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.

[摘 要] 目的：探讨健脾复胃颗粒（JPFWG）通过调控IL-6/JAK/STAT3信号通路对胃癌前病变（PLGC）大鼠胃黏膜损伤的干预效果及其作用机制。方法：采用MNNG联合复合因素造模法建立PLGC模型大鼠，随机分为6组（20只/组）：空白组（未处理）、模型组（给予生理盐水）、维酶素组（0.05 g/mL维酶素）、JPFWG低剂量组（JPFWG-L，0.088 g/mL）、JPFWG中剂量组（JPFWG-M，0.176 g/mL）、JPFWG高剂量组（JPFWG-H，0.351 g/mL）。各治疗组大鼠分别给予相应药物处理12周后，麻醉处死动物并取胃组织标本。采用H-E染色法观察胃黏膜的病理变化，通过免疫组化、qPCR和WB法检测胃黏膜组织中IL-6介导的JAK/STAT3信号通路相关因子（包括IL-6、JAK、STAT3）及其下游靶基因c-Myc、cyclin D1的 mRNA和蛋白的表达水平。结果：与模型组相比，维酶素组和JPFWG-L、JPFWG-M、JPFWG-H组大鼠胃黏膜炎性细胞浸润均减少，病理状态改善以JPFWG-H组最明显；IL-6、JAK1、STAT3蛋白表达显著降低（P < 0.05或P < 0.01）；维酶素组和JPFWG-H组大鼠胃黏膜组织中c-Myc、cyclin D1的 mRNA和蛋白表达均显著降低（P < 0.05或P < 0.01）。结论：JPFWG能够改善PLGC大鼠胃黏膜的组织病理变化，其机制可能是通过调控IL-6/JAK/STAT3信号通路，进而下调c-Myc、cyclin D1的表达，从而阻断炎-癌转化过程。

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

A 14-year-old boy presented with coma and convulsion following a 3-day high fever of unknown origin was initially diagnosed with a central nervous system infection with uncertain pathogen. Direct microscopic examination of wet slides of cerebrospinal fluid cytology revealed active amoeboid trophozoites with different shapes. The amoeba trophozoite could be seen at high magnification after Wright′s-Giemsa staining. A diagnosis of primary amoebic meningoencephalitis was made according to the cellular morphology results of the cerebrospinal fluid, imaging data, and clinical symptoms. After high-throughput gene detection targeting the infection pathogen and specific PCR verification of amoeba species, it was confirmed that the infection was caused by Naegleria fowleri. Timely antiamoebic treatment and other related treatments were implemented, but the patient progressed to brain death after 50 days, leading to the discontinuation of treatment by the family.

Background and purpose:It is still a great challenge to clarify the signal molecules that mediate the communication between cancer-associated fibroblasts(CAFs)and tumor cells.These signal molecules are very important for cancer metastasis.The purpose of this study was to explore the communication mechanism of pleckstrin-2/miR-196a signal axis mediated by lung cancer cells in tumor microenvironment.Methods:Human lung adenocarcinoma cell line H1299 and human embryonic lung cell MRC-5 were selected as the research objects.H1299 cells were transfected with lentivirus(PLEK2)expressing PLEK2 and Vector control,and exosomes(Vector_exo,PLEK2_exo)were isolated after 24 h of transfection.MRC-5 cells were transfected with miR-196a mimetic or inhibitor.The expressions of PLEK2 and epithelial-mesenchymal transition(EMT)-related proteins were analyzed by Western blot.The expression of miR-196a was analyzed by polymerase chain reaction(PCR),and the metastasis and invasion ability of cells were determined by transwell assay.Six female BALB/c-nu mice were randomly divided into Vector group and PLEK2 group,with 3 mice in each group.Mice in each group were injected with H1299 cells transfected with Vector or PLEK2 through the tail vein.After 4 weeks,lung tissue was taken out for H-E staining and immunohistochemical staining to analyze the expression of α-smooth muscle actin(α-SMA).All animal experiments were approved by the ethics committee of First Hospital of Changsha City(Changsha Hospital,Xiangya School of Medicine,Central South University)(ethics number:EI-2021-103).Results:Compared with the Vector group,the number of pulmonary metastatic nodules and the expression of α-SMA in metastatic cancer in PLEK2 group increased significantly(P＜0.001).Compared with Vector group,the expression level of miR-196a in H1229 cells in PLEK2 group increased significantly(P＜0.05),and the expression level of miR-196a was significantly higher in PLEK2_exo than in Vector_exo(P＜0.05).Compared with Vector_exo group,the expression levels of miR-196a,α-SMA and fibroblast activation protein(FAP)in MRC-5 cells in PLEK2_exo group increased significantly(P＜0.05).Compared with the negative control(NC),the expression levels of α-SMA and FAP in MRC-5 cells transfected with miR-196a increased significantly(P＜0.05).On the contrary,by transfection with miR-196a inhibitors(si-miR-196a#1 and si-miR-196a#),the expression levels of α-SMA and FAP were significantly inhibited(P＜0.05).Compared with NC-CM group,the number of metastatic cells,invasive cells and the expression of vimentin in miR-196a-CM group increased significantly(P＜0.001),and the expression of E-cadherin decreased significantly(P＜0.001).In addition,compared with Vector_exo-CM group,PLEK2_exo-CM group had significant increase in number of metastatic and invasive cells and the expression of vimentin(P＜0.01),and significant decrease in the expression of E-cadherin(P＜0.001).Conclusion:Upregulation of PLEK2 can enhance the level of exosomes miR-196a derived from lung cancer cells,thereby promoting the activation of CAFs.The activated CAFs can further enhance the invasive ability of lung cancer cells.

Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.