxuan Hu, Qiong Wang, Dongyu Liu, Xiaoxiao Jiang, Jinming Zhang, Shaoxi Cai, Hangming Dong","doi":"10.1016/j.ijbiomac.2025.149695","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.149695","url":null,"abstract":"<p><p>Asthma is a common respiratory disease characterized by chronic inflammation and airway obstruction, with airway epithelial damage playing a pivotal role in pathogenesis. Existing treatments regulate inflammation without addressing epithelial barrier repair, indicating the need for therapeutic agents that target damaged epithelial cells. This study evaluates the effects of bacterial cellulose (BC), a biocompatible polymer with anti-inflammatory and pro-regenerative properties, as a promising therapeutic candidate for asthma. In a mouse model of house dust mite (HDM)-induced allergic asthma, intranasal BC administration markedly reduces both airway inflammation and mucus hypersecretion while also improving epithelial barrier integrity. Bronchoalveolar lavage fluid (BALF) metabolomics and single-cell RNA sequencing of human asthmatic epithelium samples reveal that BC downregulates epithelial CDP-diacyl glycerol synthase 1 (CDS1), resulting in decreased synthesis of phosphatidylinositol (PI) and PI 4,5- bisphosphate (PI(4,5)P₂) and suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling. CDS1 overexpression reverses the effect of BC on asthma in vivo, confirming that CDS1 is a key target. BC administration alleviates asthma by repairing the epithelial barrier and inhibiting PI3K/AKT signaling via CDS1-dependent PI reprogramming. Thus, treatment with BC represents a promising therapeutic strategy for asthma, with dual actions in repairing epithelial barrier dysfunction and mitigating inflammation.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"149695"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773242","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149612
Rui Xiao , Changgeng Li , Lu Wu , Lingzhi Huang , Wenchao Jia , Bing Wang , Xueru Sheng , Pedram Fatehi , Haiqiang Shi
To address the poor water resistance and mechanical degradation of conventional paper straws, this study develops an environmentally benign, fully biodegradable superhydrophobic coating using cellulose nanofibers (CNF), stearic acid (SA) and citric acid (CA). CNF was first dispersed in ethanol, followed by chemical grafting of hydrophobic alkyl chains onto its surface; a synergistic micro-nano hierarchical structure was then constructed by optimizing thermal soaking and drying processes. The hybrid material's morphology was comprehensively characterized via FTIR, SEM, and AFM. The resulting coating exhibited exceptional superhydrophobicity (water contact angle, WCA = 166°), effectively resisting liquid penetration and maintaining structural integrity under humid conditions. Mechanical tests showed 216 % higher tensile strength, 137 % improved compressive performance, enhanced abrasion resistance, and better water vapor barrier properties; notably, it retained 83.67 % of dry strength after water immersion and degraded rapidly in soil. The coating formulation was further engineered into a curcumin-loaded film, thereby adding a smart, visual pH-indication function for monitoring beverage freshness over 0–6 days. This multifunctional approach provides a viable bio-based alternative to petrochemical coatings, paving the way for next-generation eco-friendly disposable paper products.
{"title":"Bio-degradable superhydrophobic cellulose-based paper straws fabricated through coating of citric acid-crosslinking CNF & stearic acid","authors":"Rui Xiao , Changgeng Li , Lu Wu , Lingzhi Huang , Wenchao Jia , Bing Wang , Xueru Sheng , Pedram Fatehi , Haiqiang Shi","doi":"10.1016/j.ijbiomac.2025.149612","DOIUrl":"10.1016/j.ijbiomac.2025.149612","url":null,"abstract":"<div><div>To address the poor water resistance and mechanical degradation of conventional paper straws, this study develops an environmentally benign, fully biodegradable superhydrophobic coating using cellulose nanofibers (CNF), stearic acid (SA) and citric acid (CA). CNF was first dispersed in ethanol, followed by chemical grafting of hydrophobic alkyl chains onto its surface; a synergistic micro-nano hierarchical structure was then constructed by optimizing thermal soaking and drying processes. The hybrid material's morphology was comprehensively characterized via FTIR, SEM, and AFM. The resulting coating exhibited exceptional superhydrophobicity (water contact angle, WCA = 166°), effectively resisting liquid penetration and maintaining structural integrity under humid conditions. Mechanical tests showed 216 % higher tensile strength, 137 % improved compressive performance, enhanced abrasion resistance, and better water vapor barrier properties; notably, it retained 83.67 % of dry strength after water immersion and degraded rapidly in soil. The coating formulation was further engineered into a curcumin-loaded film, thereby adding a smart, visual pH-indication function for monitoring beverage freshness over 0–6 days. This multifunctional approach provides a viable bio-based alternative to petrochemical coatings, paving the way for next-generation eco-friendly disposable paper products.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149612"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773217","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149702
Yalei Liu, Yuying Zhao, Sui Wang, Jie Mao
The development of green packaging is of great significance in response to the increasing demand for environmental sustainability. In this study, a composite packaging film was prepared using carrageenan and polyvinyl alcohol as the base materials, with cinnamaldehyde incorporated as a natural active ingredient. The cinnamaldehyde was successfully integrated into the carrageenan/polyvinyl alcohol composite network, endowing the film with antibacterial properties. Results indicate that the composite film possesses satisfactory mechanical properties, excellent UV-blocking performance (UV transmittance ≤37.6 %), high transparency (>80 %), and outstanding oxygen barrier properties (exhibiting an oxygen transmission rate as low as 1.696 cm3/m2·24h·0.1 MPa), meeting the requirements for fundamental application scenarios. Furthermore, the water solubility of the film allows it to be decomposed and disposed of via simple water treatment after use. This characteristic offers a promising strategy for developing green alternatives to traditional petroleum-based packaging materials, highlighting its potential for reducing white pollution and promoting the sustainable development of the packaging industry.
{"title":"Carrageenan-based antimicrobial composite film for green packaging: Fabrication and property characterization.","authors":"Yalei Liu, Yuying Zhao, Sui Wang, Jie Mao","doi":"10.1016/j.ijbiomac.2025.149702","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2025.149702","url":null,"abstract":"<p><p>The development of green packaging is of great significance in response to the increasing demand for environmental sustainability. In this study, a composite packaging film was prepared using carrageenan and polyvinyl alcohol as the base materials, with cinnamaldehyde incorporated as a natural active ingredient. The cinnamaldehyde was successfully integrated into the carrageenan/polyvinyl alcohol composite network, endowing the film with antibacterial properties. Results indicate that the composite film possesses satisfactory mechanical properties, excellent UV-blocking performance (UV transmittance ≤37.6 %), high transparency (>80 %), and outstanding oxygen barrier properties (exhibiting an oxygen transmission rate as low as 1.696 cm<sup>3</sup>/m<sup>2</sup>·24h·0.1 MPa), meeting the requirements for fundamental application scenarios. Furthermore, the water solubility of the film allows it to be decomposed and disposed of via simple water treatment after use. This characteristic offers a promising strategy for developing green alternatives to traditional petroleum-based packaging materials, highlighting its potential for reducing white pollution and promoting the sustainable development of the packaging industry.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"149702"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773195","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149692
Danli Wang , Mengjiao Xing , Le Jia , Xiaohuan Jiang , Miao Ji , Ling Li , Gongshuai Song , Tinglan Yuan , Huan Cheng , Ziyuan Wang , Haina Yuan , Mengna Zhang , Jinyan Gong
In this study, ultrasound was used to prepare the delivery system for chlorogenic acid (CA) using debranched waxy maize starch (DWMS) as carriers. The surface morphology, crystal structure, short-range molecular order and in vitro release characteristics of DWMS-CA were studied. DWMS-CA particles showed a rough and aggregated surface structure. The crystallinity of the DWMS (28.39 %) and DWMS-CA (13.72 %) was decreased along with the presence of V-shaped crystals. FT-IR and 13C CP/MAS NMR showed that CA and DWMS form a complex through hydrogen bonds, and the DWMS-CA prepared by ultrasound had a better encapsulation effect on CA with rate of 52.84 %. The DWMS-CA system showed good stability. CA released from the complex in simulated intestinal fluid (>95 %) was significantly higher than that in simulated gastric fluid (<35 %). In conclusion, the DWMS-CA delivery system prepared by ultrasound effectively increased the CA loading, and improve the bioavailability of CA.
{"title":"Effect of ultrasound on complexation of debranched starch and chlorogenic acid: Preparation, characterization and in vitro release","authors":"Danli Wang , Mengjiao Xing , Le Jia , Xiaohuan Jiang , Miao Ji , Ling Li , Gongshuai Song , Tinglan Yuan , Huan Cheng , Ziyuan Wang , Haina Yuan , Mengna Zhang , Jinyan Gong","doi":"10.1016/j.ijbiomac.2025.149692","DOIUrl":"10.1016/j.ijbiomac.2025.149692","url":null,"abstract":"<div><div>In this study, ultrasound was used to prepare the delivery system for chlorogenic acid (CA) using debranched waxy maize starch (DWMS) as carriers. The surface morphology, crystal structure, short-range molecular order and in vitro release characteristics of DWMS-CA were studied. DWMS-CA particles showed a rough and aggregated surface structure. The crystallinity of the DWMS (28.39 %) and DWMS-CA (13.72 %) was decreased along with the presence of <em>V</em>-shaped crystals. FT-IR and <sup>13</sup>C CP/MAS NMR showed that CA and DWMS form a complex through hydrogen bonds, and the DWMS-CA prepared by ultrasound had a better encapsulation effect on CA with rate of 52.84 %. The DWMS-CA system showed good stability. CA released from the complex in simulated intestinal fluid (>95 %) was significantly higher than that in simulated gastric fluid (<35 %). In conclusion, the DWMS-CA delivery system prepared by ultrasound effectively increased the CA loading, and improve the bioavailability of CA.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149692"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760597","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149708
Yuan Tian , Ruixin Hu , Ruijie Zhang , Gengxuan Yan , Yunzhi Zhang , Juan Hu , Siqin Zhao , Jiansong Ju , Bo Yu , Limin Wang
Glutamate waste liquor (GWL) is acidic wastewater from monosodium glutamate process. Poly-γ-glutamic acid (γ-PGA) production using this abundant industrial waste is an economical and environmentally friendly method. The development of cost-effective production from GWL requires understanding the inhibitory mechanism in γ-PGA producers. In this study, γ-PGA fermentation profile of Bacillus subtilis KH2 using GWL was studied. An inhibitory effect in glutamate consumption was observed during γ-PGA production. To systematically analyze the response pattern of B. subtilis KH2 to GWL addition, comparative transcriptomics was performed. Transcriptomic analysis indicated that GWL led to decreased expression of genes associated with γ-PGA polymerization, while upregulating genes related to glycolysis, TCA cycle and glutamate precursor synthesis. Subsequent gene overexpression experiments elucidated the pivotal regulatory role of swrA in the GWL-mediated suppression of γ-PGA biosynthesis. Finally, by a combination of metabolic engineering targets, the highest γ-PGA titer of 32.24 g/L was achieved by B. subtilis KH2Δres1Δres2ΔgudBΔrocG using GWL in shake-flask fermentation, accompanied by an increased glutamate consumption rate of 59.37 %. This study provides insights into the GWL inhibitory mechanisms in B. subtilis KH2 and demonstrates the potential application of B. subtilis KH2 for cost-effective production from industrial waste.
{"title":"Engineering of Bacillus subtilis KH2 for effective production of poly-γ-glutamic acid from glutamate waste based on transcriptomics","authors":"Yuan Tian , Ruixin Hu , Ruijie Zhang , Gengxuan Yan , Yunzhi Zhang , Juan Hu , Siqin Zhao , Jiansong Ju , Bo Yu , Limin Wang","doi":"10.1016/j.ijbiomac.2025.149708","DOIUrl":"10.1016/j.ijbiomac.2025.149708","url":null,"abstract":"<div><div>Glutamate waste liquor (GWL) is acidic wastewater from monosodium glutamate process. Poly-γ-glutamic acid (γ-PGA) production using this abundant industrial waste is an economical and environmentally friendly method. The development of cost-effective production from GWL requires understanding the inhibitory mechanism in γ-PGA producers. In this study, γ-PGA fermentation profile of <em>Bacillus subtilis</em> KH2 using GWL was studied. An inhibitory effect in glutamate consumption was observed during γ-PGA production. To systematically analyze the response pattern of <em>B. subtilis</em> KH2 to GWL addition, comparative transcriptomics was performed. Transcriptomic analysis indicated that GWL led to decreased expression of genes associated with γ-PGA polymerization, while upregulating genes related to glycolysis, TCA cycle and glutamate precursor synthesis. Subsequent gene overexpression experiments elucidated the pivotal regulatory role of <em>swrA</em> in the GWL-mediated suppression of γ-PGA biosynthesis. Finally, by a combination of metabolic engineering targets, the highest γ-PGA titer of 32.24 g/L was achieved by <em>B. subtilis</em> KH2<em>Δres1Δres2ΔgudBΔrocG</em> using GWL in shake-flask fermentation, accompanied by an increased glutamate consumption rate of 59.37 %. This study provides insights into the GWL inhibitory mechanisms in <em>B. subtilis</em> KH2 and demonstrates the potential application of <em>B. subtilis</em> KH2 for cost-effective production from industrial waste.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149708"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773245","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149697
Benjamin W. Moorlach , Robert Epkenhans , Di Ju , Banuja Ravidas , Christian Weinberger , Michael Tiemann , Judith Buente , Maik Gaerner , Martin Wortmann , Stefan Scholten , Michael Rostas , Waldemar Keil , Anant V. Patel
Spray-induced gene silencing (SIGS) employing double-stranded RNA (dsRNA) offers a promising, species-specific approach for protecting crops from insect pests such as the cabbage stem flea beetle (Psylliodes chrysocephala). However, the environmental instability of dsRNA presents a major limitation to its field application. In this study, we evaluate two distinct dsRNA formulation strategies for improved stability and delivery: a bottom-up approach using chitosan-based interpolyelectrolyte complexes (IPEC) and a top-down approach employing functionalized mesoporous silica carriers (SBA-15). Both systems were comprehensively characterized in terms of size, surface potential, porosity, and release behavior. The results revealed that IPECs exhibited release kinetics that were approximately one order of magnitude faster than those of SBA-15 across all tested conditions. The two formulations significantly improved dsRNA stability against UV and heat exposure compared to free dsRNA. In feeding assays with P. chrysocephala, both carriers achieved comparable gene silencing efficacy, though dsRNA@IPEC induced more immediate effects, while dsRNA@SBA-15 displayed delayed but ultimately stronger reduction in consumed leaf area, consistent with its slower release kinetics. We demonstrate that despite structural and mechanistic differences, both delivery platforms effectively stabilized and delivered dsRNA, and offered distinct advantages depending on application needs. This work highlights how formulation strategies are key to successful SIGS and supports the development of robust, field-adaptable formulation technologies for sustainable pest management.
{"title":"DsRNA-based carriers with pH-tuneable release kinetics for effective control of Psylliodes chrysocephala","authors":"Benjamin W. Moorlach , Robert Epkenhans , Di Ju , Banuja Ravidas , Christian Weinberger , Michael Tiemann , Judith Buente , Maik Gaerner , Martin Wortmann , Stefan Scholten , Michael Rostas , Waldemar Keil , Anant V. Patel","doi":"10.1016/j.ijbiomac.2025.149697","DOIUrl":"10.1016/j.ijbiomac.2025.149697","url":null,"abstract":"<div><div>Spray-induced gene silencing (SIGS) employing double-stranded RNA (dsRNA) offers a promising, species-specific approach for protecting crops from insect pests such as the cabbage stem flea beetle (<em>Psylliodes chrysocephala</em>). However, the environmental instability of dsRNA presents a major limitation to its field application. In this study, we evaluate two distinct dsRNA formulation strategies for improved stability and delivery: a bottom-up approach using chitosan-based interpolyelectrolyte complexes (IPEC) and a top-down approach employing functionalized mesoporous silica carriers (SBA-15). Both systems were comprehensively characterized in terms of size, surface potential, porosity, and release behavior. The results revealed that IPECs exhibited release kinetics that were approximately one order of magnitude faster than those of SBA-15 across all tested conditions. The two formulations significantly improved dsRNA stability against UV and heat exposure compared to free dsRNA. In feeding assays with <em>P. chrysocephala</em>, both carriers achieved comparable gene silencing efficacy, though dsRNA@IPEC induced more immediate effects, while dsRNA@SBA-15 displayed delayed but ultimately stronger reduction in consumed leaf area, consistent with its slower release kinetics. We demonstrate that despite structural and mechanistic differences, both delivery platforms effectively stabilized and delivered dsRNA, and offered distinct advantages depending on application needs. This work highlights how formulation strategies are key to successful SIGS and supports the development of robust, field-adaptable formulation technologies for sustainable pest management.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149697"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760570","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}
Pub Date : 2025-12-15DOI: 10.1016/j.ijbiomac.2025.149698
Wangcheng Xie , Tingyi Luo , Guodong Tang , Zhilong Ma , Jian Gong , Tingsong Yang , Jia Zhou , Zhenshun Song
Chronic pancreatitis (CP) is a progressive fibrotic inflammation syndrome that leads to pancreatic insufficiency, for which there is a paucity of effective therapeutic options. Owing to their multidirectional differentiation potential and immunomodulatory capabilities, mesenchymal stem cells (MSCs) hold promise for the amelioration of chronic diseases. In this study, we demonstrated for the first time that umbilical cord-derived MSCs (UCMSCs) and their extracellular vesicles (UCMSC-EVs) mitigated pancreatic acinar cell injury, reduced macrophage infiltration, and alleviated pancreatic fibrosis in a murine model of chronic pancreatitis. Furthermore, we comprehensively elucidated the intricate regulatory effects of UCMSC-EVs on fibrotic signaling pathways in pancreatic stellate cells. Mechanistically, EVs secreted by UCMSCs modulated the ANXA1-SMAD2/3 signaling axis in pancreatic stellate cells via the release of milk fat globule-EGF factor 8 (MFGE8), leading to the inhibition of fibrotic gene expression. Additionally, we developed a novel drug delivery platform named rhMFGE8 NPs, which exhibited marked antifibrotic efficacy and an outstanding biosafety profile. This investigation highlights the therapeutic potential of UCMSCs, UCMSC-EVs, and rhMFGE8 NPs for CP treatment, providing a foundation for the development of innovative antifibrotic therapies.
{"title":"From stem cells to nanomedicine: A multimodal approach targeting pancreatic fibrosis via MFGE8-dependent ANXA1-SMAD2/3 axis","authors":"Wangcheng Xie , Tingyi Luo , Guodong Tang , Zhilong Ma , Jian Gong , Tingsong Yang , Jia Zhou , Zhenshun Song","doi":"10.1016/j.ijbiomac.2025.149698","DOIUrl":"10.1016/j.ijbiomac.2025.149698","url":null,"abstract":"<div><div>Chronic pancreatitis (CP) is a progressive fibrotic inflammation syndrome that leads to pancreatic insufficiency, for which there is a paucity of effective therapeutic options. Owing to their multidirectional differentiation potential and immunomodulatory capabilities, mesenchymal stem cells (MSCs) hold promise for the amelioration of chronic diseases. In this study, we demonstrated for the first time that umbilical cord-derived MSCs (UCMSCs) and their extracellular vesicles (UCMSC-EVs) mitigated pancreatic acinar cell injury, reduced macrophage infiltration, and alleviated pancreatic fibrosis in a murine model of chronic pancreatitis. Furthermore, we comprehensively elucidated the intricate regulatory effects of UCMSC-EVs on fibrotic signaling pathways in pancreatic stellate cells. Mechanistically, EVs secreted by UCMSCs modulated the ANXA1-SMAD2/3 signaling axis in pancreatic stellate cells via the release of milk fat globule-EGF factor 8 (MFGE8), leading to the inhibition of fibrotic gene expression. Additionally, we developed a novel drug delivery platform named rhMFGE8 NPs, which exhibited marked antifibrotic efficacy and an outstanding biosafety profile. This investigation highlights the therapeutic potential of UCMSCs, UCMSC-EVs, and rhMFGE8 NPs for CP treatment, providing a foundation for the development of innovative antifibrotic therapies.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149698"},"PeriodicalIF":8.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773200","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}
Pub Date : 2025-12-14DOI: 10.1016/j.ijbiomac.2025.149561
Jun Wang , Tonghai Liu , Zhengwei Zhang , Wupeng Yan
TBC domain-containing Rab GTPase-activating proteins (TBCs) play key roles in regulating intracellular trafficking, and mutations in these proteins can disrupt Rab inactivation and contribute to human disease. However, the molecular principles governing the substrate specificity of TBCs remain poorly understood. Here, we delineate the molecular mechanism by which RN-Tre (also known as USP6NL), an RQ-dual finger TBC protein, selectively recognizes and inactivates Rab43. The crystal structure of the RN-Tre-Rab43 complex reveals a bipartite recognition mechanism: the N-terminal subdomain catalytically remodels Rab43 Switch regions, while the C-terminal subdomain engages Switch II and reorients the hydrophobic triad to confer specificity. Structural and mutational analyses identify Leu146 and several C-terminal residues as key determinants of RN-Tre specificity, which lead us to identify Rab19 as an additional substrate. Functional assays demonstrate that disease-associated RN-Tre mutations impair GAP activity, resulting in aberrant Golgi architecture and endocytic trafficking. Collectively, this study establishes a general structural paradigm for substrate discrimination by TBCs and highlights their pivotal roles in membrane trafficking and disease.
{"title":"Molecular basis of Rab43 inactivation by RN-Tre in endocytic trafficking unveils a general Rab-GAP recognition mechanism","authors":"Jun Wang , Tonghai Liu , Zhengwei Zhang , Wupeng Yan","doi":"10.1016/j.ijbiomac.2025.149561","DOIUrl":"10.1016/j.ijbiomac.2025.149561","url":null,"abstract":"<div><div>TBC domain-containing Rab GTPase-activating proteins (TBCs) play key roles in regulating intracellular trafficking, and mutations in these proteins can disrupt Rab inactivation and contribute to human disease. However, the molecular principles governing the substrate specificity of TBCs remain poorly understood. Here, we delineate the molecular mechanism by which RN-Tre (also known as USP6NL), an RQ-dual finger TBC protein, selectively recognizes and inactivates Rab43. The crystal structure of the RN-Tre-Rab43 complex reveals a bipartite recognition mechanism: the N-terminal subdomain catalytically remodels Rab43 Switch regions, while the C-terminal subdomain engages Switch II and reorients the hydrophobic triad to confer specificity. Structural and mutational analyses identify Leu146 and several C-terminal residues as key determinants of RN-Tre specificity, which lead us to identify Rab19 as an additional substrate. Functional assays demonstrate that disease-associated RN-Tre mutations impair GAP activity, resulting in aberrant Golgi architecture and endocytic trafficking. Collectively, this study establishes a general structural paradigm for substrate discrimination by TBCs and highlights their pivotal roles in membrane trafficking and disease.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149561"},"PeriodicalIF":8.5,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766729","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}
Aligned with Sustainable Development Goal 12 (Responsible Consumption and Production), this study presents a sustainable strategy to develop flame-retardant polylactide (PLA) composite films using soybean meal (SB), a food-waste byproduct, as a sustainable flame retardant. The incorporation of 10 phr SB markedly improved flame resistance, achieving a VTM-0 rating in the UL-94 test through flame inhibition in both gas and condensed phases. Thermogravimetric analysis (TGA) confirmed enhanced thermal stability with increased char residue, while the flame-retardant mechanism involved the release of phosphoric acid generating water vapor to dilute flammable gases, and cellulose and lignin promoting char formation. Despite these benefits, SB addition reduced mechanical strength due to particle agglomeration, as observed by scanning electron microscopy (SEM). To overcome this drawback, tricresyl phosphate (TCP) and tributyl phosphate (TBP) were employed as impact modifiers. The optimized formulation (PS_C20) achieved a 152 % increase in tensile-impact toughness compared with PS10, while maintaining excellent flame retardancy. Differential scanning calorimetry (DSC) revealed that TCP accelerated crystallization, lowering the cold-crystallization temperature and increasing crystallinity. Overall, this work highlights the potential of upcycling food waste into high-performance, eco-friendly PLA composites, supporting extended material lifespans and advancing SDG 12 through sustainable product design.
{"title":"Soybean meal waste as a sustainable flame retardant for green polylactide composite films with enhanced flame resistance and balanced toughness via impact modifiers","authors":"Tunsuda Suparanon , Fatihah Pohsu , Rattikarn Kumklon , Neeranuch Phusunti , Worasak Phetwarotai","doi":"10.1016/j.ijbiomac.2025.149694","DOIUrl":"10.1016/j.ijbiomac.2025.149694","url":null,"abstract":"<div><div>Aligned with Sustainable Development Goal 12 (Responsible Consumption and Production), this study presents a sustainable strategy to develop flame-retardant polylactide (PLA) composite films using soybean meal (SB), a food-waste byproduct, as a sustainable flame retardant. The incorporation of 10 phr SB markedly improved flame resistance, achieving a VTM-0 rating in the UL-94 test through flame inhibition in both gas and condensed phases. Thermogravimetric analysis (TGA) confirmed enhanced thermal stability with increased char residue, while the flame-retardant mechanism involved the release of phosphoric acid generating water vapor to dilute flammable gases, and cellulose and lignin promoting char formation. Despite these benefits, SB addition reduced mechanical strength due to particle agglomeration, as observed by scanning electron microscopy (SEM). To overcome this drawback, tricresyl phosphate (TCP) and tributyl phosphate (TBP) were employed as impact modifiers. The optimized formulation (PS_C20) achieved a 152 % increase in tensile-impact toughness compared with PS10, while maintaining excellent flame retardancy. Differential scanning calorimetry (DSC) revealed that TCP accelerated crystallization, lowering the cold-crystallization temperature and increasing crystallinity. Overall, this work highlights the potential of upcycling food waste into high-performance, eco-friendly PLA composites, supporting extended material lifespans and advancing SDG 12 through sustainable product design.</div></div>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"338 ","pages":"Article 149694"},"PeriodicalIF":8.5,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766769","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}
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