Objective To investigate the effect of acute cold stimulation on the staufen1-mediated mRNA decay(SMD)pathway in brown adipose tissue of mice and the downstream regulated target genes.Methods Mice were subjected to acute cold stimulation(CS)at 4℃.After 48 hours,the brown adipose tissue of mice was extracted to detect the expression of genes including as Stau1,Ucp1 and Pparγ,and compared with mice in room temperature control group(RT).Transcriptomic sequencing was performed on the brown adipose tissue of mice in the CS group and in the RT group,and the functional enrichment analysis of differential genes was performed on the sequencing re-sults.The Stau1 gene was knocked out in the brown adipocytes of mice using CRISPR-Cas9 technology,and the ex-pression of thermogenic genes after knockout was analyzed.Results Acute cold stimulation induced the expression of Stau1 gene and promoted the degradation of downstream target genes Serpineb1,Klf2 and c-Jun in the SMD pathway(P＜0.05).After Stau1 knockout,the glycolipid metabolism pathway of brown adipocytes in mice was significantly up-regulated,and the expression of thermogenesis-related genes Ucp1,Prdm16,ATP5o,Dio2 and Pgc1α was up-regulated(P＜0.05).Conclusions Acute cold stimulation promotes the SMD pathway in brown adipose tissue of mice,and SMD pathway mainly regulates the metabolic and thermogenic pathways in brown adipocytes.

Polylactic-co-glycolic acid (PLGA) has the characteristics of biocompatibility, biodegradability, modifiability, and slow release, which has attracted extensive attention in the treatment of gynecological diseases. This paper summarizes the relevant literature reports at home and abroad in recent years, expounds the research situation of PLGA nanoparticles as drug carriers in gynecological diseases such as ovarian cancer, breast cancer, cervical cancer and endometriosis, and looks forward to its great potential in clinical application in gynecological diseases, providing guidance for its prevention and treatment in gynecological diseases.

  Objective  This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance.  Methods  This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers.  Results  A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers.  Conclusions  The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.