Journal of Advanced Research最新文献

{"title":"Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis","authors":"Jing Yu ,&nbsp;Lili Feng ,&nbsp;Zhanhao Luo ,&nbsp;Jingyi Yang ,&nbsp;Qiang Zhang ,&nbsp;Chen Liu ,&nbsp;Dayi Liang ,&nbsp;Yanchun Xie ,&nbsp;Hongmin Li ,&nbsp;Junli Gong ,&nbsp;Zhen He ,&nbsp;Ping Lan","doi":"10.1016/j.jare.2024.11.024","DOIUrl":"10.1016/j.jare.2024.11.024","url":null,"abstract":"<div><h3>Introduction</h3><div>The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.</div></div><div><h3>Methods</h3><div>The impact of <em>Il10</em> deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of <em>Parabacteroides distasonis</em> (<em>P. distasonis</em>) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in <em>P. distasonis</em> inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both <em>in vivo</em> and <em>in vitro</em>. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.</div></div><div><h3>Results</h3><div>We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, <em>Il10</em>-deficiency (<em>Il10^−/−</em>) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, <em>Il10^−/−</em> mice reshaped gut microbiota composition, notably enriching <em>P. distasonis</em>. The enriched <em>P. distasonis</em> produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of <em>VEGFA</em>, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both <em>in vitro</em> and <em>in vivo</em> lung metastasis mouse models.</div></div><div><h3>Conclusions</h3><div>These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-<em>VEGFA</em> axis mediated by gut <em>P. distasonis</em>, suggesting that <em>P. distasonis</em> or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 467-479"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673783","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":"The significance of urine extracellular vesicle DNA methylation detection in the diagnosis and classification of prostate cancer","authors":"Ting Ding, Yanjun Diao, Ruiqing Fu, Chengxiang Gong, Qiye He, Weixiang He, Longlong Zhang, Xiaojian Yang, Xianfei Zeng, Lijuan Yu, Jiayun Liu, Weimei Shi, Kang Zhang, Xiaoke Hao","doi":"10.1016/j.jare.2025.09.056","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.056","url":null,"abstract":"<h3>Introduction</h3>As one of the most common malignant tumors in men, prostate cancer (PCa) still lacks convenient, non-invasive and highly specific diagnostic markers. The advantages of Extracellular vesicle (EV) DNA in tumor diagnosis have gradually attracted the attention of researchers. However, methylation detection, which is more advantageous than mutation detection in tumor diagnosis, has not been widely practiced in EV DNA, and its value in PCa diagnosis also remains underexplored.<h3>Objectives</h3>This study aims to establish and optimize an EV DNA methylation detection system and evaluate its diagnostic and classification potential for PCa.<h3>Methods</h3>We characterized EV DNA biological properties, optimized pretreatment strategies, validated its correlation with genomic DNA methylation, and explored urine EV DNA methylation targets in 86 benign prostatic hyperplasia (BPH) and 109 PCa patients across three cohorts (screening: 30 BPH/33 PCa; training: 27 BPH/30 PCa; validation: 29 BPH/46 PCa).<h3>Results</h3>Heterogeneous biological characteristics were observed among DNA from different subtypes of EV, but methylation profiles remained consistent across subtypes and post-DNase I treatment. EV DNA accurately reflected the methylation state of source cell genomic DNA. By combining our screening results with data from the TCGA database and previously reported, we developed a panel consisting of 667 PCa-specific methylation targets for detection. Among these, six methylation sites (MACF1、LINC01359-1、LINC01359-2、ADCY4、GAPLINC、C19orf25) demonstrated high diagnostic value for PCa, enabling construction of PCa and aggressive PCa differential diagnosis model with AUCs up to 0.74 and 0.91 respectively. The diagnostic value of these six markers was further confirmed using methylight PCR in the validation cohort which also displayed promising performance as a tool for diagnosing PCa.<h3>Conclusion</h3>This study highlights the potential of urine EV DNA methylation as a novel diagnostic marker for PCa and lays a foundation for future EV DNA research.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"71 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195107","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":"Design of highly leaf-adhesive and anti-UV herbicide nanoformulation for enhanced herbicidal activity","authors":"Dongdong Li ,&nbsp;Jianan Li ,&nbsp;Hao Li ,&nbsp;Zhendong Bai ,&nbsp;Chujian Ma ,&nbsp;Haodong Bai ,&nbsp;Dingfeng Luo ,&nbsp;Zuren Li ,&nbsp;Lianyang Bai","doi":"10.1016/j.jare.2024.12.034","DOIUrl":"10.1016/j.jare.2024.12.034","url":null,"abstract":"<div><h3>Introduction</h3><div>Conventional pesticide formulations have been widely used to boost agricultural productivity, but their weak foliar adhesion and instability under UV light during spraying lead to low utilization rates and potential environmental and health hazards. To counter these challenges, the development of nanoformulations represents a pivotal strategy. These advanced formulations are designed to enhance the efficacy of active ingredients (AIs) and reduce ecological impacts, thereby addressing the need for sustainable agricultural development.</div></div><div><h3>Objectives</h3><div>The study aims to fabricate a highly leaf-adhesive and anti-UV herbicide nanoformulation, designed to enhance the herbicidal activity and utilization rates of AIs.</div></div><div><h3>Methods</h3><div>Herein, the herbicide nanoformulations (Called CB@MSNs-TA-Fe) are synthesized by incorporating cyhalofop-butyl into tannic acid-Fe (III) ions-coated functionalized mesoporous silica. The foliar retention performance of the samples was assessed integrating SEM observation and HPLC analysis.</div></div><div><h3>Results</h3><div>The CB@MSNs-TA-Fe with rough outer surface displays typical core–shell structure featuring an average diameter of about 118 nm. After amino modification, the CB@MSNs-TA-Fe shows enhanced loading rate for CB (14.4 ± 0.2 %) and superior thermal stability. The release rate of CB within CB@MSNs-TA-Fe under acidic conditions is higher compared to that under alkaline and neutral conditions. Upon UV irradiation, the half-life of CB within CB@MSNs-TA-Fe nanoparticles is 12.4 times higher than that of CB technical (CB TC). Enhanced foliar adhesion of CB@MSNs-TA-Fe on hydrophobic leaf surfaces is observed, which can effectively mitigate the risk of wash-off by rainfall. The CB@MSNs-TA-Fe displays enhanced herbicidal efficacies against barnyard grass under UV irradiation or simulated rainwater scouring, compared with CB TC and CB oil dispersion. Furthermore, the TA-Fe-coated MSNs-NH₂ nano-carrier (MSNs-TA-Fe) reveals excellent biosafety on rice, zebrafish, and earthworms.</div></div><div><h3>Conclusion</h3><div>The developed TA-Fe-functionalized herbicide nanoformulations, with high foliar adhesion and anti-UV properties, effectively improve the utilization efficiency of AIs, thus offering innovative solutions for the development of efficient pesticide formulations.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 109-118"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874688","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":"Macrophage P2Y12 regulates iron transport and its inhibition protects against atherosclerosis","authors":"Yang-Xi Hu ,&nbsp;Hong-Min You ,&nbsp;Mei-Rong Bai ,&nbsp;Wen-Heng Yue ,&nbsp;Fang-Fang Li ,&nbsp;Bo-Wen Hu ,&nbsp;Ya-Sha Chen ,&nbsp;Xiang-Yu Shen ,&nbsp;Yue Wu ,&nbsp;Jia-Mei Wang ,&nbsp;Zhi-Qing He ,&nbsp;Xia Tao ,&nbsp;Qing Jing ,&nbsp;Chun Liang","doi":"10.1016/j.jare.2024.12.019","DOIUrl":"10.1016/j.jare.2024.12.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Iron retention is commonly observed in atherosclerotic plaques and is believed to be detrimental to atherosclerosis. Platelet P2Y12 is a target of antiplatelet therapy in preventing thrombotic complications of atherosclerosis. The protective effect of P2Y12 on hematopoiesis reported by our previous work implies the involvement of P2Y12 in iron metabolism.</div></div><div><h3>Objectives</h3><div>This study further investigated the role of P2Y12 in the iron metabolism of macrophages, the key player in systemic iron homeostasis and atherosclerosis.</div></div><div><h3>Methods</h3><div>The association between serum iron and the use of P2Y12 inhibitors was evaluated by a case-control study in human. Secondary iron overload and atherosclerosis animal models were established in <em>P2Y12</em>-deficient zebrafish to explore the role of P2Y12 in macrophage iron metabolism <em>in vivo</em>. Both iron-overloaded murine primary peritoneal macrophages (PMs) and ox-LDL–treated PMs with <em>P2Y12</em> knockdown were used for <em>in vitro</em> studies. RNA sequencing and pharmacological approaches were performed to investigate the downstream mechanisms.</div></div><div><h3>Results</h3><div>Increased serum iron level was positively associated with P2Y12 inhibitor usage [odds ratio (OR) = 10.333 (1.281–83.370)]. Elevated serum iron level and transferrin saturation, reduced hepatic and splenic iron content, and decreased iron staining in macrophages were observed in secondary iron overload <em>P2Y12</em>-deficient zebrafish. Deficiency of <em>P2Y12</em> in <em>ApoEb^-/-</em> zebrafish fed a high-fat diet reduced atherosclerosis progression and intraplaque iron retention. Furthermore, reduced ferritin, restored cell viability and expression of ferroptosis marker proteins, and decreased ROS formation and inflammatory cytokines were observed in both iron-overloaded and ox-LDL–treated PMs with <em>P2Y12</em> knockdown <em>in vitro</em>, while reversed phenotypes were observed after agonist-induced P2Y12 activation. Mechanistically, <em>P2Y12</em> inhibition in iron-overloaded or ox-LDL–treated PMs suppressed NF-κB p65 phosphorylation and hepcidin expression, both of which were reversed by P2Y12 activation.</div></div><div><h3>Conclusion</h3><div>P2Y12 inhibition decreased hepcidin autocrine through repressing NF-κB p65 phosphorylation in macrophages, preventing intracellular iron retention and atherosclerosis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 585-603"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809722","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":"ORP5 promotes cardiac hypertrophy by regulating the activation of mTORC1 on lysosome","authors":"Di Zhao ,&nbsp;Ran Xu ,&nbsp;Yufei Zhou ,&nbsp;Jiaying Wu ,&nbsp;Xiaoxue Zhang ,&nbsp;Hong Lin ,&nbsp;Jienan Wang ,&nbsp;Zhiwen Ding ,&nbsp;Yunzeng Zou","doi":"10.1016/j.jare.2024.12.014","DOIUrl":"10.1016/j.jare.2024.12.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Oxysterol binding protein (OSBP)-related protein 5 (ORP5) mainly functions as a lipid transfer protein at membrane contact sites (MCS). ORP5 facilitates cell proliferation through the activation of mTORC1 signaling. While the pro-hypertrophic effects of mTORC1 are well-documented, the specific role of ORP5 in the context of pathological cardiac hypertrophy remains inadequately understood.</div></div><div><h3>Methods</h3><div>To investigate the role of ORP5 in pathological cardiac hypertrophy, AAV9-treated mice and neonatal rat ventricular myocytes (NRVMs) were utilized. Cardiac function, morphology, and mTORC1 signaling alterations induced by pro-hypertrophic stimuli were assessed in both myocardium and NRVMs. Additionally, a range of molecular techniques were employed to elucidate the regulatory mechanisms of ORP5 on mTORC1 in hypertrophied hearts.</div></div><div><h3>Results</h3><div>Increased expression of ORP5 was observed in the hearts of patients with hypertrophic cardiomyopathy (HCM), in mice subjected to transverse aortic constriction (TAC), and in NRVMs treated with angiotensin II (AngII). We found that ORP5 binds to mTOR in cardiomyocytes. Upon exposure to TAC surgery, ORP5-deficient hearts exhibited enhanced cardiac function, reduced cardiomyocyte hypertrophy, and diminished collagen deposition than wild type. Conversely, overexpression of ORP5 significantly aggravated hypertrophic responses in both hearts and NRVMs. Notably, the promotion of cardiac hypertrophy induced by ORP5 overexpression was reversed by rapamycin, an inhibitor of mTORC1. Mechanistically, our study elucidated that the ORD domain of ORP5 interacts with mTORC1, facilitating its translocation to the outer membrane of the lysosome for subsequent activation. This activation triggers the downstream signaling pathways involving S6K1 and 4E-BP1, which initiate protein synthesis, thereby promoting pathological cardiac hypertrophy.</div></div><div><h3>Conclusions</h3><div>Our findings provide the inaugural evidence that ORP5 facilitates pathological ventricular hypertrophy through the translocation of mTORC1 to the lysosome for subsequent activation. Consequently, ORP5 has the potential to serve as a diagnostic biomarker or therapeutic target for pathological cardiac hypertrophy in the future.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 529-541"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797724","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":"Odontogenic exosomes simulating the developmental microenvironment promote complete regeneration of pulp-dentin complex in vivo","authors":"Yifan Wang ,&nbsp;Jing Mao ,&nbsp;Yujie Wang ,&nbsp;Rui Wang ,&nbsp;Nan Jiang ,&nbsp;Xiaohan Hu ,&nbsp;Xin Shi","doi":"10.1016/j.jare.2024.12.048","DOIUrl":"10.1016/j.jare.2024.12.048","url":null,"abstract":"<div><h3>Introduction</h3><div>Establishing an optimized regenerative microenvironment for pulp-dentin complex engineering has become increasingly critical. Recently, exosomes have emerged as favorable biomimetic nanotherapeutic tools to simulate the developmental microenvironment and facilitate tissue regeneration.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate the multifaceted roles of exosomes from human dental pulp stem cells (DPSCs) that initiated odontogenic differentiation while sustaining mesenchymal stem cell (MSC) characteristics in odontogenesis, angiogenesis, and neurogenesis during pulp-dentin complex regeneration.</div></div><div><h3>Methods</h3><div>Differential centrifugation was performed to isolate exosomes from normal DPSCs (DPSC-Exos) and DPSCs that initially triggered odontogenic differentiation (DPSC-Od-Exos). The impact of these exosomes on the biological behavior of DPSCs and human umbilical vein endothelial cells (HUVECs) was examined in vitro through CCK-8 assay and Transwell migration assay, as well as assays dedicated to assessing odontogenic, angiogenic, and neurogenic capabilities. In vivo, Matrigel plugs and human tooth root fragments incorporating either DPSC-Exos or DPSC-Od-Exos were subcutaneously transplanted into mouse models. Subsequent histological, immunohistochemical, and immunofluorescent analyses were conducted to determine the regenerative outcomes.</div></div><div><h3>Results</h3><div>DPSC-Exos and DPSC-Od-Exos revealed no remarkable difference in their characteristics. In vitro analyses indicated that DPSC-Od-Exos significantly facilitated the proliferation, migration, and multilineage differentiation of DPSCs compared with DPSC-Exos. Furthermore, DPSC-Od-Exos elicited a more pronounced effect on the tubular structure formation of HUVECs. Consistently, Matrigel plug assays confirmed that DPSC-Od-Exos exhibited superior performance in promoting endothelial differentiation of DPSCs and stimulating angiogenesis in HUVECs. Notably, DPSC-Od-Exos contributed to complete pulp-dentin complex regeneration in human tooth root fragments, characterized by enriched neurovascular structures and a continuous layer of odontoblast-like cells, which extended cytoplasmic projections into the newly formed dentinal tubules.</div></div><div><h3>Conclusion</h3><div>By simulating the developmental microenvironment, multifunctional DPSC-Od-Exos demonstrated promising potential for reconstructing dentin-like tissue, vascular networks, and neural architectures, thereby enhancing our understanding of the therapeutic implications of DPSC-Od-Exos in regenerative endodontic treatment.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 405-421"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929503","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":"5-Aminolevulinic acid improves strawberry salt tolerance through a NO–H2O2 signaling circuit regulated by FaWRKY70 and FaWRKY40","authors":"Hao Yang,&nbsp;Jianting Zhang,&nbsp;Yan Zhong,&nbsp;Liangju Wang","doi":"10.1016/j.jare.2024.12.031","DOIUrl":"10.1016/j.jare.2024.12.031","url":null,"abstract":"<div><h3>Introduction</h3><div>5-Aminolevulinic acid (ALA) is an essential biosynthetic precursor of tetrapyrrole compounds, naturally occurring in all living organisms. It has also been suggested as a new plant growth regulator. Treatment with ALA promotes strawberry Na⁺ homeostasis under salt stress. Regulation of this process requires the signaling molecules nitric oxide (NO) and hydrogen peroxide (H₂O₂), but the specific signaling cascade and transcriptional regulatory mechanism have not previously been characterized.</div></div><div><h3>Objectives</h3><div>Our work focused on the dissection of the NO and H₂O₂ signaling cascade and transcriptional regulatory mechanism by which FaWRKY70-FaWRKY40 participated in ALA-improved Na⁺ homeostasis and salt tolerance of strawberry.</div></div><div><h3>Methods</h3><div>It was preliminarily confirmed by transcriptome and RT-qPCR that <em>FaWRKY40</em> and <em>FaWRKY70</em> participated in ALA-induced salt tolerance of strawberry. Two WRKY transcription factors overexpressed in woodland strawberry as well as tobacco were used to identify the gene functions in salt tolerance. Yeast one-hybrid (Y1H), β-glucuronidase (GUS), dual luciferase reporter (DLR) and electrophoretic mobility shift assays (EMSA) were used to verify the interaction with the target gene.</div></div><div><h3>Results</h3><div>ALA induced NO and H₂O₂ production, which formed a signaling circuit reciprocally regulated by <em>FaNR1</em> and <em>FaRbohD</em> expression to coordinate Na⁺ homeostasis. FaWRKY40 was shown to act as a positive transcription factor in this pathway: <em>FaWRKY40</em> overexpression improved salt tolerance in woodland strawberry and tobacco, whereas <em>FaWRKY40</em> RNA interference increased plant salt injury. FaWRKY40 bound to the promoters of <em>FaRbohD</em>, <em>FaNHX1</em>, and <em>FaSOS1</em> to promote root H₂O₂ generation and Na⁺ reallocation. Conversely, FaWRKY70, a negative WRKY transcription factor, was found to increase salt sensitivity by inhibiting expression of <em>FvWRKY40</em>, <em>FvNR1</em>, and <em>FvHKT1</em>. ALA inhibited <em>FaWRKY70</em> but increased <em>FaWRKY40</em> expression, coordinating the regulation of NO-H₂O₂ signaling and Na⁺ homeostasis when strawberry was stress by salinity.</div></div><div><h3>Conclusion</h3><div>ALA inhibits NaCl-stimulated <em>FaWRYK70</em> expression, relieving the transcriptional inhibition of its downstream targets. The NO–H₂O₂ signaling circuit can then initiate mechanisms such as Na⁺ exclusion, vacuolar sequestration, and removal of Na⁺ from the xylem sap, limiting Na⁺ accumulation in the leaves and promoting Na⁺ homeostasis and plant salt tolerance.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 91-107"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901929","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":"LTX-315 is a novel broad-spectrum antimicrobial peptide against clinical multidrug-resistant bacteria","authors":"Yang Tang ,&nbsp;Chen Yang ,&nbsp;Jiamin Zhao ,&nbsp;Heng Heng ,&nbsp;Mingxiu Peng ,&nbsp;Liang Sun ,&nbsp;Liang Dai ,&nbsp;Edward Wai-Chi Chan ,&nbsp;Sheng Chen","doi":"10.1016/j.jare.2024.12.044","DOIUrl":"10.1016/j.jare.2024.12.044","url":null,"abstract":"<div><h3>Introduction</h3><div>Infections stemming from multidrug-resistant bacteria present a substantial threat to public health today. Discovering or synthesizing novel compounds is crucial to alleviate this pressing situation.</div></div><div><h3>Objective</h3><div>The main purpose of this study is to verify the antibacterial activity of LTX-315 and explore its primary action mode.</div></div><div><h3>Methods</h3><div>Through antibacterial phenotype assay screening, we obtained a potent compound named LTX-315 from diverse drug libraries, 10,926 compounds in total. Then, the bactericidal effect and its action mode were explored through biochemical and chemistry methods such as a<!--> <!-->time-killing curve, scanning electronic microscopy, isothermal titration calorimetry analysis, and nuclear magnetic resonance. Finally, the efficacy in vivo of LTX-315 against drug-resistant bacteria was proved through a<!--> <!-->mice infection model.</div></div><div><h3>Results</h3><div>In this study, LTX-315, an oncolytic peptide, was discovered to effectively eliminate gram-positive and gram-negative pathogens, even for those multidrug-resistant strains. Through strong electrostatic interactions, LTX-315 can bind to the membrane component phosphatidylglycerol (PG) with extremely high affinity (nanomolar level). Strikingly, in contrast to the typical electrostatic interactions of antibacterial peptides, the indole group of LTX-315, situated near the alkyl chain, exhibits significantly enhanced recognition and interaction with PG due to the hydrophobic effect of the alkyl chain. Furthermore, it exerts various impacts on cell membranes, including damaging integrity, increasing permeability, and decreasing membrane fluidity. Additionally, microscopy revealed significant cell disintegration. The influence, in turn, disrupts several physiological activities inside cells, such as increasing the reactive oxygen species level, ultimately leading to cell death. Finally, the efficacy of LTX-315 in vivo against multidrug-resistant and hypervirulent <em>Klebsiella pneumoniae</em> was demonstrated.</div></div><div><h3>Conclusion</h3><div>The unique mechanism of LTX-315 involves high-affinity binding to PG and subsequent membrane disruption, providing a novel approach against multidrug-resistant bacteria compared to conventional antibiotics. As a potential candidate, it shows promise in effectively treating bacterial infections, particularly those caused by drug-resistant bacteria, thereby addressing the escalating challenge of antibiotic resistance worldwide.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 715-729"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937553","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":"Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus","authors":"Shiqiang Yan ,&nbsp;Yan Lu ,&nbsp;Changming An ,&nbsp;Wanglai Hu ,&nbsp;Yaofeng Chen ,&nbsp;Ziwen Li ,&nbsp;Wenbo Wei ,&nbsp;Zongzheng Chen ,&nbsp;Xianhai Zeng ,&nbsp;Wei Xu ,&nbsp;Zhenghua Lv ,&nbsp;Fan Pan ,&nbsp;Wei Gao ,&nbsp;Yongyan Wu","doi":"10.1016/j.jare.2024.12.024","DOIUrl":"10.1016/j.jare.2024.12.024","url":null,"abstract":"<div><h3>Background</h3><div>Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions.</div></div><div><h3>Aim of Review</h3><div>Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 615-637"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841483","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":"Selective Regulation of ray tissue for achieving ultrastable Zero-Poisson’s-ratio material out of wood","authors":"Xia Yu ,&nbsp;Bo Liu ,&nbsp;Xinyi Zhou ,&nbsp;Tong Wu ,&nbsp;Bohua Ren ,&nbsp;Tao Fang ,&nbsp;Chaonan Cong ,&nbsp;Guofang Wu ,&nbsp;Lihong Yao ,&nbsp;Xiaoding Wei ,&nbsp;Yun Lu","doi":"10.1016/j.jare.2024.12.012","DOIUrl":"10.1016/j.jare.2024.12.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Materials exhibiting a Poisson’s ratio of zero have attracted considerable interest due to their unique properties and potential applications in various fields, including aerospace, athletic footwear, and sporting equipment. However, the high costs associated with their structural fabrication and the dependence on synthetic chemical materials for most zero Poisson’s ratio materials complicate the preparation processes of current elastic materials, resulting in negative environmental impacts.</div></div><div><h3>Objectives</h3><div>This study presents a sustainable treatment strategy that utilizes the inherent cellular structure of wood to achieve a zero Poisson’s ratio, thereby enhancing its elasticity.</div></div><div><h3>Methods</h3><div>By strategically selecting tree species with varying tissue compositions and employing simple chemical and heat treatments, we developed a commercially viable elastic wood material with a zero Poisson’s ratio that meets diverse stress rebound requirements.</div></div><div><h3>Results</h3><div>The unique internal structure of the wood not only provides high fatigue resistance—capable of withstanding 5000 cycles of compression at a strain of 40 %—but also ensures excellent resilience and processability. At a deformation level of 60 %, the elastic modulus reaches 90.9 MPa. Additionally, the material retains its elasticity even at extremely low temperatures of −196 °C and demonstrates the ability to endure elevated temperatures following carbonization at 1200 °C.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that wood-based materials with a zero Poisson’s ratio exhibit remarkable stability after cyclic compression, presenting a viable pathway for developing superelastic materials suitable for both high- and low-temperature applications.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 439-448"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823398","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}