Objective: To understand the allocation and use of safety seats for preschool children and explore its related factors, so as to provide a scientific reference for promoting the usage of safety seats. Methods: A stratified random cluster sampling method was used to select 3 143 parents of preschool children aged 3 to 6 from six kindergartens in Shunyi District, Beijing from January 3 to 10, 2022. An online questionnaire survey was conducted to collect and evaluate the equipment and use of child safety seats in different characteristics of preschool children, as well as their scores of health beliefs. Multiple factor Logistic regression analysis was used to investigated the related factors of safety seat configuration and use. Results: The equipping rate and usage rate of safety seats for preschool children were 66.56% and 58.45%, respectively. The proportion of equipped and used safety seats for preschool children in core families (69.52%, 62.23%) were higher than that in large families (64.35%, 55.62%), only child families ( 72.39 %, 64.87%) were higher than non only child families (61.49%, 52.86%), and urban families (71.63%, 63.04%) were higher than rural families (52.31%, 45.51%) ( χ 2=9.23, 13.86; 41.72, 46.44; 101.96 ,76.97,all P <0.05) . As the educational level of parents ( χ 2 trend =154.23,98.76) and annual income of the family ( χ 2 trend =155.78,127.69) rised, the reporting rates of the equipped and used child safety seats in the family also increased(all P <0.05 ). There were statistically significant differences in the scores of different dimensions of health beliefs for the provision ( t =-20.22-18.16) and use ( t =24.32-24.17) of safety seats for preschool children(all P <0.05). After adjusting for child sex, child age, family annual income, parental education level, family type, whether the child was an only child, and place of residence，multivariate Logistic regression analysis showed that preschool children with higher perceived susceptibility score( OR =1.11, 1.08), higher self efficacy score( OR =1.23, 1.33), and higher suggestive factors score( OR =1.08, 1.12) were more likely to have and use safety seats in their families, while preschool children with higher perceived impairments score( OR =0.82, 0.80) were less likely to have and use safety seats in their families (all P <0.05). Conclusions The installation rate of child safety seats needs to be improved, and there is also a certain gap in their use after installation. Parents of preschool children should improve susceptibility and self efficacy to safety seat equipment and use, and perceptual barriers should be reduced.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Objective : To clarify the intrinsic link between a high-fat diet(HFD) and the pathological progression and prognosis of spinal cord injury(SCI) while preliminarily exploring the potential underlying mechanisms. Methods: SCI models were established in mice that were fed either a regular diet(RD) or HFD, with injury inflicted specifically on the T9-T12segments. Hematoxylin-Eosin(HE) staining, Masson staining, and Nissl staining were used to observe the local histological changes in SCI tissues. The basso, beattie, and bresnahan(BBB) score and footprint analysis were used to evaluate and compare hindlimb functional recovery after SCI in both RD and HFD mice.In vitroexperiments were conducted to identify key fatty acids in the HFD that exacerbate neuronal damage, whilein vivoexperiments assessed the effects of 2-bromopalmitate(2-BP), a palmitic acid inhibitor, on HFD-fed mice with SCI. Results : Compared to RD-fed mice, HFD-fed mice exhibited significantly larger lesion areas, more severe neuronal damage, and poorer hindlimb functional recovery after SCI. Palmitic acid was identified as the key fatty acid aggravating neuronal damage. Further more, inhibition of palmitoylation, mediated by palmitic acid, enhanced neuronal survival, promoted tissue repair, and improved hindlimb functional recovery in HFD-fed mice post-SCI. Conclusion HFD exacerbates pathological damage following SCI in mice through palmitic acid, impairing recovery. Palmitic acid-mediated palmitoylation is likely the main mechanism underlying this effect.

Given the constraints imposed by the “14-day ethics” rule, numerous critical events occurring between the second and fourth weeks of embryonic development remain poorly understood. This underscores the necessity of a detailed understanding of embryonic development and regulation during this period, which is indispensable for preventing pregnancy failure, treating birth defects, and promoting human reproductive health.Rodents, characterized by their small size, rapid growth, strong reproductive capacity, and fully sequenced genomes, are widely used as crucial models for studying embryonic development. However, the substantial physiological differences between rodents and primates due to evolutionary divergence make it challenging to directly apply findings from rodent studies to primates. Besides, primates, our closest relatives in terms of evolutionary phylogenetics and physiological characteristics, share more than 95% genetic homology with humans, underscoring the urgent need for primate research. Furthermore, early-stage embryonic cells are both scarce and diverse, making their regulatory mechanisms and developmental pathways typically elucidated through single-cell sequencing. For instance, three significant articles published in Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics. Unfortunately, relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information. Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics, epigenomics, proteomics, and metabolomics analyses. These emerging technologies play a significant role in life sciences, enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective, including zygotic genome activation (ZGA), X-chromosome dosage compensation, origins of primordial germ cells (PGCs), mechanisms of cell fate determination, and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies, from single-cell histology to multi-omics, beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology. It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development. Finally, it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities, directions, and challenges in this rapidly evolving field. In doing so, it emphasizes the critical role of interdisciplinary approaches, combining insights from genetics, molecular biology, and bioinformatics to foster innovations in reproductive medicine and developmental biology. The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes, potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective To investigate the protective mechanism of oxidative stress injury of SD rats NR8383 by budesonide.Methods Rat alveolar macrophages NR8383 were divided into 5 groups:blank group was given serum-free K12 medium without any treatment;lipopolysaccharide(LPS)group was given 2.29 μg·mL-1 LPS standard solution;budesonide group(budesonide),c-Jun inhibitor group(AS601245)and budesonide+c-Jun inhibitor group(budesonide+AS601245)were given budesonide 28.0 μL,c-Jun inhibitor AS601245 2.50 μg,and budesonide 28.0 μL+c-Jun inhibitor AS601245 2.50 μg based on the LPS group,respectively.Cells in 5 groups were incubated in serum-free K12 medium at constant temperature for 24 h.The apoptosis rate at 24 h was examined by cell counting kit-8(CCK-8)assay;c-Jun mRNA expression was detected by real-time quantitative polymerase chain reaction(q-PCR);oxidative stress damage factor reactive oxygen species(ROS),8-hydroxy-2-deoxyguanosine(8-OHdG),glutathione peroxidase(GSH-Px),thioredoxin reductase-1(TRX-1)expression were detected by enzyme-linked immunosorbent assay(ELISA);c-Jun signaling pathway protein expression in each group by Western blot.Results Compared with LPS group(29.88±5.98)％,24 h apoptosis rate was significantly decreased in budesonide group,c-Jun inhibitor group,budesonide+c-Jun inhibitor group and blank group[(20.15±6.66)％,(15.39±3.54)％,(12.11±2.55)％and(8.52±1.27)％,respectively],the differences were statistically significant(all P＜0.05).The ROS in budesonide group,c-Jun inhibitor group,budesonide+c-Jun inhibitor group,LPS group and blank group were(3.16±0.19),(4.15±0.33),(2.21±0.21),(6.52±0.36)and(1.06±0.23)U·g-1;8-OHdG were(10.55±1.23),(11.14±1.06),(9.55±1.00),(15.66±1.99)and(8.27±1.13)ng·mL-1;GSH-PX were(188.52±12.33),(200.52±27.97),(144.52±20.55),(335.14±30.10)and(126.55±12.52)U·mL-1;TRX-1 were(40.11±6.66),(50.55±10.07),(60.25±10.55),(115.36±20.03)and(16.55±2.33)ng·mL-1;the relative c-Jun mRNA expressions were 0.56±0.03,0.44±0.11,0.25±0.04,0.89±0.12 and 0.08±0.01;c-Jun/GAPDH protein relative expression were 3.15±0.22,2.36±0.14,1.55±0.13,4.02±0.22 and 0.88±0.12.Compared with the LPS group,the differences of indicators in the budesonide group,c-Jun inhibitor group and budesonide+c-Jun inhibitor group possessed statistical significance(all P＜0.05).Conclusion Budesonide significantly increased the survival rate of NR8383 cells and significantly decreased the concentrations of oxidative damage representative factors ROS,GSH-Px,8-OHdG and TRX-1,its oxidative damage protection mechanism may be related to the regulation of c-Jun protein.