1.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
2.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
3.USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination
Sha HU ; Zhouxiang WANG ; Kun ZHU ; Hongjie SHI ; Fang QIN ; Tuo ZHANG ; Song TIAN ; Yanxiao JI ; Jianqing ZHANG ; Juanjuan QIN ; Zhigang SHE ; Xiaojing ZHANG ; Peng ZHANG ; Hongliang LI
Clinical and Molecular Hepatology 2025;31(1):147-165
Background/Aims:
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.
Methods:
USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes.
Results:
USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5.
Conclusions
USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.
4.LIM and calponin homology domains 1 may function as promising biological markers to aid in the prognostic prediction of oral squamous cell carcinoma.
Li XU ; Wen SHI ; Yuehua LI ; Yajun SHEN ; Shang XIE ; Xiaofeng SHAN ; Zhigang CAI
Journal of Peking University(Health Sciences) 2025;57(1):19-25
OBJECTIVE:
To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications.
METHODS:
By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes.
RESULTS:
The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway.
CONCLUSION
LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans
;
Mouth Neoplasms/metabolism*
;
Prognosis
;
Carcinoma, Squamous Cell/metabolism*
;
Biomarkers, Tumor/metabolism*
;
LIM Domain Proteins/metabolism*
;
Cell Line, Tumor
;
Cell Proliferation
;
Male
;
Female
5.Graph Neural Networks and Multimodal DTI Features for Schizophrenia Classification: Insights from Brain Network Analysis and Gene Expression.
Jingjing GAO ; Heping TANG ; Zhengning WANG ; Yanling LI ; Na LUO ; Ming SONG ; Sangma XIE ; Weiyang SHI ; Hao YAN ; Lin LU ; Jun YAN ; Peng LI ; Yuqing SONG ; Jun CHEN ; Yunchun CHEN ; Huaning WANG ; Wenming LIU ; Zhigang LI ; Hua GUO ; Ping WAN ; Luxian LV ; Yongfeng YANG ; Huiling WANG ; Hongxing ZHANG ; Huawang WU ; Yuping NING ; Dai ZHANG ; Tianzi JIANG
Neuroscience Bulletin 2025;41(6):933-950
Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans
;
Schizophrenia/pathology*
;
Diffusion Tensor Imaging/methods*
;
Male
;
Female
;
Adult
;
Brain/metabolism*
;
Young Adult
;
Middle Aged
;
White Matter/pathology*
;
Gene Expression
;
Nerve Net/diagnostic imaging*
;
Graph Neural Networks
6.Status and knowledge demand of health emergency literacy among college students in Shaanxi Province
ZHANG Xuefeng, ZHANG Zhigang, GUO Chen, PAN Wenbo, LI Jinting, SHI Mengrui, YANG Zhipei
Chinese Journal of School Health 2024;45(9):1280-1284
Objective:
To understand the status and related knowledge requirements of health emergency literacy among college students in Shaanxi Province, so as to provide the basis for improving college students health emergency literacy.
Methods:
A total of 2 723 students from 18 colleges and universities in Shaanxi Province were selected by multi stage random sampling and simple random sampling methods in November 2023, and the survey of health literacy in emergency and knowledge requirements of health emergency literacy was conducted. Statistical analysis was carried out by using χ 2 test, Wilcoxon rank sum test, Kruskal-Wallis H test and Logistic regression analysis.
Results:
About 28.98% of the surveyed college students had a high level of health emergency literacy, which varied by students whether being only one child, whether having left behind experience, with different personality types, whether being student cadres, and with different frequencies of community or social activities ( χ 2=9.15, 7.90, 32.73, 16.29 , 120.25, P <0.05). The equivalence scores of the four dimensions of health emergency literacy from high to low were poisoning and nuclear and radiation (0.84), medical rescue (0.83), infectious disease (0.82), and basic knowledge and behavior ( 0.77 ). Logistic regression analysis found that college students with left-behind experience were negatively correlated with health emergency literacy and its four dimensions ( OR =0.74, 0.72, 0.80, 0.80, 0.83), while personality type (rational type), community or social activity frequency were positively correlated with the cognitive levels of health emergency literacy and its four dimensions among college students ( OR =1.57, 1.50, 1.33, 1.27, 1.38)( P <0.05). There was a higher level of basic knowledge and behavioral cognition among only child college students ( OR =3.73), and female students had a higher level of health emergency literacy, as well as awareness of infectious disease outbreaks and medical rescue ( OR =1.21, 1.28, 1.21)( P <0.05). The radar map showed that the level of health emergency literacy was positive development radar map. About 67.68 % of the students had a high willingness to acquire health emergency literacy knowledge, and the demand for basic health emergency knowledge and behavioral knowledge was the highest (52.37%).
Conclusions
College students have insufficient health emergency literacy, but they have the highest demand for health emergency. Publicity and education should be strengthened for students with left behind experience, irrational type, and low frequency of community or social activities.
7.Expressions and clinical significance of UBE2I and FCGR1A in AIDS complicated with active pulmonary tuberculosis
Min WANG ; Wenqin YANG ; Mengrui SHI ; Rongqiang ZHANG ; Xiaoli WANG ; Zhigang ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):782-788
Objective To explore the effect of UBE2I and FCGR1A gene expressions on the incidence of acquired immune deficiency syndrome(AIDS)combined with active pulmonary tuberculosis(APTB),so as to provide basis for disease monitoring.Methods A total of 98 AIDS patients combined with APTB and 84 AIDS patients combined with latent tuberculosis infection(LTBI)were selected from the validated whole genome transcriptome dataset(GSE37250).The top 30 differentially expressed genes(DEGs)in the two groups of patients were screened.We established the PPI interaction network,transcription factor-differentially expressed gene(TF-DEG),DEG-miRNA,and environmental chemical regulation network of the top 30 DEGs.Receiver operating characteristic(ROC)curves of 11 key DEGs were plotted and Logistic regression analysis was performed.Results There were 6 054 DEGs in the two groups of patients,and UBE2I was an important core node of the PPI interaction network.FCGR1A had the best predictive and indicative ability for AIDS combined with APTB.Univariate Logistic regression showed that high expressions of UBE2I and FCGR1A were risk factors for AIDS combined with APTB(P<0.05).The regulatory network showed that VEGFB was a key gene in the TF-DEG network,participating in regulation with transcription factors such as SEPT9 and SMAD5.It targeted miRNAs such as hsa-mir-17-5p and hsa-mir-20a-5p,and was affected by environmental chemicals such as valproic acid and copper sulfate.Conclusion VEGFB plays an important role in the pathogenesis of AIDS combined with APTB.The abnormally high expressions of UBE2I and FCGR1A are associated with the disease progression of AIDS combined with APTB.The disease condition can be monitored by detecting the expression level of UBE2I and FCGR1A.
8.Investigation and Influencing Factors of Medication Literacy for Urban Elderly Patients with Chronic Diseases in Anhui Province
Huiting LI ; Tianlu SHI ; Yan WU ; Mingfen WU ; Fangfang LIAO ; Ling JIANG ; Zhigang ZHAO
Herald of Medicine 2024;43(12):1944-1951
Objective To explore the current status of medication literacy among urban elderly patients with chronic diseases in Anhui Province,aiming to reveal the factors influencing their medication literacy,and to propose targeted measures for improvement.Methods This research involved 381 participants aged 60 and above.It was conducted in Anhui province between December,2022 and January,2023,with data collected through face-to-face interviews by pharmacists.Single-factor analysis and ordinal multi-class logistic regression analysis were conducted to determine factors affecting medication literacy.Results Medication literacy cognition and medication literacy behavior were rated as good among urban older adults in Anhui province of the 294 valid questionnaires.Those who did not understood package insert exhibited significantly lower medication literacy behavior than those who fully understood[estimate=-1.224,95%CI=(-2.130,-0.317),P<0.01].Elderly patients with chronic diseases faced issues such as an inability to read or understand drug instructions in the investigation.90.48%of elderly patients with chronic diseases never heard or seldom heard of medication guidance services.Conclusion Medication literacy among urban elderly patients with chronic diseases is generally good in Anhui province.The ability to understood drug instructions significantly influenced the medication literacy of urban elderly patients with chronic diseases.Modifying the drug instructions to meet the reading needs of the elderly patients with chronic diseases and developing pharmaceutical care could effectively enhance rational drug use among this demographic.
9.Hospital Acquired Infections and Non-Hospital Acquired Infections in the Department of Critical Care Medicine
Medical Journal of Peking Union Medical College Hospital 2024;15(3):489-497
Patients with infections in the department of critical care medicine have complex sources and diverse sites of infection, which may be associated with multiple pathogenic bacteria and have a high rate of drug resistance, posing a significant challenge to clinical diagnosis and treatment. Infections in the department of critical care medicine can be divided into two types: hospital acquired infections and non-hospital acquired infections, with significant differences in clinical characteristics between the two. This article discusses the relevant concepts, risk factors, pathogenesis, and common characteristics of severe infections such as bloodstream infections, pulmonary infections, intra-abdominal infections, and intracranial infections, as well as diagnostic and treatment plans and prevention and control strategies from the perspectives of hospital acquired and non-hospital acquired infections, aiming to provide valuable guidance for the clinical management of critically ill patients.
10.Intravascular ultrasound assisted endovascular therapy for renal artery stenosis
Guifang TAN ; Zepeng SHI ; Zhigang LIU ; Shen LI ; Chunyu YU ; Meng ZHANG ; Yi ZHANG ; Rong XING ; Chunmei ZHANG ; Yong QIAN
Chinese Journal of Interventional Imaging and Therapy 2024;21(11):654-658
Objective To observe the value of intravascular ultrasound(IVUS)for assisting endovascular therapy for renal artery stenosis(RAS).Methods Thirty patients with RAS who underwent endovascular therapy were retrospectively analyzed.Parameters of renal artery and plaques in RAS segment measured with CT angiography(CTA)and IVUS before treatment were compared.Bland-Altman diagram was performed to evaluate the consistency of lumen cross-sectional stenosis rate and plaque eccentricity index between CTA and IVUS.The stent parameters measured with IVUS were recorded immediately after implantation of balloon-expandable covered stents.Results Before treatment,the minimum lumen diameter,lumen cross-sectional stenosis rate and stenotic segment length of IVUS were all larger,while maximum lumen diameter and lumen eccentricity index of IVUS were both smaller than those of CTA(all P<0.05).No significant difference of plaque eccentricity index,plaque type nor stenosis distal remodeling was found between CTA and IVUS(all P>0.05).The average difference between IVUS and CTA for evaluating lumen cross-sectional stenosis rate and plaque eccentricity index was-0.020(-0.096,0.050)and-0.020(-0.130,0.091),respectively.The consistency of IVUS and CTA for evaluating plaque eccentricity index was better than that of lumen cross-sectional stenosis rate.The stent symmetry,stent eccentricity index,stent expansion coefficient and stenosis coverage rate immediately after implantation measured with IVUS was(82.69±14.61)%,(1.54±9.16)%,(99.81±10.70)%and 100%,respectively.Among 30 cases,2 cases(2/30,6.67%)underwent postdilation since poor stent apposition.Conclusion IVUS could assist evaluating lumen and plaque parameters of stenotic renal arteries,guiding stent release and real-timely monitoring the effect of endovascular therapy.


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