Search

Background The novel coronavirus disease 2019 (COVID-19) is currently breaking out worldwide. COVID-19 patients may have different degrees of coagulopathy, but the mechanism is not yet clear. We aimed to analyse the relationship between coagulation dysfunction and liver damage in patients with COVID-19. Methods A retrospective analysis of 74 patients with COVID-19 admitted to the First People’s Hospital of Yueyang from 1 January to 30 March 2020 was carried out. According to the coagulation function, 27 cases entered the coagulopathy group and 47 cases entered the control group. A case control study was conducted to analyse the correlation between the occurrence of coagulation dysfunction and liver damage in COVID-19 patients. Results Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), markers of liver damage, were positively correlated with coagulopathy (p = 0.039, OR 2.960, 95% CI 1.055–8.304; and p = 0.028, OR 3.352, 95% CI 1.137–9.187). Alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bilirubin (TBIL) were not statistically correlated with coagulopathy. According to the diagnosis and treatment plan, the included cases were classified into mild, moderate, severe, and critical. The results showed that the occurrence of coagulation dysfunction had no statistical correlation with the severity of COVID-19. Conclusion Coagulation dysfunction in patients with COVID-19 is closely related to liver damage. A longer course of the disease may cause a vicious circle of coagulopathy and liver damage. Clinicians need to closely monitor coagulation and liver function tests and to give prophylactic or supportive therapy when needed.

Emerging evidence has shown that aberrant alternative splicing (AS) events are involved in the carcinogenesis. The association between genetic variants in AS and bladder cancer susceptibility remains to be fully elucidated. We searched for single nucleotide polymorphisms (SNPs) which are located in splicing quantitative trait loci (sQTLs) in bladder cancer through CancerSplicingQTL database and the 1000 Genomes Project. A case-control study including 580 cases and 1,101 controls was conducted to assess the association between the functional genetic variants and bladder cancer risk. Next, we used GTEx, TCGA, and GEO databases conducting sQTL analysis and gene expression differences analysis to evaluate the potential biological function of the candidate SNPs and related genes. We found that SNP rs4383 C>G was remarkably related with the reduced risk of bladder cancer (odds ratio = 0.68, 95% confidence interval = 0.59-0.79, P = 3.91 × 10-7 ). Similar results were obtained in codominant, dominant and recessive model. Stratified analyses revealed that the effect of SNP rs4383 C>G on bladder cancer was more significant in the older subjects (age > 65), female and nonsmokers. sQTL analysis showed that SNP rs4383 was associated with the AS events of its downstream gene MAFF with a splicing event of alternative 5' splice site. The messenger RNA expression of MAFF in bladder tumor tissues was lowered compared with normal tissues. Patients with high expression of MAFF had higher survival rates. These findings indicated that SNP rs4383 related with the AS events of MAFF was associated with bladder cancer risk and could represent a possible biomarker for bladder cancer susceptibility.

Background: Although thousands of alternative splicing related single nucleotide polymorphisms (AS-SNPs) have been uncovered in human tumors, the potential function of AS-SNPs involved in bladder cancer is rarely reported. Here we identified bladder cancer risk-associated AS-SNPs and revealed its underlying causal mechanism in bladder carcinogenesis.Methods: Variants with annotation of “splice-3” or “splice-5” were extracted as AS-SNPs through the database of Single Nucleotide Polymorphism (dbSNP). Two-stage case-control studies comprising 1,630 cases and 2,504 controls were conducted to assess the association between the AS-SNPs and bladder cancer risk. A series of experiments including luciferase reporter assays, RNA immunoprecipitation, and malignant phenotype were performed to comprehensively investigate the genetic and epigenetic biological effects of AS-SNPs in the development of bladder cancer.Results: We identified the potential causal variant rs558814 A>G located in intron of lncRNA BCLET (Bladder Cancer Low-Expressed Transcript) was significantly associated with a reduced risk of bladder cancer [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.76 to 0.92, P = 3.26 × 10−4]. The SNP rs558814 exerted transcriptional activity regulatory effect and thus facilitated the expression of BCLET transcripts including BCLET-long and BCLET-short. In addition, both BCLET transcripts overexpression remarkably inhibited in vitro and in vivo bladder cancer phenotypes including cell proliferation, clone formation, invasion, migration and apoptosis. Mechanistically, lncRNA BCLET bound to MSANTD2 mRNA, masked splicing site of MSANTD2 mRNA, and thereby facilitated the expression of MSANTD2-004 transcript, which lacks the first exon and remarkably inhibited the progression of bladder cancer.Conclusions: Our findings not only revealed the important role of AS related genetic variants rs558814 and its associated gene BCLET in bladder cancer progression, but also provided the perspective to understand the etiology and pathology of cancers from the alternative splicing regulation mechanism.

Parthenocarpy is a valuable trait in self-incompatible plants, such as pear. N-(2-chloro-4-pyridyl)-N’-phenylurea (CPPU), a synthetic cytokinin analog, can induce parthenocarpy in pear (Pyrus spp.), but the mechanism of induction is unclear. To investigate the role of gibberellin in CPPU-induced parthenocarpy in pear, CPPU supplemented with paclobutrazol (PAC) was sprayed onto ‘Dangshansu’ pear. We found that the fruit set rate of pear treated with CPPU supplemented with PAC was identical to that in a CPPU-alone treatment group. In regard to cell development, CPPU mainly promoted hypanthium cell division and expansion, and PAC application had no influence on CPPU-induced cell development. RNA sequencing revealed that gibberellin 20 oxidase and gibberellin 3 oxidase genes were not differentially expressed following CPPU treatment. According to the analysis of fruit phytohormone content, the CPPU treatments did not induce gibberellin biosynthesis. These results suggest that CPPU-induced parthenocarpy may be gibberellin independent in ‘Dangshansu’ pear. After CPPU treatment, the indole acetic acid (IAA) content in fruit was significantly increased, and the abscisic acid (ABA) content was significantly decreased. Similarly, RNA sequencing revealed that many genes involved in the auxin and ABA pathways were significantly differentially expressed in the CPPU treatment groups; among them, indole-3-pyruvate monooxygenase (YUCCA) was significantly upregulated and 9-cis-epoxycarotenoid dioxygenase (NCED) was significantly downregulated. IAA and ABA may thus play important roles in CPPU-induced parthenocarpy. PbTwo-component response regulator9 (PbRR9), PbYUCCA4, and PbNCED6 were then selected to further elucidate the mechanism of CPPU-induced parthenocarpy. A yeast one-hybrid assay indicated that PbRR9 can combine with the PbYUCCA4 and PbNCED6 promoters. Dual luciferase assays revealed that PbRR9 can promote and repress the activities of the PbYUCCA4 and PbNCED6 promoters, respectively. After the transient expression of PbRR9 in fruits, PbYUCCA4 expression was significantly upregulated, and PbNCED6 expression was significantly downregulated. This study uncovered a CPPU-induced parthenocarpy mechanism that is different from that in tomato. CPPU may upregulate PbYUCCA4 and downregulate PbNCED6 by upregulating PbRR9, thereby increasing IAA content and decreasing ABA content to ultimately induce parthenocarpy in ‘Dangshansu’ pear. However, because only a single time point was used and because ‘botanical’ and ‘accessory’ fruits have different structures, this conclusion is still preliminary.

Background Emerging evidence has shown that MUC1 and TFF2 play crucial roles in the H. pylori-infected pathogenesis of gastric cancer (GC). A recent study revealed that H. pylori infection induced obviously increased Tff2 methylation levels in Muc1−/− mice compared with controls. However, little is known of the molecular mechanism on MUC1 regulating the expression of TFF2. Methods We conducted a correlation analysis of MUC1 and TFF2 in public databases and our adjacent GC tissues. Besides, MUC1 overexpression vector or small interfering RNA (siRNA) was transfected into GC cells to assess the change in TFF2 expression. Furthermore, the methylation status of TFF2 was measured by bisulfite sequencing PCR (BSP). Results The expression of MUC1 was significantly lower in non-cardia and cardia tumor tissues than that in normal tissues. Downregulation of TFF2 expression was also observed in GC tissues. In addition, we found that MUC1 expression was positively associated with TFF2 expression in GC tissues, especially among GC patients with H. pylori infection. Overexpression of MUC1 in BGC-823 and SGC-7901 cell lines substantially increased the TFF2 expression, whereas knockdown of MUC1 reverted this effect. Moreover, MUC1 was negatively related to the methylation of TFF2 in the co-expression analysis. The results of BSP experiments showed that compared with negative vector group, the methylation level of TFF2 was decreased in GC cells transfected with MUC1 overexpression vector. Additionally, survival analysis indicated that GC patients with lower level of MUC1 or TFF2 had a worse outcome. Conclusion Our results indicated that MUC1 was associated with the methylation of TFF2, which may have implications for TFF2 expression in GC. These findings warrant further research toward the underlying mechanism of MUC1 influenced the TFF2 methylation.

PI3K/Akt/mTOR pathway is involved in tumor initiation and progression, including gastric cancer (GC). However, the single nucleotide polymorphisms (SNPs) in this pathway and underlying molecular mechanism remain largely unexplored. A case-control study of 1275 GC patients and 1436 controls was performed to explore the associations of potentially functional SNPs in PI3K/Akt/mTOR pathway genes with the risk of GC. In the logistic regression analyses, one SNP rs7536272 out of the four candidate SNPs showed a significant association with GC risk (additive model: OR = 1.16, 95% CI = 1.03–1.30; co-dominant model: AG vs. AA, OR = 1.30, 95% CI = 1.11–1.53; dominant model: AG/GG vs. AA, OR = 1.28, 95% CI = 1.10–1.49).The luciferase assay indicated that rs7536272 G allele significantly enhanced the transcriptional activity, compared with A allele. Further expression quantitative trait loci (eQTL) analysis showed that GC patients with rs7536272 AG/GG genotypes had remarkably higher PIK3R3 levels than those with AA genotype, suggesting that rs7536272 polymorphism influenced the expression of PIK3R3. Additionally, we observed that GC patients with high expression of PIK3R3 had significant poorer outcome than those with low expression (HR = 1.29, 95% CI = 1.09–1.53). Our result demonstrated that SNP rs7536272, a functional risk variant located in the promoter region of PIK3R3, showed association with increased transcriptional activity and upregulation of PIK3R3 expression, thus involved in GC development.

The emergence of carbapenem-resistant Enterobacteriaceae made the treatment difficult, which has become a significant issue of public health. A sharp increase of carbapenem-resistance rate in Klebsiella pneumoniae was observed in a maternity and child health care hospital in Zunyi, China, in 2014. In 2015 to 2016, carbapenem-resistant Klebsiella pneumoniae (CRKp) isolated from all the clinical samples were analyzed to identify the carbapenem-resistance genes. They were then fingerprinted in order to determine their genetic relationship. Clinical data such as usage of imipenem in 2012 to 2016 and the nosocomial infection surveillance data were analyzed. Thirty-five isolates of CRKp out of 4328 various pathogens were obtained, and blaNDM-1 was identified to be the most common resistant gene present in the CRKp isolates. The fingerprint analysis identified 15 major clusters of CRKp isolates. The bacteria with close proximity relationship tended to be from the same wards. However, a few CRKp isolates from different wards were found to be genetically highly related. The clinical data showed a significantly higher usage of carbapenems in 2012 to 2013 before the CRKp rate sharply increased in 2014. The nosocomial infection surveillance showed an unexpectedly high rate of failures to meet the requirement of the hospital environment hygiene and hand hygiene in the neonatal ward. The increasing isolation rate of CRKp was associated with poorly regulated usage of carbapenems, impropriate medical practices, and the poor hospital environmental hygiene and hand hygiene.

Aroma affects the sensory quality of fruit and, consequently, consumer satisfaction. Melatonin (MT) is a plant growth regulator used to delay senescence in postharvest fruit during storage, however, its effect on aroma of pear fruit remains unclear. In this study, we assessed the effects of 0.1 mmol L&minus, 1 MT on volatiles and associated gene expression in the fruit of pear cultivars &lsquo, Korla&rsquo, (Pyrus brestschneideri Rehd) and &lsquo, Abb&eacute, Fetel&rsquo, (Pyrus communis L.). MT mainly affected the production of C6 aromatic substances in the two varieties. In &lsquo, MT inhibited expression of PbHPL, and reduced hydroperoxide lyase (HPL) activity and content of hexanal and (E)-hex-2-enal. In contrast, MT inhibited activity of lipoxygenase (LOX), reduced expression of PbLOX1 and PbLOX2, promoted PbAAT gene expression, increased alcohol acyltransferase (AAT) activity, and increased propyl acetate, and hexyl acetate content in &lsquo, that similarly led to the reduction in content of hexanal and (E)-hex-2-enal. Content of esters in &lsquo, pear increased with increasing postharvest storage period. Although mechanisms differed between the two varieties, effects on aroma volatiles mediated by MT were driven by expression of genes encoding LOX, HPL, and AAT enzymes.

Background Ambient fine particulate matter (PM2.5) pollution poses a great threat on global health. Previous studies have reported that PM2.5 regulates circulating fibrinogen and IL-6 levels in the development of cardiovascular and respiratory disease. However, the correlation between PM2.5 exposure and both biomarkers remains inconsistent. Methods We searched related articles through PubMed, Web of Science and ScienceDirect. Random effects model was used to obtain a pooled estimate effect of both biomarkers as PM2.5 concentration increased by every 10 μg/m3. Meta-regression analysis, sensitivity analysis and publication bias test were conducted to evaluate the heterogeneity, stability and reliability of this meta-analysis. Results A total of 22 articles were included. Each 10 μg/m3 increase in PM2.5 concentration was significantly correlated with a 1.76% increase in circulating fibrinogen level (95% CI: 0.38%–3.14%, P = 0.013) and a 4.66% increase in IL-6 level (95% CI: 1.14%–8.18%, P = 0.010). Subgroup analysis revealed that high-level PM2.5 exposure had a more significant association with circulating IL-6 level (11.67%, 95% CI: 0.66%–22.69%, P = 0.038) than low-level exposure, but this association was not observed in fibrinogen (2.50%, 95% CI: −0.78%–5.77%, P = 0.135). Sensitivity analysis and publication bias test confirmed the stability of the results. Conclusion Circulating fibrinogen and IL-6 significantly increased with exposure to PM2.5, may serve as promising biomarkers for PM2.5-related adverse effects.

Background As a class of natural antioxidants in plants, fruit flavonol metabolites are beneficial to human health. However, the regulatory networks for flavonol biosynthesis in most fruits are largely unknown. Previously, we reported a spontaneous pear bud sport ‘Red Zaosu’ (Pyrus bretschneideri Rehd.) with a high flavonoid content in its fruit. The identification of the flavonol biosynthetic regulatory network in this mutant pear fruit is crucial for elucidating the flavonol biosynthetic mechanism in fruit. Results Here, we demonstrated the PbMYB12b positively regulated flavonols biosynthesis in ‘Red Zaosu’ fruit. Initially, we investigated the accumulation patterns of four major quercetin glycosides and two major isorhamnetin glycosides in the fruit of ‘Red Zaosu’ and its wild-type ‘Zaosu’. A PRODUCTION OF FLAVONOL GLYCOSIDES (PFG)-type MYB transcription factor PbMYB12b was also screened for because of its correlation with flavonol accumulation in pear fruit. The biofunction of PbMYB12b was verified by transient overexpression and RNAi assays in pear fruit and young leaves. Overexpression of PbMYB12b enhanced the biosynthesis of quercetin glycosides and isorhamnetin glycosides by positively regulating a general flavonoids biosynthesis gene PbCHSb and a flavonol biosynthesis gene PbFLS. This finding was also supported by dual-luciferase transient expression assay and transient β-glucuronidase (GUS) reporter assay. Conclusions Our study indicated that PbMYB12b positively regulated flavonol biosynthesis, including four major quercetin glycosides and two major isorhamnetin glycosides, by promoting the expression of PbCHSb and PbFLS in pear fruit. Electronic supplementary material The online version of this article (10.1186/s12870-019-1687-0) contains supplementary material, which is available to authorized users.

Background: Key genes related to cell cycle and apoptosis pathways play critical roles in bladder cancer. Single nucleotide polymorphisms (SNPs) in the 3’-untranslated regions (3’-UTR) of genes may impact microRNA (miRNA)-messenger RNA (mRNA) binding capacity and alter gene expression to contribute to the susceptibility of cancers. However, an association of genetic variations in cell cycle and apoptosis pathways with bladder cancer risk, has not been reported . Materials and Methods: We selected SNPs in the 3’-UTR of cell cycle and apoptosis pathways genes and genotyped them with a case-control study consisting of 578 bladder cancer patients and 1,006 cancer-free subjects. Dual luciferase reporter gene assay was performed to validate the biological function of important SNPs. Results: We found that 5 SNPs might change the binding ability of miRNA to their target genes, among which PPP3CC rs7431 A>G located in the 3’-untranslated regions with the minimum p-value (p=5.75×10–4). Analysis revealed that the rs7431 disrupted miR-212 and miR-132 targeting sites. Logistic regression revealed a significantly decreased risk of bladder cancer associated with the PPP3CC rs7431 A>G polymorphism with an odds ratio (OR) of 0.76 [95% confidence interval (CI)=0.66-0.89, p=5.75×10–4]. Luciferase report assay showed that both miR-212 and miR-132 could lead to significantly increased PPP3CC expression levels in the construct with the G allele compared to the A allele. Conclusion: PPP3CC rs7431 may alter miRNA binding ability of miR-212 and miR-132, and thus decrease bladder cancer risk.

Objective We explored the association between single nucleotide polymorphisms (SNPs) rs207454 and rs494852 located in xanthine dehydrogenase (XDH) and gastric cancer (GC) survival. Methods A total of 940 patients with gastric cancer were enrolled and genotyped using TaqMan allelic discrimination method. The Kaplan–Meier test and log-rank examine were used to assess the effect of genetic variation. Results Patients carrying rs207454 CC genotype had a longer survival time than those with the AA genotype (P = 0.042). The similar association was detected in the recessive model (P = 0.017). We conducted expression quantitative trait loci (eQTL) analysis and found that gastric cancer patients carrying rs207454 CC genotype had significant lower XDH levels than those with AA/AC genotype, suggesting that rs207454 polymorphism effected the expression of XDH. Additionally, the Kaplan-Meier curves showed that gastric cancer patients with high expression of XDH had remarkably poor survival outcome than those with low expression (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.29–1.82). Conclusions Genetic variants in XDH were associated with the survival of gastric cancer and may act as prognostic markers for individual suffered from gastric cancer.

Anthocyanin biosynthesis exhibits a rhythmic oscillation pattern in some plants. To investigate the correlation between the oscillatory regulatory network and anthocyanin biosynthesis in pear, the anthocyanin accumulation and the expression patterns of anthocyanin late biosynthetic genes (ALBGs) were investigated in fruit skin of &lsquo, Red Zaosu&rsquo, (Pyrus bretschneideri Rehd.). The anthocyanin accumulated mainly during the night over three continuous days in the fruit skin, and the ALBGs&rsquo, expression patterns in &lsquo, fruit skin were oscillatory. However, the expression levels of typical anthocyanin-related transcription factors did not follow this pattern. Here, we found that the expression patterns of four PbREVEILLEs (PbRVEs), members of a class of atypical anthocyanin-regulated MYBs, were consistent with those of ALBGs in &lsquo, fruit skin over three continuous days. Additionally, transient expression assays indicated that the four PbRVEs promoted anthocyanin biosynthesis by regulating the expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and anthocyanidin synthase (ANS) in red pear fruit skin, which was verified using a dual-luciferase reporter assay. Moreover, a yeast one-hybrid assay indicated that PbRVE1a, 1b and 7 directly bound to PbDFR and PbANS promoters. Thus, PbRVEs promote anthocyanin accumulation at night by up-regulating the expression levels of PbDFR and PbANS in &lsquo, fruit skin.

Objective The long noncoding RNA PCAT1 is an important gene involved in urinary tumors. In this study, we aimed to explore the association between polymorphisms in PCAT1 and bladder cancer susceptibility. Methods A two-stage case-control study was conducted to assess the association between four tagging SNPs (i.e., rs4871771, rs1902432, rs16901904 and rs710886) and bladder cancer risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with unconditional univariate and multivariate logistic regression. Results At the first stage of discovery, we identified that SNP rs710886A > G was significantly associated with bladder cancer risk (OR = 0.86, 95% CI = 0.74–0.99, P = 0.046). At the following stage of validation, individuals with GG genotype were found to have a significant reduction in bladder cancer risk compared with those carrying AA genotype (adjusted OR = 0.83, 95% CI = 0.74–0.93, P = 0.001). Furthermore, stratified analyses showed that protective effect of rs710886 was more pronounced in subgroup of age > 60 and never smoking, and had little to do with sex. Besides, rs710886 was identified as an eQTL for PCAT1. G allele was consistent with lower PCAT1 expression. Conclusion This study indicates that genetic variants in lncRNA PCAT1 were associated with bladder cancer susceptibility and the SNP rs710886 may act as a potential biomarker for bladder cancer risk.

Background Inactivation of tumor suppressor genes by promoter hypermethylation plays a key role in the tumorgenesis. It is necessary to uncover the detailed pattern of whole genome-wide abnormal DNA methylation during the development of gastric cancer (GC). Method We performed a genome-wide methylation detection using 12 paired of GC tissues and their corresponding normal tissues. Methylation-specific PCR (MSP) and bisulphite sequencing (BSP) were used to measure methylation status of specific CpG site. Based on the bioinformatic analysis, the cell phenotypes and mouse model experiments were constructed to detect effect of the target gene. Using the Kaplan–Meier survival curve, the clinical value of KCNMA1 was assessed in GC patients. Results The CpG site cg24113782 located at the promoter of KCNMA1 showed the most significant difference, contributing to the commonly silenced KCNMA1in gastric cancer cells and primary GC tissues. The promoter methylation of KCNMA1 was detected in 68.7% (77/112) of tumor tissues, compared with 16.2% (18/112) of normal tissues (P