Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population.

OBJECTIVE: Mutations in the NLRP3gene have previously been linked to certain forms of cancer, but there have not been any specific studies examining the association between NLRP3 polymorphisms and cervical cancer (CC). This study was therefore designed to investigate the effect of NLRP3 gene polymorphisms on HPV infection and cervical cancer in southern Chinese population. METHODS: Multiplex PCR and next-generation sequencing approaches were used to assess the NLRP3 rs10754558 and rs10733113 polymorphisms in 404 cervical lesion patients, including 227 diagnosed with CC and 177 diagnosed with cervical intraepithelial neoplasia(CIN), with 419 healthy female controls being included for comparison. Correlations between the rs10754558 and rs10733113 genotypes and alleles in these patients and CC and CIN were then analyzed. RESULTS: No correlations were found between NLRP3 rs10754558 and rs10733113 and human papillomavirus(HPV) infection status. Relative to the healthy control group, the NLRP3 rs10754558 GG genotype, CG + GG genotype, and G allele frequencies were significantly increased among patients with cervical lesions (CC and CIN) (OR = 1.815,P = 0.013;OR = 1.383, P = 0.026; OR = 1.284, P = 0.014,respectively), whereas no such differences were observed for rs10733113. A higher cervical lesion risk was detected for patients over the age of 45 exhibiting the rs10754558 GG genotype (OR = 1.848, P = 0.040). Additionally, the risk of CC was elevated in patients with the rs10754558 GG genotype or the G allele relative to patients with the CC genotype or the C allele(OR = 1.830, P = 0.029; OR = 1.281, P = 0.039). The rs10733113 genotypes or alleles were not significantly associated with CC risk (P > 0.05). No association between rs10754558 and rs10733113 genotypes and CC patient clinicopathological features were observed (P > 0.05). Serum NLRP3, IL-1ß, and IL-18 levels were significantly elevated in CC patients relative to healthy controls(P < 0.05). Relative to the CC genotype, CC patients harboring the rs10754558 GG genotype exhibited significantly elevated IL-1ß and IL-18 levels(P < 0.05). CONCLUSION: The rs10754558 polymorphism in the NLRP3 gene may contribute to an elevated risk of CC, although it is not significantly correlated with HPV infection and CC progression.

A SNP Mutation in Homeodomain-DDT (HD-DDT) Transcription Factor Results in Multiple Trichomes (mt) in Cucumber (Cucumis sativus L.).

Trichome is a natural physical barrier protecting plants against environmental stresses, natural infestations, ultraviolet rays and pathogenicity. Trichome also helps plants in maintaining appropriate water content by reducing transpiration rate. The molecular mechanism regulating unicellular trichome development in Arabidopsis has been extensively elucidated, but the molecular mechanism regulating multicellular trichome development remains unclear. In this study, we identified a multiple trichomes (mt) mutant from a cucumber EMS (Ethylmethylsulfone) mutagenesis population. Genetic analysis indicated that an incomplete dominant gene controls the mt trait. Using a combination of map-based cloning and BSA-seq (Bulked Segregant Analysis -Sequencing), we identified the candidate gene, CsaV3_6G050410, responsible for the mt mutation. Sequence alignment revealed one base substitution in gene CsaV3_6G050410, resulting in an amino acid substitution. The deduced amino acid sequence of CsaV3_6G050410 encodes a HD-DDT (homeodomain-DDT) transcriptional regulatory protein containing a conserved homeobox domain and a DDT domain. Gene expression analysis revealed that the expression level of CsaV3_6G050410 in the mt mutant was similar to that in the WT (wild type). Transcriptome analysis indicated that the mt gene may regulate the development of the epidermis by influencing plant hormone signaling pathways or participating in several transcription factor pathways. The results of this study are fundamental for a better understanding of the function of the HD-DDT transcription factor in the trichome development of cucumber.

Identification of a putative candidate gene encoding 7-dehydrocholesterol reductase involved in brassinosteroids biosynthesis for compact plant architecture in Cucumber (Cucumis sativus L.).

KEY MESSAGE: By the strategy of bulked segregant analysis sequencing combined with genetic mapping, CsDWF5, which encodes 7 dehydrocholesterol reductase that involved in brassinosteroids biosynthesis, was identified as the candidate gene for cpa. Dwarf architecture is one of the most important breeding goals in crops. The biosynthesis and signal transduction of brassinosteroids (BRs) have a great impact on plant growth and development including plant architecture. Here, we identified a compact plant architecture (cpa) mutant from an EMS-induced cucumber population. cpa displayed the extremely dwarf phenotype with shortened internode and petiole, darkened and wrinkled leaf. Genetic analysis revealed that cpa was caused by a single recessive gene. By the strategy of bulked segregant analysis sequencing combined with genetic mapping, CsDWF5, encoding a 7-dehydrocholesterol reductase that involved in sterol biosynthesis, was identified as the candidate gene for cpa. One single nucleotide mutation (G→A) in splicing site causing 3-bp insertion (TAG) was found in the first base of the sixth intron of CsDWF5 in cpa, which furtherly resulted in the frameshift mutation and got a premature stop codon. The expression of CsDWF5 gene was significantly down regulated in different tissues of the cpa mutant compared with that in wild type. The phenotype of cpa could be partially recovered by exogenous BR treatment. Transcriptome analysis identified 1096 genes that exhibited differential expression between the cpa mutant and wild type. KEGG enrichment analysis indicated that differentially expressed genes were significantly enriched in BR biosynthesis and plant-pathogen interaction pathways. These results provide perspectives on the molecular mechanisms underlying the dwarfing phenotype in cucumber.

Generation of an induced pluripotent stem cell line (PUMCHi006-A) derived from a patient with pulmonary arterial hypertension carrying heterozygous c.1339 G > A mutation in PTGIS gene.

Our previous study found that mutations in the PTGIS gene contributed high susceptibility to pulmonary arterial hypertension (PAH). We have generated disease-specific induced pluripotent stem cell (iPSC) lines from a PAH patient carrying the heterozygous c.1339 G > A mutation in PTGIS gene. The generated iPSC lines can be differentiated into endothelial cells to investigate the pathogenesis of PAH associated with PTGIS gene, which could provide valuable resources for personalized medicine.

Hematological factors associated with immunity, inflammation, and metabolism in patients with systemic lupus erythematosus: Data from a Zhuang cohort in Southwest China.

INTRODUCTION: Hematological parameters play important role in multiple diseases. This study was to investigate the possible association of the routine hematological parameters involved in immunity, inflammation, and metabolism with systemic lupus erythematosus (SLE) in patients of Zhuang ethnicity in Guangxi, southwest China. METHODS: The medical records of 195 Zhuang SLE patients between January 2013 and November 2018 were retrospectively reviewed. Random forest algorithm and multivariate logistic regression were used to identify the feature hematological parameters in patients with SLE. Association rules were explored between each parameter and immunity- (IgG, IgA, IgM, C3, and C4), inflammation- (ESR, hs-CRP, and CAR), and metabolism- (TG, TC, HDL-C, LDL-C, TP, PA, ALB, and UA) related indexes. RESULTS: Random forest algorithm and logistic regression analysis showed that neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR) were the feature parameters for distinguishing SLE patients from healthy controls. According to the ROC curves, the optimal cutoff values to predict SLE were 1.98 for NLR, 13.35 for RDW, and 145.64 for PLR. Association rule analysis showed that NLR was strongly associated with C3, hs-CRP, TG, ALB, and UA; RDW was strongly associated with C3, C4, hs-CRP, TG, and ALB; PLR was strongly associated with IgG, hs-CRP, HDL-C, and UA. CONCLUSIONS: Neutrophil-to-lymphocyte ratio, RDW, and PLR may serve as effective predictors of dysregulation in immunity, inflammation, and metabolism. These three indicators may be potential for cardiovascular risk assessment in Zhuang SLE patients in southwest China.