Journal of Advanced Research最新文献

{"title":"Next-generation diabetes diagnostics: spectrochemical staging of red blood cells using vibrational spectroscopy","authors":"Aleksandra Wilk,&nbsp;Natalia Wilkosz,&nbsp;Marzena Rugiel,&nbsp;Marta Saluga,&nbsp;Kamil Kawon,&nbsp;Tetiana Stepanenko,&nbsp;Katarzyna Bulat,&nbsp;Aleksandra Wajda,&nbsp;Michał Szuwarzynski,&nbsp;Anna Zajaczkowska,&nbsp;Anna Morgunowicz,&nbsp;Grzegorz Chodaczek,&nbsp;Víctor Navarro-Esteve,&nbsp;David Perez-Guaita,&nbsp;Joanna Chwiej,&nbsp;Katarzyna M. Marzec","doi":"10.1016/j.jare.2026.01.052","DOIUrl":"10.1016/j.jare.2026.01.052","url":null,"abstract":"<div><h3>Introduction</h3><div>Type 2 diabetes mellitus (T2DM) induces progressive biochemical and morphological alterations in red blood cells (RBCs), driven by hyperglycemia-induced oxidative stress and disrupted lipid–protein homeostasis. These changes compromise membrane integrity and serve as sensitive molecular indicators of disease severity. Yet, a non-invasive strategy for capturing such alterations at the molecular level remains an unresolved challenge.</div></div><div><h3>Objectives</h3><div>This study employs Fourier Transform Infrared Spectroscopy (FT-IR) and Raman Spectroscopy (RS) to uncover sex- and age-specific molecular alterations in RBCs induced by T2DM. By integrating classical and advanced analytical techniques, we identify novel spectrochemical markers of disease progression, offering a non-invasive, label-free framework for staging and monitoring diabetic pathology at the molecular level.</div></div><div><h3>Methods</h3><div>A total of 120 db/db and C57BL/6J mice were tested at 7, 12 and 24 weeks of age. Standard hematological and biochemical analyses were combined with vibrational spectroscopy (FT-IR, RS) and atomic force microscopy (AFM), to assess RBC morphology and molecular composition. Spectral data was analyzed using univariate and multivariate statistics to identify disease-specific spectral markers.</div></div><div><h3>Results</h3><div>Partial Least Squares Discriminant Analysis reliably distinguished diabetic and control RBC profiles, confirming the presence of robust, disease-specific molecular patterns. Integration with hematological and biochemical parameters further validated the diagnostic relevance of this label-free, non-invasive approach. Structural protein analysis revealed a consistent decline in α-helical content and an increase in β-sheet and β-turn structures, reflecting protein misfolding and aggregation, particularly in older diabetic females. Alterations in disulfide bonding, hydrated β-sheets and H-bonded antiparallel β-sheets highlighted oxidative stress-mediated membrane destabilization. Additionally, elevated plasma triglyceride levels and increased saturation of RBC membrane lipids indicate impaired lipid handling.</div></div><div><h3>Conclusion</h3><div>Vibrational spectroscopy enables non-invasive, molecular-level profiling of diabetes-induced RBC alterations, revealing sex- and age-dependent signatures of disease progression. This approach offers a promising platform for precise staging and stratification in metabolic disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 415-436"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-organ metabolic dysregulation and cecal microbiota alterations following black carbon exposure","authors":"Shengtao Wei,&nbsp;Wenxue Li,&nbsp;Shanshan Ran,&nbsp;Jingyi Zhang,&nbsp;Zilong Zhang,&nbsp;Zijun Yang,&nbsp;Fei Tian,&nbsp;Lan Chen,&nbsp;Peng Hu,&nbsp;Jun Yuan,&nbsp;Hualiang Lin","doi":"10.1016/j.jare.2026.01.027","DOIUrl":"10.1016/j.jare.2026.01.027","url":null,"abstract":"<div><h3>Background</h3><div>Black carbon (BC) has been linked to adverse health outcomes, yet underlying mechanisms remain unclear. Integrating metabolomic and metagenomic data across tissues may clarify BC-induced biological pathways.</div></div><div><h3>Methods</h3><div>We performed human epidemiology and mice experimental approaches. We included 248,288 participants with annual BC exposure estimates and plasma metabolomic profiles. Elastic net regression identified BC-associated metabolites. Male C57BL/6J mice were exposed to filtered air or BC (1 mg/m³, 1 h/day, 5 days/week, 12 weeks). Multi-tissue metabolomics and cecal contents microbiota sequencing were conducted, with histology and gene expression measurements.</div></div><div><h3>Results</h3><div>In humans, long-term BC exposure significantly altered plasma metabolites, notably increasing saturated fatty acids (β = 0.048), while decreasing docosahexaenoic acid (β = −0.002). Amino acid metabolism was broadly disrupted, involving elevated valine (β = 0.011) and reduced glutamine (β = −0.006). In mice, metabolomic profiling showed organ-specific shifts, including increased glutathione and cortisol in the liver (2.88-fold and 2.06-fold), increased PC(16:0/18:1(9Z)) in the heart (3.22-fold), elevated anandamide and arachidonic acid in the kidney (2.35-fold and 1.48-fold), and decreased multiple fatty acids and lysophospholipids across organs. Cecal microbiota exhibited reduced alpha-diversity (Shannon: 3.67 vs. 4.50, <em>P</em> &lt; 0.05) and taxonomic shifts, including an increased abundance of <em>g_Akkermansia and decrease in g_Bacteroides</em>. Multi-omics integration revealed significant microbiota-metabolome correlations in the cecum and plasma (Mantel r = 0.276, <em>P</em> = 0.012). Histological examination confirmed organ injuries, notably lung inflammation, cardiac edema, and neuronal condensation. Gene expression analysis showed increased Il-6 in the lung (5.35-fold, <em>P</em> = 0.047), increased Mb in the heart (5.18-fold, <em>P</em> = 0.010), and increased Igfbp7 in the kidney (3.03-fold, <em>P</em> = 0.001), while Tjp1 expression in cecum was reduced (0.42-fold, <em>P</em> = 0.004).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that BC exposure may alter systemic metabolism and gut microbiota, potentially contributing to tissue injury and inflammation. The gut–organ axis could be a target for mitigating BC-related health effects.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 285-295"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet score reveals total and cardiovascular mortality and identifies protein biomarkers in large cohorts","authors":"Xiaomin Li,&nbsp;Xiangju Kong,&nbsp;Shanpeng Liu,&nbsp;Chenyu Hou,&nbsp;Shali Cui,&nbsp;Xuan Zhu,&nbsp;Yue Guan,&nbsp;Songliu Hu,&nbsp;Changhao Sun,&nbsp;Yucun Niu","doi":"10.1016/j.jare.2026.01.016","DOIUrl":"10.1016/j.jare.2026.01.016","url":null,"abstract":"<div><h3>Introduction</h3><div>The high-fat diet (HFD) has complex health implications, shaped by the composition of macronutrients and food sources. However, existing dietary assessment tools lack the precision required for effective risk stratification.</div></div><div><h3>Objectives</h3><div>This study developed novel HFD scores to accurately characterize dietary patterns and examined their associations with total and cardiovascular disease (CVD) mortality, while also identifying relevant protein biomarkers.</div></div><div><h3>Methods</h3><div>Data from the UK Biobank and NHANES were utilized to develop a novel HFD scoring system incorporating both macronutrient ratios and quality indicators. Mortality associations were evaluated using Cox proportional hazards models, Kaplan-Meier analysis, and restricted cubic splines (RCS). Proteomic analysis was conducted to identify plasma proteins associated with mortality.</div></div><div><h3>Results</h3><div>The unhealthy HFD score showed a linear correlation with increased total and CVD mortality. In contrast, the healthy HFD score exhibited a U-shaped relationship with CVD mortality. On a 30-point HFD scale, individuals with low total mortality risk in the UK and US should maintain scores below 15, while those with low CVD risk in the UK should aim for scores between 10 and 15. An online HFD risk calculator was developed for practical application. Proteomic analysis revealed 48 proteins linked to total mortality and 153 proteins associated with CVD mortality, with significant enrichment in immune regulation and cardiovascular pathways. Machine learning models identified key predictors, such as EDA2R and NTproBNP, which demonstrated mediation effects of 12.92% and 13.86%, respectively.</div></div><div><h3>Conclusion</h3><div>These findings establish a precision nutrition framework that links HFD patterns, proteomic biomarkers, and mortality outcomes, offering actionable insights for clinical and public health intervention.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 247-261"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-protein diet promotes aging by activating the CG6415/AMT gene and disrupting mitochondrial homeostasis","authors":"Xiaoqing Xu,&nbsp;Wangyang Zheng,&nbsp;Qianmin Liu,&nbsp;Yue Li,&nbsp;Shuo Yang,&nbsp;Runyi Zhou,&nbsp;Yina Wang,&nbsp;Xiang Qi,&nbsp;Can Zhang,&nbsp;Fengmin Zhang,&nbsp;Yue Wu,&nbsp;Yuhao Li,&nbsp;Ying Li","doi":"10.1016/j.jare.2026.01.063","DOIUrl":"10.1016/j.jare.2026.01.063","url":null,"abstract":"<div><h3>Introduction</h3><div>Dietary protein has multiple physiological functions. However, high-protein diets have been proven to elevate the risk of all-cause mortality. Aging is a dynamic and complex process, but the impact of dietary protein on aging remains unclear.</div></div><div><h3>Objectives</h3><div>To explore the effects of high-protein diets on aging at multiple life stages and the underlying mechanisms.</div></div><div><h3>Methods</h3><div><em>Drosophila</em> were used to assess the effects of diets with 5%, 10%, 15%, 20%, 25%, and 30% protein energy supply on lifespan. Transcriptomic and proteomic analyses at multiple life-stage points screened pathways and key genes consistently affected by high-protein diets. Knockout and overexpression of the key gene <em>CG6415</em> in <em>Drosophila</em> verified its mediating role in high-protein diets’ impact on aging. Based on the insights from the omics data of gene-knockout <em>Drosophila</em>, the mechanism by which the human homologous <em>AMT</em> gene of <em>CG6415</em> affects aging was verified in the mammalian genetic background using the human embryonic kidney 293T cell. According to the effects of high-protein diets on <em>Drosophila</em>’s amino acid profiles, lifespan observations with individual supplementation of 20 amino acids, and verification using <em>CG6415</em> gene-knockout <em>Drosophila</em>, the amino acids that play key roles in the impact of high-protein diets on aging were identified.</div></div><div><h3>Results</h3><div>There is an inverted U-shaped relationship between lifespan and dietary protein energy ranging from 5% to 30%. Glycine, serine, and threonine metabolism pathway and the <em>CG6415</em> gene can be activated by high-protein diets of various proportions at multiple life-stage points. The <em>CG6415</em>/<em>AMT</em> gene inhibits oxidative phosphorylation, disrupts mitochondrial homeostasis, and subsequently activates the p53-p21 pathway, promoting aging and stress-induced damage. Supplementing isoleucine can partially simulate the role of high-protein diets in regulating <em>CG6415</em>-mediated aging.</div></div><div><h3>Conclusions</h3><div>High-protein diet promotes aging, partly via activation of the <em>CG6415</em>/<em>AMT</em> gene and subsequent disruption of mitochondrial homeostasis. Isoleucine plays a relatively key role in this process.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 995-1012"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal dynamics in frailty and incident all-cause dementia: a multicohort study","authors":"Yihong Ding,&nbsp;Zhaoping Wang,&nbsp;Jiabei He,&nbsp;Jie Shen,&nbsp;Changzheng Yuan,&nbsp;Di He,&nbsp;Yimin Zhu","doi":"10.1016/j.jare.2026.01.026","DOIUrl":"10.1016/j.jare.2026.01.026","url":null,"abstract":"<div><h3>Introduction</h3><div>Frailty changes over time, but how these changes relate to the risk of dementia remains uncertain.</div></div><div><h3>Objective</h3><div>To explore the temporal relationship between dynamic changes in frailty and incident all-cause dementia.</div></div><div><h3>Methods</h3><div>We included adults aged ≥ 60 years from four prospective cohorts in this pooled analysis. Frailty was assessed using a modified Fried phenotype at two separate time points, allowing the identification of longitudinal frailty transition patterns. The outcome was all-cause dementia, identified through active follow-up assessments or passive data collection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from Cox proportional hazards analyses.</div></div><div><h3>Results</h3><div>Among 15,897 participants (51.3% female, mean age: 66.9 years), 1015 developed incident dementia over 131,621.3 person-years of follow-up. An increased risk of dementia was observed among robust participants who progressed to pre-frail/frail status, compared to those with stable robustness (pooled HR: 1.62, 95% CI: 1.06–2.47; I² = 66.8%). Similarly, pre-frail participants who progressed to frail status exhibited a higher dementia risk compared to those who remained pre-frail (pooled HR: 1.85, 95% CI: 1.47–2.34; I² = 0.0%). Conversely, participants who reverted from pre-frail to robust status experienced a reduced dementia risk (pooled HR: 0.59, 95% CI: 0.46–0.76; I² = 0.0%). A higher cumulative frailty score was related to an increased dementia risk (HR: 1.26, 95% CI: 1.22–1.31; I² = 0.0% per score increment). Participants whose frailty scores increased over time had a higher risk of dementia compared to those with stable scores (pooled HR: 1.33, 95% CI: 1.07–1.65; I² = 75.5% per score increment), while those with decreasing scores showed a mitigated dementia risk (pooled HR: 0.77, 95% CI: 0.65–0.91; I² = 0.0% per score decrement).</div></div><div><h3>Conclusions</h3><div>Progression in frailty was associated with an increased risk of dementia, while reversal of pre-frailty reduced the risk. Our results highlight the importance of continuous monitoring and personalized interventions for managing frailty in older adults.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 855-865"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing water allocation in irrigation districts for enhanced sustainability and climate resilience","authors":"Yingshan Chen,&nbsp;Mo Li,&nbsp;Qiang Fu,&nbsp;Xiao Liu,&nbsp;Lei Yu,&nbsp;Vijay P. Singh,&nbsp;Luchen Wang","doi":"10.1016/j.jare.2026.01.055","DOIUrl":"10.1016/j.jare.2026.01.055","url":null,"abstract":"<div><h3>Introduction</h3><div>Irrigation plays a crucial role in enhancing agricultural productivity. However, it simultaneously increases water consumption and greenhouse gas (GHG) emissions, a challenge that is further exacerbated by climate change. While many irrigation strategies have been proposed, their potential to balance crop yield growth, water productivity improvement and carbon emission reduction in large-scale irrigation districts remains unclear.</div></div><div><h3>Objectives</h3><div>This study aims to establish a decision-relevant, scalable basis for climate-resilient irrigation management by testing whether coordinated irrigation allocation across large irrigation districts can jointly sustain food production while improving water-use efficiency and reducing GHG emissions under climate change. An integrated optimization perspective is used to delineate the achievable potential and limits of irrigation allocation for aligning food security with water conservation and carbon-neutrality goals.</div></div><div><h3>Methods</h3><div>In this study, the DSSAT crop model was used to simulate the biophysical response of main crops under irrigation and climate conditions, and water production function was extracted from random forest to realize rapid prediction. Then, the Pareto optimal irrigation strategy among grain yield, water productivity and greenhouse gas emission reduction was identified by NSGA-II, and it was calibrated and verified under the data of typical irrigation areas.</div></div><div><h3>Results</h3><div>Using an integrated framework, we show that irrigation optimization increases irrigation water productivity by 11.84%, while reducing water use by 8.6% and GHG emissions by 45.3%. Under climate change scenarios, optimized allocation decreases irrigation volume by 6.9–9.3%, with crop yields rising in two-thirds of scenarios, reaching gains of up to 31.3%. Nationwide, crop water productivity is projected to rise by 0.68%–18.55%, accompanied by a reduction in GHG emissions of 7.49%–32.90%. These results demonstrate that coordinated irrigation optimization can effectively decouple agricultural production from water consumption and carbon emissions, highlighting its potential as a robust and scalable strategy for safeguarding food security while advancing agricultural sustainability and carbon-neutrality objectives.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 135-147"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multiomics and machine learning identify uridine as a candidate modulator of MMP7-mediated immune cell infiltration in pulmonary fibrosis","authors":"Wanda Bi,Ying Zhou,Junhui Gong,Wenyi Liu,Jiali Li,Juan Du,Henghai Nie,Huanyu Luo,Huacai Zhang,Qingli Cai,Chu Gao,Ling Zeng,Jianxin Jiang,Saiying Hou,Li Li","doi":"10.1016/j.jare.2026.10.008","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.008","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090552","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":"Phycosphere microbiome remodeling and Brevundimonas partnership establishment enhance microalgal nonylphenol tolerance","authors":"Qilu Cheng,Leidong Hong,Cai Hui,Ligen Xu,Yangzhi Liu,Feng Wang,Qiang Wang,Junwei Ma,Hui Lin","doi":"10.1016/j.jare.2026.10.006","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.006","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"24 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090561","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":"Transcriptomics-driven antiviral drug screening identifies ATF6 as a homeostatic regulator of ER stress and innate immunity","authors":"Zhenyu Yang,&nbsp;Jing Sun,&nbsp;Yan Zhao,&nbsp;Ruoqing Feng,&nbsp;Yanhong Tang,&nbsp;Shijun Bu,&nbsp;Yuan He,&nbsp;Qinan Hu,&nbsp;Jincun Zhao,&nbsp;Yuhui Hu","doi":"10.1016/j.jare.2025.10.036","DOIUrl":"10.1016/j.jare.2025.10.036","url":null,"abstract":"<div><h3>Introduction</h3><div>SARS-CoV-2 caused a global pandemic with widespread devastation on health system and many other aspects. Traditional drug development strategies have primarily focused on single targets in either the virus or host cells. While these strategies can significantly inhibit viral replication at the cellular level, the clinical efficacy remains difficult to guarantee, and many host-targeting drugs are associated with relatively high toxicity and side effects. Therefore, to prepare for the possible future viral pandemics, there remains an urgent need for effective therapeutic strategies that are comprehensive and easy to administer.</div></div><div><h3>Objectives</h3><div>The main objective of this study is to identify the optimal antiviral transcriptomic response of host cells based on the “dynamic virus-host interaction”, conduct large-scale drug screening, and discover pan-transcriptomic responses or pan-targets capable of inhibiting viral replication through the integrated analysis of pharmacologically active compounds.</div></div><div><h3>Methods</h3><div>We used deep RNA sequencing techniques to study gene expression changes of host cells (Huh7 and Vero-E6) along with viral replication dynamics upon SARS-CoV-2 infection. The imbalanced host genes serve as the SARS-CoV-2 expression signatures for computational screening of the compounds with anti-viral potential, following the concept of Connectivity Map (cMap). Furthermore, the gene perturbation signatures of effective compounds were integrated via bioinformatics approaches, and combined with techniques such as CRISPR-Cas9 and Western Blot (WB) to elucidate the targets and mechanisms underlying viral replication inhibition.</div></div><div><h3>Results</h3><div>This study found that acute activation of host innate immunity pathway plays an essential role to suppress SARS-CoV-2 replication, and a variety of compounds with pharmacological activity against SARS-CoV-2 were successfully identified. Further transcriptomic comparison revealed the endoplasmic reticulum (ER) stress as the key machinery underneath the efficacy difference. Mechanistically, ATF6, an ER stress regulator, promotes viral replication by tempering PERK/IRE1-driven rapid activation of NF-κB and innate immunity (e.g., IL-1α, TNF-α).</div></div><div><h3>Conclusion</h3><div>This work positions ER stress modulation, particularly ATF6 targeting, as a strategy to balance antiviral defense and inflammatory toxicity, offering a roadmap for pan-coronavirus therapeutics. With these results, we established a paradigm for transcriptomic signature-based drug screening system for future treatment development of virus pandemics.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 625-641"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phocaeicola vulgatus promote growth rate via tryptophan metabolism pathway mediated gut sIgA production in Taihe Silky fowl","authors":"Wentao Li,&nbsp;Haoneng Guo,&nbsp;Qi Wang,&nbsp;Dapeng Peng,&nbsp;Yizhen Wang,&nbsp;Zeqing Lu","doi":"10.1016/j.jare.2026.01.022","DOIUrl":"10.1016/j.jare.2026.01.022","url":null,"abstract":"<div><h3>Introduction</h3><div>Taihe Silky Fowl (TSF) has a long growth cycle and slow growth rate, how to effectively improve the growth rate of TSF has become the primary concern for breeders. Currently, extensive research has established the gut microbiota’s role in modulating growth rate of commercial chicken breeds, while the specific microbial mechanisms influencing TSF growth rate remain poorly understood.</div></div><div><h3>Objectives</h3><div>Therefore, this study aimed to identify growth rate-associated key microbial species in TSF through multi-omics approaches, experimentally validate their growth-promoting roles via controlled interventions, and elucidate the species-metabolite-host interaction mechanisms.</div></div><div><h3>Methods</h3><div>Cecal metagenome and metabolome was used to search for differential key microbiota and metabolites of TSF with different growth rate, the whole genome of key microbiota was used to identify the relationship between microbiota and metabolites, and gavage key microbiota to TSF was used to demonstrate the effectiveness of probiotics and preliminarily explore their mechanisms of action.</div></div><div><h3>Results</h3><div>Cecal metagenome analysis demonstrated a significant enrichment of <em>Phocaeicola vulgatus</em> (<em>P. vulgatus</em>) in high-growth-rate fowls, <em>Erysipelotrichaceae bacterium</em> was significantly enriched in low-growth-rate fowls. The differential metabolites between the two groups were significantly enriched in tryptophan metabolism pathway. Subsequently, gene analysis revealed that <em>P. vulgatus</em> encoded tryptophan biosynthesis genes. In feeding experiment, oral gavage <em>P. vulgatus</em> improved the TSF final body weight, average growth rate and average daily gain, increased cecal <em>P. vulgatus</em> abundance, enriched the metabolites in tryptophan metabolism pathway both in the cecum and serum, and upregulated cecal tissue gene expression in the ‘intestinal immune network for IgA production’ pathway resulting in the higher secretory IgA (sIgA) concentrations in cecal tissue and luminal content than the control group.</div></div><div><h3>Conclusion</h3><div><em>P. vulgatus</em> promoted the growth rate of TSF by optimizing the cecal microbiota, elevating cecal tryptophan metabolites and stimulating sIgA production via sIgA gene upregulation in cecal tissues, thereby enhancing host immune modulation. These findings elucidated the microbiota-metabolite-host axis governing TSF growth regulation, providing both mechanistic insights and practical applications for probiotic-based strategies to enhance growth performance and gut health in this valuable poultry breed.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 77-89"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}