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.

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*

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

In May 2019, the International Diabetic Foot Working Group (IWGDF) updated and issued guidelines for the prevention and management of diabetic foot disease. This guide puts forward some suggestions for the diagnosis, treatment and effective prevention of diabetic foot: the prevention of diabetic foot should start with high-risk foot, early screening and treatment of diabetic foot infection, foot ulcer and peripheral vascular disease and early comprehensive treatment. Effective prevention and early treatment can reduce the incidence of cardiovascular and cerebrovascular events in patients with diabetes, reduce the amputation rate and mortality, and improve the prognosis and quality of life of patients.

Objective To explore the fasting blood glucose (FBG) variation trends and the prevalence of impaired fasting blood glucose(IFG)among medical staff in Beijing, 2009-2015.Methods A prospective cohort study, using seven years of follow-up data, was conducted in a large-scale tertiary hospital in Beijing.A total of 1 284 medical staff aged 35 to 60 years were recruited.We divided them into 4 groups according to age and occupational categories,and the level of FBG was tested at the same time each year. Results The number of medical staff who completed all 7 annual FBG tests was 403. There was a stepwise increase in the levels of FBG (4.92 mmol/L, 5.26 mmol/L, and 5.60 mmol/L in the years 2009, 2012,and 2015,respectively;F=100.643,P<0.001).An increasing trend in the prevalence of IFG was also evident (3.7%, 7.7%, and 13.4% in the years 2009, 2012, and 2015, respectively; χ2=39.099, P<0.001). Compared with baseline levels(in 2009),the average levels of FBG and the prevalence of IFG in men and women, as well as in all occupational classes (doctors, nurses, technicians, and other medical employees), were significantly elevated by the year 2015 (all P<0.05). The levels of FBG in male medical staff were higher than that in female medical staff,in both 2009 and 2015(both P<0.001).Conclusion The trend of increasing FBG levels and IFG cases in medical staff,especially in men,has been a problem for hospitals. Health policy action is urgently needed to deflate the IFG bubbles.

Objective To explore the correlation between homocysteine(Hcy),lipids amd type 2 diabetes mellitus (T2DM). Methods The laboratory test results of 533 cases of patients with T2DM(T2DM group)and 362 cases of healthy individuals (healthy control group)were retrospectively analyzed.Results The serum levels of Hcy and rates of abnormal serum cholesterol (TC),triacylglycerol(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)levels in the T2DM group were higher than those in the healthy control group,had statistically significant differences(P <0.05).Conclusion The high serum level of Hcy and abnormal lipid metabolism are correlated with T2DM,which might be risk factors of diabetes mel-litus and cardiovascular disease.

Objective　To investigate the development of the guinea pig's eye during the stage of embryo.Method　The guncotton grafts of the guinea pig's skull was observed on the 19th ,24th,28th,35th,40th,43th and the 45th day of embryo.Results　The optic vesicle and lens plate developed on the 19th day in embryo.The optic cup and lens fovea could be found on the 24th day.The eye of embryo of the guinea pig had formed on the 28th day.Conclusion　The results should be used for progressive study of the development of the eyes of embryo.