Journal of Advanced Research最新文献

{"title":"Plasma proteomics mediate the association between degenerative joint diseases and dementia risk","authors":"Zijian Kang,&nbsp;Jianzheng Zhang,&nbsp;Chen Zhu,&nbsp;Edward CH Lau,&nbsp;Ying Zhu,&nbsp;Ping Li,&nbsp;Kai Li,&nbsp;Qiang Tong,&nbsp;Sheng-Ming Dai","doi":"10.1016/j.jare.2025.12.044","DOIUrl":"10.1016/j.jare.2025.12.044","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the association between degenerative joint diseases (DJD) and dementia risk and to identify potential proteomic mediators.</div></div><div><h3>Methods</h3><div>We conducted a prospective cohort study using data from 500,805 participants in the UK Biobank. Three DJD diagnoses (osteoarthritis [OA], intervertebral disc degeneration [IVDD], and degenerative spinal diseases [DSD]) were identified from the clinical records. Dementia outcomes (all-cause dementia [ACD], Alzheimer’s disease [AD], and vascular dementia [VaD]) were tracked over 14.45 years. Multivariable Cox regression models were used to assess DJD-dementia associations, adjusted for demographics, lifestyle, and comorbidities. Propensity score matching (PSM) was employed for validation. Plasma proteomic profiling of 2,923 proteins was performed to identify potential mediators, followed by causal mediation analysis.</div></div><div><h3>Results</h3><div>After a median follow-up of 14.45 years, 9,884 participants developed ACD, including 4,404 with AD and 2,224 with VaD. After adjusting for covariates, the DJD group exhibited a significantly elevated risk of ACD (HR: 1.271, 95 % CI: 1.173–1.376) and VaD (HR: 1.587, 95 % CI: 1.323–1.903), but not AD (HR: 1.107, 95 % CI: 0.982–1.248). Subgroup analyses revealed significant effect modifications according to age, activity levels, and surgical procedures. PSM analyses confirmed the robustness of these associations. Proteomic analysis identified plasma proteins associated with both DJDs and ACD risk. Mediation analysis revealed that 18 proteins, including HAVCR1 (mediation proportion 52.6 %, 95 % CI: 39.1 %–78 %), GDF15 (22 %, 95 % CI: 14.5 %–46.8 %), and COL6A3 (14.3 %, 95 % CI: 7.7 %–28.4 %), significantly mediated the association between DJDs and ACD.</div></div><div><h3>Conclusion</h3><div>DJDs are independently associated with an increased risk of developing dementia. This correlation is mediated by systemic proteomic alterations. Our findings highlight inflammation and vascular dysfunction as central mechanisms, offering insights into risk stratification and therapeutic targets for preventing dementia.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 795-806"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and bioactivity evaluation of isoxazoline scaffolds using heterogeneous photocatalytic (3+2) cycloaddition","authors":"Shaochen Li,&nbsp;Bingrui Liu,&nbsp;Xinran Chen,&nbsp;Guangpeng Wang,&nbsp;Chiying Zhang,&nbsp;Shuqing Ma,&nbsp;Yahui Li","doi":"10.1016/j.jare.2026.01.033","DOIUrl":"10.1016/j.jare.2026.01.033","url":null,"abstract":"<div><h3>Introduction</h3><div>The (3+2) cycloaddition is a classic method for synthesizing bioactive isoxazoline and isoxazole heterocycles. However, its utility is hampered by a reliance on stoichiometric halogenating oxidants, bases, and multi-step protocols, generating significant waste and limiting synthetic efficiency.</div></div><div><h3>Objectives</h3><div>This study aims to develop an efficient alternative to the classical (3+2) cycloaddition. Our objective was to achieve the direct synthesis of isoxazolines and isoxazoles from oximes and alkenes under mild, additive-free conditions using a heterogeneous photocatalytic system.</div></div><div><h3>Methods</h3><div>We employed mesoporous graphitic carbon nitride (mpg–CN) as a recyclable, metal-free photocatalyst. Reactions were conducted under visible light irradiation using oxygen as a benign terminal oxidant. The scalability was demonstrated via a continuous-flow setup. Mechanistic pathways were elucidated through a combination of experimental studies and density functional theory (DFT) calculations.</div></div><div><h3>Results</h3><div>Various oximes and alkenes were successfully converted into the target heterocycles in good to excellent yields. The protocol features exceptional functional group tolerance, accommodating sensitive motifs like heterocycles and Helicid analogs. Gram-scale synthesis of pharmacologically relevant cores was achieved in a continuous-flow reactor. Mechanistic investigations indicate that an energy transfer process primarily mediates the reaction cascade. Selected synthesized compounds showed promising insecticidal activity against <em>Plutella xylostella</em>.</div></div><div><h3>Conclusion</h3><div>We have developed a heterogeneous photocatalytic (3+2) cycloaddition protocol. This one-step, additive-free method provides an efficient and scalable route to valuable isoxazoline and isoxazole scaffolds, with demonstrated potential for generating bioactive molecules.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 105-115"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen-vacancy-regulated molybdenum oxide nanosheets for a multi-phosphate discriminative colorimetric sensor array","authors":"Cheng Cheng,&nbsp;Xingying Li,&nbsp;Zhiwei Chen,&nbsp;Aiwu Wang,&nbsp;Fucong Lyu,&nbsp;Muhammad Humayun,&nbsp;Mohamed Bououdina","doi":"10.1016/j.jare.2026.01.025","DOIUrl":"10.1016/j.jare.2026.01.025","url":null,"abstract":"<div><div>The detection and identification of various phosphates are crucial in disease diagnostics. However, traditional detection techniques often require the development of multi-ion systems, and the complexity of sensor unit fabrication has limited the broad applications of sensor arrays. In this study, we report for the first-time the design of a colorimetric sensor using oxygen vacancy-regulated MoO_x(2 ≤ x ≤ 3) nanosheets. By precisely modulating the concentration of introduced oxygen vacancies, the plasmonic resonance absorption peak of the MoO_x nanosheets exhibited tunable shifts, thereby influencing their optical properties. The addition of phosphate ions with different configurations influenced the light absorption range and the plasmonic peak values of the oxygen vacancy-rich MoO_x sensor array to various extents. Through statistical analysis methods, this sensing array effectively identified ten types of phosphates (i.e., ATP, ADP, AMP, PPi, Pi, UTP, GTP, GDP, GMP, and CTP). The sensor demonstrated excellent detection and discrimination capabilities in both quantitative identification and the recognition of mixed phosphates. The practical application of this sensor array was validated by precisely detecting phosphates in complex systems such as serum. Compared to the previous reports, the fabrication process of the oxygen vacancy-regulated MoO_x nanosheets is simple, the discrimination detection effect is good, and it provides a new approach and method for the design and fabrication of highly efficient sensor arrays.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 707-718"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OSBPL6 protects against demyelination and behavioral disorder via promoting cholesterol transport in oligodendrocyte","authors":"Mengni Chang,&nbsp;Kaiqi Zhang,&nbsp;Ye Li,&nbsp;Xiao Chen,&nbsp;Tian Lan,&nbsp;Yan Zhu,&nbsp;Wenjing Wang,&nbsp;Changmin Wang,&nbsp;Xianghua Zhuang,&nbsp;Shihong Chen,&nbsp;Shuyan Yu","doi":"10.1016/j.jare.2026.01.066","DOIUrl":"10.1016/j.jare.2026.01.066","url":null,"abstract":"<div><h3>Introduction</h3><div>Demyelination is associated with behavioral disorder and cognitive impairment in neuropsychiatric diseases, including major depressive disorder (MDD). However, the mechanism underlying myelin damage remains unclear, despite stress maybe a major risk factor.</div></div><div><h3>Objectives</h3><div>Here, we demonstrate that hippocampal neurons in the chronic stress-induced depressive mice are prone to demyelination due to disrupted cholesterol transport to myelin sheaths in oligodendrocyte.</div></div><div><h3>Methods and Results</h3><div>Single-nucleus RNA sequencing of lipid metabolism-related signaling pathway revealed significant reduced levels of oxysterol binding protein-like 6 (OSBPL6) in hippocampal oligodendrocytes of depression mouse model. Consistently, specific knockdown of OSBPL6 in oligodendrocytes induced loss of myelin structure, while upregulating OSBPL6 or enhancing OSBPL6 transcription improved these impairments in depressive mice. Furthermore, restoring cholesterol transport with β-cyclodextrin decreased cholesterol accumulation, improved damaged myelin structure, and rescued depression-related behaviors in depressive mice.</div></div><div><h3>Conclusions</h3><div>These findings suggest that OSBPL6-mediated cholesterol homeostasis in oligodendrocytes can promote myelin production against chronic stress-induced cerebral demyelination and depression with behavioral disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 539-559"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An injectable microsphere-reinforced system for sustained delivery of Adipo-MBV in adipose tissue engineering","authors":"Mimi Xu,&nbsp;Jianwei Chen,&nbsp;Yi Sun,&nbsp;Han Yang,&nbsp;Hongli Ji,&nbsp;Tao Xu,&nbsp;Feng Lu,&nbsp;Yunfan He","doi":"10.1016/j.jare.2026.01.058","DOIUrl":"10.1016/j.jare.2026.01.058","url":null,"abstract":"<div><h3>Introduction</h3><div>Tissue engineering has become prominence in soft tissue reconstruction. Adipogenesis and angiogenesis are important in the formation of engineering adipose tissue. Although acellular adipose matrix (AAM) possesses potential in adipogenic induction, obvious limitations remain in the realization of the authentic physiological regeneration. Matrix-bound nanovesicles (MBVs), located on the extracellular matrix (ECM) scaffold, provide cues for the adipogenesis property of AAM. The bioactive components within ECM are influenced by the isolation procedures.</div></div><div><h3>Objective</h3><div>This study aimed to extract and identify adipose-derived MBVs (Adipo-MBVs) from adipose ECM scaffolds and clarify their effective role in engineering adipose tissue formation.</div></div><div><h3>Methods</h3><div>Adipo-MBVs were extracted from two types of adipose ECM, including chemically decellularized matrix (i.e., AAM) and mechanically concentrated ECM (i.e., adipose collagen fragment, ACF). The influence of Adipo-MBVs on cell functions were estimated <em>in vitro</em>. In addition, AAM-hyaluronic acid methacrylate (HAMA) hybrid hydrogel (A/H) with polydopamine (PDA)-coated HAMA microspheres (PDA@HMs) was designed to sustainedly release Adipo-MBVs in an animal model.</div></div><div><h3>Results</h3><div>The results showed that Adipo-MBVs effectively recapitulated AAM effects on the construction of engineering adipose tissue. Crucially, mechanical Adipo-MBVs (M-AT-MBVs) derived from mechanically concentrated ECM exhibited a significantly stronger capacity to induce both adipogenesis and angiogenesis <em>in vitro</em> and <em>in vivo</em>, compared to chemical Adipo-MBVs (C-AT-MBVs) from chemically decellularized matrix. Furthermore, we developed a novel composite delivery system that ensured the sustained release of M-AT-MBVs and robustly promoted the regeneration of vascularized adipose tissue in a mouse model. This enhanced efficacy of M-AT-MBVs was associated with their distinct miRNA profile, particularly an enrichment of pro-adipogenic miR-143, and involved the downregulation of MAPK signaling pathway.</div></div><div><h3>Conclusion</h3><div>This study demonstrated Adipo-MBVs as key regenerative components of adipose ECM. It is shown that mechanical isolation yields superior M-AT-MBVs, and our engineered delivery system presents a novel strategy for soft tissue reconstruction.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 977-994"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Global genomics of Lactococcus lactis: horizontal gene transfer and intergenic variation drive multiple domestication and dairy adaptation” [J. Adv. Res. 83 (2026) 25–36]","authors":"Weicheng Li,Jiaqi Sun,Qiong Wu,Lai-Yu Kwok,Gaifang Dong,Zhihong Sun","doi":"10.1016/j.jare.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.jare.2026.09.016","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"3 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pLM-HP: Peptide hormone prediction using pre-trained protein language model representations","authors":"Chunyan Ao,Shihu Jiao,Xi Su,Huan Yang","doi":"10.1016/j.jare.2026.10.002","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.002","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"37 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing antibody-dependent cellular phagocytosis for cancer immunotherapy: mechanisms, constraints, and therapeutic strategies","authors":"Mingyi Ju,Miao Zhang,Shuai Ma,Yufei An,Shiyu Xiao,Jiabin Xu,Nan Li,Yilin Chen,Minjie Wei,Hui Wang,Lin Zhao","doi":"10.1016/j.jare.2026.10.003","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.003","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"5 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-associated endoplasmic reticulum membranes facilitate gastric epithelial injury in hypoxia-induced gastric mucosal lesions","authors":"Siwei Tan,Jiajie Luo,Xingtong Ou,Xiaoning Guo,Bilun Ke,Shuyan Tan","doi":"10.1016/j.jare.2026.10.007","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.007","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin regeneration axis under metal-based nanozymes: from chronic wound healing to structural and functional restoration","authors":"Ze-Ming Zhuang,&nbsp;Kai Guo,&nbsp;Zhang-Rui Wu,&nbsp;Yi Wang,&nbsp;Xin-Cao Zhong,&nbsp;Chun-Ye Chen,&nbsp;Zi-Xuan Feng,&nbsp;Yan-Ze Yu,&nbsp;Hai-Qi Zhang,&nbsp;Min-Hong Tan,&nbsp;Tao Zhang,&nbsp;Xiao-Ying Lin,&nbsp;Yong Wang,&nbsp;Wei-Qiang Tan","doi":"10.1016/j.jare.2026.01.068","DOIUrl":"10.1016/j.jare.2026.01.068","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic infected wounds, representing a prototypical model of chronic non-healing wounds, leading to severe impairment of skin regeneration. However, complete skin restoration requires more than just wound closure; it crucially involves the inhibition of pathological scarring (fibrosis) and the functional regeneration of skin appendages (e.g., hair follicles). Metal-based nanozymes (MNZs), due to their highly stable, tunable enzyme-mimicking catalytic activity and excellent integration potential, have emerged as promising candidates, with initial studies demonstrating their utility in these broader regenerative aspects. But existing reviews primarily focus on MNZs’ role in basic wound healing, overlooking the structure and functional regeneration potential of skin under MNZs intervention.</div></div><div><h3>Aim of review</h3><div>This review addresses the knowledge gap by analyzing the recent literature to establish a comprehensive “Skin Regeneration Axis” for MNZs application. Specifically, the objective is to integrate and evaluate MNZs’ potential across the three essential dimensions of full-process skin repair: chronic wound healing, structural pathological scar inhibition, and functional appendage regeneration. This integration fully reports MNZs’ potential for holistic skin restoration.</div></div><div><h3>Key scientific concepts of review</h3><div>This review summarizes the fundamentals of MNZs, including their catalytic mechanisms, classifications, and synthetic strategies. It articulates a multidimensional regenerative paradigm for MNZs, elucidating their roles across the entire spectrum of skin regeneration, which constitutes the core concepts of this review: (1) Chronic Wound Healing via controlling inflammation and oxidative stress, (2) Pathological Scar Inhibition through targeted molecular pathway regulation, and (3) Structural Appendage Regeneration (e.g., hair follicles). The review also highlights critical translational challenges and proposes integrated strategies for accelerating the clinical application of MNZs for holistic skin repair.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 1013-1043"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}