Explore the vast range of titles available.

Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.

Background The GC haplotype of the vitamin D binding protein (encoded by the GC gene) might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse. We test the association between vitamin D binding protein genotypes and VD status as well as the metabolic parameters of glucose and lipids in a Han Chinese population. Methods In a cross-sectional study conducted at a health examination centre (registered in ClinicalTrials.gov as QLS2013), 2641 adults were included and grouped according to their plasma 25-hydroxyvitamin D (25OHD) concentrations as VD deficient (VDD), insufficient (VDI), or sufficient (VDS). The rs7041 and rs4588 genotypes were analysed with a molecular beacon-based qPCR method using blood samples. Results Plasma 25OHD concentrations were lower in the GC 2/2, rs7041T/T, and rs4588A/A genotypes than the GC 1f/1s, rs7041G/T, and rs4588C/C genotypes ( P  <  0.05). After adjusting for confounders, the GC 2 haplotype increased the risk of low VD status ( P  <  0.05) in both genders. More genotypic models revealed the negative contributions of rs4588A than rs7041T to low VD status ( P  <  0.05). The combined rates of VDD and VDI were 80.2% in males and 86.1% in females. Compared with VDI, VDS, or both, VDD showed higher plasma concentrations of fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides in males ( P  <  0.05); however, no significant differences were found with regard to these parameters between the subgroups defined by the GC genotypes ( P  > 0.05). Conclusions In a Han Chinese population, the GC2 haplotype or more exactly rs4588A is a risk factor for low VD status but is not associated with glucose and lipid metabolic disorders, which are inversely correlated with the circulating 25OHD concentration in males. Trial registration The study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.

Almost all selenogenes are expressed in the testis, and those have the highest and constant expressions will be the primary candidates for functional analysis of selenium (Se) in male reproduction. This study aimed to profile the mRNA expressions of the testis-abundant selenogenes of rat models in responses to growth and dietary Se concentrations. Forty-eight weaning SD male rats were fed Se deficient basal diet (BD) for 5 weeks and then randomly grouped ( n  = 12/group) for being fed BD or BD plus 0.25, 3, or 5 mg Se/kg for 4 more weeks before sacrifice. Abundances of selenogenomic mRNAs in the liver and testis were determined with relative qPCR and those of the testis-abundant selenogenes in 13 kinds of tissues were assayed with a molecular beacon-based qPCR. Spatiotemporal expressions of rat selenogenome were also analyzed with the RNA-Seq transcriptomic data published by NCBI. mRNA abundances of glutathione peroxidase 4 ( Gpx4 ), nuclear Gpx4 ( nGpx4 ), selenoprotein V ( Selenov ), and thioredoxin reductase 3 ( Txnrd3 ) in the testis were significantly higher than that in any other tissues ( P  < 0.05). Moreover, testicular mRNA abundances of Gpx4 , Selenov , and Txnrd3 were not affected by levels of dietary Se supplementation ( P  > 0.05), and much higher at 6–21 weeks old than at 2 and 104 weeks old ( P  < 0.05). The result showed that Gpx4 , Selenov , and Txnrd3 were most highly expressed in the testis of rats especially at reproductive ages and resistant to the impact of dietary Se levels, which suggested their specific importance in male reproduction.

Background To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area. Methods A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real‐time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers. Results A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%–1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%–67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene. Conclusion Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area. The carrier prevalence of spinal muscular atrophy (SMA) was calculated to be 1:59 by gradual screening procedure in 22,913 Chinese reproductive age women in Shenzhen area. Two hundred and forty‐two (62.21%) carriers' spouses were recalled and tested. Eight partners were found to be SMA carriers and two fetus was determined to have SMA.