Journal of Advanced Research最新文献

{"title":"The alternative androgen receptor isoform A mitigates toxicity of polyglutamine-elongated mutant androgen receptor in spinal and bulbar muscular atrophy","authors":"Marta Chierichetti,&nbsp;Roberta Andreotti,&nbsp;Barbara Tedesco,&nbsp;Veronica Ferrari,&nbsp;Laura Cornaggia,&nbsp;Paola Pramaggiore,&nbsp;Marta Cozzi,&nbsp;Ali Mohamed,&nbsp;Rocio Magdalena,&nbsp;Margherita Piccolella,&nbsp;Giulia Boarolo,&nbsp;Valeria Crippa,&nbsp;Paola Rusmini,&nbsp;Mariarita Galbiati,&nbsp;Carlo Rinaldi,&nbsp;Eric N. Anderson,&nbsp;Udai Bhan Pandey,&nbsp;Maria Pennuto,&nbsp;Riccardo Cristofani,&nbsp;Angelo Poletti","doi":"10.1016/j.jare.2026.01.051","DOIUrl":"10.1016/j.jare.2026.01.051","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene, translated into an elongated polyglutamine (polyQ) tract in the protein. Androgens trigger ARpolyQ toxicity, thus most potential therapeutic approaches involve androgen reduction or AR negative modulation, with severe endocrine side effects.</div></div><div><h3>Objective</h3><div>A start codon (I-AUG) controls AR translation, while a second one, (II-AUG) downstream to I-AUG and the CAG repeat, drives translation of the shorter AR isoform (AR-A) lacking the polyQ tract, but preserves all relevant AR functional domains. Here, we studied AR-A behaviour and its effect on ARpolyQ toxicity in SBMA.</div></div><div><h3>Methods</h3><div>We took advantage of cellular, mice and <em>Drosophila melanogaster</em> SBMA models to asses AR-A behaviour and effect on ARpolyQ aggregation and functions.</div></div><div><h3>Results</h3><div>Comparative expression analyses of AR isoforms revealed that AR-A is predominantly located in the mouse brainstem and spinal cord of the central nervous system, but not in muscle. AR-A retains partial androgenic activity, but does not aggregate. Since ARpolyQ and AR-A can heterodimerize, we tested the effect of AR-A on ARpolyQ behaviour, showing that AR-A has a pro-solubilizing effect on ARpolyQ aggregates and that the heterodimers retain a partial transcriptional activity. Finally, we tested the effect of AR-A in a fly model of SBMA. Flies expressing AR-A alone showed no signs of external eye degeneration, in contrast to those expressing expanded ARpolyQ. Notably, co-expression of AR-A with ARpolyQ significantly reduced ARpolyQ aggregation and eye degeneration, supporting our hypothesis that AR-A enhances ARpolyQ solubility and mitigates its toxicity <em>in vivo</em>.</div></div><div><h3>Conclusions</h3><div>Altogether, our results demonstrate that an increased expression of AR-A may have a role in protecting against ARpolyQ aggregation and toxicity. These findings suggest that AR-A could represent a promising avenue for developing an alternative therapeutic strategy that warrants further investigation.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 959-976"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001277","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":"Treatment of clonal hematopoiesis associated atherosclerosis via vaccine-based clearance of the mutant cells","authors":"Shuang Liang,&nbsp;Wenxin Tao,&nbsp;Di Qu,&nbsp;Panpan Ji,&nbsp;Zhenzhen Hao,&nbsp;Mengying Wei,&nbsp;Guodong Yang,&nbsp;Xueying Zhou,&nbsp;Chen Wang,&nbsp;Lijun Yuan","doi":"10.1016/j.jare.2026.01.040","DOIUrl":"10.1016/j.jare.2026.01.040","url":null,"abstract":"<div><div><em>Introduction:</em> Clonal hematopoiesis of indeterminate potential (CHIP), driven by somatic mutations (e.g., <em>TET2</em>), is an independent risk factor for atherosclerosis (AS). CHIP-mutant macrophages promote plaque inflammation, but targeted therapies are lacking. Crucially, whether these clones acquire immunogenic neoantigens—enabling immune clearance—remains unexplored. <em>Objective:</em> To investigate if <em>Tet2</em>-mutant cells in CHIP-associated AS develop immunogenic neoantigens and evaluate a neoantigen-targeting vaccine strategy. <em>Methods: Tet2</em> was edited in hematopoietic cells via CRISPR/Cas9 and transplanted into <em>Ldlr</em>^-/- mice fed a high-fat diet to model CHIP-accelerated AS. DNA and RNA sequencing of <em>Tet2</em>-mutant macrophages identified nonsynonymous mutations. Neoantigen immunogenicity was predicted in NetMHCpan. A therapeutic vaccine (GelVax) encapsulating mutant cell lysates (neoantigen source), GM-CSF (DC recruitment), and R848 (TLR agonist) within a biocompatible hydrogel was developed. Efficacy was assessed in the AS model. <em>Results: Tet2</em> deficiency exacerbated atherosclerosis (+72% plaque area) and systemic inflammation.  DNA and RNA sequencing results identified 2 mutations showing high MHC-I binding affinity, suggesting neoantigenicity. GelVax vaccination reduced aortic plaque burden by 45%, selectively cleared <em>Tet2</em>-mutant macrophages in plaques, attenuated systemic cytokines (TNF-α, IL-1β) and improved plaque stability (↓ necrotic core, ↑ collagen). The protection was primarily CD8⁺ T-cell dependent. <em>Conclusion: Tet2</em>-mutant cells in CHIP-associated AS acquire immunogenic neoantigens. Leveraging these antigens via a hydrogel vaccine induces clone-specific CD8⁺ T cell responses, clears pathogenic macrophages, and ameliorates atherosclerosis. This validates mutant neoantigens as actionable targets for CHIP-driven cardiovascular disease.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 335-347"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995897","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":"Non-invasive and painless mid-infrared modulation increases collagen in human and mouse skin","authors":"Zeyu Wang,&nbsp;Jiahui Zhu,&nbsp;Yuting Wang,&nbsp;Tianxing Hu,&nbsp;Shuai Chen,&nbsp;Senlin Xu,&nbsp;Yaoying Li,&nbsp;Xiang Liao,&nbsp;Shanshan Liang,&nbsp;Yang Li,&nbsp;Xuanyue Wang,&nbsp;Sunny C. Li,&nbsp;Yan Yang,&nbsp;Hongbo Jia,&nbsp;Xiaowei Chen,&nbsp;Xing Fan,&nbsp;Lan Ge,&nbsp;Jianxiong Zhang","doi":"10.1016/j.jare.2026.01.069","DOIUrl":"10.1016/j.jare.2026.01.069","url":null,"abstract":"<div><h3>Introduction</h3><div>Stimulating collagen production is a key strategy for enhancing skin vitality and counteracting aging. However, current methods to boost collagen synthesis often entail pain and tissue trauma. There is a compelling need for painless, non-invasive approaches to effectively increase skin collagen.</div></div><div><h3>Objectives</h3><div>To investigate the effects of mid-infrared modulation (MIMO) on skin collagen deposition across multiple biological scales, from human and animal models <em>in vivo</em> to human dermal fibroblasts in vitro.</div></div><div><h3>Methods</h3><div>We determined optimal MIMO irradiation parameters (energy, duration) in human and animal skin. Effects on collagen deposition were evaluated <em>in vivo</em> (human, mouse) and in vitro (human dermal fibroblasts). Levels of inflammatory and collagen metabolism-related proteins were measured by ELISA.</div></div><div><h3>Results</h3><div>MIMO irradiation (70 mW/cm²) significantly enhanced collagen deposition in human and mouse skin <em>in vivo</em> without causing excessive heating. This was associated with downregulation of the collagen-degrading enzyme MMP-1 and upregulation of collagen synthesis-promoting factors (TGF-β, HSP47, HSP70) in mouse skin. Furthermore, MIMO stimulated the secretion of multiple collagen subtypes in human dermal fibroblasts in vitro.</div></div><div><h3>Conclusions</h3><div>MIMO represents a safe, non-invasive, and painless approach for effectively enhancing skin collagen deposition <em>in vivo</em>.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 577-588"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071844","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":"Chromosome-level genome of wild-simulated Panax ginseng identifies SNP markers for germplasm and medicinal quality evaluation","authors":"Xuejiao Liao,&nbsp;Yidan Xi,&nbsp;Baosheng Liao,&nbsp;Shuiming Xiao,&nbsp;Shuai Guo,&nbsp;Haoyu Hu,&nbsp;Zhihai Huang,&nbsp;Deqiang Dou,&nbsp;Shilin Chen,&nbsp;Jiang Xu","doi":"10.1016/j.jare.2026.01.062","DOIUrl":"10.1016/j.jare.2026.01.062","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Panax ginseng</em> C. A. Mey., a precious traditional medicinal herb, demonstrates diverse pharmacological activities, including immunomodulation and anti-fatigue effects. However, prolonged cultivation has led to germplasm admixture and cultivar degeneration, resulting in inconsistent quality that severely compromises its medicinal value and industrial standardization. Therefore, establishing accurate and efficient germplasm evaluation tools is critical for ensuring the quality of <em>P. ginseng</em> medicinal materials.</div></div><div><h3>Objectives</h3><div>To integrate whole-genome sequencing and chemical fingerprinting for ginseng germplasm identification and quality consistency assessment.</div></div><div><h3>Methods</h3><div>Chromosome-level genomes of ginseng from Jilin (JA) and Liaoning (FC) were assembled using PacBio HiFi, Illumina, and Hi-C technologies. Gene family identification and phylogenetic analysis were performed across 13 representative species. Using the JA genome as the reference, we constructed a pan-genome incorporating 7 ginseng genomes to dissect gene repertoire composition and structural variation distribution across ginseng populations. Population structure analysis with 76 individual ginseng samples revealed genetic diversity, and its integration with HPLC chemical fingerprints provided a joint assessment of quality consistency.</div></div><div><h3>Results</h3><div>We assembled two chromosome-level genomes and, through comparative genomics, revealed significant expansion of ginsenoside biosynthesis-related gene families and subgenome divergence. The core gene set accounted for 54.1% of the pan-genome, indicating high genetic conservation. SNP distribution patterns from population resequencing enabled the development of germplasm-specific molecular markers and a genetic-chemical integrated evaluation model.</div></div><div><h3>Conclusion</h3><div>The molecular marker system and genetic-chemical joint assessment developed here provide reliable novel tools for germplasm identification and quality control, advancing standardization in the ginseng industry.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 505-518"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089778","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":"Cellular and molecular mechanisms of nasolacrimal duct obstruction: New insights into CD4+ T cell-MIF-fibroblast pathways","authors":"Xinyue Yu,&nbsp;Shanshan Liu,&nbsp;Youao Zhang,&nbsp;Rongxin Chen,&nbsp;Chaojuan Wen,&nbsp;Jingya Zhu,&nbsp;Xielan Kuang,&nbsp;Kerui Wang,&nbsp;Hao Huang,&nbsp;Yan Mao,&nbsp;Ping Xu,&nbsp;Jianhua Yan,&nbsp;Qingjiong Zhang,&nbsp;Xuanwei Liang,&nbsp;Huangxuan Shen","doi":"10.1016/j.jare.2026.01.060","DOIUrl":"10.1016/j.jare.2026.01.060","url":null,"abstract":"<div><h3>Introduction</h3><div>Nasolacrimal duct obstruction (NLDO) is a common ophthalmic condition characterized by epiphora and ocular discharge. Its etiology remains poorly understood, and treatment primarily relies on surgical intervention due to a lack of effective drugs.</div></div><div><h3>Objectives</h3><div>To characterize the single-cell transcriptional landscape of the nasolacrimal duct in patients with nasolacrimal duct obstruction (NLDO) and to elucidate the immunoregulatory mechanisms underlying the key fibrotic process driving disease progression.</div></div><div><h3>Methods</h3><div>Nasolacrimal duct tissues were obtained from 4 menopausal female patients by endoscopic dacryocystorhinostomy (DCR). Samples were collected from both the obstruction and <em>para</em>-blocked sites (Self-control of disease progression processes). Single-cell RNA sequencing was performed on the samples, and the cell composition and cell–cell interactions were analyzed. Subsequently, body fluid and tissue samples were obtained from 13 patients for histological and <em>in vitro</em> functional assays.</div></div><div><h3>Results</h3><div>Ten major cell types were identified in 67,658 cells of the nasolacrimal duct. Intercellular communication analysis revealed the critical role of macrophage migration inhibitory factor (MIF) in the interaction between fibroblasts and immune cells. Histological analysis revealed significant inflammation and fibrosis in nasolacrimal duct obstruction. Mechanistically, CD4⁺ T cell-derived MIF activated fibroblasts, promoting their proliferation. Subsequently, these fibroblasts secreted pro-inflammatory cytokines and extracellular matrix, which further stimulated CD4⁺ T cells. This created a self-perpetuating feedback loop that exacerbated disease progression. Overall, targeting MIF to disrupt this cycle presents a novel therapeutic approach to delay the progression to complete obstruction.</div></div><div><h3>Conclusion</h3><div>This study delineates the cellular transcriptomic profile of the nasolacrimal duct in NLDO patients and demonstrates that the MIF-centered immunoregulatory axis acts as a key driver of fibrotic obstruction, while plasma cells and CD8⁺ T cells also contribute to the immune landscape. These findings provide critical insights into the immunoregulatory mechanisms underlying NLDO and highlight MIF-related pathways as potential therapeutic targets for impeding disease progression.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 485-504"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072658","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":"MAC5A dual-functionally regulates cold responses at both transcriptional and post-transcriptional levels","authors":"Shuo Wang,&nbsp;Zhiyin Meng,&nbsp;Hua Liu,&nbsp;Deyin Deng,&nbsp;Yunfei Du,&nbsp;Liangyu Guo,&nbsp;Bijun Cai,&nbsp;Huan Yang,&nbsp;Chengyang Li,&nbsp;Yongjun Zhou,&nbsp;Yirong Shen,&nbsp;Xiaoxue Ye,&nbsp;Wenwu Wu,&nbsp;Yan Li","doi":"10.1016/j.jare.2026.01.015","DOIUrl":"10.1016/j.jare.2026.01.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Plant cold responses have been extensively studied at the transcriptional level, particularly focusing<!--> <!-->on conserved transcription factors (TFs) such as C-repeat binding factors (CBFs). However, the post-transcriptional roles of RNA-binding proteins (RBPs) remain largely unexplored, with evolutionarily conserved cold-responsive RBPs yet to be investigated across species.</div></div><div><h3>Objectives</h3><div>This study aimed to identify conserved cold–responsive RBPs across plant species and investigate how a candidate RBP, MAC5A, regulates cold tolerance.</div></div><div><h3>Methods</h3><div>Integrative analyses of multi-species comparative genomes and low-temperature transcriptomes identified conserved cold-responsive RBPs. <em>MAC5A</em> loss-of-function and<!--> <!-->overexpression lines were examined<!--> <!-->to validate its genetic role in cold tolerance. Comparative transcriptomics and CUT&amp;Tag-seq were applied<!--> <!-->to determine MAC5A-modulated alternative splicing (AS) and cold-regulated (<em>COR</em>) gene expression, which were further validated<!--> <!-->through minigene and dual-luciferase assays.</div></div><div><h3>Results</h3><div>We identified multiple conserved cold-responsive RBPs and focused on <em>Arabidopsis</em> MAC5A, a spliceosome component. Cold-induced <em>MAC5A</em> expression was independent of both CBF regulation and ABA signaling. Loss-of-function of <em>MAC5A</em> decreased freezing tolerance, while its overexpression enhanced it. The <em>mac5a</em> mutant exhibited extensive cold-responsive transcriptome alterations, with thousands of genes showing differential AS. Minigene assays confirmed MAC5A modulates splicing of <em>COR</em> genes, including <em>CCA1</em>,<!--> <em>PRR9</em>,<!--> <em>ABF3</em> and<!--> <em>bHLH112</em>. Additionally, MAC5A regulated expression of other <em>COR</em> genes such as <em>ABI1</em>, <em>COR28</em>, <em>GolS2</em>, <em>RD20</em>, <em>GRP4</em>, <em>DIN10</em> and <em>NIA1</em> at the transcriptional level, likely through protein complexes. Notably, limited overlap existed between<!--> <!-->MAC5A-modulated AS genes and<!--> <!-->transcriptionally regulated <em>COR</em> <!-->genes, suggesting largely independent regulatory pathways.</div></div><div><h3>Conclusions</h3><div>MAC5A functions as a dual regulator to orchestrate cold response through both transcriptional and post-transcriptional control of <em>COR</em> genes. The limited overlap between genes regulated by these two layers indicates potential uncoupled regulatory manners, warranting further investigation into their coordination during cold stress.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 45-59"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895087","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":"Distinct effector functions and synergy of CAR mRNA-engineered T cells and macrophages in the clearance of CD19+ leukemia cells","authors":"Liangliang Liao,&nbsp;Cheng Lin,&nbsp;Adrian Kuzmanović,&nbsp;Nan Wang,&nbsp;Alexander Jans,&nbsp;Christian Penners,&nbsp;Kim Ohl,&nbsp;Sandra Johnen,&nbsp;Reka Geczy,&nbsp;Martin Rabel,&nbsp;Samuel Clarke,&nbsp;Aruna Balgi,&nbsp;Christian Liedtke,&nbsp;Matthias Bartneck","doi":"10.1016/j.jare.2026.01.049","DOIUrl":"10.1016/j.jare.2026.01.049","url":null,"abstract":"<div><h3>Introduction</h3><div>Chimeric antigen receptor (CAR) technology represents a groundbreaking advancement in gene therapy. While CAR-T cells are approved for specific types of leukemia, the therapeutic potential of CAR-macrophages remains largely unexplored. Additionally, potentially synergistic effects between CAR-T cells and CAR-macrophages in cancer cell clearance are still elusive.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the efficiency and mechanisms of human CAR-T cells and CAR-macrophages for clearing cancer cells using co-culture experiments.</div></div><div><h3>Methods</h3><div>We encapsulated a second generation CD19 CAR mRNA or enhanced green fluorescent protein (<em>Egfp</em>) encoding control mRNA into lipid nanoparticles (LNP) using different methods. We transfected human primary T cells or macrophages with these LNP and studied their CAR expression using flow cytometry or confocal microscopy. Killing and phagocytosis assays were conducted to evaluate the impact of CAR-T cells and CAR-macrophages on CD19⁺ NALM6 leukemia and CD19^- control cells. Motility analyses of macrophages, T cells, and cancer cells were done using live-cell imaging.</div></div><div><h3>Results</h3><div>Activated T cells upregulated the low-density lipoprotein receptor (LDLR), resulting in higher CAR surface expression post-transfection than in non-activated T cells. CAR-T cells efficiently induced death of lymphoma cells. CAR-macrophages cleared cancer cells mainly via phagocytosis and CAR mRNA altered the expression of both M1 and M2-associated genes. Interestingly, CAR macrophages also upregulated the <em>Signal regulatory protein alpha</em> (<em>SIRPA</em>), a receptor of the CD47 ligand expressed by cancer cells, and knockdown of <em>SIRPA</em> by siRNA efficiently counteracted this phenomenon. We noted a decrease in the motility of macrophages, T cells, and cancer cells in co-cultures containing CAR-transfected effector cells. Co-culturing CAR-T cells with CAR-macrophages synergistically enhanced tumor cell eradication.</div></div><div><h3>Conclusion</h3><div>Our findings underscore the superior cancer cell-killing capability of CAR-T cells. Additionally, CAR-macrophages play a crucial role in clearing cancer cells through phagocytosis, thereby synergistically supporting the activity of CAR-T cells.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 1119-1136"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995577","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":"A DNA triangular prism scaffold-guided directionally-controlled derailment-free DNAzyme walker","authors":"Limei Xiao,&nbsp;Yaqin Wang,&nbsp;Hong Huang,&nbsp;Chang Xue,&nbsp;Qian Gao,&nbsp;Linhuan Chen,&nbsp;Xin Yu,&nbsp;Zai-Sheng Wu","doi":"10.1016/j.jare.2026.01.046","DOIUrl":"10.1016/j.jare.2026.01.046","url":null,"abstract":"<div><h3>Introduction</h3><div>Deoxyribozyme (DNAzyme) with RNA cleavage activity, including a DNAzyme walker, has been extensively explored as the tool for cancer diagnosis and therapy due to its excellent programmability, stability, and activity. However, the precise control over the directionality and progressivity of molecular movement towards its predetermined destination remains a formidable challenge.</div></div><div><h3>Objectives</h3><div>We aim to construct a three-dimensional DNA walker capable of addressing the uncertainty of motion direction because of the deviation from the predesignated track in uniform solutions.</div></div><div><h3>Methods</h3><div>The cleavage sequence of substrates by DNAzyme was explored through gel electrophoresis analysis .</div></div><div><h3>Results</h3><div>Gel electrophoresis analyses show that DNAzyme cleaves the substrates in a sequential manner and preferentially digests the ones in the shortest spatial distance regardless of their nature, indicating a distance-dependent cleavage process. Moreover, the substrate stands freely moving in a homogenous solution (not confined onto DNA scaffold) cannot be cleaved, implying that the derailment of DNAzmye walker from the tri-prism scaffold is completely circumvented. When the adjacent substrates were removed to leave the vacant sites, the cleavage order of substrates is changed, indicating that the controllability of cleavage behavior of DNAzyme is realized.</div></div><div><h3>Conclusion</h3><div>DNA triangular prism-controlled DNAzyme walker circumvents the intractable derailment event and has several advantages, such as low cost, programmability, high cleavage specificity and directional controllability, showing great potential applications in biosensing, cancer, diagnosis and therapy.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 401-414"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995576","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":"Rhizosphere Penicillium and phosphorus availability drive bioactive compound accumulation in Amomum villosum","authors":"Zhenkai Li,Yufei Qin,Jiayi Cai,Xin Luo,Yanli Yao,Yukun Wang,Qiuling Liang,Lili Xie,Mei Bai,Xiangxiu Liang,Cuiyue Liang,Junjun He,Hong Wu","doi":"10.1016/j.jare.2026.10.030","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.030","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"13 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150569","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":"Podocyte-derived exosomes instruct dendritic cell-dependent CD8+ T cell activation and proliferation in renal inflammation","authors":"Bin Qian,&nbsp;Shuya Mao,&nbsp;Yang Chen,&nbsp;Ying Liu,&nbsp;Mingchao Zhang,&nbsp;Dihan Zhu,&nbsp;Ke Zen,&nbsp;Yu Wang,&nbsp;Zhihong Liu,&nbsp;Limin Li","doi":"10.1016/j.jare.2026.01.032","DOIUrl":"10.1016/j.jare.2026.01.032","url":null,"abstract":"<div><h3>Introduction</h3><div>Minimal Change Disease (MCD) represents a prevalent pathological cause of nephrotic syndrome. While podocyte injury is recognized as the direct cause of proteinuria in MCD, aberrant T-cell activation is a key driver of this podocyte damage. However, the absence of T-cell infiltration in renal biopsies and ineffectiveness of immunosuppressive therapy in a subset of patients suggest the existence of undiscovered key mechanisms underlying MCD immunopathogenesis.</div></div><div><h3>Objectives</h3><div>This study investigates the role of podocyte-derived exosomes (Pdo-Exos) in T cell activation via antigen presentation in MCD.</div></div><div><h3>Methods</h3><div>Using an <em>in vitro</em> co-culture system, a puromycin aminonucleoside (PAN)-induced MCD mouse model, and clinical samples, we evaluated the immunostimulatory capacity of Pdo-Exos, focusing on antigen presentation via MHC-I and Rab27a-regulated exosome secretion.</div></div><div><h3>Results</h3><div>Pdo-Exos activated CD8⁺ T cells through MHC-I without promoting proliferation, indicating a role for dendritic cell-mediated cross-presentation. In OT-I mice, OVA-loaded Pdo-Exos exacerbated proteinuria and activated both tissue-resident and lymphoid T cells. MCD patients exhibited increased circulating activated T cells, and their podocyte exosomes showed significantly elevated MHC-I and co-stimulatory molecule CD80. Rab27a-dependent exosome secretion exacerbated disease severity, while inhibition of Rab27a mitigated proteinuria and inflammation.</div></div><div><h3>Conclusion</h3><div>Podocyte-derived exosomes mediate CD8⁺ T cell activation by acting as antigen-presenting vesicles, with DCs facilitating T cell expansion. Rab27a-dependent exosome secretion contributes to MCD progression, highlighting a novel therapeutic strategy.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 885-898"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956611","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}