Journal of Advanced Research最新文献

{"title":"Natural, safety immunomodulatory derivatives of lactobacillus biofilms promote diabetic wound healing by metabolically regulating macrophage phenotype and alleviating local inflammation","authors":"Qingwei Zhou, Junjie Chi, Jintao Yang, Xiaoyu Dong, Jiali Guo, Feifei Lian, Abdullah Al Mamun, Tianling Chen, Haijuan Zhang, Jiaojiao Chen, Yibing Tao, Yunmiao Ma, Keqing Shi, Jian Xiao","doi":"10.1016/j.jare.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.jare.2025.04.001","url":null,"abstract":"<h3>Introduction</h3>Long-term inflammatory microenvironment further impairs the healing process of diabetic wounds. Many studies have shown that <em>Lactobacillus</em> can regulate immune function and promote injured tissue repair. However, the immunomodulatory function and safety of <em>Lactobacillus</em> biofilm (LB) on wounds need further investigation.<h3>Objectives</h3>In this present research, we proposed a “bacteria-free biofilm derivative therapy” and successfully extracted <em>Lactobacillus</em> biofilm derivatives (LBDs) by ultrasonic separation and filtration technology for the natural and safe treatment of diabetic wounds.<h3>Methods</h3>The study first cultured <em>Lactobacillus</em> anaerobically and extracted LBDs using ultrasound separation combined with filtration technology. LBDs were characterized via scanning electron microscopy, Concanavalin A fluorescence staining, and protein gel electrophoresis. In vivo diabetic wound model, wound closure rates were dynamically monitored, and tissue sections were analyzed using hematoxylin-eosin and immunofluorescence staining to evaluate LBDs’ healing effects. An in vitro macrophage inflammation model was established, employing immunofluorescence, flow cytometry, and Western blotting techniques to explore the molecular mechanisms underlying LBDs’ effects on macrophage phenotypes. Furthermore, whole-genome sequencing and proteomics of LBDs-treated macrophages were performed to further elucidate the intrinsic molecular mechanisms through which LBDs regulate macrophage phenotypes.<h3>Results</h3>LBDs were effectively extracted utilizing ultrasonic separation coupled with filtration technology. Studies revealed that LBDs modulate the systemic metabolic reprogramming in wound-site macrophages, suppress JAK-STAT1 signaling pathway, alleviate the local inflammatory microenvironment, promote neovascularization and ultimately accelerate wound healing.<h3>Conclusion</h3>The LBDs retains most bioactive components of the LB. As a natural, safe and immunomodulatory agent, LBDs promote diabetic wound healing by metabolically reprogramming macrophage phenotypes and improving the local immune microenvironment, offering promising potential for regenerative applications in diabetic wound management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"14 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766683","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 and validation of a deep learning model based on cascade mask regional convolutional neural network to noninvasively and accurately identify human round spermatids","authors":"Yujiao Sun, Shihao Shao, Jiangwei Huang, Hao Shi, Liying Yan, Yongjie Lu, Ping Liu, Yuqiang Jiang, Jie Qiao, Li Zhang","doi":"10.1016/j.jare.2025.03.059","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.059","url":null,"abstract":"<h3>Introduction</h3>The difficulty of identifying human round spermatids (hRSs) has impeded applications of the human round spermatid injection (ROSI) technique. RSs can be accurately screened through flow cytometric analysis utilizing the Hoechst fluorescence profile reflecting DNA, but this method is not suitable for isolating hRSs due to the toxicity associated with Hoechst staining.<h3>Objective</h3>To evaluate the capacity of a deep learning model grounded in a cascade mask region-based convolutional neural network (R-CNN) for the noninvasive and accurate identification of hRSs.<h3>Methods</h3>In this study, we presented the development and validation of a deep learning model for identifying hRSs through the analysis of 3457 optical light microscope images of sorted hRSs obtained via flow cytometric analysis. The model’s accuracy and specificity were evaluated by calculating the mean average precision (mAP). Furthermore, a double-blind experiment was conducted to access the reliability of the proposed model in accurately identifying hRSs. It detected the expression of protamine (PRM1) and/or peanut lectin (PNA), which are established markers for RSs.<h3>Results</h3>Our deep learning-based model demonstrated a high precision, achieving a mAP of over 0.80 for isolating hRSs in test datasets. The expression of PRM1 and/or PNA was observed in all cells noninvasively selected by our AI model during an independent double-blind test. This phenomenon confirmed the accuracy and effectiveness of the proposed model. The model’s capability for noninvasive and accurate isolation of hRSs among spermatogenic cells highlighted its robustness and generalizability for clinical applications.<h3>Conclusion</h3>The deep learning AI model based on a cascade R-CNN has the ability to accurately identify hRSs among spermatogenic cells. The application of this noninvasive method, which requires no additional procedures in clinical practice, is able to facilitate the widespread implementation of ROSI technique. Therefore, it can provide patients with spermatogenic arrest the opportunity to become biological fathers.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"37 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766686","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":"Lipidomic signatures as predictive biomarkers for early-onset lung cancer: Identification and development of a risk prediction model","authors":"Fei Wang, Zeming Guo, Wei Tang, Wei Cao, Xuesi Dong, Yongjie Xu, Chenran Wang, Jiaxin Xie, Xiaoyue Shi, Zilin Luo, Yadi Zheng, Guochao Zhang, Na Ren, Nan Zhang, Donghua Wei, Lingbin Du, Fengwei Tan, Ni Li","doi":"10.1016/j.jare.2025.03.045","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.045","url":null,"abstract":"<h3>Introduction</h3>Lung cancer is the leading cause of cancer-related mortality worldwide. While traditionally associated with older adults, early-onset lung cancer (EOLC) is rising, particularly in Asia, which accounts for 75.9% of global cases. Existing lung cancer screening guidelines primarily focus on older populations, which may result in missed opportunities for early detection in younger individuals. Given its distinct clinical characteristics, EOLC warrants dedicated research and targeted interventions.<h3>Objectives</h3>This study aims to characterize the lipidomic profiles specific to EOLC patients (aged 18–49 years) and develop a biomarker-based predictive model to improve risk assessment and early detection.<h3>Methods</h3>The discovery and validation sets included 111 EOLC cases and 127 non-EOLC controls, all aged 18–49 years. Targeted lipidomics analysis, combined with logistic regression, was performed on plasma samples to identify differentially expressed lipids species. Clustering and pathway analyses were conducted to uncover and visualize the internal signatures of the identified lipids. Key lipids were refined using the LASSO-bootstrap regression method combined with the Boruta algorithm. A random forest model was subsequently employed to develop a robust prediction model for EOLC.<h3>Results</h3>A total of 843 lipids were identified, with 60 differentially expressed lipids detected, of which 33 were validated in the validation set. Cluster analysis revealed that passive smoking (OR: 3.11, 95% CI: 0.97–12.11) and current smoking (OR: 15.65, 95% CI: 2.55–142.10) were associated with elevated lipid metabolite profiles in EOLC patients. The validated lipids were further refined using LASSO and Boruta methods, which ultimately selected 6 lipids for inclusion in a prediction model constructed with random forest. This model achieved an area under the curve (AUC) of 0.874 in the validation set.<h3>Conclusion</h3>Our study identified lipidomic signatures associated with the risk of EOLC, offering potential translational implications for lung cancer prevention strategies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"72 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745145","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 insights into emerging advances in the Neurobiology of anorexia","authors":"Liwei Mao, Lian Wang, Zhihai Huang, Jian-Kang Chen, Lorelei Tucker, Quanguang Zhang","doi":"10.1016/j.jare.2025.03.046","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.046","url":null,"abstract":"<h3>Background</h3>Anorexia is a complex eating disorder influenced by genetic, environmental, psychological, and socio-cultural factors. Research into its molecular mechanisms and neural circuits has deepened our understanding of its pathogenesis. Recent advances in neuroscience, molecular biology, and genetics have revealed key molecular and neural circuit mechanisms underlying anorexia.Aim of reviewClarify the peripheral and central molecular mechanisms regulating various types of anorexia, identify key cytokines and neural circuits, and propose new strategies for its treatment.Key scientific concepts of reviewAnorexia animal models, including activity-induced, genetic mutation, and inflammation-induced types, are explored for their relevance to studying the disorder. Anorexic behavior is regulated by cytokines, hormones (like GDF15, GLP-1, and leptin), and neural circuits such as AgRP, serotonergic, dopaminergic, and glutamatergic pathways. Disruptions in these pathways, including GABAergic signaling in AgRP neurons and 5-HT2C and D2 receptors, contribute to anorexia. Potential therapies target neurotransmitter receptors, ghrelin receptors, and the GDF15-GFRAL pathway, offering insights for treating anorexia, immune responses, and obesity.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1147 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745143","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":"Multifunctional nanoplatform for tumor chemodynamic and Self-Amplified photodynamic Cascade therapy","authors":"Xingyu Luo, Haifeng Qi, Manqi Yan, Tong Xu, Ting Wu, Yin Ding, Wei Han","doi":"10.1016/j.jare.2025.03.056","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.056","url":null,"abstract":"<h3>Introduction</h3>5-Aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) has demonstrated considerable potential in breast cancer treatment. However, its efficacy is limited by low tissue selectivity and the rapid conversion of 5-ALA to non-photosensitive heme in tumor tissues, reducing its therapeutic effectiveness.<h3>Objectives</h3>This study aims to develop a multifunctional nanomedicine to enhance 5-ALA’s PDT efficacy while introducing chemodynamic therapy (CDT) for synergistic tumor inhibition. By designing a zinc-ion-doped cuprous metal–organic framework (MOF) nanocarrier loaded with 5-ALA (5-ALA@Zn-CuTz), we seek to improve tumor targeting, prolong photosensitizer retention, and enhance therapeutic outcomes.<h3>Methods</h3>To enhance biocompatibility and active tumor targeting, the surface of 5-ALA@Zn-CuTz nanoparticles (NPs) was modified with a platelet membrane (PM), forming 5-ALA@Zn-CuTz@PM NPs. The therapeutic efficacy was evaluated in vitro and in vivo using mice breast cancer models. Cellular uptake, reactive oxygen species (ROS) generation, and tumor inhibition efficiency were analyzed through fluorescence imaging, biochemical assays, and histological analysis.<h3>Results</h3>Upon intravenous administration, 5-ALA@Zn-CuTz@PM NPs selectively accumulated in breast cancer cells. Within the tumor, Zn²⁺ bound to intracellular protoporphyrin IX (PpIX) to form PpIX-Zn, inhibiting heme oxygenase-1 (HO-1) activity and preventing the conversion of PpIX into heme. This increased the effective intracellular concentration of the photosensitizer, thereby enhancing PDT. Additionally, Cu⁺ catalyzed the decomposition of excess H₂O₂ in the tumor microenvironment, generating oxygen and hydroxyl radicals, which alleviated hypoxia and activated CDT. The synergistic PDT/CDT effect significantly enhanced tumor growth inhibition in vitro and in vivo.<h3>Conclusion</h3>5-ALA@Zn-CuTz@PM NPs effectively enhance PDT efficacy through selective tumor targeting and HO-1 inhibition while simultaneously leveraging CDT for additional tumor suppression. The combined PDT/CDT strategy demonstrated superior therapeutic outcomes, highlighting the potential of this nanoplatform as a promising approach for breast cancer treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"34 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737098","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":"Metformin attenuates colitis via blocking STAT3 acetylation by reducing acetyl-CoA production","authors":"Xiangyun Li, Zixuan Xiang, Xiaoli Wang, Haodong He, Miao Xu, Cheng Tan, Xiaohan Wu, Jixiang Zhang, Weiguo Dong","doi":"10.1016/j.jare.2025.03.058","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.058","url":null,"abstract":"<h3>Background and aims</h3>While metformin has been shown to alleviate dextran sulfate sodium (DSS)-induced colitis in murine models, the mechanisms underlying its anti-inflammatory and barrier-restorative effects remain poorly defined. This study investigates the role of acetyl coenzyme A (acetyl-CoA)-dependent STAT3 acetylation in mediating metformin’s therapeutic actions, with the goal of identifying novel molecular targets for ulcerative colitis (UC) treatment.<h3>Methods</h3>Acute colitis was induced in wild-type C57BL/6J mice via oral DSS administration, followed by daily intraperitoneal metformin treatment. Intestinal inflammation, barrier integrity, and STAT3 signaling were assessed using histopathology, western blotting, and transmission electron microscopy. To validate STAT3′s critical role in colitis pathogenesis, intestinal epithelium-specific STAT3 knockout mice were employed, enabling targeted investigation of STAT3 acetylation and its regulation by metformin.<h3>Results</h3>Metformin attenuated DSS-induced colitis by suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), reducing epithelial apoptosis, and restoring tight junction proteins (ZO-1, E-cadherin, Occludin). Mechanistically, metformin reduced acetyl-CoA levels, thereby inhibiting STAT3 acetylation and downstream pathway activation. The pivotal role of STAT3 in colitis progression was confirmed using STAT3 knockout mice, as the therapeutic effects of metformin were significantly diminished in the absence of STAT3-mediated inflammatory signaling.<h3>Conclusion</h3>This study identifies acetyl-CoA-dependent STAT3 acetylation as a novel mechanism through which metformin ameliorates intestinal inflammation and barrier dysfunction. These findings not only advance our understanding of metformin’s immunomodulatory properties but also highlight the therapeutic potential of targeting acetyl-CoA metabolism in UC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"24 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737106","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":"Thousands-years-old deep-sea DNA viruses reveal the evolution of human pathogenic viruses","authors":"Tianliang He, Xinyi Zhang, Xiaobo Zhang","doi":"10.1016/j.jare.2025.03.057","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.057","url":null,"abstract":"<h3>Introduction</h3>In the last two decades, outbreaks of pathogenic viruses have led to significant human mortality and economic repercussions. Despite extensive investigations into tracing these viruses in terrestrial environments, their origins remain enigmatic.<h3>Objectives</h3>The Earth’s biosphere encompasses both sunlight-dependent terrestrial and surface ocean ecosystems, as well as the sunlight-independent deep-sea ecosystem. However, the traceability of human pathogenic viruses in the deep sea has not been thoroughly explored. This study aimed to investigate the presence of human pathogenic viruses in the deep sea.<h3>Methods</h3>In this study, we performed a viral metagenomic analysis using a global deep-sea sediment virome 2.0 dataset which contained 159 deep-sea sediment samples with geologic ages from 2,500 to 7,750 years.<h3>Results</h3>A total of 554,664 viral operational taxonomic units (vOTUs) were identified and further obtained 2,254 potential pathogenic viruses of vertebrates. Among them, 23 vOTUs exhibited high homology with 12 species of human pathogenic viruses which belonged to 4 viral families. Notably, variola virus, the first human pathogenic virus eradicated from humans and now only found in laboratories, was discovered in the ancient deep-sea sediments. The evolution analysis showed that these DNA viruses might represent the ancestors or variants of human pathogenic viruses, suggesting that the deep sea could be a crucial reservoir for human pathogenic viruses.<h3>Conclusion</h3>Our findings present all the ancient pathogenic DNA viruses of humans found in the deep sea for the first time, highlighting the source of the future epidemics. It is imperative to implement the stringent virus monitoring and management measures for human activities in marine environments to address the emerging challenges of marine biosecurity and promote sustainable use of oceans.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"34 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745216","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":"Loss of life expectancy attributed to long-term ozone exposure in Chinese older adults: Cross-cohort analysis from 3 national cohorts","authors":"Minjin Peng, Yang Yuan, Haitong Zhe Sun, Jing Wu, Lifeng Zhu, Yi Zeng, Yunquan Zhang, Yao Yao","doi":"10.1016/j.jare.2025.03.044","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.044","url":null,"abstract":"<h3>Background</h3>Cohort evidence linking ozone (O₃) exposure with mortality was sparsely investigated among the elderly in low- and middle-income countries. This study aims to quantify mortality risk and burden attributed to chronic O₃ exposure in Chinese older adults.<h3>Methods</h3>A total of 30,874 older adults aged ≥ 65 years were recruited from 3 national dynamic cohorts across 29 provincial regions in China, 2005–2018. Annual warm-season (April–September) O₃ and year-round PM_2.5 concentrations were estimated through well-validated satellite-based spatiotemporal models and were assigned to participants for each survey year. Time-dependent Fragility Cox models with random intercept for study cohort were employed to quantify O₃-mortality association, adjusting for demographic, behavioral, health, and environmental covariates. A counterfactual causal framework was used for assessment of O₃-attributable premature deaths in older adults based on exposure–response relationship derived from multi-cohort two-pollutant analysis (+PM_2.5). Years of life lost and loss of life expectancy were subsequently evaluated based on the burden estimation model by incorporating the comparative risk assessment method and reference life tables.<h3>Results</h3>16,939 death events occurred during 0.16 million person-years of follow-up surveys. Each 10-ppb increase in O₃ exposure was linked with a hazard ratio of 1.076 (95 % confidence interval [CI]: 1.050, 1.102) for all-cause mortality. By achieving the counterfactual target (WHO AQG 2021) of 60 μg/m³ for warm-season O₃, 0.88 (95 % CI: 0.60, 1.14) million premature deaths could be avoidable among Chinese older population in 2019, yielding an inconspicuous reduction of 0.11 million compared to the estimate in 2011 (0.99 million, 95 % CI: 0.68, 1.28). O₃-attributable deaths amounted to 9.05 (95 % CI: 6.19, 11.70) million years of life lost in 2019, equivalent to a loss of life expectancy of 0.93 (95 % CI: 0.63, 1.20) years for older population in China.<h3>Conclusions</h3>Our multi-cohort analysis suggested that reducing ambient O₃ exposure could effectively increase the life expectancy of Chinese older adults, which may contribute to the development of healthy aging strategies and national cleaning air policies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"219 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737099","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":"Exploiting metabolic vulnerabilities through synergistic ferroptosis and disulfidptosis for breast cancer therapy","authors":"Yu Liang, Haibo Lan, Qiuyu Li, Mengdan Gao, Minyi Liu, Ziting Xu, Yang Gao, Li Zhang, Yingjia Li, Bingxia Zhao","doi":"10.1016/j.jare.2025.03.052","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.052","url":null,"abstract":"<h3>Introduction</h3>Ferroptosis represents a promising therapeutic approach for breast cancer treatment. However, cancer cells can develop resistance through the SLC7A11–GSH–GPX4 axis, wherein increased SLC7A11 expression enhances cystine uptake, replenishes GSH, and reactivates GPX4. Notably, cells with high SLC7A11 expression become vulnerable to disulfidptosis under glucose-deprived conditions.<h3>Objectives</h3>We aimed to develop a dual-mode therapeutic strategy that simultaneously induces ferroptosis and disulfidptosis by targeting both lipid peroxidation and glucose metabolism in breast cancer cells.<h3>Methods</h3>Fe-Cu-SS metal–organic frameworks (MOFs) loaded with BAY876 (FCSP@876 MOFs) were synthesized to enhance ferroptosis and trigger disulfidptosis in breast cancer cells. The MOFs were characterized using transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and UV–Vis spectroscopy. In vitro experiments demonstrated that FCSP@876 MOFs increased reactive oxygen species (ROS) levels and lipid peroxidation while depleting NADPH. Western blotting and actin filament staining confirmed the underlying mechanisms. In vivo xenograft experiments in BALB/c mice assessed the synergistic effects of ferroptosis and disulfidptosis induction.<h3>Results</h3>During ferroptosis induction, cancer cells exhibited an adaptive upregulation of SLC7A11 expression. FCSP@876 MOFs effectively counteracted this resistance mechanism by simultaneously inducing ferroptosis and restricting glucose uptake through BAY876, leading to NADPH depletion and subsequent disulfidptosis. Both in vitro and <em>in vivo</em> experiments demonstrated the enhanced therapeutic efficacy of this dual-mode strategy compared with single-mode treatments.<h3>Conclusion</h3>This study successfully developed a novel therapeutic strategy that combines ferroptosis and disulfidptosis using FCSP@876 MOFs, offering a promising approach for overcoming ferroptosis resistance in breast cancer therapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"30 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734406","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":"Online and personalised control of the Depth of hypnosis during induction using fractional order PID","authors":"Marcian Mihai, Isabela Birs, Erwin Hegedus, Amani Ynineb, Dana Copot, Robain De Keyser, Clara M. Ionescu, Samir Ladaci, Cristina I. Muresan, Martine Neckebroek","doi":"10.1016/j.jare.2025.03.053","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.053","url":null,"abstract":"<h3>Introduction</h3>The integration of information technology and control engineering has significantly increased in clinical practice research, especially in the management of drug dosing for general anaesthesia.<h3>Objective</h3>The main focus of the research is to achieve a personalised control of the Depth of Hypnosis based on a novel approach. The primary objective is to regulate the Bispectral Index by administering Propofol during the hypnotic phase of anaesthesia.<h3>Methods</h3>A fractional order time delay model is proposed to replace the conventional PK-PD model. This model is estimated online during the induction phase. A fractional order Proportional-Integral-Derivative (PID) controller is then individually tuned for each patient.<h3>Results</h3>The closed loop simulation results demonstrate that the proposed controllers effectively minimise undershoot and achieve a short time to reach the desired time-to-target for the majority of the patients. The analysis indicates that the proposed controller is capable of maintaining the BIS signal within a safe range. Comparative analyses with similar research are provided to effectively contextualise this study within the existing literature. Disturbance rejection tests during the maintenance phase are performed to demonstrate the effectiveness of personalised control.<h3>Conclusion</h3>The online adaptation that this research brings, compared to the previous attempts, allows for significantly improved results for the hypnosis phase.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"31 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734403","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}