Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

Humans ; Adolescent ; Fractures, Avulsion ; Fractures, Bone ; Fracture Fixation, Internal ; Ischium/surgery*

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Abstract: To explore the mechanism of the intestinal microecology regulation by polysaccharide prebiotics, ELISA, histopathologic analysis, immunohistochemical analysis, 16S rRNA high-throughput sequencing, and gas chromatography-mass spectrometry were applied to investigate the effects of fermented polysaccharides on changes in the intestinal microbiota and short-chain fatty acids (SCFAs) in mice with dextran sulfate sodium (DSS)-induced colitis model and their relationship with the level of intestinal inflammation and barrier protein expression. It was found that fermented Lycium barbarum polysaccharides (FLBP) significantly reduced intestinal inflammation level, improved colonic tissue structure, up-regulated the expression of tight junction proteins Claudin-1 and ZO-1, and significantly increased the content of intestinal SCFAs in mice. Gut bacteria analyses showed that FLBP enriched intestinal Dubosiella and Akkermansia in mice and decreased the abundance of Turicibacter, Faecalibaculum, and Escherichia-Shigella. Results showed that remodeled Dubosiella activated by FLBP played a dominant role in ameliorating colitis by significantly increasing SCFAs content, improving intestinal barrier and reducing intestinal inflammation. The study aimed to provide a safer and better option for the amelioration of colitis and to provide a theoretical basis for the development of functional foods with FLBP.

Objective To investigate the effect of antinuclear antibodies(ANAs)on hormone response in patients with autoimmune hepatitis(AIH)-primary biliary cholangitis(PBC)overlap syndrome(AIH-PBC OS)and AIH-only within half a year.Methods A retrospective analysis of 77 patients with autoimmune liver disease(AILD)admitted to First Clinical Medical College of Lanzhou University from January 2018 to December 2021,all of whom were confirmed by liver biopsy and receiving glucocorticoid treatment.Among them,46 patients were in AIH-PBC OS group and 31 were in AIH-only group.The general clinical characteristics,liver puncture-related indexes,autoantibodies and immunoglobulin indexes of patients in each group at the time of diagnosis were collected and compared,and the biochemical and immunoglobulin indexes of patients at the time of hormone use and at the time of review within 6 months were also collected,and the hormone response within 6 months was evaluated according to the levels of glutamic transaminase(AST),glutamic alanine transaminase(ALT)and immunoglobulin G(IgG),and the effect of ANAs on hormone response outcomes in both groups over a six-month period was analyzed.Multifactorial ordered logistic analysis was performed to evaluate the effect of ANAs on hormone response between two groups.Results There was no statistically significant difference in the percentage of AIH-PBC OS and AIH-only patients among both ANAs-positive and-negative AILD patients(55.6%vs.44.4%and 65.6%vs.34.4%,P>0.05).Among 46 patients with AIH-PBC OS,there were 25 in ANAs-positive group and 21 in ANAs-negative group.The rate of complete hormone response within 6 months was lower than that of ANAs-negative group(44.0%vs.76.2%),while the rate of hormone non-response was higher than that of ANAs-negative group(20.0%vs.0),and the difference was statistically significant(P<0.05).There were 20 cases of ANAs-positive and 11 cases of ANAs-negative in the 31 AIH-only patients.There was no statistically significant difference in the results of hormone response within 6 months between the two groups(P>0.05).Multifactorial ordered logistic analysis showed that AIH-PBC OS patients were more likely to have a higher likelihood of 6-month hormone non-response rate in ANAs-positive patients,and the difference was statistically different(P<0.05).And there was no significant effect of ANAs type on hormone response outcome in AIH-only patients(P>0.05).Conclusion AIH-PBC OS ANAs-positive patients have a poor hormone response within half a year.In AIH-only patients,ANAs have no significant effect on hormone response results.

Objective: To examine the causal relationships between obesity, peripheral blood lipid indicators and non-small cell lung cancer (NSCLC) using Mendelian randomization (MR) method, so as to provide the basis for developing NSCLC prevention and control strategies. Methods: Genetic variation data of three obesity evaluation indicators, including body mass index (BMI), body fat ratio (BFR) and waist-to-hip ratio (WHR), and seven peripheral blood lipid indicators, including triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein a [LP (a)] were collected through genome-wide association studies (GWAS) and related public databases. Potential causal relationships between obesity, peripheral blood lipid indicators and NSCLC were analyzed using inverse-variance weighted (IVW) method and multivariable MR analysis upon a random effect model. Heterogeneity and horizontal pleiotropy of instrumental variables were evaluated using Cochran's Q test and MR-Egger regression. Results: There was statistically association between BMI with NSCLC (OR=1.256, 95%CI: 1.087-1.451); there were no statistically associations between BFR, WHR, seven peripheral blood lipid indicators and NSCLC (all P>0.005). There was heterogeneity in the association between BMI, BFR, WHR, TG, HDL-C and NSCLC (all P<0.05); no horizontal pleiotropy of instrumental variables was found (all P>0.05). There was no statistically association between BMI and NSCLC after adjusting BFR (OR=1.367, 95%CI: 0.878-2.128); there was still statistically association between BMI and NSCLC after adjusting WHR and peripheral blood lipid indicators (both P<0.05). Conclusions The increase of BMI is associated with the increased risk of NSCLC incidence. BFR may be a potential influencing factor for the association between BMI and NSCLC.

ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.