Ming Lu, ZhaoHong Miao, YunWei Niu, ZuoBing Xiao, Di Zhao
{"title":"Application of γ-cyclodextrin encapsulation of eugenol and isoeugenol: characterization, stability, and taste impact","authors":"Ming Lu, ZhaoHong Miao, YunWei Niu, ZuoBing Xiao, Di Zhao","doi":"10.1016/j.jare.2025.12.033","DOIUrl":"10.1016/j.jare.2025.12.033","url":null,"abstract":"<div><h3>Introduction</h3><div>Eugenol and isoeugenol, key flavor isomers, exert distinct effects on sweetness perception but suffer from poor thermal and oxidative stability, as well as rapid aroma volatilization, during food processing and storage. γ-Cyclodextrin (γ-CD) ameliorates these drawbacks via host–guest inclusion; however, the structural differences of their inclusion complexes and the T1R2/T1R3-mediated sweetness regulation mechanism remain elusive, limiting their applications in sugar-reduced food formulations.</div></div><div><h3>Objectives</h3><div>This study aimed to comprehensively characterize γ-CD inclusion complexes of eugenol and isoeugenol, elucidate their differential sweetness regulation via T1R2/T1R3 at molecular and sensory levels, and reveal structural-stability relationships, hypothesizing that cis–trans isomeric differences (eugenol: <em>cis</em>-double bond; isoeugenol: <em>trans</em>-double bond) drive distinct complex properties and sweetness effects.</div></div><div><h3>Methods</h3><div>Complexes were prepared via the solvent-dropping method (optimized with 1:2 M ratio, 60 °C, 7 h). XRD, DSC, TGA, FTIR, and <sup>1</sup>H NMR characterized structures; molecular docking and MD simulation analyzed molecular interactions; sensory evaluation coupled with an electronic tongue assessed sweetness regulation in 5 % sucrose solution.</div></div><div><h3>Results</h3><div>XRD, FTIR, and <sup>1</sup>H NMR confirmed successful inclusion by revealing characteristic structural changes (e.g., XRD peak shifts, FTIR band masking). The eugenol complex (126 °C endothermic peak) shows better thermal stability than the isoeugenol complex (95 °C), with both delaying aroma volatilization. The isoeugenol complex has lower T1R2/T1R3 binding energy (−9.841 kcal/mol) than eugenol (−9.518 kcal/mol). Eugenol enhanced sweetness (≤7 mg/L); isoeugenol inhibited it (≥0.1 mg/L), with inhibition alleviated by heating.</div></div><div><h3>Conclusion</h3><div>γ-CD encapsulation enhances eugenol/isoeugenol stability and sustained aroma release. Isomeric differences lead to distinct T1R2/T1R3 binding modes and differential sweetness regulation, providing theoretical and technical support for precise flavor-sweetness control in sugar-reduced foods and laying a foundation for their practical integration into low-sugar food systems.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 73-92"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845329","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":"Development and validation of dynamic clinical subphenotypes for acute pancreatitis using hematocrit and blood urea nitrogen trajectories in intensive care unit: a multicenter retrospective cohort study","authors":"Jianhua Wan, Maobin Kuang, Shixuan Xiong, Yaoyu Zou, Huajing Ke, Wenhua He, Yin Zhu, Nonghua Lu, Liang Xia","doi":"10.1016/j.jare.2026.01.004","DOIUrl":"10.1016/j.jare.2026.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Acute Pancreatitis (AP) is a common gastrointestinal emergency in which early fluid therapy is critical, yet optimal strategies remain debated. Although Hematocrit (HCT) and Blood Urea Nitrogen (BUN) are recommended to guide fluid management, the prognostic value of their dynamic changes is unclear.</div></div><div><h3>Methods</h3><div>This multicenter retrospective cohort study utilized a development cohort from Jiangxi Province (n = 2027) and a validation cohort from the U.S. MIMIC-IV and eICU-CRD databases (n = 1381). Group-based multi-trajectory modeling (GBMTM) was applied to analyze the dynamic changes of HCT and BUN during the first week of ICU admission to identify distinct subphenotypes. Multivariate logistic regression and survival analysis were used to assess the association between each subphenotype and outcomes, including mortality and organ failure. The Boruta algorithm compared predictive importance.</div></div><div><h3>Results</h3><div>Five trajectory subphenotypes were identified: T1 (Renal Dysfunction Subphenotype, n = 287), T2 (Fluid-Responsive Subphenotype, n = 448), T3 (Volume-Deficient Subphenotype, n = 445), T4 (Stable Subphenotype, n = 516), and T5 (Hemodilution Subphenotype, n = 331). The T1 subphenotype had the highest mortality (36.6 % in the development cohort; adjusted OR = 16.27 (95 % CI 6.55–40.45) for in-hospital mortality in the validation cohort), while T4 had the lowest (2.7 %). Subphenotypes exhibited significantly different responses to fluid therapy: for T1, a fluid volume exceeding 4000 mL on the first day increased mortality risk; T3 tolerated a higher initial fluid load (up to 7000 mL on day one) but required fluid restriction on the second day. Consistent results in subgroup and sensitivity analyses demonstrated the robustness of this classification system.</div></div><div><h3>Conclusion</h3><div>This study developed and validated a subphenotype classification system for the acute phase of AP based on the dynamic trajectories of HCT and BUN. It effectively distinguishes patient prognosis and responsiveness to fluid therapy, providing a crucial phenotypic framework for future randomized trials on individualized fluid management.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 881-890"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895096","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":"Cu/Fe co-doped Sphagnum palustre-derived biochar for the synergistic adsorption and photocatalytic removal of tetracycline hydrochloride","authors":"Qing Xiang, Zhen Wang, Liang Luo, Yu Fang, Yuheng Cui, Junbo Zhou, Daixiong Zhang, Bo Yang, Zhaohui Zhang, Xuefeng Zou, Bin Xiang","doi":"10.1016/j.jare.2025.12.051","DOIUrl":"10.1016/j.jare.2025.12.051","url":null,"abstract":"<div><h3>Introduction</h3><div>The widespread presence of antibiotic pollutants, such as tetracycline hydrochloride (TCH), causes significant environmental and public health concerns. Biochar-based photocatalysts derived from renewable biomass have attracted increasing attention due to their low cost, structural tunability, and environmental sustainability. However, their photocatalytic performance is often limited by poor charge separation and a lack of active sites.</div></div><div><h3>Objectives</h3><div>This study aims to construct a visible-light-responsive Cu/Fe co-doped biochar composite using <em>Sphagnum palustre</em> as a biomass precursor for the synergistic adsorption and photocatalytic removal of TCH from aqueous environments.</div></div><div><h3>Methods</h3><div>The Cu/Fe co-doped photocatalyst (CFO/S) was synthesized via a hydrothermal method by integrating Cu–Fe oxides with <em>Sphagnum</em>-derived biochar. The composite was comprehensively characterized, and its visible-light performance was evaluated. The photocatalytic mechanism was elucidated through radical trapping experiments and DFT+U simulations.</div></div><div><h3>Results</h3><div>The CFO/S-10 composite achieved a TCH removal efficiency of 94.56% within 60 min under visible-light irradiation. Adsorption was identified as the primary removal mechanism, while photocatalysis contributed to the degradation of adsorbed molecules. A layered FeO/CuFe<sub>2</sub>O<sub>4</sub>/S structure promoted charge separation and intermediate desorption. Multiple degradation products were detected, involving demethylation, hydroxylation, and ring-opening reactions.</div></div><div><h3>Conclusion</h3><div>The Cu/Fe co-doped biochar composite exhibited excellent removal performance through a synergistic adsorption-photocatalysis mechanism. Photogenerated electrons were the dominant reactive species, supported by •OH, •O<sub>2</sub><sup>−</sup>, and h<sup>+</sup>. An S-scheme charge transfer mechanism was proposed to explain the enhanced redox capability. These findings demonstrate the potential of CFO/S as a promising candidate for visible-light-driven removal of antibiotic contaminants in water.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 405-418"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879798","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":"Thbs1+ extracellular vesicles from irradiated tumors induce cardiac wasting via PERK-eIF2α-Atf4 signaling","authors":"Song Gao, Wenzhi Liu, Jingquan He, Zhirui Shan, Yue Wang, Tian Li, Zicheng Zhang","doi":"10.1016/j.jare.2025.12.053","DOIUrl":"10.1016/j.jare.2025.12.053","url":null,"abstract":"<div><h3>Aims</h3><div>Cardiac muscle wasting is a significant complication observed in lung cancer patients receiving radiotherapy. Radiotherapy, a commonly used anticancer treatment, is known to cause cardiovascular complications; however, the mechanisms linking tumor irradiation to cardiac wasting remain poorly understood.</div></div><div><h3>Methods</h3><div>Lewis lung carcinoma (LLC) and CT26 tumor-bearing mice received localized tumor irradiation. Conditioned medium or EVs from irradiated tumor cells were collected and used to treat cardiomyocytes. Autophagy, protein synthesis, and atrophy were assessed. The roles of tumor Thbs1 and cardiac PERK signaling were determined via shRNA-mediated knockdown and PERK mutation <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>We demonstrated that localized tumor irradiation induces cardiac muscle wasting in mice, which is associated with PERK-eIF2α-Atf4 pathway activation and increased Thbs1 protein—but not mRNA—levels in cardiomyocytes. Mechanistically, Thbs1 is delivered via extracellular vesicles (EVs) derived from irradiated tumors. Tumor-derived Thbs1<sup>+</sup> EVs are necessary and sufficient to trigger autophagy, suppress protein synthesis, and cause atrophy in cardiomyocytes, which is dependent on the Thbs1-PERK interaction and downstream signaling.</div></div><div><h3>Conclusion</h3><div>These results indicate that radiotherapy promotes the release of Thbs1<sup>+</sup> EVs, which drive cardiac muscle wasting via PERK-eIF2α-Atf4 signaling, revealing a novel mechanism underlying cancer-associated cardiac damage.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 419-435"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866953","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}
Hengxing Yuan, Yulu Zhang, Long Tan, Yue Yang, Ji Luan, Hailong Wang
{"title":"Combinatorial genome engineering of pseudorabies virus Bartha by developing a reverse genetic system based on three overlapping genomic segments","authors":"Hengxing Yuan, Yulu Zhang, Long Tan, Yue Yang, Ji Luan, Hailong Wang","doi":"10.1016/j.jare.2025.12.013","DOIUrl":"10.1016/j.jare.2025.12.013","url":null,"abstract":"<div><h3>Introduction</h3><div>The 138-kilobase genome of pseudorabies virus vaccine strain Bartha K61 harbors many nonessential genes for replication and exhibits remarkable capacity for incorporating foreign genes for therapeutic applications. However, the large size of the Bartha genome complicates its efficient engineering.</div></div><div><h3>Objectives</h3><div>Development of a reverse genetic system for pseudorabies virus Bartha based on three overlapping genomic segments to facilitate multiplex genome engineering.</div></div><div><h3>Methods</h3><div>The 138-kb genome of Bartha was split into three overlapping segments (42 kb, 43 kb, and 53 kb), each cloned in a bacterial artificial chromosome (BAC) to facilitate genome engineering. The infectious virus was reconstituted by transfecting the 3 genomic fragments released from the BACs into Vero cells in which a complete virus genome was assembled using 2-kb overlaps between adjacent pieces.</div></div><div><h3>Results</h3><div>Employing the reverse genetic system, we individually deleted 15 candidate nonessential genes and confirmed that 10 were dispensable for viral growth in cell culture. Deletion of 7 nonessential genes had no impact on viral growth, whereas <em>UL47</em> deletion reduced viral growth rate and deletions of <em>UL44</em>, <em>UL47</em>, or <em>US3</em> resulted in smaller viral plaques. A total of 45 viral genomes with double deletions of nonessential genes were constructed, among which 22 were successfully rescued into infectious virions. Fifteen double-deletion mutant viruses had a viral titer comparable with the wild-type Bartha, while the remaining 7 showed a lower titer. Additionally, expressions of the <em>mNeonGreen</em> reporter gene at nonessential gene loci were evaluated. Cells infected with recombinant viruses carrying <em>mNeonGreen</em> at 8 loci showed strong green fluorescence, whereas those with <em>mNeonGreen</em> at 2 loci exhibited very weak fluorescence.</div></div><div><h3>Conclusion</h3><div>The reverse genetic system developed in this study enables rapid and combinatorial engineering of viruses with the large DNA genome, and will accelerate development of large DNA virus-based therapeutics including live-attenuated vaccines, vector vaccines, and oncolytic herpesviruses.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 267-277"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731868","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}
Xuecheng Zhu, Jing Su, Yuzhen Wang, Dianwei Zhang, Huilin Liu
{"title":"Aromatic short peptide-metal nanoassemblies in smart hydrogel sensors for real-time food freshness monitoring","authors":"Xuecheng Zhu, Jing Su, Yuzhen Wang, Dianwei Zhang, Huilin Liu","doi":"10.1016/j.jare.2025.11.071","DOIUrl":"10.1016/j.jare.2025.11.071","url":null,"abstract":"<div><h3>Introduction</h3><div>The accumulation of volatile biogenic amines (BAs) during food spoilage constitutes a global economic and public health burden. Conventional BA detection methods based on chromatography and electrochemistry are limited by expensive instrumentation and specialized procedures, making on-site monitoring difficult for supply chain personnel and consumers. The lack of portable, user-friendly sensing technologies for complex food matrices leaves a technological gap for real-time spoilage monitoring.</div></div><div><h3>Objectives</h3><div>The aim of this study is to develop a hydrogel digital sensor (HDS) based on peptide self-assemblies (PSAs) for visual on-demand BA detection. Quantification of spoilage by smartphone analysis and validation of its efficacy in real-time freshness assessment of meat.</div></div><div><h3>Methods</h3><div>Histidine-rich short peptides were coordinated to Zn<sup>2+</sup> <em>via</em> noncovalent interactions to form blue-emitting PSA (B-PSA). Its fluorescence response to BA was investigated, revealing the mechanism of photo-induced electron transfer quenching. To enhance visualization, B-PSAs were co-encapsulated with red-emitting carbon dots in a stimuli-responsive hydrogel to generate white HDS. The semi-micro Kjeldahl method was applied as a control and validated by real-time monitoring using environmentally stored shrimp samples.</div></div><div><h3>Results</h3><div>B-PSAs exhibited bright blue fluorescence with quantum yield up to 63 % and selective quenching in the presence of BAs (detection limit: 0.784–3.752 ppm, response time < 60 s). HDS showed a clear white to red fluorescence color transition upon exposure to BAs, enabling quantitative analysis in RGB chromaticity space, with a response range that covered all freshness grades in the national standard. Real-time validation in meat samples confirmed strong correlation with the standard TVBN assay (<em>Pearson</em> coefficient: 0.97).</div></div><div><h3>Conclusion</h3><div>This HDS combines a molecular level design with a user-friendly digital readout to provide a biocompatible, portable, low-cost and rapid spoilage detection platform. The system is expected to improve the efficiency of food supply chain management and provide consumers with a convenient freshness assessment tool.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 17-28"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689923","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}
Dan You, Yunzhong Zhang, Kunkun Wang, Luo Guo, Jin Guo, Chenhao Che, Wen Li, Liping Zhao, Huawei Li, Shan Sun
{"title":"BMP4 cocktail promotes utricular progenitor reprogramming and vestibular functional recovery in adult mice","authors":"Dan You, Yunzhong Zhang, Kunkun Wang, Luo Guo, Jin Guo, Chenhao Che, Wen Li, Liping Zhao, Huawei Li, Shan Sun","doi":"10.1016/j.jare.2025.11.065","DOIUrl":"10.1016/j.jare.2025.11.065","url":null,"abstract":"<div><h3>Introduction</h3><div>Vestibular hair cells (HCs) are essential for maintaining balance and detecting head movements. In mammals, following vestibular damage HC regeneration derives from epithelial non-hair cells (ENHCs), which possess limited capacity for proliferation and reprogramming.</div></div><div><h3>Objectives</h3><div>To examine the role of BMP4 in reprogramming utricular HCs following ototoxic injury in postnatal mice.</div></div><div><h3>Methods</h3><div>The study utilized both wild-type mice and transgenic strains on a C57BL/6J background, including <em>Notch1</em><sup>flox/flox</sup>, <em>Pou4f3</em><sup>+/DTR</sup>, ROSA26<sup>tdTomato</sup>, <em>Atoh1</em>-eGFP; <em>Sox9</em>-CreER<sup>T2</sup>, and <em>Fos</em>-CreER<sup>T2</sup>, to investigate and lineage-trace the reprogramming of new HCs initiated by BMP4 protein. Advanced sequencing techniques, including single-cell RNA sequencing, bulk RNA sequencing, and CUT&Tag sequencing, were employed for transcriptomic and epigenomic analyses. To induce vestibular dysfunction, intraperitoneal injections of IDPN were administered to postnatal day 30 (P30) mice. Vestibular function was assessed through behavioral tests, including vestibulo-ocular reflex, off-vertical axis rotation, and gait analysis, to evaluate the functional outcomes of HC regeneration. For cellular studies, sphere or explant tissues from P2 mice, with gentamicin or small molecule cocktail <em>in vitro</em>, were used to evaluate proliferation and differentiation of ENHCs through EdU labelling or tdTomato lineage tracing, histological analyses, immunofluorescence staining, and Western blot analysis.</div></div><div><h3>Results</h3><div>We found that increased BMP4 expression enhances ENHC reprogramming, accompanied by elevated levels of key HC transcription factors, including <em>Gfi1</em>, <em>Pou4f3</em>, and <em>Atoh1</em>, via c-Fos activation. Moreover, exogenous BMP4 further sensitized ENHCs to Notch inhibition and Wnt pathway activation, thus amplifying the regenerative outcomes. Conversely, inhibition of c-Fos or BMP4 diminished these effects, demonstrating that BMP4 is essential for both Notch inhibition and Wnt activation. Notably, the use of a combination of small molecules targeting these pathways successfully restored vestibular function and promoted HC regeneration in adult mice.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that BMP4 and its associated signaling pathways represent promising therapeutic targets for the restoration of hearing and balance.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 523-538"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619716","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":"Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande)","authors":"Jing Wang, Sirui Chen, Yulei Wu, Haolan Yang, Xiaobin Zheng, Jiangjiang Yuan, Kanghua Qian, Hongyi Cao, Yingxi Tang, Xin Yang, Zhaojiang Guo, Wen Xie, Shaoli Wang, Qi Su, Pei Liang, Youjun Zhang, Qingjun Wu","doi":"10.1016/j.jare.2025.12.052","DOIUrl":"10.1016/j.jare.2025.12.052","url":null,"abstract":"<div><h3>Introduction</h3><div>The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized.</div></div><div><h3>Objective</h3><div>To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of <em>Frankliniella occidentalis</em>.</div></div><div><h3>Methods</h3><div>We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains.</div></div><div><h3>Results</h3><div>The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (<em>FoGSTd1</em>, <em>d4</em>, and <em>d9</em>) and sigma (<em>FoGSTs1</em>, <em>s2</em>, and <em>s6</em>) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies.</div></div><div><h3>Conclusion</h3><div>Our results indicate that <em>F. occidentalis</em> may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 107-120"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845321","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}
Yoonji Lee, Ji Eon Kim, Wonsik Kim, Soyeon Kim, Ri Han, Donghyuk Suh, Eunmi Kim, Eun-Ae Shin, Kyung-hee Pyo, Jae-Ho Lee, Sanghee Yoon, Yong-In Kim, Je-Yoel Cho, Sun Choi, Jung Weon Lee
{"title":"Unique molecular architecture of N-glycosylated TM4SF5 dimer highlights evolutionary and structural divergence among small four-transmembrane protein families","authors":"Yoonji Lee, Ji Eon Kim, Wonsik Kim, Soyeon Kim, Ri Han, Donghyuk Suh, Eunmi Kim, Eun-Ae Shin, Kyung-hee Pyo, Jae-Ho Lee, Sanghee Yoon, Yong-In Kim, Je-Yoel Cho, Sun Choi, Jung Weon Lee","doi":"10.1016/j.jare.2025.11.066","DOIUrl":"10.1016/j.jare.2025.11.066","url":null,"abstract":"<div><h3>Introduction</h3><div>Membrane proteins, including small four-transmembrane proteins, play roles in membrane organization and signal transduction. Generally, they share capacities for protein–protein association and subcellular translocation to regulate cellular functions.</div></div><div><h3>Objectives</h3><div>Despite known commonalities and differences in structure and function, the relationships among the tetraspanin, CD20-like, golgi 4-transmembrane spanning transporter (Mtp), and transmembrane 4 L six (L6) families remain unclear.</div></div><div><h3>Methods</h3><div>Here, we mostly compared TM4SF5, a transmembrane 4 L6 family member, to the genuine tetraspanins and the CD20-like family, exploring unique aspects that evolved from the small four-transmembrane proteins.</div></div><div><h3>Results</h3><div>TM4SF5 and other L6 membrane proteins have two conserved cysteines, affecting <em>N-</em>glycosylation in the large extracellular loop (LEL) and favoring a dimeric state, whereas the tetraspanins maintained their cysteine residues in addition to the CCG motif. However, TM4SF5 and other L6 membrane proteins have more sequence similarity to proteins in the CD20-like family, which lack these features in the LEL. Uniquely, TM4SF5 and other L6 membrane proteins have a β-sheet configuration in the LEL, unlike other small four-transmembrane proteins with α-helices.</div></div><div><h3>Conclusion</h3><div>Therefore, the unique features in the LEL and the <em>N</em>-glycosylation of TM4SF5 may contribute to dimer formation and cholesterol binding, potentially influencing regulatory roles in liver malignancy development.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"87 ","pages":"Pages 149-162"},"PeriodicalIF":17.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657572","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}