Journal of Advanced Research最新文献

{"title":"Bio-friendly multi-stimuli responsive α-CD polymer-gated mesoporous carbon nanoherbicides for enhanced paraquat delivery","authors":"Jiangtao Dong, Guoquan Wang, Xiaona Li, Anhui Han, Wanpeng Zhang, Yuhang Yue, Yue Yang, Yishan Wang, Bowen Yuan, Jiahui Wang, Yuhui Peng, Runqiang Liu, Si Chen, Xuezhong Du","doi":"10.1016/j.jare.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.005","url":null,"abstract":"<h3>Introduction</h3>Weeds seriously affect crop yield in global agricultural production. Paraquat (PQ), as one of low cost and highly effective herbicide, is forbidden or severely restricted in production and sales owing to its lethal toxicity to humans. Creating an efficient and bio-friendly PQ formulation is crucial to facilitate the open use of PQ in world’s agriculture.<h3>Objectives</h3>This study aims to construct one intelligent and bio-friendly mesoporous carbon nanoparticles (MCN) nanoherbicides coated with α-CD polymer (CDP) gatekeepers.<h3>Methods</h3>MCN was prepared through the low-concentration hydrothermal way, calcined and carbonized. PEG stalks were immobilized on MCN surface by amidation reaction. The PQ was trapped in the MCN pores via physical diffusion adsorption and the robust π–π effects between electron-deficient PQ and electron-rich MCN. CDP gatekeepers were fastened via host–guest effects between the chamber of α-CD units and PEG stalks.<h3>Results</h3>The PQ-loaded MCN-PEG@CDP nanoherbicides integrated with multi-stimuli responses to amylase, elevated temperature under sunlight, and competitors at leaf interface to control the PQ release for efficient weed control, while appeared low PQ leakage under the simulated human gastric or intestinal conditions, low cytotoxicity to human normal cells <em>in vitro</em>, and high mouse survival rate <em>in vivo</em>. Even through the nanoherbicides inevitably contact with water or intake by beneficial insects, they appear good biosafety on zebrafish (<em>D. rerio</em>) and honeybees (<em>Apis mellifera L</em>.).<h3>Conclusion</h3>The as-prepared nanoherbicides have high herbicidal efficacy and low risks to non-target species, and could promote the open use of PQ in agriculture.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809721","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, Hong-Min You, Mei-Rong Bai, Wen-Heng Yue, Fang-Fang Li, Bo-Wen Hu, Ya-Sha Chen, Xiang-Yu Shen, Yue Wu, Jia-Mei Wang, Zhi-Qing He, Xia Tao, Qing Jing, Chun Liang","doi":"10.1016/j.jare.2024.12.019","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.019","url":null,"abstract":"<h3>Introduction</h3>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.<h3>Objectives</h3>This study further investigated the role of P2Y12 in the iron metabolism of macrophages, the key player in systemic iron homeostasis and atherosclerosis.<h3>Methods</h3>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.<h3>Results</h3>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.<h3>Conclusion</h3>P2Y12 inhibition decreased hepcidin autocrine through repressing NF-κB p65 phosphorylation in macrophages, preventing intracellular iron retention and atherosclerosis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"200 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","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":"CD34+CLDN5+ tumor associated senescent endothelial cells through IGF2-IGF2R signaling increased cholangiocellular phenotype in hepatocellular carcinoma","authors":"Xin-yu Zhu, Wen-ting Liu, Xiao-juan Hou, Chen Zong, Wei Yua, Zhe-min Shen, Shu-ping Qu, Min Tao, Meng-meng Xue, Dao-yu Zhou, Hao-ran Bai, Lu Gao, Jing-hua Jiang, Qiu-dong Zhao, Li-xin Wei, Xue Yang, Zhi-peng Han, Li Zhang","doi":"10.1016/j.jare.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.008","url":null,"abstract":"<h3>Introduction</h3>The heterogeneity of hepatocellular carcinoma (HCC) is linked to tumor malignancy and poor prognosis. Nevertheless, the precise mechanisms underlying the development of the cholangiocellular phenotype (CCA) within HCC remain unclear. Emerging studies support that the cross-talk among the host cells within tumor microenvironment (TME) sustains the cancer cell plasticity.<h3>Objectives</h3>This study sought to identify the specific cell types involved in the formation of CCA and to elucidate their functional roles in the progression of HCC.<h3>Methods</h3><strong>S</strong>ingle-cell RNA sequencing was employed to identify the specific cell types involved in the formation of CCA. Both in vitro and vivo analyses were used to identify the tumor-associated senescent ECs and investigate the function in TME. The diethylnitrosamine-induced model was utilized to investigate the interaction between senescent ECs and MSCs, aiming to elucidate their synergistic contributions to the progression of CCA.<h3>Results</h3>Using single-cell RNA sequencing, we identified a distinct senescent-associated subset of endothelial cells (ECs), namely CD34⁺CLDN5⁺ ECs, which mainly enriched in tumor tissue. Further, the senescent ECs were observed to secrete IGF2, which recruited mesenchymal stem cells (MSCs) into the TME through IGF2R/MAPK signaling. In primary liver cancer model, MSCs exhibited a strong tumor-promoting effect, increasing the CCA and tumor malignancy after HCC formation. Interestingly, knockdown of IGF2R expression in MSCs inhibited the increase of CCA caused by MSCs in HCC. Meanwhile, it was revealed that MSCs released multiple inflammatory and trophic-related cytokines to enhance the cancer stem cell-like characteristics in HCC cells. Finally, we demonstrated that CEBPβ up-regulated IGF2 expression in tumor senescent ECs by combining with <em>Igf2</em>-promtor-sequence.<h3>Conclusions</h3>Together, our findings illustrated that tumor associated senescent ECs in HCC recruited the MSCs into TME, enhancing cancer stem cell (CSC)-like features of HCC cells and contributing to the CCA formation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816332","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":"Predictive value of remnant cholesterol inflammatory index for stroke risk: Evidence from the China health and Retirement Longitudinal study","authors":"Jiaying Chen, Qiheng Wu, Haotian Liu, Weike Hu, JiaJia Zhu, Zhong Ji, Jia Yin","doi":"10.1016/j.jare.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.015","url":null,"abstract":"<h3>Introduction</h3>Remnant cholesterol (RC) and high-sensitivity C-reactive protein (hs-CRP) are established stroke risk factors, but their joint impact remains unclear.<h3>Objectives</h3>This study aimed to evaluate the predictive value of the remnant cholesterol inflammatory index (RCII), a novel index integrating RC and hs-CRP, in assessing stroke risk.<h3>Methods</h3>We analyzed 9,898 participants aged 45 years or older, with no history of stroke at baseline, from the China Health and Retirement Longitudinal Study (CHARLS). RCII was calculated using the formula: RCII = RC (mg/dL) × hs-CRP(mg/L)/10. A subset of 5,704 participants was studied to investigate the relationship between cumulative RCII exposure and stroke incidence. The associations of both baseline and cumulative RCII with stroke risk were assessed using Cox proportional hazards regression model.<h3>Results</h3>During a median 7-year follow-up, 560 participants (5.7 %) experienced an incident stroke. Stroke incidence escalated with increasing RCII quartiles, from 3.5 % (Q1) to 7.6 % (Q4). In multivariable-adjusted analyses, each standard deviation increase in RCII was significantly associated with a 10.6 % increased risk of stroke (HR = 1.106, 95 % CI: 1.048–1.167). ROC analysis revealed that RCII had the highest AUC at 0.581, higher than RC (0.566) and hs-CRP (0.560), though the difference with RC was not statistically significant (P = 0.166). Mediation analysis indicated a reciprocal mediation between RC and hs-CRP on stroke risk. In a 3-year subset analysis, 288 participants suffered a stroke. Participants with cumulative RCII levels exceeding 36.14 had a significantly increased risk of incident stroke (HR = 1.462, 95 % CI: 1.102–1.939). Subgroup analyses showed a significant positive association between elevated RCII levels and stroke risk in males, but not in females.<h3>Conclusions</h3>Elevated levels of RCII, both at baseline and cumulative, are significantly associated with an increased risk of stroke. Early intervention in patients with high RCII may further help reduce stroke risk.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"38 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816383","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":"Improving grain yield and salt tolerance by optimizing plant height with beneficial haplotypes in rice (Oryza sativa)","authors":"Ruidang Quan, Juan Wang, Hua Qin, Liang Chen, Dinglin Xiao, Zihan Zhao, Zhanying Zhang, Xiaoyang Zhu, Zichao Li, Rongfeng Huang","doi":"10.1016/j.jare.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.007","url":null,"abstract":"<h3>Introduction</h3>Rice (<em>Oryza sativa</em> L.), a staple food for billions worldwide, is challenged by salt stress. Owing to the limited understanding of the physiological and genetic basis of rice salt tolerance, few genes have been identified as valuable in rice breeding, causing a major bottleneck in the development of high-yield, salt-tolerant rice varieties.<h3>Objective</h3>This study aims to identify salt tolerance genes/quantitative trait loci (QTLs) with breeding potential in rice.<h3>Methods</h3>Field trials were conducted with 166 Chinese rice cultivars from saline-affected regions and 412 global rice accessions to assess salt tolerance. Genome-wide association study (GWAS) was performed to identify key loci related to high yield and salt tolerance. Additionally, the impact of introducing beneficial haplotypes on grain yield and salt tolerance was assessed.<h3>Results</h3>The optimal rice plant height of 100–120 cm was crucial for sustaining high yield under both normal and salt stress conditions. GWAS revealed 6 novel QTLs/genes associated with rice plant growth and grain yield across various environments, distinct from previously recognized salt stress-related genes. Notably, the gene <em>PHS10.1</em>, encoding a serine/threonine protein kinase, may regulate carbon metabolism, starch and sucrose metabolism, influencing plant growth and grain yield. Certain haplotypes of the genes regulating plant height and grain yield, including <em>SD1</em>, <em>Ghd7.1</em>, <em>GH3.5,</em> and <em>PHS10.1</em>, were selected in traditional breeding. Moreover, optimizing plant height through the introgression of beneficial alleles of these genes increased grain yield in recipient lines under both normal and saline conditions.<h3>Conclusion</h3>We propose that utilizing beneficial haplotypes to optimize plant height can effectively balance the growth–stress trade-offs in rice plants. This represents a promising breeding strategy for the development of crop varieties that are both high-yielding and salt-tolerant.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816330","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":"Genome-wide profiling and functional study of short N-terminal H2B variants in Arabidopsis","authors":"Peng Yao, Qin He, Ying Wang, Danyang Sun, Xiangsong Chen, Li Lu","doi":"10.1016/j.jare.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.001","url":null,"abstract":"<h3>Introduction</h3>Nucleosomes harboring specific histone variants show distinct chromatin localization patterns and regulatory functions, thereby playing crucial roles in epigenetic regulation. Compared to the well-understood variants of H2A and H3, the study about H2B variants is emerging. Deciphering the roles and regulatory mechanisms of H2B variants in plants will provide more knowledges about epigenetic regulations in plant biology.<h3>Objectives</h3>Using the model plant <em>Arabidopsis thaliana</em> as the research subject, we systematically analyzed histone H2B variants, four short N-terminal histone H2B variants (snH2Bs) were identified. The genomic distribution characteristics of these snH2Bs, their impact on plant growth, and the potential regulatory mechanisms were studied.<h3>Methods</h3>By integrating whole-genome chromatin immunoprecipitation sequencing (ChIP-seq) and fluorescence microscopy localization analysis, the distribution of snH2Bs across the genome was identified. Single, double, and triple knock-out mutants were constructed using CRISPR-Cas9 to further explore the functions of snH2Bs in the growth process of <em>Arabidopsis thaliana</em>, the possible mechanisms were also discussed.<h3>Results</h3>These snH2B variants are preferentially expressed in reproductive tissues and are detected in the nuclei of pollen grains. Further genome-wide profiling indicates that the snH2Bs distribute at active chromatin regions and are positively correlated with gene expression. By creating knock-out single, double, and triple mutants for these snH2Bs, we demonstrate that H2B.5 influences vegetative to reproductive transition. We also show that H2B.5 is required for proper accumulation of H3 lysine 9 acetylation and H2B mono-ubiquitination.<h3>Conclusion</h3>Overall, our study not only provide insights into the functions and chromatin characteristics of plant snH2Bs, but also supplies examples that illustrate the interplay between histone variants and histone modification. These findings contribute to the understanding of the fundamental principles of epigenetic regulation in eukaryotes and also highlight potential targets for crop improvement.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"47 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809724","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":"KBTBD8/RRP15 as a potential novel therapeutic target associates with lenvatinib-inhibited progression in hepatocellular carcinoma both in vitro and in vivo","authors":"Saili Zhao, Xuran Wang, Rui Wu, Fenglan Wang, Xiaoxuan Tang, Junhui Chen, Runqiu Jiang, Wei Kang, Guifang Xu, Lei Wang, Zhangding Wang, Xiaoping Zou, Bin Zhang","doi":"10.1016/j.jare.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.017","url":null,"abstract":"<h3>Introduction</h3>We have previously demonstrated that RRP15 (Ribosomal RNA Processing 15 Homolog) was significantly elevated in hepatocellular carcinoma (HCC) and correlated directly with poor prognosis. RRP15 suppression curtails HCC progression through induction of cellular senescence and apoptosis. However, the impact of RRP15 on the precise therapeutic potential of lenvatinib has remained underexplored.<h3>Objective</h3>To investigate the relationship between RRP15 expression and sensitivity of lenvatinib in HCC treatment, and also explore the potential of targeting RRP15 by lenvatinib to inhibit HCC progression.<h3>Methods</h3>RRP15 and KBTBD8 (Kelch Repeat and BTB Domain Containing 8) expression was examined using western blot and immunohistochemistry. Cell viability, proliferation, migration and invasion as well as apoptosis were assessed using CCK-8, clonogenic assays, transwell, TUNEL (Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling) and Annexin V staining assays. The interaction between RRP15 and KBTBD8 was identified through pull-down and mass spectrometry analysis and further validated by immunofluorescence and co-immunoprecipitation assays. RRP15 ubiquitination and degradation were assessed using cycloheximide treatment, plasmid transfection and co-immunoprecipitation, followed by western blot analysis. Tail vein injection lung metastasis model was performed to determine tumor metastasis <em>in vivo</em>.<h3>Results</h3>We reveled a correlation between RRP15 downregulation and enhanced sensitivity to lenvatinib, presenting marked suppression of metastasis and invasiveness. Proteomic analyses and subsequent validation disclosed the pivotal role of the E3 ubiquitin ligase KBTBD8 in mediating the ubiquitination and subsequent degradation of RRP15 protein post-lenvatinib treatment in HCC cells. KBTBD8 inhibition stalled RRP15 ubiquitination and degradation, while its overexpression accelerated these processes. Moreover, RRP15 overexpression fosters HCC cell proliferation and metastasis, a pathological effect mitigated by KBTBD8 overexpression. <em>In vivo</em> experiments further validate the role of lenvatinib in promoting RRP15 degradation via KBTBD8 upregulation.<h3>Conclusions</h3>Our study elucidated a previously unidentified mechanism of lenvatinib action and identified the RRP15-KBTBD8 axis as a novel therapeutic target in HCC, offering new avenues for treatment strategies in combating HCC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"22 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809723","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":"Dissecting the anti-obesity components of ginseng: How ginseng polysaccharides and ginsenosides target gut microbiota to suppress high-fat diet-induced obesity","authors":"Han-Yan Luo, Jing Fang, Wei-Hao Zhang, Kam-Chun Chan, Yui-Man Chan, Cai-Xia Dong, Song-Lin Li, Ai-Ping Lyu, Jun Xu","doi":"10.1016/j.jare.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.002","url":null,"abstract":"<h3>Introduction</h3>Ginseng demonstrates therapeutic potential in treating obesity, with both experimental and clinical studies suggesting its anti-obesity effects are mediated by gut microbiota. Nonetheless, the specific chemical components responsible for this effect remain largely unidentified.<h3>Objectives</h3>This study aims to investigate the anti-obesity effects and mechanisms of ginseng polysaccharides (GP) and ginsenosides (GS), the primary chemical components of ginseng, with a focus on their impact on gut microbiota.<h3>Methods</h3>The impact of GP and GS on high-fat diet (HFD)-induced obesity was assessed using a mouse model. Molecular mechanisms were explored through a combination of chemical analysis, metagenomics, RT-qPCR, ELISA, and biochemical assays.<h3>Results</h3>GP or GS administration effectively prevented adiposity in HFD-fed mice, and both effects were mediated by gut microbiota. Chemical analysis revealed diverse glycosyl groups in GP and GS. Metagenomics data suggested that GP-enriched species, e.g., <em>Bacteroides stercorirosoris</em> and <em>Clostridiales bacterium</em> encoded carbohydrate-active enzymes GH35, GH43 and PL9_1, while GS-enriched <em>Sulfurospirillum halorespirans</em> encoded GH16_5. These enzymes facilitated the utilization of glycosyl groups in GP and GS, selectively stimulating bacterial growth and reshaping the gut microbiota. Furthermore, bacterial species enriched by GP or GS encoded specific functional genes involved in short-chain fatty acid (SCFA) synthesis (K00625 and K00925 for GP; K18118, K00100, and K18122 for GS) and intestinal gluconeogenesis (IGN) (K01678, K00024, and K01596 for GP; K18118 and K00278 for GS). Consequently, the SCFA-GLP-1/PYY signaling and IGN were activated by both GP and GS to ameliorate obesity phenotypes.<h3>Conclusion</h3>GP and GS, containing diverse glycosyl groups, selectively stimulate specific gut bacteria, triggering mechanisms involved in SCFA-GLP-1/PYY signaling and IGN activation to reduce adiposity in HFD-fed mice. The study enhances understanding of the chemical components crucial for the gut microbiota-mediated anti-obesity effect of ginseng. The mechanistic understanding provides valuable insights for developing ginseng-based drugs or health products to combat obesity.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809776","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":"Key β1-4 galactosylated glycan receptors of SARS-CoV-2 and its inhibitor from the galactosylated glycoproteins of bovine milk","authors":"Hanjie Yu, Wentian Chen, Jian Shu, Xin Wu, Jia Quan, Hongwei Cheng, Xiaojuan Bao, Di Wu Resource, Xilong Wang, Zheng Li","doi":"10.1016/j.jare.2024.12.010","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.010","url":null,"abstract":"<h3>Introduction</h3>The binding of the spike (S) protein of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) is a critical stage in the process of infection. While previous studies indicated that the S protein and ACE2 are extensively glycosylated, the functions of glycans in their interactions remain uncertain.<h3>Objectives</h3>This study aimed to investigate the glycan receptors of SARS-CoV-2 and evaluate the inhibitory effects of galactosylated glycoproteins derived from bovine milk on the attachment of SARS-CoV-2 pseudovirus.<h3>Methods</h3>An antibody-overlay lectin microarray was used to profile the glycopatterns of the S protein-S1 of SARS-CoV-2 and ACE2. Molecular dynamics simulation was used to mimic the interaction between the S protein and ACE2. The effects of N-glycans and β1-4 galactosylation on the interactions between SARS-CoV-2, its variations (B1.617.2 (Delta) and B1.1.529 (Omicron)), and ACE2 was assessed using molecular docking simulation and protein microarrays. The impact of glycoproteins (specifically sialylated glycoproteins or de-sialylated glycoproteins) derived from bovine milk on the interaction between S1 and ACE2, as well as on pseudoviral attachment and entry, was assessed using protein microarrays and pseudovirus-based microneutralization assays.<h3>Results</h3>Our findings indicated that the galactosylated glycoforms were the most prevalent for both S1 and ACE2. Importantly, we demonstrated that the β1-4 galactosylated N-glycans of ACE2 played a crucial role in the binding of S1 of SARS-CoV-2 and its variations to ACE2. The glycoproteins derived from bovine milk had a large amount of galactosylated glycans, which are comparable to the glycoforms of ACE2. The glycoproteins effectively blocked the attachment and entry of the SARS-CoV-2 pseudovirus by competitively blocking the binding of S1 to ACE2.<h3>Conclusions</h3>Our findings demonstrated that the β1-4 galactosylated N-glycans of ACE2 play a crucial role as glycan receptors for the binding of S1 of SARS-CoV-2 and its variations. Moreover, the glycoproteins with ’receptor-like’ glycoforms could be an effective inhibitor to prevent SARS-CoV-2 infection.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804649","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, Ran Xu, Yufei Zhou, Jiaying Wu, Xiaoxue Zhang, Hong Lin, Jienan Wang, Zhiwen Ding, Yunzeng Zou","doi":"10.1016/j.jare.2024.12.014","DOIUrl":"https://doi.org/10.1016/j.jare.2024.12.014","url":null,"abstract":"<h3>Introduction</h3>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.<h3>Methods</h3>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.<h3>Results</h3>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.<h3>Conclusions</h3>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.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-12-10","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}