Qingjie Li

Objective: Tuberculosis (TB) is the leading cause of mortality worldwide. Previous studies have reported that TB susceptibility can be caused by vitamin D deficiency, which is affected by polymorphisms in the vitamin D receptor (VDR) gene. However, these results have been inconsistent. Therefore, we performed a meta-analysis to investigate the association between VDR polymorphisms and TB susceptibility.Methods: We systematically searched for relevant literature in PubMed, Embase, and Medline databases through December 31st, 2022. Inclusion and exclusion criteria were made to ensure that HIV-negative population is the targeted subjects. The pooled odds ratio (OR) and 95% confidence interval (CI) were then used to assess the strength of the association, and the quality of the included articles was evaluated using the Newcastle–Ottawa Scale. Potential sources of heterogeneity were evaluated based on subgroup and meta-regression analyses.Results: In our meta-analysis, we found that the FokI polymorphism in the VDR gene was associated with increased TB susceptibility in the allele and recessive genotype models (OR f vs. F = 1.235, 95%CI: 1.035–1.475; OR ff vs. Ff + FF = 1.317, 95%CI: 1.005–1.727. Further subgroup analysis based on ethnicity demonstrated the association with the risk of TB in all genotype models of the FokI polymorphism for Han population. Meta-regression analysis also indicated that ethnicity could be a potential source of heterogeneity in the FokI and BsmI polymorphisms in the VDR gene. However, publication year was another source of heterogeneity for the TaqI polymorphism.Conclusion: In summary, the FokI polymorphism in the VDR gene was found to increase the risk of TB in the HIV-negative population, both overall and in Asian populations. The findings presented in this paper could provide clues for preventing TB from the perspective of vitamin D supplementation, which is a controversial topic in the field of medicine and health.

Nephrotoxicity remains a major adverse reaction of the anticancer drug cisplatin (CDDP) chemotherapy, which is an important risk factor for chronic renal disease. Ginsenoside Rh2 from Panax ginseng has been shown to protect against CDDP‐induced nephrotoxicity in vivo, but its pharmacological effect on renal tubular epithelial cells is not clearly understood. This study examined the molecular mechanisms underlying the nephroprotective effects of Rh2 on CDDP‐induced HK‐2 cells and acute kidney injury (AKI) mice. As a result of Rh2 treatment, CDDP‐induced HK‐2 cells showed increased cell viability and reduced lactate dehydrogenase release. Moreover, Rh2 ameliorated CDDP‐induced mitochondrial membrane potential, increased antioxidant enzyme activities, and reduced pro‐inflammatory cytokine expression to reduce damage. Rh2 inhibited apoptosis and enhanced the antioxidant capacity of HK‐2 cells by reducing proteins associated with endoplasmic reticulum (ER) stress, as well as by attenuating tunicamycin‐induced ER stress. In addition, treatment of CDDP‐induced AKI mice with Rh2 substantially reduced blood urea nitrogen and serum creatinine levels, attenuated histological damage of kidney. Further, Rh2 also improved kidney function by inhibiting ER stress to support in vitro findings. These results consistently demonstrated that Rh2 protects renal tubular epithelial cells from CDDP‐induced nephrotoxicity and apoptosis by restoring ER homeostasis, which might suggest a therapeutic potential and providing new insights into AKI alternative therapies.

The purpose was to screen type III secretory system (T3SS) inhibitors of Salmonella enterica serovar Typhimurium (S. Typhimurium) from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-β-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited S. Typhimurium invasion into host cells and reduced S. Typhimurium mediated host cell damage. β-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes (hilA and sopA) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against S. Typhimurium infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of S. Typhimurium. Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by S. Typhimurium T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against S. Typhimurium infection.

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene ( PRRX1 ⁺ mesenchymal cells). We also identified a population of “antler blastema progenitor cells” (ABPCs) that developed from the PRRX1 ⁺ mesenchymal cells and directed the antler regeneration process. Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.

The suite of adaptations associated with the extreme stature of the giraffe has long interested biologists and physiologists. By generating a high-quality chromosome-level giraffe genome and a comprehensive comparison with other ruminant genomes, we identified a robust catalog of giraffe-specific mutations. These are primarily related to cardiovascular, bone growth, vision, hearing, and circadian functions. Among them, the giraffe FGFRL1 gene is an outlier with seven unique amino acid substitutions not found in any other ruminant. Gene-edited mice with the giraffe-type FGFRL1 show exceptional hypertension resistance and higher bone mineral density, both of which are tightly connected with giraffe adaptations to high stature. Our results facilitate a deeper understanding of the molecular mechanism underpinning distinct giraffe traits, and may provide insights into the study of hypertension in humans.

Canine distemper (CD), caused by the CDV variant strain with H^I542N/Y549H, has become an epidemic in fur-bearing animals in China since 2012. To well understand the genomic and replicated characteristics of the CDV variants, we determined the viral growth kinetics and completed the genome sequences of two CDV strains, namely SDZC(17)M2 and LNDL(17)M4, isolated from CDV-infected minks from Shandong and Liaoning province in China, in 2017. SDZC(17)M2 showed higher viral titers and extensive syncytia in BHK-minkSLAM (BMS) cells than LNDL(17)M4. Although both two strains belong to the Asia-1 genotype and clustered an independent clade in the phylogenetic tree, SDZC(17)M2, harboring I542N/Y549H substitutions in the H protein, shared high identity (99.3–99.6% nt) with the other variant strains, whereas LNDL(17)M4, with the only Y549H substitution, shared a lower identity (97.7%–97.9% nt) with the other variant strains. Furthermore, a novel R223K substitution was identified in the conserved cleavage site (RRQRR → RRQKR) of the F protein in the SDZC(17)M2 strain. However, it which did not significantly affect the cell to cell fusion activity when combined with the CDV H/minkSLAM in BHK-21 cells. The key variations in the genome contributed to the virulence and the evolutionary trend need to be determined in the future.