Journal of Advanced Research最新文献

{"title":"Multi-omics analysis of glycolytic reprogramming and ROS dynamics in host-specific responses to Salmonella Typhi infection in mice","authors":"Yanrui Bai, Wenxiu Liu, Zhiyuan Liu, Dandan Ding, Huiya Jin, Shangyu Xiao, Jiayin Guo, Xiaoe He, Qian Wang, Han Xiao, Yan Wang, Tiansheng Zhang, Yana Li, Jing Yang, Hui Sun","doi":"10.1016/j.jare.2025.05.027","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.027","url":null,"abstract":"<h3>Introduction</h3><em>Salmonella</em> Typhi (<em>S.</em> Typhi), a Gram-negative, serves as the etiological agent of typhoid fever. In contrast to other <em>Salmonella</em> serovars, <em>S.</em> Typhi exclusively infects humans. However, the molecular interactions it engages in with the host immune system remain inadequately characterized. This study adopts a multi-omics strategy to elucidate the immune and metabolic dynamics within the murine spleen during <em>S.</em> Typhi infection.<h3>Objectives</h3>To identify and analyze transcriptomic, proteomic, and metabolomic alterations in the spleens of mice infected with <em>S.</em> Typhi. By comparing these host responses with those elicited by <em>Salmonella</em> Typhimurium (<em>S.</em> Typhimurium), a closely related serovar possessing a broad host range, the study seeks to uncover the unique metabolic reprogramming and immune-modulatory mechanisms specific to <em>S.</em> Typhi infection.<h3>Methods</h3>A multi-omics strategy was adopted, integrating transcriptomic, proteomic, and metabolomic data obtained from the spleen tissues of <em>S.</em> Typhi-infected mice. <em>S.</em> Typhimurium was utilized as a comparative control to distinguish host-specific responses. Additionally, the dynamics of reactive oxygen species (ROS), which play pivotal roles in mediating immune responses during infection, were examined.<h3>Results</h3>Integration of multi-omics datasets demonstrated distinct metabolic and immunological responses orchestrated by <em>S.</em> Typhi infection. Host metabolism was reprogrammed by <em>S.</em> Typhi through the upregulation of glycolysis and the facilitation of glucose-to-pyruvate conversion, while concurrently suppressing the tricarboxylic acid cycle (TCA cycle). These changes culminated in increased lactate accumulation, and augmented ROS production, all of which were associated with intensified immune activation.<h3>Conclusion</h3><em>S.</em> Typhi infection induces metabolic reprogramming in the host, characterized by a redirected glycolytic flux and altered pyruvate metabolism. This metabolic shift enhances ROS production and modulates the immune response. These findings yield novel insights into host-specific strategies employed by <em>S.</em> Typhi and highlight the significance of metabolic remodeling in immune defense, thereby presenting potential therapeutic targets for combating typhoid fever.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"75 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083356","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":"Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer","authors":"Jie Mei, Hui-Xiang Tian, Xiao-Ye Zhang, Yuan-Shen Chen, Lei-Yun Wang, Zhao Zhang, Yu-Long Zhang, Ding-Chao Rong, Jun Zeng, Min Dong, Yang Gao, Ji-Ye Yin, Hai-Jun Wu, Peng-Yuan Wang, Wei Zhang","doi":"10.1016/j.jare.2025.05.033","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.033","url":null,"abstract":"<h3>Introduction</h3>Platinum-based drugs, the most widely used chemotherapeutic drugs in clinical oncology, have long faced the problem of drug resistance, which is urgently in need of resolution. Identifying biomarkers of drug resistance may help reduce platinum resistance and improve therapeutic efficacy.<h3>Objectives</h3>This study aims to identify potential biomarkers associated with the development of cisplatin resistance in non-small cell lung cancer (NSCLC) and explore mechanisms to overcome chemoresistance.<h3>Methods</h3>NSCLC cisplatin resistance cell lines were constructed, and transcriptome sequencing was performed. Results were validated using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Molecular docking, proteomics sequencing, and <em>in vitro</em> and <em>in vivo</em> experiments were conducted to evaluate the role of Heme Oxygenase 1 (HMOX1) in cisplatin resistance.<h3>Results</h3>NSCLC cisplatin resistance cell lines, GEO and TCGA data identified HMOX1, downstream of Nrf2, as a key drug resistance gene induced by cisplatin. Activation of the Nrf2/HO-1 pathway was found to induce ferroptosis resistance, a critical mechanism of cisplatin resistance. Candidate compounds SB 202190 and Nordihydroguaiaretic acid (NDGA) effectively reactivated ferroptosis by inhibiting HO-1, thereby increasing cisplatin sensitivity.<h3>Conclusion</h3>The Nrf2/HMOX1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"38 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083284","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":"Beyond the Brain: Exploring the multi-organ axes in Parkinson’s disease pathogenesis","authors":"Tingting Liu, Haojie Wu, Jianshe Wei","doi":"10.1016/j.jare.2025.05.034","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.034","url":null,"abstract":"<h3>Background</h3>Parkinson’s Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration. For example, lung dysfunction in PD involves respiratory impairment and inflammatory signaling, while gut dysbiosis triggers α-synuclein aggregation via the vagus nerve. Such cross-organ interactions underscore PD’s systemic nature, challenging traditional brain-centric models.<h3>Aim of Review</h3>1. Decipher mechanisms linking peripheral organs (e.g., lung, gut) to PD via shared pathways.2. Explore bidirectional organ-brain interactions (e.g., liver metabolism affecting neurotoxin clearance).3. Propose multi-organ therapeutic strategies targeting integrated signaling networks.Key Scientific Concepts of Review.1. Lung-Brain Axis: Respiratory dysfunction (motor impairment, inflammation) exacerbates neurodegeneration.2. Liver-Brain Axis: Metabolic dysregulation alters neurotoxin clearance; drugs (e.g., levodopa) impact liver function.3. Heart-Brain Axis: Autonomic dysfunction reduces cerebral blood flow; neuroendocrine changes promote α-synuclein pathology.4. Muscle-Brain Axis: Neuromuscular/metabolic disruptions worsen motor symptoms.5. Bone-Brain Axis: Bone-derived hormones (osteocalcin, OCN) and inflammation influence cognition.6. Gut-Brain Axis: Dysbiosis drives α-synuclein misfolding; gut metabolites modulate neuroinflammation.Integrated Mechanisms: Shared pathways (neuroinflammation, oxidative stress) create a regulatory network, suggesting therapies targeting multi-organ crosstalk (e.g., probiotics, anti-inflammatory agents).","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067462","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":"Novel function of macrophage migration inhibitory factor in regulating post-infarct inflammation and the therapeutic significance","authors":"Ling Zhao, Guo-Li Du, Amanguli Ruze, Hong-Zhi Qi, Chuan-Shan Zhang, Qiu-Lin Li, An-Xia Deng, Bang-Hao Zhao, Su Hu, Min-Tao Gai, Xiao-Ming Gao","doi":"10.1016/j.jare.2025.05.030","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.030","url":null,"abstract":"<h3>Introduction</h3>Recent studies indicate that macrophage migration inhibitory factor (MIF) has a dual role in myocardial infarction (MI), with different cellular sources of MIF influencing inflammation and healing differentially.<h3>Objectives</h3>To investigate the role and underlying mechanism of MIF in MI and interventional efficacy targeting MIF.<h3>Methods</h3>Wild-type (WT), global MIF gene knockout (KO) and chimeric mice were subjected to coronary artery occlusion. The inflammatory responses and healing processes following MI were studied in both <em>in vivo</em> and <em>in vitro</em> settings. Furthermore, the therapeutic potential of pharmacological MIF inhibition to improve the prognosis of MI was explored.<h3>Results</h3>Globally, MIF enhanced systemic and local inflammatory responses, as well as splenic monocyte mobilization, in mice with MI. MIF promoted monocyte migration through CCR2 and CXCR4 in peripheral blood mononuclear cells (PBMCs) and the infarcted myocardium. Additionally, MIF augmented angiotensin Ⅱ type 1 receptor (AT-1R) expression and interacted with AT-1R to promote the splenic monocyte mobilization following acute MI. MIF derived from bone marrow cells (KO^WT mice) had stronger systemic and local inflammatory responses and augmented mobilization of splenic monocytes. In contrast, deficiency of MIF in leukocytes (WT^KO mice) increased Ly-6C^low monocyte accumulation, M2 macrophage infiltration, and degree of myocardial fibrosis in infarcted myocardium. <em>In vitro</em>, MIF derived from ischemic heart enhanced M2 but impaired M1 macrophage marker expression in PBMCs. Anti-MIF treatment effectively attenuated splenic monocyte mobilization and both systemic and regional inflammatory responses post-MI without affecting the healing process, thereby improving the long-term prognosis.<h3>Conclusion</h3>Deletion of global and inflammatory-cell-derived MIF diminished inflammation following MI by inhibiting monocyte mobilization and downregulating pro-inflammatory mediators, while cardiac-derived MIF exerted anti-inflammatory influence and facilitated healing. Furthermore, MIF antibody therapy protected the heart from severe ischemic injury and improved long-term prognosis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"139 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067408","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":"Fe-S cluster deficiency drives small colony variant formation in persistent infections","authors":"Tianchi Chen, Zhiyi Ye, Weiyi Huang, Qi Zhang, Feng Jiang, Ziyu Yang, Ying Jian, Yanan Wang, Guoxiu Xiang, Qian Liu, Hao Shen, Min Li, Lei He","doi":"10.1016/j.jare.2025.05.018","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.018","url":null,"abstract":"<h3>Introduction</h3>Small colony variants (SCVs) of <em>Staphylococcus aureus</em> (<em>S. aureus</em>) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of <em>S. aureus</em> and identifies a novel genetic determinant linked to SCV formation.<h3>Objectives</h3>To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the <em>sufB</em> gene, which is critical for Fe-S cluster biosynthesis.<h3>Methods</h3>Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model.<h3>Results</h3>A novel frameshift mutation in <em>sufB</em> was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of <em>sufB</em> reversed these phenotypes, confirming its pivotal role in SCV-associated persistence.<h3>Conclusion</h3><em>sufB</em> is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"141 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979921","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":"Association between dietary amino acid intake and the risk of metabolic dysfunction-associated steatotic liver disease","authors":"Ruoqi Zhou, Xinrong Zhang, Xinxin Liu, Rui Huang, Yuwei Wang, Dajing Xia, Xue Li, Yihua Wu, Yu Shi","doi":"10.1016/j.jare.2025.05.029","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.029","url":null,"abstract":"<h3>Introduction</h3>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is becoming the major chronic liver disease, and diet plays crucial role in MASLD prevention.<h3>Objectives</h3>The study aimed to explore the association between dietary amino acids with MASLD risk.<h3>Methods</h3>Utilizing data from the U.S. NHANES (2017–2020) and UK Biobank (2006–2010), we investigated the association between dietary intake of combined or specific amino acids, and the risk of MASLD, severe MASLD and MASLD-related events. And we identified MASLD-risk amino acid intake patterns and their primary food sources.<h3>Results</h3>The study included 5,568 participants from the U.S. NHANES and 48,261 from the UK Biobank, with MASLD prevalence of 34.3 % and 28.4 %, respectively. In QGC model, each quartile increase in combined amino acid intake was associated with a higher MASLD risk in the U.S. NHANES (aOR = 1.17, 95 % CI: 1.01–1.37, <em>P =</em> 0.035) and UK Biobank (aOR = 1.07, 95 % CI: 1.002–1.15, <em>P</em> = 0.042). Increased lysine intake was particularly linked to elevated MASLD risk in U.S. NHANES (aOR = 1.49, 95 % CI: 1.08–2.05, <em>P</em> = 0.023) and UK Biobank (aOR = 1.12, 95 % CI: 1.01–1.24, <em>P</em> = 0.032). Substituting lysine with other amino acids was associated with reduced MASLD risk. Lysine intake was also associated with a higher risk of severe MASLD (aHR = 1.13, 95 % CI: 1.04–1.23, <em>P =</em> 0.002) but not liver cirrhosis or HCC. The ‘Lys-Met’ pattern was identified as a MASLD-risk pattern, with red meats being a representative food source.<h3>Conclusion</h3>Lysine plays a major role in the association between amino acid intake and risk of MASLD. Dietary patterns rich in lysine, such as red meat, could be key targets for MASLD prevention strategies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979925","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":"Trends, patterns, and risk factors of esophageal cancer mortality in China, 2008–2021: A national mortality Surveillance System data analysis","authors":"Yunfei Jiao, Tinglu Wang, Lin Fu, Ye Gao, Zhiyuan Cheng, Lei Xin, Jinfang Xu, Han Lin, Wei Wang, Maigeng Zhou, Jinlei Qi, Zhaoshen Li, Luowei Wang","doi":"10.1016/j.jare.2025.05.021","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.021","url":null,"abstract":"<h3>Introduction</h3>According to the International Agency for Research on Cancer, China had the highest mortality burden of esophageal cancer (EC) globally in 2022.<h3>Objectives</h3>This study aims to analyze the national and provincial trends, patterns, and risk factors of EC deaths in China.<h3>Methods</h3>Data from the National Mortality Surveillance System were used to estimate national and provincial deaths, age-standardized mortality rates (ASMRs), and years of life lost (YLL). An age-period-cohort-based Nordpred model was used to predict trends until 2030. Multilevel Poisson and logistic regression were conducted<!-- --> <!-- -->to assess factors influencing EC mortality and the place of death.<h3>Results</h3>From 2008 to 2021, EC deaths and YLLs decreased from 227,677 to 167,529 and from 5.32 million to 3.50 million, respectively. Meanwhile, the ASMR and age-standardized YLL rate decreased from 24.34 to 11.01 per 100,000 and from 535.91 to 231.08 per 100,000, respectively. By 2030, EC deaths and ASMR are predicted to decline to 150,768 and 7.85 per 100,000, respectively. Nationwide, the average age at death increased from 68.46 to 72.45 years, with an increasing proportion of YLLs in the 65–69 age group. Overall premature mortality was observed to decrease, except for an increase in YLLs among urban populations aged ≥60 years. Higher burdens were observed in rural areas compared to urban areas and among males compared to females. Nationwide, individuals with agriculture-related occupations and lower educational levels exhibited significantly higher risks of EC death. Regions with higher prevalences of smoking and harmful drinking, and lower educational, economic, and medical levels were significantly associated with high mortality. Home was the leading place of EC deaths (80.02 %).<h3>Conclusion</h3>The EC mortality burden in China is decreasing but remains a significant threat to public health. Promoting education, occupational prevention, healthy lifestyles, and medical treatment for targeted populations and regions is essential.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979922","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":"Overexpression of soybean flavonoid 3′-hydroxylase enhances plant salt tolerance by promoting ascorbic acid biosynthesis","authors":"Jianfei Wu, Xiaokun Wang, Jiawei Xu, Tongtong Li, Guangyao Shan, Li Zhang, Tongdi Yan, Xuejiao Song, Yuxiao Sun, Huihui Guo, Fanchang Zeng","doi":"10.1016/j.jare.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.009","url":null,"abstract":"<h3>Introduction</h3>Salt stress is a major cause of crop loss. Soybean (<em>Glycine</em> max), a globally vital legume crop, faces mounting yield constraints due to soil salinization. It is known that the flavonoid biosynthesis pathway involving flavonoid 3′-hydroxylase (F3′H) plays an important role in salt tolerance. However, the precise molecular basis of F3′H-mediated salt tolerance remains inadequately characterized.<h3>Objectives</h3>This study aimed to elucidate the function and explore the pleiotropic molecular basis of F3′H protein in soybean salt tolerance. Innovation on elite new crop varieties facilitates breeding and production applications on salt tolerance.<h3>Methods</h3>We employed CRISPR/Cas9-mediated knockout and <em>Agrobacterium</em>-based overexpression to generate <em>GmF3′H</em> allelic variants and ectopic expression in soybeans. Sanger sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to confirm the specificity of gene editing and quantify expression levels in overexpression transgenic plants, respectively. As well as Subcellular localization analysis, Yeast two-hybrid (Y2H) assay, LUC activity assay and plant physiological measurements were carried out to elucidate the F3′H-mediated salt tolerance molecular basis in plants.<h3>Results</h3>In this study, we identified the flavonoid 3′ hydroxylase gene (<em>GmF3′H</em>) in soybeans, which as a master regulator of salt stress adaptation during seed germination and seedling stages in both soybean and <em>Arabidopsis thaliana</em>. Furthermore, our study revealed that the evolutionarily conserved F3′H protein competitively binds to the photomorphogenic factor COP9 signalosome subunit 5B (CSN5B) and disrupts its interaction with GDP-mannose pyrophosphorylase 1 (VTC1), a key enzyme in ascorbate biosynthesis. This competitive inhibition redirects metabolic flux toward the L-galactose pathway, leading to an increase in ascorbic acid (AsA) biosynthesis. The enhanced AsA production subsequently improves seedling salt stress tolerance in plants by maintaining redox homeostasis through ROS scavenging.<h3>Conclusion</h3>The discovery and characterization of F3′H-mediated salt tolerance provide a crucial framework for the genetic improvement of crops. This work provides new insights into plant salt stress tolerance and develops innovative strategies to enhance broad-spectrum salt tolerance, a crucial aspect for ensuring food security in crops.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979923","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":"Mechanical mechanics-reclaiming a new battlefield for chronic liver disease","authors":"Yiheng Zhang, Tianle Ma, XingXing Lu, Haibing Hua, Li Wu, Zhipeng Chen","doi":"10.1016/j.jare.2025.05.028","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.028","url":null,"abstract":"<h3>Background</h3>In the 21st century, significant breakthroughs have been made in the research of chronic liver disease. New biochemical markers of pathogenicity and corresponding drugs continue to emerge. However, current treatment strategies remain unsatisfactory due to complex pathological changes in the liver, including vascular dysfunction, myofibroblast-like transition, and local tissue necrosis in liver sinusoids. These challenges have created an urgent need for innovative, synergistic treatments. Mechanical mechanics is a growing field, with increasing evidence suggesting that mechanical signals play a role similar to that of biochemical markers. These signals influence response speed, conduction intensity, and functional diversity in regulating cell activities.<h3>Aim of review</h3>This review summarizes the three main mechanical characteristics involved in the progression of “liver fibrosis-cirrhosis-hepatocellular carcinoma” and provides an in-depth interpretation of several mechanically-related targets. Finally, current and cutting-edge therapeutic strategies are proposed from a cellular perspective. Despite the many challenges that remain, this review is both relevant and significant.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"23 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946253","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":"Anthocyanin accumulation differences in European pears caused by Phytochrome-interacting factor 3 (PcPIF3) promoter mutations under UV-B","authors":"Haowei Cao, Yingying Qu, Lei Guo, Mengjia Wu, Guorong Zhang, Ying Tang, Hongjuan Zhang, Rui Zhai, Chengquan Yang, Lingfei Xu, Zhigang Wang","doi":"10.1016/j.jare.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.010","url":null,"abstract":"The phenomenon of red fading in late-stage red-skinned pear fruit development significantly impacts its value. This phenomenon also occurs in ’Starkrimson’, albeit to a lesser extent compared to ’Red Bartlett’ and other varieties. The reasons for the differences in anthocyanin accumulation during the late stages of fruit development in red-skinned European pears varieties are not yet understood. Here, we report a novel pattern of anthocyanin accumulation in response to UV-B in ’Starkrimson’ pears, which is associated with mutations in the <em>PcPIF3</em> promoter. Through transcriptome analysis of ’Red Bartlett’ and ’Starkrimson’ pears, we identified the differentially expressed gene <em>PcPIF3</em>, which is capable of promoting anthocyanin biosynthesis through direct binding to the promoter region of <em>PcMYB10</em>. Under moderate UV-B conditions, the ’Starkrimson’ <em>PcPIF3</em> were significantly increased. By analyzing the <em>PcPIF3</em> promoter regions of different red-skinned pear varieties, we identified the differential binding element as W-BOX 1 and subsequently screened for the upstream positive regulator, PcWRKY11. Y1H and related experiments demonstrated that under UV-B exposure, PcWRKY11 binds specifically to the W-BOX 1 element in the ’Starkrimson’ <em>PcPIF3</em> promoter, thereby enhancing its transcription. These findings indicate that PcWRKY11, in response to UV-B, interacts with the W-BOX 1 element in the ’Starkrimson’ <em>PcPIF3</em> promoter, promoting anthocyanin biosynthesis and mitigating the fading of red coloration in ’Starkrimson’ pears. The difference in the <em>PcWRKY11-PcPIF3</em> module represents a novel mechanism for the variation in anthocyanin accumulation among different red-skinned pear varieties.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"41 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940159","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}