Transcriptional regulation of the yersiniabactin receptor fyuA gene by the ferric uptake regulator in Klebsiella pneumoniae NTUH-K2044.

The ferric uptake regulator (Fur) is a global regulator that influences the expression of virulence genes in Klebsiella pneumoniae. Bioinformatics analysis suggests Fur may involve in iron acquisition via the identified regulatory box upstream of the yersiniabactin receptor gene fyuA. To observe the impact of the gene fyuA on the virulence of K. pneumoniae, the gene fyuA knockout strain and complementation strain were constructed and then conducted a series of phenotypic experiments including chrome azurol S (CAS) detection, crystal violet staining, and wax moth virulence experiment. To examine the regulatory relationship between Fur and the gene fyuA, green fluorescent protein (GFP) reporter gene fusion assay, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), gel migration assay (EMSA), and DNase I footprinting assay were used to clarify the regulatory mechanism of Fur on fyuA. CAS detection revealed that the gene fyuA could affect the generation of iron carriers in K. pneumoniae. Crystal violet staining experiment showed that fyuA could positively influence biofilm formation. Wax moth virulence experiment indicated that the deletion of the fyuA could weaken bacterial virulence. GFP reporter gene fusion experiment and RT-qPCR analysis revealed that Fur negatively regulated the expression of fyuA in iron-sufficient environment. EMSA experiment demonstrated that Fur could directly bind to the promoter region of fyuA, and DNase I footprinting assay further identified the specific binding site sequences. The study showed that Fur negatively regulated the transcriptional expression of fyuA by binding to upstream of the gene promoter region, and then affected the virulence of K. pneumoniae.

Association between alcohol consumption and risk of stroke among adults: results from a prospective cohort study in Chongqing, China.

BACKGROUND: The incidence of stroke in China is increasing, along with a clear trend in the prevalence of risk factors. Alcohol consumption is also a risk factor for stroke. Many cohort studies have explored the relationship between alcohol consumption and stroke risk. However, findings have been inconsistent. METHODS: We used cluster sampling to select 13 districts and counties (at the same level) in Chongqing, China. Then, we used stratified random sampling to distribute the number of people in each district and county. 23,308 adults aged 30-79 were recruited between October 2018 and February 2019. Follow-up was conducted through a monitoring system and questionnaires until September 2022. Information on alcohol consumption and other covariates was collected using a standardized questionnaire. Participants were asked to report their weekly frequency of drinking over the past year and weekly intake of various alcoholic beverages in general. The frequency of drinking was divided into three categories: 1-2 d/week, 3-5 d/week, and 6-7 d/week. The average daily alcohol consumption is calculated based on the amount of alcohol contained in different alcoholic beverages. It is classified as nondrinker (0 g/day), light (0 to 12 g/day), moderate (13 to 36 g/day), and high (> 36 g/day). Cox proportional hazard regression models were used to estimate the association between alcohol consumption and stroke risk. Results are shown as multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: With an average follow-up of 3.80 years, there were 310 new stroke events. The incidence of total stroke was 368.69 per 100,000 person-years. Overall, after adjusting for covariates, moderate alcohol consumption (average daily alcohol consumption 13-36 g/d) was associated with a lower risk of total stroke (HR: 0.48; 95% CI: 0.25-0.92) compared with nondrinkers. The adjusted HR and 95% CI for total stroke and ischemic stroke for those who drank alcohol 6-7 days per week were 0.60(0.37, 0.96) and 0.53(0.30, 0.94), respectively. The risk of total stroke (HR: 0.39; 95% CI: 0.17-0.89) was reduced in a pattern of drinking 6-7 days per week but with a mean alcohol consumption of less than 36 g/d. There was no significant association between alcohol consumption and hemorrhagic stroke. CONCLUSION: This study suggests moderate alcohol consumption is associated with a lower risk of total stroke. And healthy drinking patterns should be of more significant concern.

Involvement of gut-brain communication in arsenite-induced neurobehavioral impairments in adult male mice.

Arsenite is a well-documented neurotoxic metalloid that widely distributes in the natural environment. However, it remains largely unclear how arsenite affects neurological function. Therefore, in this study, the healthy adult male mice were exposed to 0.5 mg/L and 5 mg/L arsenite through drinking water for 30 and 90 days, respectively. Our results showed that there was no significant alteration in the intestine and brain for 30 days exposure, but exposure to arsenite for 90 days significantly induced a reduction of locomotor activity and anxiety-like behavior, caused pathological damage and inflammatory responses in the brain and intestine. We also found that arsenite remarkably disrupted intestinal barrier integrity, decreased the levels of lysozyme and digestive enzymes. Intriguingly, chronic exposure to arsenite significantly changed the levels of gut-brain peptides. Taken together, this study provides meaningful insights that gut-brain communication may involve in the neurobehavioral impairments of arsenite.

Exposure to di (2-ethylhexyl) phthalate causes locomotor increase and anxiety-like behavior via induction of oxidative stress in brain.

Di (2-ethylhexyl) phthalate (DEHP) is one of the most prevalent xenoestrogen endocrine disruptor in daily life. A growing number of studies showed that DEHP could exhibit long-term adverse health effects on the human body, particularly in the liver, kidneys, heart and reproductive systems. However, the impact of oral intake of DEHP on the nervous system is extremely limited. In the present study, the adult C57BL/6J male mice were intragastrically administered with two dosages of DEHP for 35 days. The behavioral parameters were assessed using the elevated plus maze and open-field test. The mRNA expression levels of neuropeptides and the oxidative stress-associated proteins were detected by qPCR and western blot seperately. The histopathologic alterations of the brain were observed by H&E and Nissl staining. The results demonstrated that DEHP exposure could result in neurobehavioral impairments such as locomotor increase and anxiety-like behavior. Furthermore, pathological damages were clearly observed in the cerebral cortex and hippocampus, accompanied by a decrease in neuropeptides and an increase in oxidative stress, which were all positively correlated with the dose of DEHP. Together, these findings provide valuable clues into the DEHP-induced neurotoxicity.

Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein.

BACKGROUND: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin-angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated. METHODS AND RESULTS: Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT1R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII. CONCLUSION: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT1R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.

Novel Ti3C2Tx MXene nanozyme with manageable catalytic activity and application to electrochemical biosensor.

In this work, Ti3C2Tx MXene was identified as efficient nanozyme with area-dependent electrocatalytic activity in oxidation of phenolic compounds, which originated from the strong adsorption effect between the phenolic hydroxyl group and the oxygen atom on the surface of Ti3C2Tx MXene flake. On the basis of the novel electrocatalytic activity, Ti3C2Tx MXene was combined with alkaline phosphatase to construct a novel cascading catalytic amplification strategy using 1-naphthyl phosphate (1-NPP) as substrate, thereby realizing efficient electrochemical signal amplification. Taking advantage of the novel cascading catalytic amplification strategy, an electrochemical biosensor was fabricated for BCR/ABL fusion gene detection, which achieved excellent sensitivity with linear range from 0.2 fM to 20 nM and limit of detection down to 0.05 fM. This biosensor provided a promising tool for ultrasensitive fusion gene detection in early diagnosis of chronic myelogenous leukemia and acute lymphocytic leukemia. Moreover, the manageable catalytic activity of MXene broke a path for developing nanozymes, which possessed enormous application potential in not only electrochemical analysis but also the extensive fields including organic synthesis, pollutant disposal and so on.

Polystyrene nanoparticles enhance the adverse effects of di-(2-ethylhexyl) phthalate on male reproductive system in mice.

Coexposure of nanoplastics (NPs) with other pollutants adsorbed from the surroundings has received extensive attention. Currently, the combined effects of NPs and plasticizers remain unclear. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that has raised much concern owing to its ubiquitous pollution and endocrine-disrupting potential. This study aimed to investigate the toxic effects on the male reproductive system upon coexposure to NPs and DEHP. The C57BL/6J mice were orally administrated with polystyrene nanoparticles (PSNPs), DEHP or both for 35 days to evaluate their effects on sperm quality, histology of testes and epididymides, testicular transcriptomic characteristics as well as expression of some important genes in the epididymides. The low-dose PSNPs used here did not induce significant changes in sperm quality, while DEHP alone or cotreatment with DEHP and PSNPs caused notable impairment, mainly manifesting as decreased sperm quality and aberrant structure of the testis and epididymis. Moreover, enhanced toxic effects were found in the cotreatment group when compared with the individual DEHP treatment group, as manifested by more obvious alterations in the sperm parameters as well as histological changes in the testis and epididymis. Testicular transcriptomic analysis revealed differential regulation of genes involved in immune response, cytoplasmic pattern recognition receptor signaling pathways, protein ubiquitination, oxidative stress, necrotic cell death, ATP synthesis and the cellular respiratory chain. RT-qPCR verified that the expression patterns of Cenpb, Crisp1 and Mars were changed in testes, and genes relevant to epididymal function including Aqp9 and Octn2 were downregulated in epididymides, particularly in the cotreatment group. Collectively, our results emphasize that DEHP at an environmentally relevant dose can induce male reproductive toxicity, and PSNPs may aggravate the toxic effects.

Genome sequencing and comparative genome analysis of 6 hypervirulent Klebsiella pneumoniae strains isolated in China.

Hypervirulent Klebsiella pneumoniae (hvKP) has been increasingly reported over the past three decades and causes severe infections. To increase our understanding of hvKP at the genome level, genome sequencing and comparative genome analysis were performed on 6 hvKPs. The whole genome DNA from 6 hvKPs with different capsular serotypes isolated in China was extracted. The genome sequencing and assembly results showed the genome size of the six hvKPs and GC content. Comparative analyses of the genomes revealed the gene homology and genome rearrangement in the 6 hvKPs compared with Klebsiella pneumonia NTUH-K2044. The phylogenetic tree based on full-genome SNPs of the 7 hvKPs showed that NTUH-K2044 formed a single clade, showing distant evolutionary distances with the other six strains, and the non-K1 hvKP strains had a relatively closer phylogenetic relationship. BLAST comparison analysis found that some selected virulence genes had different degrees of deletion in the non-K1 hvKPs. SNP-based virulence gene mutation analysis showed that some virulence genes had different degrees of SNP mutations. The whole-genome sequencing and comparative genome analysis of six hvKP strains with NTUH-K2044 provide us with a basic understanding of the genome composition, genetic polymorphism, evolution and virulence genes of hvKP and a basis for further research on these genes and the pathogenesis of hvKP.

Pregnancy exposure of titanium dioxide nanoparticles causes intestinal dysbiosis and neurobehavioral impairments that are not significant postnatally but emerge in adulthood of offspring.

BACKGROUND: Pregnancy exposure to titanium dioxide nanoparticles (TiO2NPs) is a vital consideration due to their inadvertent ingestion from environmental contamination. The potential health effects of TiO2NPs on the neurodevelopmental process should be seriously concerned in health risk assessment, especially for the pregnant women who are susceptible to the neurodevelopmental toxicity of nano-sized particles. However, the available evidence of neurodevelopmental toxicity of TiO2NPs remains very limited. METHODS: In the present study, the pregnant mice were intragastric administered with 150 mg/kg TiO2NPs from gestational day (GD) 8 to 21, the maternal behaviors and neurodevelopment-related indicators in offspring were all assessed at different time points after delivery. The gut microbial community in both dams and their offspring were detected by using 16S ribosomal RNA (rRNA) gene sequencing. The gut-brain axis related indicators were also determined in the offspring. RESULTS: The results clearly demonstrated that exposure to TiO2NPs did not affect the maternal behaviors of pregnant mice, or cause the deficits on the developmental milestones and perturbations in the early postnatal development of offspring. Intriguingly, our data revealed that pregnancy exposure of TiO2NPs did not affect locomotor function, learning and memory ability and anxiety-like behavior in offspring at postnatal day (PD) 21, but resulted in obvious impairments on these neurobehaviors at PD49. Similar phenomena were obtained in the composition of gut microbial community, intestinal and brain pathological damage in offspring in adulthood. Moreover, the intestinal dysbiosis induced by TiO2NPs might be highly associated with the delayed appearance of neurobehavioral impairments in offspring, possibly occurring through disruption of gut-brain axis. CONCLUSIONS: This is the first report elucidated that pregnancy exposure to TiO2NPs caused delayed appearance of neurobehavioral impairments in offspring when they reached adulthood, although these perturbations did not happen at early life after delivery. These findings will provide valuable insights about neurodevelopmental toxicity of TiO2NPs, and call for comprehensive health risk assessment of TiO2NPs on the susceptible population, such as pregnant women.

Silicon dioxide nanoparticles induced neurobehavioral impairments by disrupting microbiota-gut-brain axis.

BACKGROUND: Silicon dioxide nanoparticles (SiO2NPs) are widely used as additive in the food industry with controversial health risk. Gut microbiota is a new and hot topic in the field of nanotoxicity. It also contributes a novel and insightful view to understand the potential health risk of food-grade SiO2NPs in children, who are susceptible to the toxic effects of nanoparticles. METHODS: In current study, the young mice were orally administrated with vehicle or SiO2NPs solution for 28 days. The effects of SiO2NPs on the gut microbiota were detected by 16S ribosomal RNA (rRNA) gene sequencing, and the neurobehavioral functions were evaluated by open field test and Morris water maze. The level of inflammation, tissue integrity of gut and the classical indicators involved in gut-brain, gut-liver and gut-lung axis were all assessed. RESULTS: Our results demonstrated that SiO2NPs significantly caused the spatial learning and memory impairments and locomotor inhibition. Although SiO2NPs did not trigger evident intestinal or neuronal inflammation, they remarkably damaged the tissue integrity. The microbial diversity within the gut was unexpectedly enhanced in SiO2NPs-treated mice, mainly manifested by the increased abundances of Firmicutes and Patescibacteria. Intriguingly, we demonstrated for the first time that the neurobehavioral impairments and brain damages induced by SiO2NPs might be distinctively associated with the disruption of gut-brain axis by specific chemical substances originated from gut, such as Vipr1 and Sstr2. Unapparent changes in liver or lung tissues further suggested the absence of gut-liver axis or gut-lung axis regulation upon oral SiO2NPs exposure. CONCLUSION: This study provides a novel idea that the SiO2NPs induced neurotoxic effects may occur through distinctive gut-brain axis, showing no significant impact on either gut-lung axis or gut-liver axis. These findings raise the exciting prospect that maintenance and coordination of gastrointestinal functions may be critical for protection against the neurotoxicity of infant foodborne SiO2NPs.

Titanium dioxide nanoparticles via oral exposure leads to adverse disturbance of gut microecology and locomotor activity in adult mice.

Titanium dioxide nanoparticles (TiO2NPs) have been widely used as food additives in daily life. However, the impact of oral intake of TiO2NPs on the nervous system is largely unknown. In this study, 7-week-old mice were treated with either vehicle or TiO2NPs suspension solution at 150 mg/kg by intragastric administration for 30 days. Our results demonstrated that oral exposure to TiO2NPs resulted in aberrant excitement of enteric neurons, although unapparent pathological changes were observed in gut. We also found the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed in the TiO2NP-treated group as compared with vehicle controls. Interestingly, oral exposure to TiO2NPs was capable to induce the inhibitory effects on locomotor activity, but it did not lead to significant change on the spatial learning and memory ability. We further revealed the mechanism that TiO2NPs could specifically cause locomotor dysfunction by elevating the excitement of enteric neuron, which might spread to brain via gut-brain communication by vagal pathway. However, inflammation response, enteric neurotransmitter 5-HT and major gut peptides might not be involved in this pathological process. Together, these findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.

Association between self-reported snoring and hypertension among Chinese Han population aged 30-79 in Chongqing, China.

BACKGROUND: We aim to explore the association between self-reported snoring and hypertension among adults aged 30-79 in Chongqing, China. METHODS: A total of 23,342 individuals aged 30-79 were included at baseline from August 2018 to January 2019, and the final sample size for the analysis was 22,423. Face-to-face interviews and physical examinations were conducted by trained investigators. Logistic regression was performed to study age-specific and gender-specific associations between snoring and hypertension. RESULTS: Frequent snoring was associated with the risk of hypertension for each age and gender group, and the frequency of snoring was positively correlated with the risk for hypertension. For the three age groups (< 45, 45-59, ≥ 60), compared with the non-snoring group, those who snore often had a 64.5%, 53.3%, and 24.5% increased risk of hypertension (< 45: OR = 1.65, 95%CI 1.34-2.02; 45-59: OR = 1.53, 95%CI 1.37-1.72; ≥ 60: OR = 1.25, 95%CI 1.09-1.42), respectively. For men and women, those who snore often had a 46.8% and 97.2% increased risk of hypertension, respectively, than the non-snoring group (men: OR = 1.47, 95%CI 1.33-1.63; women: OR = 1.97, 95%CI 1.75-2.23). CONCLUSIONS: People who snore frequently should pay close attention to their blood pressure levels in order to achieve early prevention of hypertension, particularly for snorers who are female and aged under 45; importance should be attached to their blood pressure control.

Risk factors of bloodstream infections in recipients after liver transplantation: a meta-analysis.

PURPOSE: Bloodstream infection (BSI) is an important cause of adverse outcomes for recipients with liver transplantation (LT). This meta-analysis aimed to identify risk factors associated with post-LT BSI. METHODS: Relevant studies published up to June 2017 were searched from seven electronic databases. The studies were reviewed according to the inclusion and exclusion criteria. The Z test was used to determine the pooled odds ratio (OR) or standardized mean difference (SMD) of the risk factors. ORs and their corresponding 95% confidence intervals (CIs), or SMDs and their corresponding 95% CIs were used to identify the significant difference of risk factors. RESULTS: Seventeen studies enrolling 4410 recipients were included. Eleven risk factors were identified to be associated with BSI after LT: male recipient (OR = 1.28), ascites (OR = 1.68), model for end-stage liver disease (MELD) score (SMD = 0.20), Child-Pugh class C (OR = 1.69), operation time (SMD = 0.18), incompatible blood type (OR = 2.87), operative blood loss (SMD = 0.33), rejection (OR = 1.72), biliary complications (OR = 1.91), hemodialysis (OR = 3.37), and retransplantation (OR = 2.86). CONCLUSIONS: Although some risk factors were identified as significant factors for BSI after LT, which may provide a basis for clinical prevention, well-designed prospective studies should be done to overcome the limitations of this study.

The zinc finger protein GATA4 induces mesenchymal-to-epithelial transition and cellular senescence through the nuclear factor-κB pathway in hepatocellular carcinoma.

BACKGROUND AND AIM: The high mortality and poor prognosis of hepatocellular carcinoma (HCC) have raised the public attention. Gene therapy is considered as a promising treatment option for cancer; thus, finding a new therapeutic target for HCC is urgently needed. GATA4 is a tumor suppressor gene in multiple cancers, but its role in HCC is unclear. In this study, we explored the function of GATA4 in HCC. METHODS: Reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction were used to detect the mRNA expression of GATA4 in HCC cells and tissues. Cell viability, transwell, colony formation, and flow cytometry assays were applied to examine different aspects of biological effects of GATA4 in vitro. Xenografts, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assays were performed to evaluate the effect of GATA4 on tumorigenicity in vivo. Western blotting, immunofluorescence, and ß-galactosidase staining were used to investigate the mechanism underlying the function of GATA4. RESULTS: We found that GATA4 was silenced in 15/19 (79%) HCC tissues. Restoring the expression of GATA4 induced G0 /G1 phase arrest, promoted apoptosis, suppressed HCC proliferation in vitro, and inhibited HCC tumor growth in vivo. Our data further showed that the ectopic expression of GATA4 induced cellular senescence through regulating nuclear factor-κB and inducing mesenchymal-to-epithelial transition. CONCLUSIONS: Our data demonstrated that by inducing cellular senescence and mesenchymal-to-epithelial transition, GATA4 plays a crucial role as a tumor suppressor in HCC. It may thus be a potential cancer therapeutic target for HCC.

Genome-wide identification of genes regulated by RcsA, RcsB, and RcsAB phosphorelay regulators in Klebsiella pneumoniae NTUH-K2044.

Rcs phosphorelay system is a two-component signal transduction system, which can regulate the transcription of capsule polysaccharide and biofilm related genes in Enterobacteriaceae. In this study, microarray technology was used to investigate the overall genes regulated by RcsA, RcsB, and RcsAB and the regulation mechanism in Klebsiella pneumoniae, then COG analysis was performed to explore the functions of the differentially expressed genes. According to the microarray data result, a total of 45, 223 and 217 genes regulated by RcsA, RcsB, and RcsAB were screened. The result of COG analysis suggested that inorganic ion transport and metabolism related genes have a majority in RcsA regulating genes. Most of RcsB regulated genes were showed involved in energy production and conversion process. Besides Carbohydrate transport and metabolism genes were identified as the major components of the RcsAB regulated genes. 15 differentially expressed genes were confirmed by quantitative real-time PCR (RT-qPCR). The RT-qPCR results indicated that 13 genes consistent with microarray data. The results of this study provided important evidence for further research to investigate the influence of RcsA, RcsB, RcsAB regulators and further efforts to address the diseased caused by K.pneumoniae, such as pneumonia, bacteremia, and urinary tract infection.

Molecular characterisations of integrons in clinical isolates of Klebsiella pneumoniae in a Chinese tertiary hospital.

BACKGROUND: Integrons are mobile genetic elements that play an important role in the distribution of antibiotic-resistance genes among bacteria. This study aimed to investigate the distribution of integrons in clinical isolates of Klebsiella pneumoniae and explore the molecular mechanism of integron-mediated multiple-drug resistance in K. pneumoniae. METHODS: Class 1, 2, and 3 integrases were identified by polymerase chain reaction (PCR) among 178 K. pneumoniae clinical isolates. Antibiotic susceptibility was examined by disk-diffusion method. Conjugation experiments were conducted to evaluate the horizontal-transfer capability, and multilocus sequence typing (MLST) assays were conducted to explore the genetic relationships among the isolates. Highly virulent serotypes were identified by PCR from the 44 integron-positive isolates with variable regions. RESULTS: Class1 and 2 integrons were detected in 60.1% and 1.7% of isolates, respectively. One isolate carried both class 1 and 2 integrons. Class 3 integrons were not detected in all 178 isolates. Among the 44 integrons containing variable regions, 39 were located in conjugative plasmids. Dihydrofolate reductase (dfrA) and aminoglycoside adenyltransferase (aad) were found to be the most common in class 1 and 2 integrons. These gene cassettes encoded resistance to trimethoprim and aminoglycosides. Moreover, the association between integron carriage and antibiotic resistance was most significant for aminoglycosides, phenicols, and fluoroquinolones. Among the 44 integron-positive isolates with variable regions, 9 were classified as highly virulent serotypes (k1, k2, k20, and k54). In addition, MLST analysis detected 13 sequence types (STs), with the predominant ones being ST11 and ST15. The eBURST analysis revalued the existence of 11 singleton STs and one group, which is comprised of ST11 and ST437. CONCLUSIONS: The wide diversity of detected integrons suggested that the horizontal transfer by mobile genetic elements played a major role in the distribution of antimicrobial resistance genes, thereby indicating the urgent need to use effective means of avoiding the spread of drug-resistant bacteria.

The equity of China's emergency medical services from 2010-2014.

BACKGROUND: With the depth development of health care system reform in China, emergency medical services (EMS) is confronted with challenges as well as opportunities. This study aimed to analyze the equity of China's EMS needs, utilization, and resources distribution, and put forward proposal to improve the equity. METHOD: Three emergency needs indicators (mortality rate of cardiovascular and cerebrovascular diseases, harm, and digestive system disease), two utilization indicators (emergency outpatient visits and rate of utilization) and one resource allocation indicator (number of EMS facilities) were collected after the review of the China Statistical Yearbook and the National Disease Surveillance System. Next, EMS related indicators were compared among 31 provinces from the eastern, central, and western regions of the country. Concentration Index (CI) were used to measure the equity of EMS needs and utilization among the western, central, and eastern regions. The Gini coefficient of demographic and geographic distribution of facilities represented the equity of resource allocation. RESULT: During 2010-2014, the CI of cardiovascular and cerebrovascular disease mortality changed from positive to negative, which indicates that the concentrated trend transferred from richer regions to the poorer area. Injury mortality (CI: range from - 0.1241to -0.1504) and digestive disease mortality (CI: range from - 0.1921 to - 0.2279) consistently concentrated in the poorer region, and the inequity among regions became more obviously year-by-year. The utilization of EMS (CI: range from 0.1074 to 0.0824) showed an improvement; however, the inequity reduced gradually. The EMS facilities distribution by population (Gini coefficient: range from 0.0922 to 0.1200) showed high equitability but the EMS facilities distribution by geography (Gini coefficient: range from 0.0922 to 0.1200) suggested a huge gap between regions because the Gini coefficients were greater than 0.5 in the past 5 years. CONCLUSION: There are some inequities of needs, utilization, and resource allocation in the China EMS. The government needs to stick to the principle of increasing investment in poorer regions, perfecting ambulance configuration and improving health workers' professional skills to improve the equity and quality of EMS.

Inhibition of α-Synuclein contributes to the ameliorative effects of dietary flavonoids luteolin on arsenite-induced apoptotic cell death in the dopaminergic PC12 cells.

Arsenite is a toxic metalloid that may increase the risk of Parkinson's disease by inducing dopaminergic neuronal apoptosis. Luteolin, a common dietary flavonoid, possesses variety of biological functions, but potential effects of luteolin on arsenite toxicity remain elusive. In this study, we demonstrated that luteolin prevented arsenite-induced apoptosis in the dopaminergic PC12 cells. Administration of luteolin to cells attenuated arsenite-induced ROS production, enhanced caspase-3 activity and γ-H2AX expression. Our results further showed the expression of α-Synuclein (α-Syn) was significantly increased in arsenite-treated cells, but co-treatment with luteolin reversed the expression of α-Syn back toward normal level. Inhibition of α-Syn by siRNA remarkably enhanced the beneficial effect of luteolin against arsenite-induced apoptotic cell death. Taken together, these results demonstrate that the ameliorative effects of luteolin against arsenite in the dopaminergic cell may be modulated by α-Syn, and indicating that luteolin may be developed as a chemopreventive supplementary agent to ameliorate dopaminergic cell apoptosis resulting from arsenite exposure.