{"title":"Schiff-base cross-linked pullulan-chondroitin sulfate hydrogel incorporating raloxifene-poly(2-methyl-2-oxazoline) micelles for localized therapy of postmenopausal osteoarthritis.","authors":"Atul Mourya, Hoshiyar Singh, Shristi Arya, Arbaaz Sujat Shaikh, Bhavana Bojja, Pawan Devangan, Mohd Rabi Bazaz, Manoj P Dandekar, Venkata Rao Kaki, Santosh Kumar Guru, Priyanka Bajaj, Jitender Madan","doi":"10.1016/j.ijbiomac.2026.154794","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154794","url":null,"abstract":"<p><p>Postmenopausal osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage erosion and subchondral bone loss, intensified by estrogen deficiency in menopausal women. Raloxifene (RLX), a selective estrogen receptor modulator, shows anti-inflammatory and chondroprotective potential but is associated with limited oral bioavailability (~2%) and systemic side effects. Therefore, in the present investigation, raloxifene-conjugated poly(2-methyl-2-oxazoline) micelles hybridized self-cross-linking hydrogel (R-PMeOZ@SCH) was engineered for intra-articular therapy. Next, the R-PMeOZ micelles exhibited a narrow particle size distribution with an average hydrodynamic diameter of 147.63 ± 0.66 nm, a polydispersity index (PDI) of 0.14 ± 0.01, and a ζ-potential of -7.33 ± 1.75 mV. The hydrogel was synthesized via Schiff-base reaction between oxidized pullulan (OxyPul) and chondroitin sulfate-adipic hydrazide (CSADH), enabling controlled release and site-specific delivery. R-PMeOZ@SCH demonstrated suitable rheology, swelling, and controlled release profile for intra-articular administration. In a postmenopausal OA rats treated with R-PMeOZ@SCH demonstrated a progressive improvement in motor coordination, cartilage integrity, subchondral bone architecture and reduced inflammatory cytokine levels compared to disease control. X-ray and μ-CT analyses unveiled improvement in articular space width and reduction in Kellgren-Lawrence score for R-PMeOZ@SCH treated group compared to the disease control. It also reduced mRNA expression of MMP-9, ADAMTS-4, and ADAMTS-5 by 5.89, 2.54, and 7.12-fold, respectively, compared to disease control. Histological evaluation demonstrated a significant reduction in OARSI and modified Mankin's scores and an improvement in relative GAG level in comparison to disease control, highlighting the disease-modifying potential of R-PMeOZ@SCH for clinical translation.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154794"},"PeriodicalIF":8.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134374","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}
Su Jinle, Ge Lingrui, Niu Chunyu, Chen Yan, Zhang Leifang, Chen Yin
{"title":"Structural characterization of a distinct neutral polysaccharide fraction (SP0-1) from sea buckthorn (Hippophae rhamnoides L.) and its antioxidant-related intestinal protection in Drosophila melanogaster.","authors":"Su Jinle, Ge Lingrui, Niu Chunyu, Chen Yan, Zhang Leifang, Chen Yin","doi":"10.1016/j.ijbiomac.2026.154785","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154785","url":null,"abstract":"<p><p>SP0-1, a neutral polysaccharide fraction isolated from sea buckthorn berries (Hippophae rhamnoides L.), was purified and structurally characterized, and its antioxidant-related intestinal protective effects were evaluated in Drosophila melanogaster. HPGPC analysis showed a single symmetrical peak and indicated a relatively homogeneous fraction with a moderate molecular weight (Mw, 5.59 × 10<sup>4</sup> Da; ≈55.9 kDa). PMP-HPLC analysis revealed that SP0-1 was mainly composed of galactose, xylose, and arabinose (Gal/Xyl/Ara-rich; Gal:Xyl:Ara = 1:0.38:0.93). Methylation analysis combined with 1D/2D NMR spectroscopy supported the presence of major →4)- and →4,6)-linked Galp motifs, →5)- and →3,5)-linked Araf motifs, and terminal Xylp residues. The consecutive Gal-Gal arrangement, the residue adjacent to Gal O-6, the overall connection of the Ara/Xyl-containing region to the Gal-containing region, and the O-3 substituent of residue D remain unresolved. Functionally, SP0-1 exhibited concentration-dependent radical-scavenging activities against DPPH, ABTS•<sup>+</sup>, and hydroxyl radicals in vitro. In a Drosophila oxidative-stress model, dietary SP0-1 supplementation significantly improved survival and climbing performance, enhanced endogenous antioxidant enzyme activities, and reduced malondialdehyde levels. Moreover, SP0-1 markedly alleviated H<sub>2</sub>O<sub>2</sub>-induced intestinal oxidative injury, as evidenced by decreased reactive oxygen species accumulation and reduced intestinal epithelial cell death. These findings suggest that the structural characteristics of SP0-1, including its proposed Gal-rich linkage features and Ara/Xyl-containing residue motifs, may be associated with the observed antioxidant-related intestinal protection. Collectively, this study provides a structural and functional basis for further investigation of SP0-1 as a potential bioactive polysaccharide fraction.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154785"},"PeriodicalIF":8.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134385","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}
Aojie Wang, Yi Liu, Youqin Yin, Zhende Su, Wenbao Qi, Lihong Huang, Renhong Yan, Ming Liao
{"title":"Structure-based design and immunogenicity of an H5 hemagglutinin stem nanoparticle vaccine candidate.","authors":"Aojie Wang, Yi Liu, Youqin Yin, Zhende Su, Wenbao Qi, Lihong Huang, Renhong Yan, Ming Liao","doi":"10.1016/j.ijbiomac.2026.154799","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154799","url":null,"abstract":"<p><p>Highly pathogenic avian influenza viruses (HPAIVs), particularly the H5N6 subtype, pose a serious global public health threat. Conventional influenza vaccines primarily target the highly variable globular head of hemagglutinin (HA), resulting in limited breadth of protection. Here, we employed a structure-guided vaccine design strategy to develop a self-assembling nanoparticle immunogen targeting conserved epitopes within the HA stem region. The HAstem antigen was rationally engineered to incorporate major neutralizing epitopes and further stabilized through the introduction of a GCN4 trimerization motif, engineered disulfide bonds, and prefusion conformation optimization. Using the I53_dn5 platform, HAstem was displayed in a highly ordered and multivalent array on the surface of icosahedral nanoparticles. Cryo-electron microscopy at 4.99 Å resolution confirmed the structural integrity of the nanoparticle core and the successful assembly of the vaccine construct. Immunization with HAstem-I53_dn5 elicited robust HAstem-specific antibody responses, with endpoint titers reaching 1:12,800, significantly exceeding those induced by both trimeric antigen and inactivated whole-virus vaccines. In addition, the vaccine induced diverse HA stem-specific IgG subclasses, potent FcγRIV-binding antibodies, and cross-reactive antibodies preferentially targeting H5 subtype HA antigens. In summary, these findings establish the structural and immunogenic characteristics of the HAstem-I53_dn5 nanoparticle and support its further development as an H5-focused HA stem nanoparticle vaccine candidate.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154799"},"PeriodicalIF":8.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134380","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}
Mei-Hwa Lee, James L Thomas, Yu-Ling Lin, Hung-Yin Lin
{"title":"Corrigendum to \"In vitro activation of anti-cancer gene expression by delivery of CRISPR/dCas9 ribonucleoproteins to suppress glioblastoma\" [Int. J. Biol. Macromol. 308P1 (2025) 142289].","authors":"Mei-Hwa Lee, James L Thomas, Yu-Ling Lin, Hung-Yin Lin","doi":"10.1016/j.ijbiomac.2026.154717","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154717","url":null,"abstract":"","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154717"},"PeriodicalIF":8.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134359","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}
Sixue Li, Tao Tang, Ying Yan, Lirong Lei, Songqing Hu, Junling Zhang, Yi Hou
{"title":"Phosphorylated cellulose based macromolecular films with high charge density for high-performance moisture-powered generators.","authors":"Sixue Li, Tao Tang, Ying Yan, Lirong Lei, Songqing Hu, Junling Zhang, Yi Hou","doi":"10.1016/j.ijbiomac.2026.154774","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154774","url":null,"abstract":"<p><p>As a renewable polysaccharide macromolecule, cellulose has attracted significant attention in green moisture-powered generators due to its widespread availability and excellent hydrophilicity. However, the performance of cellulose macromolecules in humidity-driven power generation is constrained by inadequate protonation and ion diffusion properties. In this work, a highly charged cellulose macromolecule with a charge density of 4.02 mmol/g was obtained through one-step phosphorylation using the urea/phosphate system under optimal conditions of 170 °C for 30 min. Phosphorylation introduces phosphate ester groups onto the anhydroglucose units (AGUs) of the cellulose backbone, yielding a degree of substitution (DS) of 0.65. A cellulose membrane-based moisture-powered generator (P-MEG) was developed via vacuum filtration. Meanwhile, the enhanced hydrophilicity resulting from phosphorylation promotes both moisture absorption and ion diffusion within the film. The P-MEG demonstrated an average output voltage of 0.55 V (maximum 0.61 V) and a short-circuit current of ~12 μA under 95% relative humidity, with a maximum output power of 1.07 μW at a load resistance of 25 kΩ. The device maintained continuous voltage output for more than 7 h. The surface charge density and hydrophilicity of cellulose are critical factors in enhancing the voltage output performance of moisture-powered generators. Phosphorylation modification of cellulose is a green and effective approach to improving its surface charge density and hydrophilicity for high-performance energy harvesting applications.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154774"},"PeriodicalIF":8.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126310","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}
Santoshi Rawat, C K Sunil, D V Chidanand, Ashish Rawson, N Venkatachalapathy
{"title":"Corrigendum to \"Broccoli byproducts protein concentrate: Microwave treatment effect on functional, thermal, and structural properties\" [Int. J. Biol. Macromol. 379 (2026) 154018].","authors":"Santoshi Rawat, C K Sunil, D V Chidanand, Ashish Rawson, N Venkatachalapathy","doi":"10.1016/j.ijbiomac.2026.154725","DOIUrl":"10.1016/j.ijbiomac.2026.154725","url":null,"abstract":"","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154725"},"PeriodicalIF":8.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126147","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":"Expression of Concern: \"Application of chitosan-based edible films reinforced with nanofibers to improve the shelf life of rapeseed oil: Release kinetics of essential oils and biodegradability\" [Int. J. Biol. Macromol. 307 (2025) 141832 10.1016/j.ijbiomac.2025.141832].","authors":"","doi":"10.1016/j.ijbiomac.2026.154786","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154786","url":null,"abstract":"","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154786"},"PeriodicalIF":8.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126157","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":"In vitro digestion and molecular dynamics reveal mechanisms of digestion resistance in type V resistant starch: Binary versus ternary complexes with lipids and/or proteins.","authors":"Fangyuan Chen, Xiaoyi Deng, Ruolan Fang, Cuie Tang, Huilong Dong, Qi Liu, Siming Zhao, Caihua Jia","doi":"10.1016/j.ijbiomac.2026.154769","DOIUrl":"10.1016/j.ijbiomac.2026.154769","url":null,"abstract":"<p><p>To elucidate the resistance of type V resistant starch to enzymatic digestion, this study investigated the relationship between the crystalline structure and digestibility of complexes formed with lipids or proteins. The incorporation of octadecanoic acid (OA) and rice protein (RP) facilitated the formation of type V crystalline structures in native rice starch (NRS), increasing its crystallinity in the early stages of digestion. During in vitro digestion, the short-range ordered structure and type V crystal content of the NRS-RP and NRS-OA-RP complexes progressively increased. In contrast, these parameters in the NRS-OA complex initially increased and then decreased. Molecular dynamics simulations revealed that binding with the NRS-RP and NRS-RP-OA reduced the stability of the digestive enzyme, as evidenced by increased radius of gyration (Rg), root-mean-square deviation (RMSD), and solvent-accessible surface area (SASA) values, accompanied by highly unstable fluctuations. This instability was further characterized by a reduced number of hydrogen bonds and a Gibbs free energy landscape displaying multiple energy minima. Binding free energy analysis further demonstrated that complex formation reduced the binding affinity between the enzyme and starch, with the ternary NRS-OA-RP complex exhibiting the lowest binding energy (-17.52 kJ/mol). In conclusion, these findings suggest that the enhanced resistance to digestion of various type V RS complexes arises from a dual mechanism involving the formation of structural barriers and the modulation of molecular interactions that reduce enzyme-starch binding affinity.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154769"},"PeriodicalIF":8.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102089","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":"PDZ domain containing 1 sensitizes renal cancer cells to everolimus via inhibiting phosphatase and tensin homolog phosphorylation-mediated mTOR pathway activation.","authors":"Yinong Niu, Zhiyu Fang, Lei Wang, Mingshi Liu, Shuang Chen, Peng Yang, Yuanfeng Lan, Duiping Feng, Junqi He, Ran Song, Junfang Zheng","doi":"10.1016/j.ijbiomac.2026.154763","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154763","url":null,"abstract":"<p><p>Aberrant activation of the phosphatase and tensin homolog (PTEN)-PI3K/AKT/mTOR pathway is a key driver of renal cell carcinoma (RCC) progression, making mTOR inhibition with everolimus a critical therapeutic strategy. However, the mechanisms driving mTOR pathway activation and the emergence of drug resistance remain poorly understood. In this study, we found that phosphorylated PTEN (pPTEN at S380/T382/T383) level was increased in RCC. Increased pPTEN level was associated with impaired suppression of mTOR pathway activation, and was accompanied by RCC progression and resistance to everolimus. Conversely, inhibition of PTEN phosphorylation restored PTEN function, reducing tumor growth and restoring sensitivity to everolimus. Further investigation revealed that downregulation of PDZ domain-containing 1 (PDZK1) in RCC tissues increased pPTEN level, resulting in mTOR pathway activation. PDZK1 was found to inhibit RCC malignancy by preventing PTEN phosphorylation and mTOR activation. Moreover, PDZK1 overexpression sensitized RCC cells to everolimus across cell, animal and organoid models. In conclusion, our findings indicate that PDZK1 downregulation in RCC cells contributes to pPTEN accumulation, mTOR pathway activation, and everolimus resistance. This highlights the PDZK1-pPTEN axis as a potential therapeutic target in RCC, suggesting that modulating PDZK1 or PTEN phosphorylation could enhance the efficacy of everolimus treatment.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154763"},"PeriodicalIF":8.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102052","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":"Aqueous self-assembly of wheat starch paste into low-responsive microgels for stabilizing mounted paper-based artworks.","authors":"Zihuan Hou, Bei He, Ruofan Yang, Junhao Zhang, Xintian Liu, Daodao Hu, Junli Ren, Yuhu Li, Huiping Xing","doi":"10.1016/j.ijbiomac.2026.154777","DOIUrl":"10.1016/j.ijbiomac.2026.154777","url":null,"abstract":"<p><p>Wheat starch paste has been historically employed as the core adhesive for the mounting of Chinese paper-based artworks. However, it is inherently prone to aging-induced deformation, mainly due to the recrystallization of amylose. Herein, an aqueous self-assembly strategy was proposed to transform wheat starch paste into microgels, aiming to induce amylose recrystallization prior to application while preserving its adhesion. During periodic water exchange, the paste underwent a time-dependent structural evolution. Amylose first recrystallized via hydrogen bonding, followed by encapsulation of recrystallized amylose by amylopectin to form microgels, and subsequent densification with prolonged soaking. Consequently, the paste's viscosity, temperature responsiveness, and bonding strength gradually decreased, mainly due to reduced free hydroxyl groups from hydrogen bonding. Meanwhile, the paste was purified, and its pH rose as residual proteins and acidic impurities were removed. After evaluation, with longer soaking time of paste, the mounted paper showed weakened moisture responsiveness, decreased flexibility and chromatic aberration (ΔE), and stable pH after natural drying and accelerated aging, indicating improved dimensional stability and aging resistance. However, it is worth noting that excessively long soaking time may also increase the risk of insufficient bonding and brittle fracture in the mounted works, especially for scroll calligraphy and paintings.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154777"},"PeriodicalIF":8.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102023","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}