Influence of glucagon-like peptide-1 receptor agonists on fat accumulation in patients with diabetes mellitus and non-alcoholic fatty liver disease or obesity: A systematic review and meta-analysis of randomized control trials.

AIM: This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity. METHODS: A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020). RESULTS: GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95 % CI [-0.90, -0.19]), SAT (SMD -0.59, 95 % CI [-0.99, -0.19]), body weight (SMD -1.07, 95 % CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95 % CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I2 = 79 %, P < 0.01), SAT (I2 = 73 %, P < 0.01), body weight (I2 = 82 %, P < 0.01), and BMI (I2 = 82 %, P < 0.01). No publication bias was detected for VAT (P = 0.57) and SAT (P = 0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4). CONCLUSIONS: This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction.

Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.

Background: Osteosarcoma (OS) is a common malignant bone cancer in children and teenagers that originates from osteoblast cells. Although many biomarkers have been reported in OS, they have not improved the prognosis of this disease. This study sought to identify effective biomarkers for the early diagnosis and prognosis of OS using a comprehensive bioinformatics analysis. Methods: OS-associated microRNAs (miRNAs) were screened in the Human microRNA Disease Database (HMDD). The differentially expressed genes (DEGs) related to OS were screened using 3 data sets (GSE16088, GSE36001, and GSE56001) from the Gene Expression Omnibus (GEO) database. By comparing the targets of these miRNAs with DEGs in response to OS, we identified OS-associated candidate genes. The gene expression and clinical data of 96 OS samples with complete clinical information was downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Comprehensive bioinformatics analyses, including univariate, multivariate Cox, and Kaplan-Meier (KM) analyses were conducted based on these data to identify the prognostic genes and construct prognostic signature for OS survival and recurrence. Logistic regression analysis was performed based on the GSE42352 data set (including 103 OS and 15 normal samples) to develop a diagnostic model for OS. Results: By comparing the DEGs and predicted targets of the 28 OS survival-associated miRNAs, we identified 267 OS-associated candidate genes. Additionally, 14 genes were found to be significantly associated with the survival of OS patients. Finally, 3 genes [i.e., signal transducer and activators of transcription factor 4 (STAT4), heat shock protein family E member 1 (HSPE1), and actin-related protein 2/3 complex subunit 5 (ARPC5)] were integrated into a prognostic index. The 3-gene signature was an independent factor for OS survival [hazard ratio (HR) =1.699; P<0.001] and recurrence (HR =2.532; P=0.004) and was found to have an excellent predictive performance [area under the receiver operating characteristic (ROC) curve (AUC) >0.7]. Additionally, 2 genes (i.e., STAT4 and HSPE1) were identified to be associated with OS diagnosis (P<0.05). This 2-gene diagnostic signature for OS presented a good discriminative power (AUC =0.981) and the error between the predicted and actual value was 0.029. Conclusions: We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic.

Pd-Catalyzed Carbonylation of Acyl Azides.

Pd-catalyzed reactions of azides with CO to access an isocynate intermediate have been developed extensively in recent years. However, the catalytic carbonylation of sensitive acyl azides has not been reported. Herein, we report a simple Pd-catalyzed carbonylation reaction of acyl azides with broad substrate scope, high efficiency, and simple operation under mild conditions, which provides facile access to acyl ureas. In addition, a mechanistic study was carried out by both experiment and DFT calculation. Control experiments and kinetic study revealed that the real active palladium species were Pd(0). The result of kinetic study suggested that palladium catalyst, azide, and CO were all involved in the turnover-limiting step except for amine. Further DFT study suggested that an unprecedented five-membered palladacycle intermediate was the key intermediate in the carbonylation reaction.

Rh(III)-Catalyzed C-H Activation of Boronic Acid with Aryl Azide.

A Rh(III)-catalyzed C-H activation of boronic acid with aryl azide to obtain unsymmetric carbazoles, 1 H-indoles, or indolines has been developed. The reaction constructs dual distinct C-N bonds via sp2/sp3 C-H activation and rhodium nitrene insertion. Synthetically, this approach represents an access to widely used carbazole derivatives. The practical application to CBP and unsymmetric TCTA derivatives has also been performed. Mechanistic experiments and DFT calculations demonstrate that a five-membered rhodacycle species is the key intermediate.

Tandem Coupling of Azide with Isonitrile and Boronic Acid: Facile Access to Functionalized Amidines.

Amidine is a notable nitrogen-containing structural motif found in bioactive natural products and pharmaceuticals. Herein, a novel rhodium(I)-catalyzed tandem reaction of readily accessible azides with isonitriles and boronic acids via a carbodiimide intermediate is achieved. This protocol offers an alternative approach toward N-sulfonyl-, N-acyl-, and N- phosphoryl-functionalized, as well as general N-aryl and N-alkyl amidines with broad substrate scope. In addition, functionalized guanidines can also been synthesized when amines are used instead. The accomplishment of estrone-derived amidine and glibenclamide bioisosteres further reveals the practical utility of this strategy.

Cyclization of Alkyne-Azide with Isonitrile/CO via Self-Relay Rhodium Catalysis.

A self-relay rhodium(I)-catalyzed cyclization of alkyne-azides with two σ-donor/π-acceptor ligands (isonitriles and CO) to form sequentially multiple-fused heterocycle systems via tandem nitrene transformation and aza-Pauson-Khand cyclization has been developed. In this approach, an intriguing chemoselective insertion process of isonitriles superior to CO was observed. This reaction provides an alternative strategy to synthesize functionalized pyrrolo[2,3-b]indole scaffolds.