Journal Detail

Research Article

ArticleID :JAUSM/2025/11/01/01

Associations between heavy metal exposure and vascular age: a large cross‑sectional study

Issue No. 01 (Jan-Mar)

Authors: Yuntao Feng, Chengxing Liu, Litang Huang, Jun Qian, Na Li, Hongwei Tan and Xuebo Liu

Background Heavy metal exposure is an emerging environmental risk factor linked to cardiovascular disease (CVD) through its effects on vascular ageing. However, the relationship between heavy metal exposure and vascular age have not been fully elucidated.

Methods This cross-sectional study analyzed data from 3,772 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016. We measured urinary concentrations of nine heavy metals and assessed their associations with vascular age, estimated pulse wave velocity (ePWV) and heart vascular age (HVA). Additionally, sex-stratified analyses, Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression were conducted to explore the effects of individual and mixed metal exposures.

Results Exposure to metals such as cadmium (Cd) cesium (Cs), cobalt (Co), and lead (Pb) was significantly associated with increased vascular age, with odds ratios (OR) ranging from 1.05 to 3.48 in full adjusted models. Sex-stratified analyses indicated that individual metal including cobalt (Co) and cadmium (Cd) exposures had a more substantial impact on males. WQS analysis consistently showed combined heavy metals exposure had stronger associations with increased vascular age in men (OR for HVA = 3.89, 95% CI 2.91–5.28).

Conclusions This study highlights a significant association between heavy metal exposure and increased vascular age. Stratified analyses illustrated men might be more susceptible to the combined effects of multiple heavy metal exposure. The findings underscore the importance of considering sex-specific responses and interventions measures in cardiovascular risk assessments and managements. Further research is needed to validate these findings and to develop more precise public health strategies targeting environmental risks

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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by- nc- nd/4. 0/.

Research Article

ArticleID :JAUSM/2025/11/01/02

Deciphering the cellular and molecular landscape of pulmonary fibrosis through single‑cell sequencing and machine learning

Issue No. 01 (Jan-Mar)

Authors: Yong Zhou, Zhongkai Tong, Xiaoxiao Zhu, Chunli Wu, Ying Zhou and Zhaoxing Dong

Pulmonary fibrosis is characterized by progressive lung scarring, leading to a decline in lung function and an increase in morbidity and mortality. This study leverages single-cell sequencing and machine learning to unravel the complex cellular and molecular mechanisms underlying pulmonary fibrosis, aiming to improve diagnostic accuracy and uncover potential therapeutic targets. By analyzing lung tissue samples from pulmonary fibrosis patients, we identified distinct cellular phenotypes and gene expression patterns that contribute to the fibrotic process. Notably, our findings revealed a significant enrichment of activated B cells, CD4 T cells, macrophages, and specific fibroblast subpopulations in fibrotic versus normal lung tissue. Machine learning analysis further refined these observations, resulting in the development of a diagnostic model with enhanced precision, based on key gene signatures including TMEM52B, PHACTR1, and BLVRB. Comparative analysis with existing diagnostic models demonstrates the superior accuracy and specificity of our approach. Through In vitro experiments involving the knockdown of PHACTR1, TMEM52B, and BLVRB genes demonstrated that these genes play crucial roles in inhibiting the expression of α-SMA and collagen in lung fibroblasts induced by TGF-β. Additionally, knockout of the PHACTR1 gene reduced inflammation and collagen deposition in a bleomycin-induced mouse model of pulmonary fibrosis in vivo. Additionally, our study highlights novel gene signatures and immune cell profiles associated with pulmonary fibrosis, offering insights into potential therapeutic targets. This research underscores the importance of integrating advanced technologies like single-cell sequencing and machine learning to deepen our understanding of pulmonary fibrosis and pave the way for personalized therapeutic strategies.

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by- nc- nd/4. 0/.

Research Article

ArticleID :JAUSM/2025/11/01/03

Human endometrial stem cell‑derived small extracellular vesicles enhance neurite outgrowth and peripheral nerve regeneration through activating the PI3K/AKT signaling pathway

Issue No. 01 (Jan-Mar)

Authors: Mojdeh Salehi Namini, Nima Beheshtizadeh, Somayeh Ebrahimi‑Barough and Jafar Ai

Nowadays, extracellular vesicles (EVs) such as exosomes participate in cell-cell communication and gain attention as a new approach for cell-free therapies. Recently, various studies have demonstrated the therapeutic ability of exosomes, while the biological effect of human endometrial stem cell (hEnSC)-derived small EVs such as exosomes is still unclear. Herein, we obtained small EVs from hEnSC and indicated that these small EVs activate the vital cell signaling pathway and progress neurite outgrowth in PC-12 cell lines. For this purpose, hEnSC-derived small EVs were extracted by ultracentrifuge and characterized by DLS, SEM, TEM, and western blot. Also, dil-staining of hEnSC-derived small EVs was done to determine the penetration of hEnSC-derived small EVs into PC12 cells. The MTT assay, scratch assay, and western blot assay were applied to PC12 cells that were exposed to different concentrations of small EVs (0, 50, 100, and 150 μg/ml). Our results demonstrated that small EVs significantly increased neurite outgrowth, proliferation, and migration in PC12 cells in a dose-dependent manner. Moreover, the analysis of western blots showed increased expression of the PI3k/AKT signaling pathway in PC12 cells exposed to hEnSC-derived small EVs in a dose-dependent manner. Also, the results of this study indicated that hEnSC-derived small EVs can enhance cell proliferation and migration and promote neural outgrowth by activating the PI3k/AKT signaling pathway. Accordingly, hEnSC-derived small EVs became an effective strategy for cell-free therapies. Altogether, these positive effects make hEnSC-derived small EVs a new efficient approach in regenerative medicine, especially for the cure of neural injury.

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by-​nc-​nd/4. 0/.

Research Article

ArticleID :JAUSM/2025/11/01/04

FOSL1 transcriptionally dictates the Warburg effect and enhances chemoresistance in triple-negative breast cancer

Issue No. 01 (Jan-Mar)

Authors: Gang Zhao, Yutong Liu, Shiqi Yin, Runxiang Cao, Qian Zhao, Yifan Fu and Ye Du

Background: Dysregulated energy metabolism has emerged as a defining hallmark of cancer, particularly evident in triple-negative breast cancer (TNBC). Distinct from other breast cancer subtypes, TNBC exhibits heightened glycolysis and aggressiveness. However, the transcriptional mechanisms of aerobic glycolysis in TNBC remains poorly understood.

Methods: The Cancer Genome Atlas (TCGA) cohort was utilized to identify genes associated with glycolysis. The role of FOSL1 in glycolysis and tumor growth in TNBC cells was confirmed through both loss-of-function and gain-offunction experiments. The subcutaneous xenograft model was established to evaluate the therapeutic potential of targeting FOSL1 in TNBC. Additionally, chromatin immunoprecipitation and luciferase reporter assays were employed to investigate the transcriptional regulation of glycolytic genes mediated by FOSL1. 

Results: FOSL1 is identified as a pivotal glycolysis-related transcription factor in TNBC. Functional verification shows that FOSL1 enhances the glycolytic metabolism of TNBC cells, as evidenced by glucose uptake, lactate production, and extracellular acidification rates. Notably, FOSL1 promotes tumor growth in TNBC in a glycolysis-dependent manner, as inhibiting glycolysis with 2-Deoxy-D-glucose markedly diminishes the oncogenic effects of FOSL1 in TNBC. Mechanistically, FOSL1 transcriptionally activates the expression of genes such as SLC2A1, ENO1, and LDHA, which further accelerate the glycolytic flux. Moreover, FOSL1 is highly expressed in doxorubicin (DOX)-resistant TNBC cells and clinical samples from cases of progressive disease following neoadjuvant chemotherapy. Targeting FOSL1 proves effective in overcoming chemoresistance in DOX-resistant MDA-MB-231 cells. 

Conclusion: In summary, FOSL1 establishes a robust link between aerobic glycolysis and carcinogenesis, positioning it as a promising therapeutic target, especially in the context of TNBC chemotherapy

How To Cite this Article

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit h t t p : / / c r e a t i v e c o m m o n s . o r g / l i c e n s e s / b y - n c - n d / 4. 0 / .

Research Article

ArticleID :JAUSM/2025/11/01/05

PD‑L1 and IFN‑γ modulate Non‑Small Cell Lung Cancer (NSCLC) cell plasticity associated to immune checkpoint inhibitor (ICI)‑mediated hyperprogressive disease (HPD)

Issue No. 01 (Jan-Mar)

Authors: Stefania Angelicola, Francesca Giunchi, Francesca Ruzzi, Mariateresa Frascino, Mary Pitzalis, et.al.,

Background: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear. 

Methods: This study investigated the mechanisms of ICI resistance in an HPD-NSCLC model. Two primary cell cultures were established from samples of a NSCLC patient, before ICI initiation (“baseline”, NSCLC-B) and during HPD (“hyperprogression”, NSCLC-H). The cell lines were phenotypically and molecularly characterized through immunofluorescence, Western Blotting and RNA-Seq analysis. To assess cell plasticity and aggressiveness, cellular growth patterns were evaluated both in vitro and in vivo through 2D and 3D cell growth assays and patient-derived xenografts establishment. In vitro investigations, including the evaluation of cell sensitivity to interferon-gamma (IFN-γ) and cell response to PD-L1 modulation, were conducted to explore the influence of these factors on cell plasticity regulation. 

Results: NSCLC-H exhibited increased expression of specific CD44 isoforms and a more aggressive phenotype, including organoid formation ability, compared to NSCLC-B. Plastic changes in NSCLC-H were well described by a deep transcriptome shift, that also affected IFN-γ–related genes, including PD-L1. IFN-γ–mediated cell growth inhibition was compromised in both 2D-cultured NSCLC-B and NSCLC-H cells. Further, the cytokine induced a partial activation of both type I and type II IFN-pathway mediators, together with a striking increase in NSCLC-B growth in 3D cell

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by-​nc-​nd/4. 0/.

Research Article

ArticleID :JAUSM/2025/11/02/01

Bioinformatics analysis and experimental validation of potential targets and pathways in chronic kidney disease associated with renal fibrosis

Issue No. 02 (Apr-June)

Authors: Cui Huimin, Zhao Yuxin, Wang Peng, Gong Wei, Lin Hong, Li Na, and Yang Jianjun

Background: Chronic kidney disease (CKD) has emerged as a major health problem worldwide. Previous studies have shown that specific miRNA expression profiles of patients with CKD are significantly changed. In this study, we aim to elucidate the role of miRNAs as potential biomarkers in CKD progression by integrating bioinformatics analysis with experimental validation, thereby providing medical evidence for the prevention and treatment of CKD.

Method: Bioinformatics analysis was used to identify potential targets and pathways in CKD-associated renal fibrosis through randomly obtaining miRNA microarray data related to CKD patients in the Gene Expression Omnibus (GEO) database according to the inclusion and exclusion criteria, conducting pathway enrichment analysis and constructing protein-protein interaction (PPI) networks and miRNA-mRNA network by Cytoscape 3.8.0. In vitro experiments were employed to verify the role and mechanism of miR-223-3p in human renal tubular epithelial cells (HK2) through Quantitative real-time PCR assays, Western blot, Immunofluorescence analysis and Double luciferase reporter gene experiment. Multi-group one-way analysis of variance (ANOVA) and the Dunnett-t test were used to analyze the results by SPSS24.0.

Results: 10 up-regulated and 11 down-regulated miRNAs of CKD patients were screened out. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was the first pathway of pathway enrichment analysis. MiR-223-3p (logFC= 2.047, p = 0.002) was one of the four hub miRNAs. Furthermore, we observed a reduction in α-smooth muscle actin (α-SMA) (p = 0.001) and Collagen type I alpha 1 (Col1-a1) (p = 0.023) levels upon miR-223-3p overexpression, which aligned with our bioinformatics predictions. This downregulation was attributed to the inhibition of nuclear factor kappa-B (NF-κB) nuclear translocation and subsequent decrease in the secretion of inflammatory cytokines, such as interleukin-6 (IL-6) (p = 0.005). Conversely, when CHUK was further overexpressed, the inhibitory effect of miR-223-3p on epithelial-mesenchymal transition (EMT) was attenuated, confirming the specific interaction between miR-223-3p and CHUK

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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/ 

Review Article

ArticleID :JAUSM/2025/11/02/02

Glucagon-like Peptide-1 receptor agonists for obstructive sleep apnea in patients with obesity and type 2 diabetes mellitus: a systematic review and meta-analysis

Issue No. 02 (Apr-June)

Authors: Ruifeng, Yang, Lindong, Zhang, Jiangfan, Guo, Ning, Wang Qiue Zhang, Zhiwei Qi, Lili Wu, Lingling Qin, and Tonghua Liu

The systematic review was registered on the PROSPERO website (CRD42024558287). Our objective is to systematically summarise the clinical evidence of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for obstructive sleep apnea (OSA) in patients with Obesity or/and type 2 Diabetes Mellitus (T2DM). This analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. 10 databases and registers Web of Science, Scopus, PubMed, APA PsycInfo, Embase, Ovid, Cochrane Library, CINAHL, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) were retrieved from the establishment to July 14, 2024 for related randomized controlled trials (RCT) and non-RCTs. Data were extracted by two investigators separately, and only the RCTs were included in the quantitative synthesis. The outcome was operated by Review Manager 5.4 and Stata 15.0. Ten studies containing eight RCTs and two non-RCTs were included. The efficacy of the GLP-1 RA group in reducing apnea-hypopnea index (AHI) was superior to that of the control group in patients with T2DM (MD = -5.68, 95%CI [-7.97, -3.38], P < 0.00001, I2 = 0%). GLP-1 RAs also possessed a tendency to reduce AHI in patients with obesity but more evidence is needed to support the findings due to the inconsistency. In consideration of the enhanced metabolic parameters observed with GLP-1 RAs, they may be recommended as useful hypoglycaemic medication for the management of T2DM with OSA. Patients with obesity and OSA may consider GLP-1 RA as a potential treatment option if the adverse events are deemed tolerable.

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by-nc-nd/4.0/.

Review Article

ArticleID :JAUSM/2025/11/02/03

Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges

Issue No. 02 (Apr-June)

Authors: Yuqi Xie, Xuan Wang, Wenquan Wang, Ning Pu and Liang Liu

The epithelial-mesenchymal transition (EMT) is a critical process in cancer progression, facilitating tumor cells to develop invasive traits and augmenting their migratory capabilities. EMT is primed by tumor microenvironment (TME)-derived signals, whereupon cancer cells undergoing EMT in turn remodel the TME, thereby modulating tumor progression and therapeutic response. This review discusses the mechanisms by which EMT coordinates TME dynam ics, including secretion of soluble factors, direct cell contact, release of exosomes and enzymes, as well as metabolic reprogramming. Recent evidence also indicates that cells undergoing EMT may differentiate into cancer-associated f ibroblasts, thereby establishing themselves as functional constituents of the TME. Elucidating the relationship between EMT and the TME offers novel perspectives for therapeutic strategies to enhance cancer treatment effi cacy. Although EMT-directed therapies present significant therapeutic potential, the current lack of effective target ing approaches—attributable to EMT complexity and its microenvironmental context dependency—underscores the necessity for mechanistic investigations and translational clinical validation.

How To Cite this Article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licen ses/by-nc-nd/4.0/.

Research Article

ArticleID :JAUSM/2025/11/02/04

CircPRKCA facilitates esophageal squamous cell carcinoma metastasis via m5C-dependent CSF2 mRNA stabilization

Issue No. 02 (Apr-June)

Authors: Lixia Wu, Lina Gu, Yang zheng, Jingjing Liu, Zishuan Wei, Fei Liu, Jiali Li, Lingjiao Meng, Yang Sang, Meixiang Sang, Lianmei Zhao, and Baoen Shan

Background: Esophageal squamous cell carcinoma (ESCC) is a serious invasive malignancy with an ambiguous etiology. Evidence indicates that circular RNA (circRNA) is significantly involved in the regulatory processes associated with cancer development. Nevertheless, the specific molecular mechanisms through which circRNA facilitates the progression of ESCC are still largely undefined.

Methods: Here, we identified that the expression of hsa_circ_0007580 (designated circPRKCA) was markedly elevated in ESCC. Fluorescence in situ hybridization (FISH) was conducted to verify the expression, intracellular localization, and potential prognostic value of circPRKCA based on the tissue microarray. Gain- and loss-of-function assays were employed to investigate the effects of circPRKCA both in vitro and in vivo. RNA pull-down and mass spectrometry (MS) were performed to identify the proteins bound to circPRKCA. mRNA sequencing was conducted to screen the downstream target genes of circPRKCA. Furthermore, immunoprecipitation and methylated RNA immunoprecipitation (MeRIP) analysis were used to explore the regulatory mechanisms.

Results: We found that circPRKCA exhibited significant upregulation in ESCC tissues and correlated with unfavorable prognostic outcomes. Biological function experiments further confirmed that circPRKCA enhances the capabilities of migration, invasion, and angiogenesis in ESCC. Mechanistically, circPRKCA engages in interaction with Y-box binding protein 1 (YBX1) within the cytoplasmic milieu, consequently preventing the ubiquitination-mediated degradation of YBX1. Increased concentrations of YBX1 increase the stability of granulocyte–macrophage colony-stimulating factor (CSF2) mRNA in a 5-methylcytosine (m5C)-dependent manner. This process facilitates metastasis in ESCC.

Conclusion: In this research, we identified a correlation between circPRKCA and unfavorable prognoses in patients with ESCC. It is instrumental in the metastatic progression of ESCC via the YBX1/CSF2 signaling pathway. Consequently, targeting circPRKCA may represent a promising therapeutic strategy for ESCC

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© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licen ses/ by-nc-nd/4.0/.

Research Article

ArticleID :JAUSM/2025/11/03/01

Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer

Issue No. 03 (July-Sept)

Authors: Jiannan Chen, Lianfeng Zhao, Wenying Li, Shuai Wang, Jiayi Li, Zhongyuan Lv, Yaoyao Zhao, Junqing Liang, Zhigang Hu, Feiyan Pan, Lingfeng He, Lili Gu and Zhigang Guo

Background: Chimeric antigen receptor T (CAR-T) cell therapy holds promise for cancer treatment, but its efficacy is often hindered by metabolic constraints in the tumor microenvironment. This study investigates the role of glutamine in enhancing CAR-T cell function against ovarian cancer.

Methods: Metabolomic profiling of blood samples from ovarian cancer patients treated with MSLN-CAR-T cells was conducted to identify metabolic changes. In vitro, glutamine pretreatment was applied to CAR-T cells, and their proliferation, CAR expression, tumor lysis, and cytokine production (TNF-α, IFN-γ) were assessed. Mechanistic studies focused on the mTOR-SREBP2 pathway and its effect on HMGCS1 expression, membrane stability and immune synapse formation. In vivo, the antitumor effects and memory phenotype of glutamine-pretreated CAR-T cells were evaluated.

Results: Elevated glutamine levels were observed in the blood of ovarian cancer patients who responded to MSLN-CAR-T cell treatment. Glutamine pretreatment enhanced CAR-T cell proliferation, CAR expression, tumor lysis, and cytokine production. Mechanistically, glutamine activated the mTOR-SREBP2 pathway, upregulating HMGCS1 and promoting membrane stability and immune synapse formation. In vivo, glutamine-pretreated CAR-T cells exhibited superior tumor infiltration, sustained antitumor activity, and preserved memory subsets.

Conclusions: Our findings highlight glutamine-driven metabolic rewiring via the mTOR-SREBP2-HMGCS1 axis as a strategy to augment CAR-T cell efficacy in ovarian cancer.

Trial registration: NCT05372692A

How To Cite this Article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by- nc- nd/4. 0/.

Research Article

ArticleID :JAUSM/2025/11/03/02

Tongue-coating microbiota as a predictive biomarker of washed microbiota transplantation efficacy in pediatric autism: integration with clinical features

Issue No. 03 (July-Sept)

Authors: Hao-Jie Zhong, Zhao-Yu Pan, Yao-Fei Wei, Qian Yu, Lei Wu, Hong Wei and Xing-Xiang He

Background: Alterations in both oral and gut microbiota have been identified in children with autism spectrum disorder (ASD), but the interaction between these microbiota and their potential to predict outcomes of fecal microbiota transplantation (FMT) remain poorly understood.

Methods: This study investigated the structure and function of the tongue-coating microbiota in children with ASD and explored its correlation with ASD symptoms and gut microbiota. Germ-free ASD mice, colonized with healthy gut microbiota, and children with ASD treated with washed microbiota transplantation (WMT) were assessed for changes in autism symptoms and microbiota composition. Predictive models were also developed based on pre-treatment tongue-coating microbiota and clinical features to forecast WMT outcomes.

Results: Significant alterations were detected in the tongue-coating microbiota of children with ASD, with several bacterial species showing associations with ASD symptoms and gut microbiota composition. Following WMT, both mice and children exhibited substantial improvements in autism-related behaviors, alongside marked shifts in their gut and tongue-coating microbiota. A significant decrease in Haemophilus in the tongue-coating microbiota, which positively correlated with ASD severity, was observed. Additionally, a reduction in chemoheterotrophic and fermentation functions in the tongue-coating microbiota was identified. Predictive models utilizing pre-treatment tongue-coating microbiota and clinical data demonstrated comparable accuracy to those based on gut microbiota for forecasting WMT outcomes.

Conclusions: These findings highlight a significant interaction between gut and tongue-coating microbiota in ASD, which may play a pivotal role in treatment outcomes. Predictive models integrating pre-treatment microbiota and clinical features could improve precision treatment strategies for children with ASD undergoing WMT.

How To Cite this Article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Research Article

ArticleID :JAUSM/2025/11/03/03

Enhancing doxorubicin sensitivity in osteosarcoma via iRGD-modified biomimetic nanoparticles targeting MCAM m6A modification

Issue No. 03 (July-Sept)

Authors: Dongjian Song, Qiuliang Liu, Da Zhang, Zechen Yan, Meng Su, Qian Zhang, Hui Zhang, Longyan Shi, Yingzhong Fan and Heying Yang

Background: Doxorubicin (Dox) resistance remains a significant challenge in osteosarcoma (OS) treatment, limiting its therapeutic efficacy and contributing to poor clinical outcomes. This study aims to investigate the use of iRGD modified biomimetic nanoparticles (NPs) for the targeted delivery of METTL3-specific inhibitors, addressing Dox resistance by regulating the m6A modification of MCAM.

Methods: Biomimetic NPs were fabricated by fusing OS cell membranes with lipid NPs, followed by iRGD peptide modification to enhance tumor targeting capability. These NPs were loaded with the METTL3 inhibitor STM2457 and characterized for stability, drug encapsulation efficiency, and cellular uptake by Dox-resistant OS cells. Functional assays were implemented to examine their impact on cell biological functions in vitro. Therapeutic efficacy was further validated utilizing a mouse xenograft model to monitor tumor progression and metastatic behavior.

Results: The iRGD-modified NPs exhibited excellent stability, high drug encapsulation efficiency, and significantly improved cellular uptake in vitro. METTL3 inhibition reduced MCAM m6A modification, leading to decreased proliferation and invasion of Dox-resistant OS cells. In vivo, the combination of Dox and METTL3-loaded NPs significantly inhibited tumor growth and lung metastasis in the mouse model.

Conclusions: iRGD-modified biomimetic NPs offer a promising approach to overcoming Dox resistance in OS by targeting the METTL3-MCAM axis. This strategy may improve therapeutic outcomes and holds potential for clinical application in resistant cancers.

How To Cite this Article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by- nc- nd/4. 0/.

Review Article

ArticleID :JAUSM/2025/11/03/04

Innovative organ-on-a-chip platforms for exploring tumorigenesis and therapy in head and neck cancer

Issue No. 03 (July-Sept)

Authors: Chen Lin, Zilin Zhang, Feili Yang, Shanshan Gu, Jiyang Zuo, Yi Wu, Jing Zhang, Tiantian Zhou, Yuna Zhang, Zaozao Chen, Zhongze Gu and Zhisen Shen

Background: Head and neck cancer (HNC) presents significant research challenges due to the complexity of its tumor microenvironment (TME) and the heterogeneity across different cancer subtypes. Recent advancements in three-dimensional (3D) culture models and organ-on-a-chip (OOC) technology offer new avenues for mimicking the TME and enhancing the study of tumor biology, drug responses, and personalized treatment strategies. This study aims to summarize the current state of these models in HNC research and their potential in bridging the gap between preclinical models and clinical applications. 

Methods: This review synthesizes findings from recent literature on the use of 3D models such as tumor spheroids, organoids, and co-culture systems in HNC research. A focus is placed on their applications in different cancer types, including laryngeal, oral, and nasopharyngeal cancers. Additionally, the integration of OOC technology in studying cancer metastasis, immunotherapy, and radiotherapy is discussed. Relevant studies on the role of AI and robotics in improving model efficiency and scalability are also examined. 

Results: The review identifies key developments in 3D model systems and OOC technologies, highlighting their ability to replicate patient-specific tumor behaviors and predict therapeutic responses. While these models have advanced the understanding of HNC pathophysiology, challenges remain in terms of technical limitations, validation, and physiological relevance. The integration of AI and robotics has shown promise in enhancing the scalability and data analysis capabilities of these models. 

Conclusions: Advancements in 3D and OOC technologies are essential for overcoming the current limitations in HNC research. These models offer valuable insights into tumor biology and therapeutic efficacy, and their integration

How To Cite this Article

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ 

Research Article

ArticleID :JAUSM/2025/11/04/01

Implementation of precision medicine in treating non-communicable diseases: a systematic review

Issue No. 04 (Oct-Dec)

Authors: Shuang Liang, Elizabeth Kennedy, Nyree Gale, Paul Watson, Mahitha Ramanathan, Arya Shinde

Background: Non-communicable diseases (NCDs) are a major global health and economic burden. Precision medicine has merged as a promising approach for treating NCDs by tailoring health interventions to individual profiles. Despite rapid advances, its effective implementation remains slow. This systematic review aimed to examine the implementation landscape for delivering precision medicine interventions, services, or programs for NCDs, focusing on barriers, facilitators, strategies, and outcomes.

Methods: Comprehensive searches were performed in PubMed, Embase, CINAHL, and Web of Science until November 2024. The search strategy comprised of four key concepts, i.e. precision medicine, NCDs, implementation, and public health. Articles published from 2014 onwards were included. Extracted data included study characteristics, populations, precision medicine intervention details, and information related to implementation. Relevant data were coded to implementation science frameworks and taxonomies. These included the updated Consolidated Framework for Implementation Research (CFIR 2.0), Expert Recommendations for Implementing Change (ERIC), and Proctor’s outcomes framework. The QuADs tool was used to assess the risk of bias of included studies.

Results: A total of 10,039 records were identified, with 8,684 abstracts and 463 full texts screened. Of these, 68 studies met the inclusion criteria. While 64 studies reported implementation determinants [i.e. barriers (n = 61) and/ or facilitators (n = 40)], approximately two-thirds proposed or implemented strategies that were primarily based on intuition. Key barriers identified included ‘access to knowledge and information’ (n = 34) and ‘work infrastructure’ (n = 21) within the Inner Setting, and ‘financing’ (n = 20) within the Outer Setting. While financial burdens were clearly attributed to patients and healthcare settings, there was less clarity and strategic direction regarding potential funding sources to support implementation strategies. Implementation Outcomes were reported in 46 instances,

How To Cite this Article

Liang, S., Kennedy, E., Gale, N. et al. Implementation of precision medicine in treating non-communicable diseases: a systematic review. J Transl Med 23, 1174 (2025). https://doi.org/10.1186/s12967-025-07201-y

Research Article

ArticleID :JAUSM/2025/11/04/02

Computerized cognitive training enhances cognitive function in Alzheimer’s disease by downregulating Ruminococcus-TMAO pathway

Issue No. 04 (Oct-Dec)

Authors: Wenbo Zhang, Jiaqi Song, Fuxin Zhong, Wuhan Yu, Zhangjin Qin, Ziying Yang, Jiarui Liu, Xiaoqin Wang, Lihua Chen, Wenqi Lü, Dianxia Xing, Junjin Liu, Chengcheng Huang, Jiani Wu

Background: The microbiota-gut-brain (MGB) axis is implicated in Alzheimer’s disease (AD), but evidence for interventional strategies targeting this axis remains limited. Methods In a 24-week, single-blind, randomized controlled trial, 84 individuals with mild cognitive impairment (MCI) or mild AD received either computerized cognitive training (CCT) or treatment as usual (TAU). Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) was the primary outcome. We also assessed functional connectivity (fNIRS), plasma trimethylamine N-oxide (TMAO) levels, and gut microbiota at baseline and 24 weeks.

Results: Seventy-four participants completed the study. The CCT group showed significant improvement in ADAS cog scores compared to controls (Cohen’s d = 1.57 by week 24). Notably, CCT also induced a distinct reorganization of prefrontal functional connectivity and significantly reduced plasma TMAO levels. Microbiome analysis revealed that CCT mitigated the expansion of Ruminococcus torques group (R.torques), which was observed in the control group. Crucially, R.torques was the only genus significantly correlated with improvements in cognition (ADAS-cog, r = 0.407), neuropsychiatric symptoms (NPI, r = 0.395), TMAO reduction (r = 0.443), and functional connectivity changes (r = 0.449).

Conclusion: A 24-week CCT program improves cognitive function in MCI and mild AD, potentially through downregulating the R.torques-TMAO pathway within the MGB axis. This pathway represents a promising novel target for multi-domain intervention in AD.

How To Cite this Article

Zhang, W., Song, J., Zhong, F. et al. Computerized cognitive training enhances cognitive function in Alzheimer’s disease by downregulating Ruminococcus-TMAO pathway. J Transl Med 23, 1173 (2025). https://doi.org/10.1186/s12967-025-07209-4

Research Article

ArticleID :JAUSM/2025/11/04/03

Immunoglobulin G N-glycosylation predicts long-term risk of ischemic stroke: a nested case-control study

Issue No. 04 (Oct-Dec)

Authors: Shuyu Sun, Jiheng Hao, Chengxu Yu, Hongzhi Liu, Qihua Guan, Yinghao Wang, Jie Wang, Xinyue Wang, Mingzhu Zhang, Xu Zan, Siqi Ge, Hualei Dong, Liyong Zhang, Shaocan Tang

Background: Ischemic stroke (IS) ranks as the leading cause of disability and the second cause of mortality in adults worldwide. This investigation aimed to describe the fingerprint of immunoglobulin G (IgG) N-glycans and feature of circulating inflammatory cytokines that were associated with the progression of IS, as well as to screen potential biomarkers for screening individuals at higher IS risk.

Methods: A prospective cohort, Liaocheng City Stroke Risk Cohort (LCSRC), was launched in December 2014, in which 1,599 healthy participants were enrolled from Liaocheng People’s Hospital (LPH). During nine years of follow-up, 67 participants who were diagnosed with IS were enrolled in the case group. Meanwhile, 201 individuals who did not develop IS were randomly selected as the controls. The hydrophilic interaction chromatography based on ultra-performance liquid chromatography (HILIC-UPLC) was utilized to detect the IgG N-glycans profiles in serum. A prediction model for the occurrence of IS was constructed using a logistic regression.

Results: The levels of GP1, GP2, GP3, GP4, GP6, GP7, GP11, GP13, GP19 and GP24 were considerably higher in the IS group compared with the controls, whereas GP5, GP8, GP14 and GP18 were lower among the IS cases. In addition, compared to the controls, the IS patients had substantially higher levels of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). In terms of four major features of IgG N-glycosylation, a high level of fucosylation, monogalactosylation, and digalactosylation was significantly associated with a decreased risk for IS occurrence. Moreover, the glycosylation-based prediction model was of promising capability to predict IS risk with an area under the curve (AUC) of 0.756 (95%CI: 0.696 to 0.815).

How To Cite this Article

Sun, S., Hao, J., Yu, C. et al. Immunoglobulin G N-glycosylation predicts long-term risk of ischemic stroke: a nested case-control study. J Transl Med 23, 1175 (2025). https://doi.org/10.1186/s12967-025-07236-1

Review Article

ArticleID :JAUSM/2025/11/04/04

Transformative advances in single-cell omics: a comprehensive review of foundation models, multimodal integration and computational ecosystems

Issue No. 04 (Oct-Dec)

Authors: Taylor Yiu, Bin Chen, Haoyu Wang, Genyi Feng, Qiangqiang Fu and Huijing Hu

Recent advances in single-cell multi-omics technologies have revolutionized cellular analysis, enabling comprehensive exploration of cellular heterogeneity, developmental trajectories, and disease mechanisms at unprecedented resolution. Foundation models, originally developed for natural language processing, are now driving transformative approaches to high-dimensional, multimodal single-cell data analysis. Frameworks such as scGPT and scPlantFormer excel in cross-species cell annotation, in silico perturbation modeling, and gene regulatory network inference. Multimodal integration approaches, including pathology-aligned embeddings and tensor-based fusion, harmonize transcriptomic, epigenomic, proteomic, and spatial imaging data to delineate multilayered regulatory networks across biological scales. Federated computational platforms facilitate decentralized data analysis and standardized, reproducible workflows, fostering global collaboration. Challenges persist, including technical variability across platforms, limited model interpretability, and gaps in translating computational insights into clinical applications. Overcoming these hurdles demands standardized benchmarking, multimodal knowledge graphs, and collaborative frameworks that integrate artificial intelligence with human expertise. This review synthesizes recent technological advancements and proposes actionable strategies to bridge single-cell multi-omics innovations with mechanistic biology and precision medicine.

How To Cite this Article

Yiu, T., Chen, B., Wang, H. et al. Transformative advances in single-cell omics: a comprehensive review of foundation models, multimodal integration and computational ecosystems. J Transl Med 23, 1176 (2025). https://doi.org/10.1186/s12967-025-07091-0

Research Article

ArticleID :JAUSM/2025/11/04/05

Mechanism by which CAP regulates the “cold–heat” balance in osteosarcoma model mice: an integrative study of metabolomics, transcriptomics, and network pharmacology

Issue No. 04 (Oct-Dec)

Authors: Ziming Wang, Shun Zhang, Shipeng Li, Guosheng Zhao, Yuan Zhang, Xiaohong Zhang, Mingwei Sun, Yun Lu, Enfeng Song, Cantao Quan, Chuanzhu Lv and Yang Wang

Background: Osteosarcoma (OS) is a prevalent malignant bone cancer in children and adolescents, yet the mechanisms driving its progression and therapeutic resistance remain inadequately understood. Current treatment modalities often overlook the significance of the “cold–heat” imbalance as conceptualized in traditional Chinese medicine (TCM), highlighting a critical gap in integrating TCM principles with modern cancer therapies. 

Objectives: We aimed to investigate the therapeutic effects of capsaicin (CAP) on the “cold–heat” imbalance in OS model mice and elucidate the mechanisms involved by utilizing a multi-omics approach. 

Methods: We employed metabolomics, transcriptomics, and network pharmacology to analyze the impact of CAP on OS progression. Tumor-bearing mice were treated with CAP, and metabolic profiles, tumor volumes, and key molecular targets were assessed. 

Results: Our findings revealed that CAP significantly shifted the metabolic phenotype of OS model mice from a “cold” state to a “heat” state, resulting in a reduced tumor volume and increased metabolic activity. Notably, CAP was shown to target key pathways involving AKT1, STAT3, NF-κB, EGFR and Caspase 3. 

Conclusion: CAP effectively modulated tumor growth and restored the “cold–heat” balance in OS model mice, providing valuable insights into the potential integration of TCM with conventional oncologic therapies. These findings underscore the importance of multifaceted strategies in developing innovative cancer treatments and contribute to the advancement of translational medicine.

How To Cite this Article

Wang, Z., Zhang, S., Li, S. et al. Mechanism by which CAP regulates the “cold–heat” balance in osteosarcoma model mice: an integrative study of metabolomics, transcriptomics, and network pharmacology. J Transl Med 23, 1177 (2025). https://doi.org/10.1186/s12967-025-07238-z