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.

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

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*

With the deepening reform of ideological and political education, Medical Parasitology teaching needs to update the teaching concept, change the teaching ideas, as well as keep trying to combine ideological and political education with the curriculum content closely. In addition to teaching students’ basic knowledge and practical skills, teachers are needed to cultivate their moral literacy and political awareness through course teaching, so as to provide the basis for students’ subsequent adaptations to social environments and jobs. Currently, the study of ideological and political education in Medical Parasitology teaching is still in the exploratory stage. Therefore, colleges and universities need to carry out effective construction of ideological and political education in Medical Parasitology teaching, in order to achieve good teaching outcomes and provide insights into ideological and political education in teaching.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

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.

OBJECTIVE To explore the influence of reusing and recycling times on the quality of ethanol recovered from ethanol deposition solution of aqueous extract of Lonicerae Japonicae Flos. METHODS The ethanol in five consecutive batches of Lonicerae Japonicae Flos water extract ethanol deposition was recovered by vacuum distillation. The impurities in five batches of recovered ethanol and the recovered ethanol when partial coking caused by temperature runaway were qualitatively analyzed by headspace solid phase micro extraction combined with gas chromatography-mass spectrometry(HS-SPME/GC-MS), and the ultraviolet absorbance of each batch of recovered ethanol was also analyzed. RESULTS Styrene was the only impurity in the first and second batch of recovered ethanol; there were five impurities in the third and fourth batch of recovered ethanol; the number of impurities in the fifth batch of recovered ethanol increases to 17. When partial coking was occurred, the exogenous impurities in the recovered ethanol increased dramatically to forty-one, and there were harmful substances such as ninhydrin and naphthalene. The ultraviolet absorbance of the third to fifth batch of recovered ethanol exceed the upper limit stipulated in the second part of Chinese Pharmacopoeia, 2020 Edition. While the ultraviolet absorbance of the recovered ethanol when partial coking takes place exceeds the standard of the pharmacopoeia greatly. CONCLUSION The recovered ethanol should be treated after being reused two times, so that its ultraviolet absorbance level and impurity type are equivalent to that of fresh ethanol before it can be used again. The method provides reference for the quality control and compliance use of recovered ethanol.

【Objective】 To evaluate the safety and efficacy of balloon-expandable vertebral body stenting （VBS） in treating elderly patients with osteoporotic vertebral compression fractures. 【Methods】 Thirty-eight elderly patients with osteoporotic vertebral compression fractures were randomly divided into two groups according to the parity of their hospital admission numbers to receive VBS and traditional percutaneous kyphoplasty （PKP）， respectively. The two groups were compared regarding changes in the intensity of pain， functional score， imaging parameters related to vertebral compression， and sagittal Cobb angle as well as the incidence of bone cement leakage after treatment， to evaluate the safety and efficacy of VBS. 【Results】 All the patients underwent the operations smoothly， which were performed with the bilateral percutaneous puncture technique under local anesthesia by the same surgeon， and were followed up for more than half a year. Both VBS group and PKP group showed significant improvement in the visual analogue scale score， the Oswestry disability index， the height of the fractured vertebral body， and the Cobb angle at 3 days， 1 month， 3 months and 6 months after treatment （all P<0.05）. There were significant differences in those indicators between the two groups （all P<0.05）. 【Conclusion】 VBS is an effective treatment approach for elderly patients with osteoporotic vertebral compression fractures. It can effectively recover fractured vertebral body height， relieve patients’ pain， and have fewer complications such as bone cement leakage.