Journal of Advanced Research最新文献

{"title":"Autoimmune responses to myelin-associated proteins as diagnostic and prognostic biomarkers of relapsing-remitting multiple sclerosis: Associations with human herpesvirus-6 and Epstein-Barr virus reactivation","authors":"Aristo Vojdani, Abbas F. Almulla, Elroy Vojdani, Jing Li, Yingqian Zhang, Michael Maes","doi":"10.1016/j.jare.2025.02.021","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.021","url":null,"abstract":"<h3>Background</h3>The pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is linked to autoimmune attacks against myelin proteins, and reactivation of Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). However, the connection between viral reactivation and autoimmune biomarkers has remained unclear.<h3>Objectives</h3>To investigate immunoglobulin (Ig)G/IgA/IgM responses targeting myelin-related proteins in association with EBV and HHV-6 replication markers in RRMS.<h3>Methods</h3>We recruited 55 patients with RRMS and 63 healthy controls and assessed IgG/IgA/IgM responses against seven myelin-related components, as well as EBV nuclear antigen 1 (EBNA-1) and deoxyuridine-triphosphate nucleotidohydrolase (dUTPases). Disability was evaluated using the Expanded Disability Status Scale (EDSS) and disease progression using the Multiple Sclerosis Severity Score (MSSS).<h3>Results</h3>IgG/IgA/IgM levels targeting seven myelin-related proteins were significantly higher in RRMS than in controls. IgG against myelin basic protein (MBP) (IgG-MBP), IgM-myelin-associated glycoprotein (IgM-MAG)-37–60, IgA-MBP, and IgA-myelin-oligodendrocyte-glycoprotein (IgA-MOG-31–55) distinguished RRMS from controls with a predictive accuracy of 96.6 % (sensitivity = 95.7 %, specificity = 95.2 %) and an area under the ROC curve of 0.991. A large part of the variance in the EDSS (around 75 %) and MSSS score (62.8 %) was explained by IgG-MBP, IgM-MBP, IgA-MOG-31–55, and IgM-MAG. Part of the variance (47.4 %) in the IgG/IgA/IgM responses to myelin-related proteins was explained by immune responses to EBNA and dUTPases of EBV and HHV-6.<h3>Conclusions</h3>Autoimmune reactivities targeting myelin-related proteins are valuable biomarkers of RRMS and the severity and progression of RRMS. Reactivation of EBV and HHV-6 may trigger or maintain these autoimmune responses thereby impacting disease progression.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427342","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":"H4K12 lactylation potentiates mitochondrial oxidative stress via the Foxo1 pathway in diabetes-induced cognitive impairment","authors":"Ying Yang, Lulu Song, Liping Yu, Jinping Zhang, Bo Zhang","doi":"10.1016/j.jare.2025.02.020","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.020","url":null,"abstract":"<h3>Aims</h3>To investigate the role and potential mechanisms of H4K12 lactylation modifications in diabetes-related cognitive impairment (DACD).<h3>Methods</h3>Behavioral tests, HE staining, and immunohistochemistry were employed to assess cognitive function and the extent of brain tissue injury. Metabolomics and proteomics were applied to profile the metabolic regulatory network. We measured lactic acid and Pan-Kla levels in the brains of T2DM mice and high glucose-treated microglia. CUT&amp;Tag technology was utilized to identify genes regulated by H4K12la. Small interfering RNA (siRNA) sequences and adeno-associated viruses (AAVs) were used to knock down key components in signaling pathways, evaluating the impact of histone lactylation on microglial polarization.<h3>Results</h3>Lactic acid levels were significantly higher in the brains of T2DM mice and high glucose-treated microglia compared to controls, leading to an increase in pan histone lysine lactylation (Kla). We found that lactate directly induced an increase in H4K12la. CUT&amp;Tag analysis revealed that elevated H4K12la activates the FOXO1/PGC-1α signaling pathway by enhancing binding to the FOXO1 promoter, promoting mitochondrial oxidative stress.<h3>Conclusion</h3>This study demonstrated that elevated H4K12la directly activates the FOXO1 signaling pathway, promoting oxidative stress and contributing to DACD phenotypes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"136 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427341","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 single-cell analysis deciphered the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury","authors":"Juan Li, Mengjuan Xuan, Li Yang, Yingru Liu, Na Lou, Leiya Fu, Qingmiao Shi, Chen Xue","doi":"10.1016/j.jare.2025.02.018","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.018","url":null,"abstract":"<h3>Introduction</h3>Sepsis-related acute liver injury involves complex immune dysfunctions. Epoxyeicosatrienoic acids (EETs), bioactive molecules derived from arachidonic acid (AA) via cytochrome P450 (CYP450) and rapidly hydrolyzed by soluble epoxide hydrolase (sEH), possess anti-inflammatory properties. Nevertheless, the impact of the sEH inhibitor TPPU on sepsis-related acute liver injury remains uncertain.<h3>Objectives</h3>This study utilized comprehensive single-cell analysis to investigate the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury.<h3>Methods</h3>Hepatic bulk RNA sequencing and proteomics analyses were employed to investigate the mechanisms underlying sepsis-related acute liver injury induced by cecal ligation and puncture in mice. Cytometry by time-of-flight and single-cell RNA sequencing were conducted to thoroughly examine the immunoregulatory role of TPPU at single-cell resolution.<h3>Results</h3>Downregulation of AA metabolism and the CYP450 pathway was observed during sepsis-related acute liver injury, and TPPU treatment reduced inflammatory cytokine production and mitigated sepsis-related hepatic inflammatory injury. Comprehensive single-cell analysis revealed that TPPU promotes the expansion of anti-inflammatory CD206⁺CD73⁺ M2-like macrophages and PDL1^-CD39^-CCR2⁺ neutrophils, reprogramming liver neutrophils to an anti-inflammatory CAMP⁺NGP⁺CD177⁺ phenotype. Additionally, TPPU inhibits the CCL6-CCR1 signaling mediated by M2-like macrophages and CAMP⁺NGP⁺CD177⁺ neutrophils, altering intercellular communication within the septic liver immune microenvironment.<h3>Conclusion</h3>This study demonstrated TPPU’s protective efficacy against sepsis-related acute liver injury, underscoring its vital role in modulating liver macrophages and neutrophils and enhancing prospects for personalized immunomodulatory therapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"24 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418165","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":"Specific Macronutrient clusters associated with lower mortality Risk: Evidence from NHANES 1999–2018","authors":"Jiaying Yu, Yang Chen, Defang Li, Lan Zhang, Yuting Zhang, Jiaqi Zhang, Jiayu Zhu, Zican Li, Hongxin Fu, Dongwei Guan, Runan Zhang, Liyan Liu, Cheng Wang, Changhao Sun, Rennan Feng","doi":"10.1016/j.jare.2025.02.019","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.019","url":null,"abstract":"<h3>Introduction</h3>Accumulating evidence suggest that imbalanced macronutrient composition would increase the risk of chronic diseases. However, previous studies that predominantly focused on individual macronutrients often failed to thoroughly elucidate this complex association.<h3>Objectives</h3>This study aimed to comprehensively analyze the relationship between macronutrient clusters and all-cause mortality.<h3>Methods</h3>The study included 26,615 adults aged 20–75 years from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. A three-dimensional cube method was employed to categorize clusters of macronutrients intake. The association between dietary macronutrient clusters and all-cause mortality was investigated using Cox proportional hazards modeling and restricted cubic spline (RCS) analysis.<h3>Results</h3>Over a weighted median follow-up duration of 7.58 years, 3,998 deaths were recorded. After adjusting for potential confounders, compared with the reference Cluster _Pm:Fm:Cmh, 4 specific Clusters were associated with reduced all-cause mortality: Cluster _Pm:Fm:Cm (HR: 0.79, 95 % CI: 0.67–0.92), Cluster _Pm:Fmh:Cml (HR: 0.76, 95 % CI: 0.61–0.95), Cluster _Pm:Fmh:Cm (HR: 0.86, 95 % CI: 0.75–0.97), and Cluster _Pl:Fm:Cmh (HR: 0.73, 95 % CI: 0.60–0.89). Three-node RCS analysis revealed non-linear relationships between carbohydrate within Cluster _Pm:Fm:Cm and protein within Cluster _Pl:Fm:Cmh and overall mortality. Subgroup and sensitivity analyses corroborated the robustness of these associations across different age, gender, and energy intake levels.<h3>Conclusions</h3>This study employed a three-dimensional cube approach to categorize the human macronutrients intake into 24 clusters. Cluster _Pm:Fm:Cm, Clusters _Pm:Fmh:Cml, Cluster _Pm:Fmh:Cm, and Cluster _Pl:Fm:Cmh exhibited a lower mortality risk. Different clusters of macronutrients could be a precondition in nutrition intervene strategy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"24 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual absorption pathway of novel oyster-derived peptide-zinc complex enhances zinc bioavailability and restores mitochondrial function","authors":"Ximing Yang, Siyi Wang, Hanxiong Liu, Tuo Zhang, Shuzhen Cheng, Ming Du","doi":"10.1016/j.jare.2025.02.005","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.005","url":null,"abstract":"Zinc deficiency is a global health issue that impairs immune function, growth, and energy metabolism. Although conventional zinc supplements have been developed, their effectiveness is limited by poor bioavailability and susceptibility to dietary inhibitors. In this study, a peptide-zinc complex (IE-Zn) derived from oysters was developed to enhance zinc uptake and address metabolic disruptions caused by deficiency. It was determined that Zn²⁺ binds with high affinity to the IE peptide, promoting structural flexibility that facilitates zinc transport through both zinc ion transporters and oligopeptide transporters. In Caco-2 and IEC-6 cell models, IE-Zn was shown to significantly improve zinc absorption and retention compared to ZnSO₄, driven by the upregulation of ZIP4 and PEPT1 transporters. <em>In vivo</em> studies in a zinc-deficient mouse model confirmed enhanced zinc absorption and distribution across serum, intestine, and liver. Moreover, IE-Zn restored energy homeostasis by activating the AMPK/PGC1-α/NRF-1/TFAM signaling pathway, promoting mitochondrial biogenesis and reducing oxidative stress. These findings suggest that IE-Zn is a superior zinc supplement with higher bioavailability and serves as a potent regulator of cellular energy metabolism, offering therapeutic potential for managing conditions related to zinc deficiency and mitochondrial dysfunction. This study lays the foundation for further exploration of peptide-mineral complexes as advanced nutritional supplements with broad applications. Subsequent studies will further investigate the absorption pathway and targeting of peptide-zinc complex. The hope is to provide potential preventive applications for people in need, including zinc deficiency and a range of diseases caused by zinc deficiency.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401281","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":"Mebendazole induces ZBP-1 mediated PANoptosis of acute myeloid leukemia cells by targeting TUBA1A and exerts antileukemia effect","authors":"Wei Yang, Ying Xu, Shuai Liu, Lin Gao, Shi Li, Xina Xie, Qiaoxia Zhang, Obaid Habib, Ronglin Chen, Xiongfei Sun, Zesong Li","doi":"10.1016/j.jare.2025.02.013","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.013","url":null,"abstract":"<h3>Background</h3>Despite notable advancements in AML therapy in recent years, a substantial proportion of patients remain refractory or at high risk of recurrence with limited efficacy. Therefore, it’s urgent to develop novel drugs for treating AML.<h3>Methods</h3>The small molecule drug library was utilized to screen for drugs that elicit the inflammatory death of AML cells. Cell viability, cell morphological analysis, western blotting, and RNA-seq were used to determine the pathway of Mebendazole (MBD)-induced AML cell death. Cell cycle analysis, protein expression profiling, molecular docking, western blotting and lentivirus overexpression were used to analyze the target protein of MBD in AML cells. The anti-AML activity of MBD <em>in vivo</em> was evaluated using tumor xenograft models constructed by AML cell lines and patient-derived primary AML cells.<h3>Results</h3>In this study, we have identified Mebendazole (MBD), a conventional anthelmintic drug known for its low toxicity and cost, as a potent agent that exerts significant anti-AML effects <em>in vitro</em>. Furthermore, we have observed its inhibitory effects on the invasion of AML cell lines and primary AML cells in xenograft mouse models, while noting its negligible toxic side effects in normal mice <em>in vivo</em>. Mechanically, MBD inhibits the cell cycle in G2/M phase by inhibiting tubulin α1A (TUBA1A) and promotes ZBP-1 mediated PANoptosis in AML cells. Our results confirm that MBD exerts anti-AML activity in preclinical models.<h3>Conclusion</h3>These results highlight the remarkable clinical translational potential of MBD, providing new potential medicine for AML patients. In addition, TUBA1A can be used potential novel therapeutic target in tumors with abnormal TUBA1A expression.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401279","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":"Blocking S1P4 signaling attenuates brain injury in mice with ischemic stroke","authors":"Nikita Basnet, Hyunkyung Cho, Arjun Sapkota, Seungbae Park, Chaemin Lim, Bhakta Prasad Gaire, Donghee Kim, Joo-Youn Lee, Jae Hui Been, Seunghee Lee, Bong Yong Lee, Ji Woong Choi, Sanghee Kim","doi":"10.1016/j.jare.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.012","url":null,"abstract":"<h3>Introduction</h3>The functions of S1P receptors have been revealed using genetic and pharmacological tools, including the potent non-selective modulator FTY720. However, studies on subtype-specific agonists and antagonists are limited; hence, the role of S1P₄ remains unclear.<h3>Objectives</h3>To identify a novel function of S1P₄ as a pathogenic factor in stroke using a newly developed S1P₄-selective modulator and S1P₄ knockdown.<h3>Methods</h3>Heteroaromatic analogs of FTY720 were synthesized, a β-arrestin assay was conducted against S1P receptors, and the developed compound (NXC736) was characterized as a functional S1P₄ antagonist. To clarify the function of S1P₄, the therapeutic potential of NXC736 in ischemic stroke was determined using a transient middle cerebral artery occlusion (tMCAO) mouse model, which was validated using S1P₄ knockdown. The S1P₄-dependent pathogenic mechanisms were determined using immunohistochemical and biochemical analyses.<h3>Results</h3>Molecular modeling studies provide valuable clues for understanding S1P₄ selectivity of NXC736. NXC736 contains a triazole ring instead of a phenyl ring and exhibits S1P₄-selective activity as a functional antagonist. Its action on S1P₄ does not require phosphorylation by sphingosine kinase 2. Notably, NXC736 exhibited substantial therapeutic activity against ischemic stroke by attenuating tMCAO-induced acute brain injuries, including brain infarction, neurological deficits, and neuronal apoptosis. This suggested that S1P₄ is a pathogenic factor in ischemic stroke. This function was confirmed using AAV-based S1P₄ knockdown. NXC736 or S1P₄ knockdown attenuated blood–brain barrier disruption, neutrophil infiltration, microglial activation and proliferation, and the upregulation of pro-inflammatory cytokines, thereby demonstrating that S1P₄ influences neuroinflammatory responses in ischemic stroke. The underlying mechanisms were activation of NLRP3 inflammasome, NF-κB, and MAPKs. S1P₄ also contributed to chronic brain injuries caused by ischemic stroke because NXC736 exerted long-term neuroprotective effects against tMCAO challenge.<h3>Conclusion</h3>Using a functional S1P₄ antagonist (NXC736) and a genetic tool for S1P₄ knockdown, we identified S1P₄ as a novel pathogenic factor in ischemic stroke.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"132 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393647","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":"Ai-enabled language models (LMs) to large language models (LLMs) and multimodal large language models (MLLMs) in drug discovery and development","authors":"Chiranjib Chakraborty, Manojit Bhattacharya, Soumen Pal, Srijan Chatterjee, Arpita Das, Sang-Soo Lee","doi":"10.1016/j.jare.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.011","url":null,"abstract":"<h3>Background</h3>Due to the recent revolution of artificial intelligence (AI), AI-enabled large language models (LLMs) have flourished and started to be applied in various sectors of science and medicine. Drug discovery and development are time-consuming, complex processes that require high investment. The conventional method of drug discovery is costly and has a high failure rate. AI-enabled LLMs are used in various steps of drug discovery to solve the challenges of time and cost.<h3>Aim of Review</h3>The article aims to provide a comprehensive understanding of AI-enabled LLMs and their use in various steps of drug discovery to ease the challenges.<h3>Key Scientific Concepts of Review</h3>The review provides an overview of the LLM and their current state-of-the-art application in structure-based drug molecule design and de novo drug design. The different applications of AI-enabled LLMs<!-- --> <!-- -->have been illustrated, such as drug target identification, validation, interaction, and ADME/ADMET. Several domain-specific models of LLMs are developed in this direction and applied in drug discovery and development to speed up the process. We discussed all these domain-specific models of LLMs and their applications in this field. Finally, we illustrated the challenges and future perspectives on the applications of AI-enabled LLMs to drug discovery and development.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"63 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between caffeine and decreased liver fibrosis risk in patients with different glucose metabolism status","authors":"Jiahao Han, Chuan Liu, Huanhuan Yang, Zihe Dong, Xiaoguo Li, Ruixia Gao, Jie Li, Qun Zhang, Wai-kit Ming, Zhihui Li, Jia Li, Xiaolong Qi","doi":"10.1016/j.jare.2025.02.004","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.004","url":null,"abstract":"<h3>Background and aims</h3>To investigate the prevalence of liver fibrosis, and the association between caffeine intake and fibrosis in populations with different glucose metabolism status.<h3>Methods</h3>This was a cross-sectional study based on the National Health and Nutrition Examination Survey (2005-March 2020). Of the 39,221 adult individuals with no missed necessary laboratory results, a total of 23,711 eligible individuals were included in the study. Individuals were divided into T2DM, prediabetes, and diabetes-free groups. Fibrosis-4 index was calculated to evaluate the risk of liver fibrosis. Caffeine intake was obtained through a 24-hour dietary recall.<h3>Results</h3>The mean ± SE age of prediabetes group was 53 ± 0.4 years, and in type 2 diabetes mellitus group, the individuals have a mean ± SE age of 62 ± 0.3 years. The participants with type 2 diabetes mellitus had significantly higher risk of liver fibrosis than those with prediabetes or normal glucose tolerance (5·9% vs. 3·2% vs. 2·5%, <em>P &lt;</em> 0.001). Compared to individuals with daily caffeine intake &lt; 78 mg, individuals with daily caffeine intake ≥ 78 mg had significantly lower risk of liver fibrosis in all subgroups (odds ratio: diabetes-free group: 0.698[0.577–0.846]; prediabetes group: 0·553[0·397-0·769]; type 2 diabetes mellitus group: 0·720[0·556-0·933]; all <em>P &lt;</em> 0·05).<h3>Conclusions</h3>Prevalence of liver fibrosis is high in patients with type 2 diabetes mellitus and prediabetes. It is indicated that individuals with prediabetes should also be screened for fibrosis. Caffeine intake ≥ 78 mg per day is associated with a lower risk of liver fibrosis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"33 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393648","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":"Development of dual disease resistant Basmati rice varieties offer significant economic advantage and impetus to sustainable crop production","authors":"Ranjith Kumar Ellur, Apurva Khanna, Ashutosh Kumar Yadav, Santoshkumar Magdum, Sarvesh Kumar Maurya, K.K. Vinod, Alexander Balamurugan, G. Prakash, K.K. Mondal, S. Gopala Krishnan, M. Nagarajan, Praveen Koovalamkadu Velayudhan, Prolay Kumar Bhowmick, B. Haritha, A.K. Singh","doi":"10.1016/j.jare.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.014","url":null,"abstract":"<h3>Introduction</h3>Bacterial blight and blast are the major diseases causing production losses to an extent of 31.52% to 67.79%, respectively. Use of chemical pesticides leads to increased cost of cultivation, degradation of environment and human health while affecting international trade.<h3>Objective</h3>The study aimed at developing bacterial blight and blast resistant Basmati rice varieties and to assess their impact in farmers’ field.<h3>Methods</h3>A marker assisted selection from intercross of backcross derived lines was implemented to incorporate bacterial blight resistance genes <em>xa13</em> and <em>Xa21</em>; along with blast resistance genes <em>Pi2</em> and <em>Pi54.</em> The developed lines were evaluated across multiple environments before release as commercial varieties. The technology was assessed for its impact based on the feedback of farmers’.<h3>Results</h3>Marker assisted breeding integrated with stringent phenotypic selection for Basmati quality traits and multi-season trials has led to isolating top performing lines with genome similarity ranging from 94.56% to 96.16% among Pusa Basmati 1121 (PB1121) derivatives and 93.72% to 94.59% among the Pusa Basmati 6 (PB6) derivatives. Reassuring the effectiveness of the target genes in the recurrent parent backgrounds, the selected lines showed no loss of yield when managed without pesticide application. Besides, the lines performed stably across target population of environments (TPEs) covering the entire Basmati growing region. The best performing lines were released for commercial cultivation as varieties, Pusa Basmati 1885 (PB1885) and Pusa Basmati 1886 (PB1886). By growing these varieties, farmers have realised a saving of US$ 95/ha in PB1885 and US$ 134/ha in PB1886, towards managing bacterial blight and blast diseases.<h3>Conclusion</h3>The technology developed holds great potential for producing pesticide residue free Basmati rice under environment friendly production conditions. The developed varieties can strengthen trade of Indian Basmati rice in international market while significantly reducing cost of cultivation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394005","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}