Journal of Advanced Research最新文献

{"title":"Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment","authors":"Lihua Tan ,&nbsp;Zhimin Miao ,&nbsp;Yuxin Zhao ,&nbsp;Yongkai Liang ,&nbsp;Nan Xu ,&nbsp;Xin Chen ,&nbsp;Yanbei Tu ,&nbsp;Chengwei He","doi":"10.1016/j.jare.2024.12.009","DOIUrl":"10.1016/j.jare.2024.12.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis is an osteolytic disorder resulting from an inequilibrium between osteoblast-mediated osteogenesis and osteoclast-driven bone absorption. Safe and effective approaches for osteoporosis management are still highly demanded.</div></div><div><h3>Purpose</h3><div>This study aimed to examine the osteoprotective effect and the mechanisms of phaseol (PHA) <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>Virtual screening identified the potential inhibitors of transforming growth factor-beta-activated kinase 1 (TAK1) from coumestans. The interaction between PHA and TAK1 was investigated by molecular simulation, pronase and thermal resistance assays. The maturation and function of osteoclasts were determined using tartrate-resistant acid phosphatase staining, bone absorption and F-actin ring formation assays. The differentiation and calcification of osteoblasts were assessed by alkaline phosphatase staining and Alizarin Red S staining. The activity of related targets and pathways were detected using immunoblotting, immunofluorescence and co-immunoprecipitation assays. The <em>in vivo</em> osteoprotective effect of PHA was evaluated using a lipopolysaccharide (LPS)-induced mouse osteoporosis model.</div></div><div><h3>Results</h3><div>Firstly, we confirmed that TAK1 was essential in controlling bone remodeling by regulating osteogenesis and osteoclastogenesis. Moreover, PHA, a coumestan compound predominantly present in leguminous plants, was identified as a potent TAK1 inhibitor through virtual and real experiments. Subsequently, PHA was observed to enhance osteoblast differentiation and calcification, while suppress osteoclast maturation and bone resorptive function <em>in vitro</em>. Mechanistically, PHA remarkably inhibited the TRAF6-TAK1 complex formation, and inhibited the activation of TAK1, MAPK and NF-κB pathways by targeting TAK1. In the <em>in vivo</em> study, PHA strongly attenuated bone loss, inflammatory responses, and osteoclast over-activation in lipopolysaccharide-induced osteoporosis mice.</div></div><div><h3>Conclusion</h3><div>PHA had a dual-functional regulatory impact on osteogenesis and osteoclastogenesis by targeting TAK1, suppressing TRAF6-TAK1 complex generation, and modulating its associated signaling pathways, ultimately leading to mitigating osteoporosis. This study offered compelling evidence in favor of using PHA for preventing and managing osteoporosis as both a bone anabolic and anti-resorptive agent.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 761-779"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793741","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":"Dimeric guaianolide sesquiterpenoids from the flowers of Chrysanthemum indicum ameliorate hepatic steatosis through mitigating SIRT1-mediated lipid accumulation and ferroptosis","authors":"Yu Liu ,&nbsp;Fei Zhou ,&nbsp;Haoyu Zhao ,&nbsp;Jianguo Song ,&nbsp;Min Song ,&nbsp;Jianzhong Zhu ,&nbsp;Ying Wang ,&nbsp;Maggie Pui Man Hoi ,&nbsp;Ligen Lin ,&nbsp;Qingwen Zhang","doi":"10.1016/j.jare.2024.12.047","DOIUrl":"10.1016/j.jare.2024.12.047","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-alcoholic fatty liver disease (NAFLD) acts as the primary contributor to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma. The flowers of <em>Chrysanthemum indicum</em>, a traditional edible medicinal herb, have been widely used in China for more than 2000 years. However, the function of <em>C. indicum</em> in managing NAFLD has seldom been investigated.</div></div><div><h3>Objectives</h3><div>To reveal the novel active components and underlying mechanisms of <em>C. indicum</em> in treating NAFLD.</div></div><div><h3>Methods</h3><div>An MS/MS-based molecular networking-guided strategy was used for the chemical investigation. The structure identification of the new compounds involved high resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance (NMR) spectra, electronic circular dichroism (ECD), and X-ray crystallographic analysis. The biological evaluation was performed using Nile Red staining, flow cytometry, commercial kits, western blotting, co-immunoprecipitation, isothermal titration calorimetry, cellular thermal shift assay, drug affinity responsive target stability assay, molecular docking, and confocal immunofluorescence.</div></div><div><h3>Results</h3><div>A total of 27 new dimeric sesquiterpenoids, chryindicolides A-Z (<strong>1</strong>-<strong>26</strong>) and chrysanthemolide C (<strong>27</strong>), together with seven known compounds, were isolated from the flowers of <em>C. indicum</em> under the guide of MS/MS-based molecular networking. Among them, compounds <strong>1</strong>-<strong>7</strong> were rare chlorine-containing guaianolide dimers. Chryindicolide O (<strong>15</strong>) directly bound and activated the deacetylase Sirtuin 1 (SIRT1) to reduce <em>de novo</em> lipogenesis, enhance fatty acid β-oxidation, and inhibit ferroptosis in palmitic acid and oleic acid (P/O)-induced AML12 hepatocytes. In addition, chryindicolide O significantly ameliorated liver steatosis in high-fat diet-fed zebrafish.</div></div><div><h3>Conclusion</h3><div>Novel guaianolide dimers from <em>C. indicum</em> alleviated hepatic steatosis through mitigating SIRT1-mediated lipid accumulation and ferroptosis, suggesting that they could be further developed as candidates against NAFLD.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 345-370"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935358","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":"Protein palmitoylation in hepatic diseases: Functional insights and therapeutic strategies","authors":"Ying Wang ,&nbsp;Haoyuan Ma ,&nbsp;Bowen Zhang ,&nbsp;Sainan Li ,&nbsp;Beijia Lu ,&nbsp;Yingcheng Qi ,&nbsp;Tingting Liu ,&nbsp;Hua Wang ,&nbsp;Xiaohong Kang ,&nbsp;Yinming Liang ,&nbsp;Eryan Kong ,&nbsp;Liu Cao ,&nbsp;Binhui Zhou","doi":"10.1016/j.jare.2024.12.041","DOIUrl":"10.1016/j.jare.2024.12.041","url":null,"abstract":"<div><h3>Background</h3><div>Liver pathologies represent a spectrum of conditions ranging from fatty liver to the aggressive hepatocellular carcinoma (HCC), as well as parasitic infections, which collectively pose substantial global health challenges. S-palmitoylation (commonly referred to as palmitoylation), a post-translational modification (PTM) characterized by the covalent linkage of a 16-carbon palmitic acid (PA) chain to specific cysteine residues on target proteins, plays a pivotal role in diverse cellular functions and is intimately associated with the liver’s physiological and pathological states.</div></div><div><h3>Aim of review</h3><div>This study aims to elucidate how protein palmitoylation affects liver disease pathophysiology and evaluates its potential as a target for diagnostic and therapeutic interventions.</div></div><div><h3>Key scientific concepts of review</h3><div>Recent studies have identified the key role of protein palmitoylation in regulating the development and progression of liver diseases. This review summarizes the intricate mechanisms by which protein palmitoylation modulates the pathophysiological processes of liver diseases and explores the potential of targeting protein palmitoylation modifications or the enzymes regulating this modification as prospective diagnostic biomarkers and therapeutic targets.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 307-326"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888534","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":"Comprehensive analysis of heterogeneity and cell-cell interactions in Crohn’s disease reveals novel location-specific insights","authors":"Jing Feng ,&nbsp;Li-Na He ,&nbsp;Ruchen Yao ,&nbsp;Yuqi Qiao ,&nbsp;Tian Yang ,&nbsp;Zhe Cui ,&nbsp;Xiangjun Meng ,&nbsp;Jinlu Tong ,&nbsp;Keyu Jia ,&nbsp;Zhixiang Zuo ,&nbsp;Jun Shen","doi":"10.1016/j.jare.2024.12.042","DOIUrl":"10.1016/j.jare.2024.12.042","url":null,"abstract":"<div><h3>Introduction</h3><div>In Crohn’s disease (CD), lesions are mainly distributed in a segmental manner, with the primary sites of involvement being the ileum and colon. Heterogeneity in colon and ileum results in location-specific clinical presentations and therapeutic responses. Mucosal healing tends to be more readily and quickly achieved in the colon than in the ileum, where lesions are more likely to develop into complex behaviors. The heterogeneity of colon and ileum in CD, which is essential for tailored therapeutic approaches, has not yet been systematically illustrated.</div></div><div><h3>Objectives</h3><div>CD presents with unique intestinal lesions, mainly impacting the terminal ileum and colon. It is essential to comprehend the diversity in pathogenesis and treatment response among various segments.</div></div><div><h3>Methods</h3><div>We conducted comparative single-cell RNA sequencing analysis in treatment-naïve CD patients, concentrating on the colon and ileum.</div></div><div><h3>Results</h3><div>A novel subset of epithelial cells expressing high levels of <em>DUOX2</em> and <em>DUOXA2</em> (DUOX2-epi) was discovered. This DUOX2-epi subcluster predominantly distributed in the tip epithelium of the inflamed colon, potentially in response to microbial infection, as evidenced by the significant enrichment of inflammatory and microbial response pathways. The colonic and ileal DUOX2-epi subsets trigger inflammatory responses through distinct mechanisms. The colonic DUOX2-epi primarily affects monocytes via the SAA1-FPR2 ligand-receptor interaction, whereas the ileal DUOX2-epi directly interacts with regulate T cells through the CXCL16-CXCR6 ligand-receptor pair. Moreover, the cell–cell communication networks involving DUOX2-epi in the colon and ileum can help predict the location-specific effects of biological therapies.</div></div><div><h3>Conclusion</h3><div>This study delves into the heterogeneity within the ileum and colon of Crohn’s disease at the single-cell level, identifying a new epithelial subset DUOX2-epi. Predictive gene modules tailored to different locations for biological therapies are developed as well, based on the cell–cell communication network modulated by DUOX2-epi.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 679-694"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142888401","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":"Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis","authors":"Ren-yi Su ,&nbsp;Chen-hao Xu ,&nbsp;Hai-jun Guo ,&nbsp;Li-jun Meng ,&nbsp;Jian-yong Zhuo ,&nbsp;Nan Xu ,&nbsp;Hui-gang Li ,&nbsp;Chi-yu He ,&nbsp;Xuan-yu Zhang ,&nbsp;Zheng-xin Lian ,&nbsp;Shuai Wang ,&nbsp;Chenhao Cao ,&nbsp;Ruhong Zhou ,&nbsp;Di Lu ,&nbsp;Shu-sen Zheng ,&nbsp;Xu-yong Wei ,&nbsp;Xiao Xu","doi":"10.1016/j.jare.2024.11.021","DOIUrl":"10.1016/j.jare.2024.11.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Alcohol consumption and hepatitis B virus (HBV) infection are common risk factors for hepatocellular carcinoma (HCC). However, few studies have focused on elucidating the mechanisms of HCC with combined alcohol and HBV etiology.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the molecular features of alcohol and HBV on HCC and to seek out potential therapeutic strategies.</div></div><div><h3>Methods</h3><div>Two independent cohorts of HCC patients (n = 539 and n = 140) were included to investigate HCC with synergetic alcohol and HBV (AB-HCC) background. Patient-derived cell lines, organoids, and xenografts were used to validate the metabolic fragile. High-throughput drug screening (1181 FDA-approved anticancer drugs) was leveraged to explore the potential therapeutic agents.</div></div><div><h3>Results</h3><div>Here, we delineated AB-HCC as a distinctive metabolic subtype, hallmarked by oncogenic cholesterol, through the integration of clinical cohorts, proteomics, phosphoproteomics, and spatial transcriptome. Mechanistically, our findings revealed that cholesterol directly binds to CSNK2A1 (Casein Kinase 2 Alpha 1), augmenting its kinase activity and leading to phosphorylation of IGF2R (Insulin-Like Growth Factor 2 Receptor) at Ser2484. This cascade rewires lipid-driven mitochondrial oxidative phosphorylation, spawns reactive oxygen species measured by malondialdehyde assay, and perpetuates a positive feedback loop for cholesterol biosynthesis, ultimately culminating in tumorigenesis. Initial transcriptional activation of CSNK2A1 is driven by upregulation of RAD21 in AB-HCC. Our cholesterol profiling exposes AB-HCC’s compensatory mechanism of AB-HCC, which capitalizes on both uptake and biosynthesis of cholesterol to confer survival edge. Moreover, high-throughput drug screening coupled with <em>in vivo</em> validation has uncovered the susceptibilities of AB-HCC, which can be effectively addressed by a combination of dietary cholesterol restriction and oral administration of Fostamatinib. The CSNK2A1-mediated cholesterol biosynthesis pathway has been implicated in various cancers characterized by cholesterol metabolism.</div></div><div><h3>Conclusion</h3><div>These findings not only pinpoint the oncogenic metabolite cholesterol as a hidden culprit in AB-HCC subtype, but also enlighten a novel combination strategy to rejuvenate tumor metabolism.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 449-465"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609976","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":"Non-destructive detection strategy of maize seed vigor based on seed phenotyping and the potential for accelerating breeding","authors":"Keling Tu ,&nbsp;Shaozhe Wen ,&nbsp;Yanan Xu ,&nbsp;Hongju He ,&nbsp;He Li ,&nbsp;Rugen Xu ,&nbsp;Baojian Guo ,&nbsp;Chengming Sun ,&nbsp;Riliang Gu ,&nbsp;Qun Sun","doi":"10.1016/j.jare.2024.12.022","DOIUrl":"10.1016/j.jare.2024.12.022","url":null,"abstract":"<div><h3>Introduction</h3><div>Seeds are fundamental to agricultural production, and their vigor affects seedling quality, quantity, and crop yield. Accurate vigor assessment methods are crucial for agricultural productivity.</div></div><div><h3>Objectives</h3><div>Traditional seed vigor testing and phenotypic trait acquisition methods are complex, time-consuming, or destructive. Thus, this study aims to develop a non-destructive method for assessing maize seed vigor based on seed phenotyping and to delve into the underlying mechanism of this method.</div></div><div><h3>Methods</h3><div>Utilizing 368 maize inbred lines with diverse genetic backgrounds as research material, the cold-soaking germination percentage, closely related to the field emergence percentage, was selected to evaluate seed vigor. High and low-vigor groups were ultimately obtained through mixed grouping based on the consistent performance of seeds harvested across years. Subsequently, non-destructive techniques such as hyperspectral imaging, machine vision, and gas chromatography with ion mobility spectrometry, along with machine learning, were employed to establish models for distinguishing high and low-vigor maize seeds in their natural state. After determining the optimal strategy, key phenotypic features were identified for relevant genetic and metabolic analyses to elucidate the effectiveness of the seed vigor testing model.</div></div><div><h3>Results</h3><div>Among the evaluated methods, the machine vision-based emerged as the optimal seed vigor detection method (accuracy ≈ 90%). Subsequently, four key features (B_mean, b_mean, S_mean, and b_std) were selected for genome-wide association analysis, revealing two confident candidate genes involved in hormone regulation affecting seed germination. Further investigations confirmed significant differences in several endogenous hormones’ levels and flavonoid, chlorophyll, and anthocyanidin content between high and low-vigor maize seeds.</div></div><div><h3>Conclusion</h3><div>This study validates a reliable, non-destructive seed vigor detection model supported by genetic and physiological-biochemical evidence. The findings enhance the application of non-destructive seed quality testing models and provide reliable and high-throughput measurable phenotypic traits associated with seed vigor, thereby facilitating gene mining and accelerating high-vigor maize variety breeding.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 45-56"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884681","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":"An AP2/ERF transcription factor controls generation of the twin-seedling rice","authors":"Kaichong Teng ,&nbsp;Neng Zhao ,&nbsp;Yonghong Xie ,&nbsp;Rongbai Li ,&nbsp;Jianxiong Li","doi":"10.1016/j.jare.2024.12.013","DOIUrl":"10.1016/j.jare.2024.12.013","url":null,"abstract":"<div><h3>Introduction</h3><div>The floret of rice is a main component of the spikelet, and the ovule of pistil is a critical organ for successful reproduction and determines the number of seeds. However, the molecular mechanisms underlying the ovule development remain elusive.</div></div><div><h3>Objective</h3><div>Twin-seedling rice has great potential for application in rice production. The study was to isolate the gene that controls twin-seedling in rice and explore the molecular function of the gene in floret development.</div></div><div><h3>Methods</h3><div>We discovered a twin-seedling rice (<em>tsr</em>) mutant and constructed different segregating populations to clone <em>TSR</em> gene using map-based cloning method. To explore the molecular functions of <em>TSR</em> in determination of the ovary number and development, we applied molecular technologies such as yeast two-hybrid assay, electrophoretic mobility shift assay (EMSA), and dual-LUC transient expression assay to search for the TSR-interacting proteins and the target genes regulated by <em>TSR</em>.</div></div><div><h3>Results</h3><div>We report here the map-based cloning of <em>TSR</em> which encodes an AP2/ERF transcription factor. Mutations in <em>TSR</em> lead to occurrence of the twin-seedling rice. The <em>tsr</em> mutant showed open hulls of the spikelets and displayed changes in the number of stamens and ovules of the florets. The ovary of <em>tsr</em> mutant contained two conjugated ovules which developed into a mature seed with two viable embryos. Mechanistic studies revealed that <em>TSR</em> regulates the expression levels of genes related to spikelet determination and ovule identity by binding to their promoters. Furthermore, TSR interacted with OsMADS1 and this interaction allowed OsMADS1 to modulate the transcriptional activityy of TSR on gene expression. The molecular study of <em>TSR</em> provides new insights into the formation and development of rice floret and helps breeders generate twin-seedling rice in production.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 33-43"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833065","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 ,&nbsp;Wentian Chen ,&nbsp;Jian Shu ,&nbsp;Xin Wu ,&nbsp;Jia Quan ,&nbsp;Hongwei Cheng ,&nbsp;Xiaojuan Bao ,&nbsp;Di Wu ,&nbsp;Xilong Wang ,&nbsp;Zheng Li","doi":"10.1016/j.jare.2024.12.010","DOIUrl":"10.1016/j.jare.2024.12.010","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 159-172"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","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":"An accurate prediction for respiratory diseases using deep learning on bronchoscopy diagnosis images","authors":"Weiling Sun ,&nbsp;Pengfei Yan ,&nbsp;Minglei Li ,&nbsp;Xiang Li ,&nbsp;Yuchen Jiang ,&nbsp;Hao Luo ,&nbsp;Yanbin Zhao","doi":"10.1016/j.jare.2024.11.023","DOIUrl":"10.1016/j.jare.2024.11.023","url":null,"abstract":"<div><h3>Introduction</h3><div>Bronchoscopy is of great significance in diagnosing and treating respiratory illness. Using deep learning, a diagnostic system for bronchoscopy images can improve the accuracy of tracheal, bronchial, and pulmonary disease diagnoses for physicians and ensure timely pathological or etiological examinations for patients. Improving the diagnostic accuracy of the algorithms remains the key to this technology.</div></div><div><h3>Objectives</h3><div>To deal with the problem, we proposed a multiscale attention residual network (MARN) for diagnosing lung conditions through bronchoscopic images. The multiscale convolutional block attention module (MCBAM) was designed to enable accurate focus on lesion regions by enhancing spatial and channel features. Gradient-weighted Class Activation Map (Grad-CAM) was provided to increase the interpretability of diagnostic results.</div></div><div><h3>Methods</h3><div>We collected 615 cases from Harbin Medical University Cancer Hospital, including 2900 images. The dataset was partitioned randomly into training sets, validation sets and test sets to update model parameters, evaluate the model’s training performance, select network architecture and parameters, and estimate the final model. In addition, we compared MARN with other algorithms. Furthermore, three physicians with different qualifications were invited to diagnose the same test images, and the results were compared to those of the model.</div></div><div><h3>Results</h3><div>In the dataset of normal and lesion images, our model displayed an accuracy of 97.76% and an AUC of 99.79%. The model recorded 92.26% accuracy and 96.82% AUC for datasets of benign and malignant lesion images, while it achieved 93.10% accuracy and 99.02% AUC for normal, benign, and malignant lesion images.</div></div><div><h3>Conclusion</h3><div> <!-->These results demonstrated that our network outperforms other methods in diagnostic performance. The accuracy of our model is roughly the same as that of experienced physicians and the efficiency is much higher than doctors. MARN has great potential for assisting physicians with assessing the bronchoscopic images precisely.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 423-438"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673784","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":"Evaluating current status of network pharmacology for herbal medicine focusing on identifying mechanisms and therapeutic effects","authors":"Won-Yung Lee ,&nbsp;Kwang-Il Park ,&nbsp;Seon-Been Bak ,&nbsp;Seungho Lee ,&nbsp;Su-Jin Bae ,&nbsp;Min-Jin Kim ,&nbsp;Sun-Dong Park ,&nbsp;Choon Ok Kim ,&nbsp;Ji-Hwan Kim ,&nbsp;Young Woo Kim ,&nbsp;Chang-Eop Kim","doi":"10.1016/j.jare.2024.12.040","DOIUrl":"10.1016/j.jare.2024.12.040","url":null,"abstract":"<div><h3>Introduction</h3><div>Network pharmacology has gained significant traction as a tool for identifying the mechanisms and therapeutic effects of herbal medicines. However, despite the usefulness of these approaches, their diversity underscores the critical need for a systematic evaluation to ensure consistency and reliability.</div></div><div><h3>Objectives</h3><div>We aimed to evaluate the network pharmacological analyses, focusing on identifying the mechanisms and therapeutic effects of herbal medicines.</div></div><div><h3>Methods</h3><div>We employed a comprehensive approach involving systematic data retrieval, network construction, and analysis. Herbal compounds and their targets were meticulously extracted from five distinct network pharmacology databases to ensure extensive coverage and high data reliability. Advanced network-based methods were used to identify key herbal targets and predict therapeutic effects, thereby enriching the depth and breadth of the analysis. Experimental validation was performed on prostate cancer models to substantiate the computational predictions.</div></div><div><h3>Results</h3><div>The results of the recapitulating task for known herbal ingredient targets revealed distinct patterns in performance and coverage based on network construction and aggregation methods. We performed the same analysis to identify herbal targets and found that network centrality, path counts, and downweighted path counts had their own pros and cons. By comparing network-based methods, we found that considering the impact on the multiscale interactome yielded the highest accuracy in discriminating known therapeutic effects. Using optimal conditions, we successfully identified new indications for herbal medicines and validated these findings through follow-up <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Conclusion</h3><div>This study presents the first comprehensive and critical evaluation of the current network pharmacology analyses in the field of herbal medicine and provides valuable guidance for continued advances in the elucidation of the mechanisms and therapeutic effects.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 ","pages":"Pages 799-815"},"PeriodicalIF":13.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884682","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}