Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Viral myocarditis is a myocardial disease resulting from various viral infections.Due to the com-plexity of its pathogenesis,effective prevention and treatment options are currently lacking.Establishing appropriate ex-perimental models is crucial for studying the pathogenic mechanisms,disease progression,early diagnosis,and the devel-opment of new drugs and therapies for viral myocarditis.This article reviews the construction methods,research advance-ments,and applications of common experimental models of viral myocarditis,which range from cell models to small ani-mal models,including mice,hamsters,and rabbits,as well as larger animals such as pigs and non-human primates.Ad-ditionally,we summarize and discuss future research directions,providing a theoretical foundation and technological guid-ance for the prevention and treatment of viral myocarditis in clinical settings.

Viral myocarditis is a myocardial disease resulting from various viral infections.Due to the com-plexity of its pathogenesis,effective prevention and treatment options are currently lacking.Establishing appropriate ex-perimental models is crucial for studying the pathogenic mechanisms,disease progression,early diagnosis,and the devel-opment of new drugs and therapies for viral myocarditis.This article reviews the construction methods,research advance-ments,and applications of common experimental models of viral myocarditis,which range from cell models to small ani-mal models,including mice,hamsters,and rabbits,as well as larger animals such as pigs and non-human primates.Ad-ditionally,we summarize and discuss future research directions,providing a theoretical foundation and technological guid-ance for the prevention and treatment of viral myocarditis in clinical settings.

Objective To explore the value of coronary fat attenuation index(FAI)combined with laboratory indicators in predicting the risk of acute coronary syndrome(ACS)in patients with coronary heart disease(CHD).Methods A retrospective analysis was conducted on 454 patients who were diagnosed with CHD in Guangdong Provincial People's Hospital SCAD group(n=233)and an ACS group(n=221).Univariate and multivariate Logistic regression analyses were performed on the FAI values of the main coronary branches[right coronary artery(RCA),left anterior descending branch(LAD),left circumflex branch(LCX)],laboratory indicators,and clinical data,to identify independent risk factors for ACS in CHD patients.Receiver operating characteristic curves were constructed,and area under the curve(AUC)was calculated to evaluate the predictive performance of the independent risk factors and their combinations.Results LAD-FAI,RCA-FAI,and high-sensitivity C-reactive protein(hs-CRP)were independent influencing factors for ACS in CHD patients.The AUC for the prediction of ACS occurrence in CHD patients based on LAD-FAI,RCA-FAI,and elevated hs-CRP values alone were 0.568,0.703,and 0.749,respectively.When these three factors were analyzed in combination,the AUC was 0.815.Conclusion The combined analysis of LAD-FAI,RCA-FAI,and hs-CRP has good predictive performance for assessing the risk of ACS in CHD patients.

Objective To analyze the status of occupational disease hazards in Shantou City for 2019 to 2022 and propose corresponding management measures. Methods Technical reports on various occupational-disease-specific activities in Shantou City from 2019 to 2022 were collected and the data were comprehensively analyzed. Results Among the 3 066 enterprises surveyed in the 2020 occupational disease hazard investigation in Shantou City, occupational hazards were reported in 2 982 enterprises (accounting for 97.3%), with 2 955 being small and micro enterprises, accounted for 99.1%(2 955/2 982). The exposure rate of occupational hazards was 58.7% (42 894/73 054) among workers in the surveyed enterprises, with dust and noise exposure rates of 59.7% and 77.8%, respectively. The reported rate of occupational disease hazard projects by employers, regular detection rate of workplace occupational hazards, detection rate of occupational medical examination among workers, and occupational health training rate of key responsible personnel and occupational health management staff were 8.4%, 1.4%, 2.4%, and 4.3%, respectively. The results of occupational hazards monitoring of workplace in key industries from 2019 to 2022 showed that noise had the highest rate of exceeding national standards workplace, followed by silica dust, accounting for 34.2% and 13.8%, with the on-site exceedance rate of 32.2% and 10.0%, respectively. From 2019 to 2022, 31 suspected occupational disease cases were identified in key occupational disease monitoring, including 27 suspected cases of occupational pneumoconiosis and four suspected cases of occupational noise-induced deafness. Conclusion The workers in Shantou City have a high exposure rate to occupational hazards, and the occupational health management level of employers remains low, with noise and silica dust being the most severe occupational hazards. It is essential to improve technical support and service system development for occupational disease prevention and treatment, strengthen supervision and management in key industries and positions, explore occupational health assistance mechanisms for small and micro enterprises, and enforce employers' responsibility in occupational disease prevention to protect workers' occupational health and safety.

Objective To investigate the computed tomography (CT) features of solitary nodular invasive mucinous lung adenocarcinoma (IMA) in stage IA and establish its prediction model. Methods We included 53 lesions of 53 patients with stage-IA IMA and 141 control lesions of 141 patients with invasive non-mucinous lung adenocarcinoma (NIMA) that were confirmed by surgical pathology in our hospital from January 2017 to December 2019. Univariable analysis was used to compare the demographics and CT signs of the two groups. Multivariable logistic regression analysis was performed to determine the main factors influencing solitary nodular IMA. A risk score prediction model was constructed based on the regression coefficients of the main influencing factors. A receiver operating characteristic (ROC) curve was used to assess the performance of the model. Results The univariable analysis showed significant differences between the two groups in age, largest nodule diameter, tumor-lung interface, lobulation, spiculation, air-bronchogram or vacuole sign, vessel abnormalities (P < 0.05). The spiculation sign was different between the two groups, which was longer and softer in the IMA group while shorter and harder in the NIMA group. There was no significant difference in sex, nodule shape, or pleural retraction (P > 0.05), but irregular shapes were slightly more frequent in the IMA group. The multivariable logistic regression analysis showed that obscure tumor-lung interface (odds ratio (OR = 20.930, P < 0.05), air-bronchogram or vacuole sign (OR = 7.126, P < 0.05), spiculation sign (OR = 4.207, P < 0.05), and vessel abnormalities (OR = 0.147, P < 0.05) were the main influencing factors. The prediction model based on those factors’ regression coefficients had an area under the ROC curve of 0.829 (P < 0.05). Conclusion Compared with those with NIMA, patients with solitary nodular IMA in stage IA were older and more likely to have the CT features of obscure tumor-lung interface, air-bronchogram or vacuole sign, and longer and softer spiculation. Based on the regression coefficients of tumor-lung interface, air-bronchogram or vacuole sign, spiculation, and vessel abnormalities, the risk score prediction model showed good predictive performance for solitary nodular IMA.

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development