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.

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.

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.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective:To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard.Methods:From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation.Results:A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant ( M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items ( rs=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion:GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

Objective:To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard.Methods:From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation.Results:A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant ( M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items ( rs=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion:GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

The theory of "liver opens at the eyes" was first seen in Yellow Emperor's Internal Canon of Medicine， which is the ancient people's summary of the connection between the liver and the eyes. The theory of "liver opens at the eyes" suggests the characteristic of "co-damage and co-recover of liver and eyes". It has been found in clinical practice that liver diseases and eye diseases often occur together， and "liver and eyes co-recover" is an ideal choice. The key to achieving "liver and eyes co-recover" is to analyze its pharmacological material basis and mechanism. With the development of modern medicine， more and more evidence indicates that the liver and eyes have complex and close relationships in physiological and pathological aspects. In a pathological state， there is a phenomenon of "liver and eyes co-damage"， and after the intervention of traditional Chinese medicine， "liver and eyes co-recover" occurs. "Liver and eyes co-damage and co-recover" can be explained through the "co-material basis and co-action mechanism". On this basis， the research group tentatively proposed that the liver and eyes had "four common characteristics" （4CCs）， namely "co-damage， co-recover， co-material basis， and co-action mechanism" from the theoretical connotation of traditional Chinese medicine， clinical practice， and molecular biology. Additionally， the group also took the intervention of Prunella vulgaris， traditional Chinese medicine， for removing liver fire and improving eyesight on immune liver injury （ILI） and allergic conjunctivitis （AC） as examples to analyze 4CCs. This project aims to deeply analyze the scientific connotation of the theory of "liver opens at the eyes"， reveal the common characteristics and biological essence of liver and eyes， explore a new research paradigm of "liver and eyes co-recover"， and provide a reference for the study of common problems of multi-organ associated diseases.