Journal of Advanced Research最新文献

{"title":"Blood metabolites mediate causal inference studies on the effect of gut microbiota on the risk of vascular calcification","authors":"Aoran Huang, Jianshuai Ma, Huijin Zhu, Yanli Qi, Yang Jin, Mingxuan Zhang, Li Yin, Minhong Luo, Sifan Chen, Chen Xie, Hui Huang","doi":"10.1016/j.jare.2025.03.038","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.038","url":null,"abstract":"<h3>Background</h3>Emerging evidence indicates a notable connection between gut microbiota and Vascular Calcification (VC). Gut microbiota influences various disease processes through host metabolic pathways; however, the causative link between gut microbiota and VC, along with the potential mediating role of metabolites, is still not well understood.<h3>Methods</h3>We leveraged data from the largest Genome-Wide Association Studies (GWAS) concerning gut microbiota, blood metabolites, and VC. To explore the causal relationships among these variables, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses. Furthermore, mediation analyses were conducted to determine if metabolites act as an intermediary in the impact of gut microbiota on VC. In addition, we recruited CKD patients for mass spectrometry and CT examination, and performed a correlation analysis between the expression of blood metabolites and VC score. Finally, we experimentally validated the effects of intermediate metabolites on VC.<h3>Results</h3>We identified 19 positive gut microbiota species and 52 positive blood metabolites with causal effects on VC. Additionally, the onset of VC was found to induce changes in the abundance of 24 gut microbiota species and 56 metabolites. Further analyses revealed that up to 13 positive gut microbiota species regulate the expression of 20 positive metabolites. Mediation analysis suggests that the gut microbiota g_KLE1615 promotes VC by downregulating the methionine-to-phosphate ratio. Mass spectrometry results indicate that over half of the metabolites identified through MR analysis show altered expression during CKD progression. Among them, 7 metabolites were significantly associated with the progression of VC. Further in vitro experiments confirmed the inhibitory effect of the intermediate metabolite methionine on VC.<h3>Conclusion</h3>Gut microbiota and blood metabolites are causally linked to VC. These findings provide a theoretical basis for microbiome- and metabolome-based therapeutic strategies for targeting VC and enhances our comprehension of the gut-vascular axis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"94 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677939","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":"Transducin-like enhancer of split 3 protects against lipopolysaccharide-induced inflammation through DDX5-ATF1-PPP2R5A signaling","authors":"Di Fan, Yi Zhong, Yin Dong, Meng Du, Kai Huang, Xiaoguang Li","doi":"10.1016/j.jare.2025.03.041","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.041","url":null,"abstract":"<h3>Introduction</h3>Sepsis consists of life-threatening multi-organ dysfunction caused by an excessive systemic inflammatory response to infection. Therefore, identifying negative regulators of innate inflammation is crucial for treating this condition.<h3>Objectives</h3>In this study, we aimed to understand how transducin-like enhancer of split 3 (TLE3) regulates inflammatory responses.<h3>Methods</h3>We detected <em>Tle3</em> changes in sepsis patients by analyzing public databases, which were confirmed in septic survivors, septic mouse models, and inflammatory macrophages using Western blotting, qRT-PCR, and immunohistochemistry staining. We investigated the role and mechanism of TLE3 in sepsis by utilizing bone marrow-transplantation (BMT) and adenovirus-infected mice. Furthermore, Protein-Protein Docking, BiFC, LC-MS/MS analysis, CUT &amp; Tag-seq, and CHIP experiments were utilized to disclose the mechanism underlying TLE3 involving macrophage inflammation.<h3>Results</h3>In this study, we found that <em>Tle3</em> transcript is upregulated in peripheral blood samples of sepsis survivors and is decreased in non-survivors, suggesting the critical role of TLE3 in sepsis outcomes. TLE3 is also upregulated in lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophages (MDMs), murine bone marrow-derived macrophages (BMDMs), and septic mice. Gain-of- and loss-of-function of TLE3 in LPS-stimulated murine BMDMs, human MDMs, and mouse models of sepsis showed that TLE3 alleviates LPS-induced cytokine production, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) activation in macrophages, which protects against LPS-induced acute systemic inflammation, multi-organ injury, and death caused by sepsis. Mechanistically, upregulated TLE3 interacts with the transcriptional coactivator, DEAD-box helicase 5 (DDX5), promoting its retention in the cytoplasm and ultimately decreasing transcription of the DDX5/ activating transcription factor 1 (ATF1)-targeted gene <em>Ppp2r5a</em>. Furthermore, the TLE3-DDX5-ATF1 axis downregulates PPP2R5A, a negative regulatory subunit of protein phosphatase 2A (PP2A), thereby increasing PP2A activity and promoting the dephosphorylation of NF-κB and MAPK.<h3>Conclusion</h3>Our study shows that TLE3 represents a novel suppressor of LPS-induced inflammatory signaling in macrophages.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675432","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":"From repellent to risk: DEET’s adverse effects on hormones and bone health in kids","authors":"Xinyu Zhu, Wanlu Liu, Baihao Lin, Haixia Qian, Mengya Xu, Yuyu Zheng, Yansen Bai","doi":"10.1016/j.jare.2025.03.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.037","url":null,"abstract":"<h3>Introduction</h3>Early life bone accumulation, which predicts future fragility fracture risk, is intimately associated with sex hormones. N, N-diethyl-3-methylbenzamide (DEET) is the primary and most effective active ingredient widely used globally, especially among children and adolescents. However, the effects of DEET on sex hormones and bone mass remain unclear.<h3>Objective</h3>We aimed to explore the adverse effects of DEET exposure on bone mass and to elucidate the potential mediating roles of sex hormones in children and adolescents.<h3>Methods</h3>This cross-sectional study analyzed 864 children and adolescents from NHANES 2013–2016. Urinary 3-diethyl-carbamoyl benzoic acid (DCBA) was employed as a biomarker for DEET exposure. The study examined the relationships between DCBA, sex hormones, and bone mass, with a particular focus on evaluating the independent and serial mediation effects of sex hormones on DEET-bone mass associations.<h3>Results</h3>Increased DCBA was associated with decreased testosterone (TT), estrogen (E2), and free androgen index (FAI), alongside an increase in sex hormone-binding globulin (SHBG) levels, particularly pronounced among subjects &lt; 12 years [β% (95 % CI) = -0.081 (−0.144, −0.017), −0.064 (−0.114, −0.013), −0.101 (−0.177, −0.024), and 0.020 (−0.009, 0.048), respectively] and non-overweight subjects [β% (95 % CI) = -0.160 (−0.234, −0.086), −0.103 (−0.158, −0.048), −0.195 (−0.282, −0.107), and 0.035 (0.012, 0.058), respectively]. Negative dose–response relationships between DCBA and bone mass were observed in non-overweight participants [β% (95 % CI) = -0.011 (−0.018, −0.005) and −0.027 (−0.041, −0.013) for total bone mineral density (BMD) and total bone mineral content (BMC), respectively], and in children &lt; 12 years for total BMC [β% (95 % CI) = -0.012 (−0.024, 0.000)]. Additionally, TT, E2, and SHBG were found to significantly and independently mediate 15.41 % to 79.84 % of the relationship between DCBA and bone mass. Furthermore, serial mediation effects among sex hormones were detected between TT, E2, and SHBG.<h3>Conclusions</h3>DEET exerts a detrimental effect on bone health by interfering with sex hormones in children and adolescents, warranting heightened public concern.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666483","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":"Pathogenicity of novel GLA gene missense mutations in Fabry disease and the therapeutic impact of migalastat","authors":"Wenkai Guo, Pengcheng Ji, Yaqing Li, Yixuan Zhang, Jingru Bi, Yuansheng Xie","doi":"10.1016/j.jare.2025.03.023","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.023","url":null,"abstract":"<h3>Introduction</h3>Fabry disease, a rare X-linked hereditary lysosomal storage disorder caused by mutations in the <em>GLA</em> gene, affecting multiple organs. However, functional validation data on the pathogenicity of newly identified mutations and research on the effects of migalastat intervention at different mutation sites is lacking.<h3>Objectives</h3>To explore the pathogenicity of newly identified missense mutations in the <em>GLA</em> gene in Fabry disease and the intervention effect of migalastat on the disease model of newly identified mutation sites.<h3>Methods</h3>We retrospectively screened newly identified mutations from the clinical data of 163 patients with Fabry disease, investigated the pathogenicity of these mutations by clinical data and pedigree analysis, bioinformatics prediction, protein structure modeling prediction, and cell experiment. Additionally, this study further assessed the effects of migalastat intervention on these newly identified mutation sites combined with the amenable mutation criteria for <em>GLA</em> gene mutations applicable to DGJ proposed by the Good Laboratory Practice Human Embryonic Kidney 293 in vitro cell experiment analysis (GLP HEK assay).<h3>Results</h3>Ninety-five different mutation sites were detected, comprising 13 newly identified mutation sites with nine definite pathogenic mutations (nonsense mutations, frameshift mutations and large fragment deletions) and four missense mutations. The variants c.102 T &gt; A, c.130 T &gt; G, and c.778G &gt; T showed high pathogenicity (pathogenicity prediction score: 9), suggesting significant spatial conformation changes in the mutated protein, while c.194G &gt; A showed a low pathogenicity (score: 5), indicating a mild impact on protein conformation. Cellular functional experiments revealed significantly reduced <em>GLA</em> gene mRNA, α-Gal A protein expression, and enzyme activity levels in the mutant cells. Migalastat intervention significantly normalized α-Gal A protein expression and enzyme activity, particularly in the variant c.194G &gt; A, meeting amenable mutation criteria for migalastat.<h3>Conclusion</h3>This study reports 13 newly identified mutation sites in the <em>GLA</em> gene for Fabry disease, including nine definite pathogenic mutations and four missense mutations confirmed to be pathogenic in this study, thereby enriching the Fabry disease gene mutation database. Migalastat intervention improved enzyme activity in these mutation models, especially in cases with minor changes in protein structure and function, which are expected to guide clinical treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"14 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660640","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":"A mouse model of sepsis-associated DIC induced by Kappa-carrageenan and Lipopolysaccharides: Establishment and characteristics","authors":"Ping Tang, Boning Huang, Qianqing Ou, Fangle Liu, Liuqing Lin, Yuying Zheng, Huiyi Xie, Xinrong Yang, Xiubing Zhang, Zhongsheng Kuang, Yuhui Xie, Jingjing Sun, Bingqing Lin, Jun Li, Baoqin Lin","doi":"10.1016/j.jare.2025.03.029","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.029","url":null,"abstract":"<h3>Background</h3>No animal models fully replicate the pathogenesis and clinical features of sepsis-associated disseminated intravascular coagulation (DIC), which hinders mechanistic understanding and treatment development. Kappa-carrageenan (KCG) and lipopolysaccharides (LPS) induce thrombosis and systemic inflammation in mice, respectively. The combination of LPS and KCG serves as a promising method to establish a mouse model of sepsis-associated DIC.<h3>Objective</h3>This study aimed to establish a standardized mouse model of sepsis-associated DIC using KCG and LPS.<h3>Methods</h3>Kunming (KM) mice were intraperitoneally injected with KCG (25–200 mg/kg) alone or in combination with LPS (50–1250 μg/kg) to determine optimal dose. The effects of ambient temperature, gender and mouse strains on the mouse model were evaluated. Time-dependent changes in the model was examined.<h3>Results</h3>The combined injection of KCG (100 mg/kg) and LPS (50 μg/kg) effectively induced tail thrombosis and prolonged partial thromboplastin time (APTT). Mice housed at 16 ± 1℃ exhibited more severe thrombosis and hypocoagulability than those at 24 ± 1℃. Male and female mice exhibited similar responses. Time-course analysis revealed inflammation and blood hypocoagulability beginning from 1.5 to 24 h, with fibrinolysis inhibition occurring within 1 h. Tail thrombosis and auricle petechial developed at 3 and 6 h, respectively, and stabilized by 12 h. Thrombi in the tail, lung and liver along with organ dysfunction were obeserved at 12 h. KM and BALB/c mice exhibited longer tail thrombi than Institute of Cancer Research (ICR) mice. KM mice showed more severe blood hypocoagulability than ICR and BALB/c mice.<h3>Conclusions</h3>This study establishes a standardized mouse model of sepsis-associated DIC using KCG and LPS, which more accurately replicates the key clinical and pathological characteristics of sepsis-associated DIC compared to existing models. This model serves as a novelty and valuable tool for investigating the mechanisms of sepsis-associated DIC and therapeutic evaluation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653856","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":"Inhalation exposure to tire rubber particle-sourced pollutant 6PPD-quinone involving basolateral amygdala impairment in male ICR mice","authors":"Qu-Nan Wang, Chunzhi Wang, Yán Wāng","doi":"10.1016/j.jare.2025.03.033","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.033","url":null,"abstract":"<h3>Introduction</h3>The extensive use of 6PPD in tire rubber has led to its increase in atmospheric tire wear particles. 6PPD reacts with ozone to form 6PPD-quinone (6PPD-Q), a respiratory toxicant enriched in tire and road wear particles.<h3>Objectives</h3>The aim of this study is to decipher the potential sensitive target organs and toxic actions by inhalation exposure to atmospheric 6PPD-Q.<h3>Methods</h3>This study employed a mouse inhalation exposure model to simulate environmental levels of 6PPD-Q at three concentrations of 0, 0.14, and 14 mg/m³. Using a 28-day exposure period followed by an equivalent recovery phase, we systematically evaluated the toxicological targets and effects of subacute exposure.<h3>Results</h3>The findings revealed that, compared to pulmonary, cardiovascular, and metabolic organ damage, 6PPD-Q-induced neurotoxicity was more persistent and irreversible, particularly characterized by prolonged anxiety-like behaviors. Histopathological analyses of the basolateral amygdala, using Nissl staining and markers of neuronal aging, indicated substantial neuronal degeneration linked to elevated oxidative stress, identifying this region as a critical target of 6PPD-Q neurotoxicity. Transcriptomic analysis uncovered that the expression of <em>Egr1</em>, a transcription factor crucial for neuronal plasticity, was markedly dysregulated. Findings of significant downregulation at the gene level and an upward trend in protein expression suggest that<!-- --> <em>Egr1</em> <!-- -->expression is influenced by translational efficiency, epigenetic modifications, and post-translational regulatory mechanisms. <em>Egr1</em> <!-- -->dysregulation disrupted downstream networks involving solute carrier proteins and calcium-binding proteins, contributing to aberrant neurobehavioral outcomes. Notably, the elevation of<!-- --> <em>Egr1</em> <!-- -->protein levels in the basolateral amygdala but not in the cerebral cortex highlights the region-specific nature of 6PPD-Q’s neurotoxic effects.<h3>Conclusion</h3>This study provides the first insights into the neurotoxicity and irreversibility of inhaled 6PPD-Q exposure, paving the way for future research into the long-term neurological consequences and regulatory mechanisms of 6PPD-Q.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"91 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653853","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":"Evidence for the role of soil C/N ratio in shaping plant responses to root-knot nematode infection","authors":"Jiafan Li, Shikai La, Mengyuan Song, Lihong Gao, Yongqiang Tian","doi":"10.1016/j.jare.2025.03.036","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.036","url":null,"abstract":"<h3>Introduction</h3>Root-knot nematodes (RKNs) pose a major threat to global crop production. Soil properties influence plant responses to RKN infestation, but the specific soil factors that are most influential in determining these responses remain poorly understood.<h3>Objective</h3>This study aims to identify the key soil factors that influence plant responses to <em>Meloidogyne incognita</em>, develop a dynamic model to quantify plant disease severity in response to variations in these soil factors, and further elucidate the underlying mechanisms driving this interaction.<h3>Methods</h3>We collected 28 soils with diverse physicochemical and microbial properties at a national scale and conducted nematode infection experiments under controlled environmental conditions, using cucumber plants (a typical susceptible host for <em>M. incognita</em>) to assess disease severity. Based on the resulting dataset, a Mantel test was applied to identify the key soil factor influencing <em>M. incognita</em> infection. To further validate these findings, we performed organic carbon (C) addition experiments and <em>M. incognita</em> chemotaxis assays.<h3>Results</h3>We found that 28 soils exhibit a broad range of plant performance indices (PPI) and disease indices (DI). The Mantel test revealed that soil carbon/nitrogen (C/N) ratio is the strongest correlate of both plant performance and disease symptoms. The DI follows an inverted hump-shaped response curve with increasing soil C/N ratio, indicating the existence of an optimal soil C/N ratio (about 8.0) for minimizing DI. This finding is further supported by the fact that organic C addition decreases DI in soils with low initial C/N ratio, but increases DI in soils with high initial C/N ratio. The shaping effects of soil C/N ratio are underpinned by its regulation of overall soil quality and plant resistance to <em>M. incognita</em> chemotaxis.<h3>Conclusion</h3>Optimizing C/N ratio reduces soil sensitivity and suppresses RKN infestation, offering valuable insights for sustainable agricultural management practices.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640873","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":"Discovery of mannose as an alternative non-nutrient-deficient regulator of lipid accumulation in microalgae","authors":"Pengyang Liu, Yuanhang Ai, Muzi Li, Jiacheng Shi, Ning Xiao, Xiaoyu Zhang, Hongbo Yu, Fuying Ma, Su Sun, Shangxian Xie","doi":"10.1016/j.jare.2025.03.019","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.019","url":null,"abstract":"<h3>Introduction</h3>Microalgae are considered promising bioenergy producers, but their commercial potential is limited by low lipid yields. Nutrient deprivation, particularly nitrogen starvation, is a primary strategy to enhance lipid synthesis efficiency in microalgae. However, controlling this process flexibly, effectively, and accurately remains challenging. Moreover, nutrient deficiency triggers expression changes of numerous genes, complicating the identification of key lipid biosynthesis regulators.<h3>Objectives</h3>For the first time, we investigated mannose as a novel non-nutrient-deficient regulator of lipid accumulation in microalgae and explored its potential underlying mechanisms.<h3>Methods</h3>We examined how mannose induction affects<!-- --> <!-- -->lipid accumulation in <em>Chlorella sorokiniana</em> W1 under various culture conditions and compared its effects with nitrogen-starvation. Transcriptome analysis and genome-scale metabolic modeling were used to elucidate the regulatory mechanisms underlying mannose-induced lipid synthesis. Additionally, potential transcription factors were identified using weighted gene co-expression network analysis.<h3>Results</h3>Mannose drives rapid and sustained lipid accumulation in <em>C. sorokiniana</em> under various cultivation conditions, independent of nutrient deficiencies. Under autotrophic conditions, mannose increased lipid content of microalgae by 80.1 %. Notably, mannose was not consumed during cultivation, supporting its role as an inducer. Transcriptomic analysis revealed that mannose increased carbon flux by upregulating genes associated with the Calvin cycle, glycolysis, the TCA cycle, and starch degradation. It also redirected carbon towards lipid accumulation by upregulating lipid synthesis pathways and downregulating lipid degradation pathways. Additionally, two SBP1 transcription factors specifically responsive to mannose were identified and may regulate carbon metabolism in microalgae.<h3>Conclusion</h3>Our study introduces mannose as a novel non-nutrient-deficiency regulatory factor for lipid accumulation in <em>C. sorokiniana</em> W1, and explores its metabolic and regulatory mechanisms under various nutrient conditions. The research demonstrates that mannose induction has significant potential for improving microalgal lipid production in practical applications.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"33 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640872","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":"Spatiotemporal translation of sperm acrosome associated proteins during early capacitation modulates sperm fertilizing ability","authors":"Yoo-Jin Park, Won-Ki Pang, Do-Yeal Ryu, Md Saidur Rahman, Myung-Geol Pang","doi":"10.1016/j.jare.2025.03.035","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.035","url":null,"abstract":"<h3>Introduction</h3>Despite the lack of essential cytoplasmic organelles in mature spermatozoa, which creates unfavorable conditions for transcription and translation, the presence of various mRNA and proteins during capacitation suggests potential for de novo protein synthesis.<h3>Objectives</h3>We applied a metabolic labeling method using a fluorescent noncanonical amino acid tagging system (FUNCAT) and proximity ligation method (PLA) in normal and reduced fertility spermatozoa to detect different translation phenomena during sperm capacitation according to their fertility.<h3>Methods</h3>We explored different proteome changes in spermatozoa according to the time-sequential capacitation process (0, 20, 40, 60, and 120 min) between normal [average fertility rate (FR) = 77.44 % ± 1.51] and reduced fertility (average FR = 58.57 % ± 1.64) spermatozoa bull spermatozoa, as the representative male fertility models owing to their broad spectrum of fertility phenotypes. Moreover, the FUNCAT/PLA method was used to detect and visualize different translation phenomena during sperm capacitation according to fertility.<h3>Results</h3>We found that sperm-associated protein (SPACA) 1 and SPACA5 were newly synthesized in the head of normal-fertility spermatozoa, whereas a lack of newly synthesized proteins in the head and a relatively earlier loss of SPACA1 and SPACA5 were observed in the reduced-fertility spermatozoa. Moreover, the mitochondrial translation inhibitor, chloramphenicol, partially inhibited sperm translation and delayed translocation, suggesting that mitochondria participate in sperm translation.<h3>Conclusion</h3>Our results unveil time-sequential microenvironmental changes in sperm proteomes during capacitation, which lead to the orchestra of proteins that complete fertilization. Fertile spermatozoa are selected through inter-competition during the journey of fertilization in the female reproductive tract. This study provides an overview of how translation dynamics acts on the sperm selection and influence the evolution of sperm fertility.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"22 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653854","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":"Minichromosome maintenance 4 plays a key role in protecting against acute kidney injury by regulating tubular epithelial cells survival and regeneration","authors":"Jing Huang, Feng Liu, Zhi-Feng Xu, Hui-Ling Xiang, Qian Yuan, Chun Zhang","doi":"10.1016/j.jare.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.032","url":null,"abstract":"<h3>Introduction</h3>Minichromosome maintenance 4 (MCM4), a constituent of the MCM family, playing a pivotal role in DNA replication. Although MCM4 expression has been widely linked to various malignant tumors, its role in kidney diseases is not well-studied. This study primarily investigates the role and underlying mechanism of MCM4 in acute kidney injury (AKI).<h3>Objectives</h3>Characterizing a novel target of MCM4 in patients with AKI.<h3>Methods</h3>We used CRISPR/Cas9 gene editing to delete MCM4 gene in tubular cells from C57BL/6J mice. Adeno-associated virus 9 harboring MCM4 was administered via intraparenchymal injection into the kidney to enhance MCM4 expression <em>in vivo</em>. These mice were used to established cisplatin- and ischemic reperfusion injury (IRI)-induced AKI mouse models, for detecting the functional role of MCM4 in the pathological process of AKI.<h3>Results</h3>MCM4 level was increased in the tubules of cisplatin- and IRI-induced AKI mouse models. Compare to wide-type mice, MCM4 knockout mice demonstrated greater degree of histological damage and a higher ratio of apoptotic tubular cells, as well as kidney dysfunction upon cisplatin- and IRI-induced AKI models. Conversely, MCM4 overexpression ameliorated the severity of kidney injury and promoted regenerative capacity of tubular cells during AKI development. Mechanically, loss of MCM4 induced the expression of p53-binding protein 1, activating the p53/p21 pathway and exacerbating AKI progression. Additional, MAD2B, as an upstream molecule of MCM4, regulates the transcription level of MCM4 by affecting the level of E2F1.<h3>Conclusions</h3>These findings demonstrate that MCM4 upregulation during AKI development is an adaptive response that preserves tubular cell regenerative capacity and limits the severity of renal injury, thus highlighting the potential value of MCM4 as a biomarker or therapeutic target in patients with AKI.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"36 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640874","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}