Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.

Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Objective:To investigate the current situation of depressive symptoms, effort-reward imbalance (ERI), and sleep quality among train drivers, explore the interaction mechanism between various factors and depressive symptoms, and provide a certain theoretical basis for reducing the level of depressive symptoms among train drivers.Methods:From January to December 2022, train drivers were selected as the research subjects from the locomotive depot of a certain railway bureau through cluster sampling, with a total of 1392 people. A questionnaire survey was conducted to assess the basic situation, ERI, sleep quality and depressive symptoms of train drivers. Multiple stepwise regression was used to analyze the effects of each dimension of ERI and sleep quality on depressive symptoms, and binary logistic regression was used to analyze the effects of ERI and sleep quality on depressive symptoms.Results:Among 1392 train drivers, 897 (64.4%) were classified as having depressive symptoms. The results of multiple stepwise regression analysis showed that the dimensions of external effort, reward and overcommitment of ERI explained 10.3% of the variation in depressive symptoms ( P<0.01). Sleep quality explained 9.9% of the variation in depressive symptoms ( P< 0.01). The results of binary logistic regression analysis showed that after adjusting for confounding variables such as age, length of service, and educational level, high external effort ( OR=2.22, 95% CI: 1.76-2.79) and high overcommitment ( OR=1.90, 95% CI: 1.50-2.39) and poor sleep quality ( OR=5.82, 95% CI: 4.52-7.49) increased the risk of depressive symptoms for train drivers ( P<0.01), while reward was a protective factor for depressive symptoms ( OR=0.44, 95% CI: 0.35-0.55, P<0.01). In the ERI model, high effort and low reward was the greatest risk factor for depressive symptoms ( OR=4.77, 95% CI: 3.41-6.69, P<0.01). In the interaction between ERI and sleep quality, high ERI and poor sleep quality had the greatest negative impact on depressive symptoms ( OR=15.90, 95% CI: 7.27-34.76, P<0.01) . Conclusion:The influence of ERI on depressive symptoms of train drivers has both direct and indirect effects, and sleep quality plays a partial mediating role in the influence of ERI on depressive symptoms.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.

Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness.Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU)rat model was employed for the study.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:control group(administered 0.5%carboxymethylcellulose by gavage),HLU group(hindlimb unloading),and HLU+treatment group(hindlimb unloading+active compound gavage),with 8 rats in each group.After 28 days of hindlimb unloading,depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test.Hippocampal morphology was examined with H&E staining,and GO and KEGG enrichment analyses were conducted on the targets of active compounds.Results A total of 38 active compounds were screened from Polygonati Rhizoma,among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21.Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values,suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma.In the forced swimming and tail suspension tests,rats in the HLU group showed a significant increase in immobility time compared to the control group,indicating successful establishment of the depression model.However,compared to the HLU group,rats in the HLU plus apigenin group exhibited significantly reduced immobility time.The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons,along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group.In contrast,the treatment group exhibited an increased number of hippocampal neurons,with improved cellular morphology.Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancer-related signaling pathways.Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading,and it has a protective effect on hippocampal tissue.It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.

Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.