Extreme Temperature Events, Fine Particulate Matter, and Myocardial Infarction Mortality.

BACKGROUND: Extreme temperature events (ETEs), including heat wave and cold spell, have been linked to myocardial infarction (MI) morbidity; however, their effects on MI mortality are less clear. Although ambient fine particulate matter (PM2.5) is suggested to act synergistically with extreme temperatures on cardiovascular mortality, it remains unknown if and how ETEs and PM2.5 interact to trigger MI deaths. METHODS: A time-stratified case-crossover study of 202 678 MI deaths in Jiangsu province, China, from 2015 to 2020, was conducted to investigate the association of exposure to ETEs and PM2.5 with MI mortality and evaluate their interactive effects. On the basis of ambient apparent temperature, multiple temperature thresholds and durations were used to build 12 ETE definitions. Daily ETEs and PM2.5 exposures were assessed by extracting values from validated grid datasets at each subject's geocoded residential address. Conditional logistic regression models were applied to perform exposure-response analyses and estimate relative excess odds due to interaction, proportion attributable to interaction, and synergy index. RESULTS: Under different ETE definitions, the odds ratio of MI mortality associated with heat wave and cold spell ranged from 1.18 (95% CI, 1.14-1.21) to 1.74 (1.66-1.83), and 1.04 (1.02-1.06) to 1.12 (1.07-1.18), respectively. Lag 01-day exposure to PM2.5 was significantly associated with an increased odds of MI mortality, which attenuated at higher exposures. We observed a significant synergistic interaction of heat wave and PM2.5 on MI mortality (relative excess odds due to interaction >0, proportion attributable to interaction >0, and synergy index >1), which was higher, in general, for heat wave with greater intensities and longer durations. We estimated that up to 2.8% of the MI deaths were attributable to exposure to ETEs and PM2.5 at levels exceeding the interim target 3 value (37.5 µg/m3) of World Health Organization air quality guidelines. Women and older adults were more vulnerable to ETEs and PM2.5. The interactive effects of ETEs or PM2.5 on MI mortality did not vary across sex, age, or socioeconomic status. CONCLUSIONS: This study provides consistent evidence that exposure to both ETEs and PM2.5 is significantly associated with an increased odds of MI mortality, especially for women and older adults, and that heat wave interacts synergistically with PM2.5 to trigger MI deaths but cold spell does not. Our findings suggest that mitigating both ETE and PM2.5 exposures may bring health cobenefits in preventing premature deaths from MI.

Ozone, Heat Wave, and Cardiovascular Disease Mortality: A Population-Based Case-Crossover Study.

A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O3) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O3 and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O3; 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O3 exposures ranged from 1.029 to 1.107 compared with low-level O3, while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O3 and heat wave exposures, which were generally greater with higher levels of the O3 exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O3 and heat wave. Women and older adults were more vulnerable to the exposure to O3 and heat wave exposure. Exposure to both O3 and heat wave was significantly associated with an increased odds of CVD mortality, and O3 and heat wave can interact synergistically to trigger CVD deaths.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES: To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS: We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS: Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 µg/m3), OC (4.56 µg/m3), and nitrate (1.41 µg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS: This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Long-term exposure to fine particulate matter and site-specific cancer mortality: A difference-in-differences analysis in Jiangsu province, China.

BACKGROUND: Accumulating studies have reported that chronic exposure to ambient fine particulate matter (PM2.5) can lead to adverse effects on lung cancer mortality; however, such chronic effects are less clear for mortality from other site-specific cancers. OBJECTIVE: To explore the causal effect of long-term PM2.5 exposure on mortality from all-site and a variety of site-specific cancers in Jiangsu province, China during 2015-2020 using a difference-in-differences analysis. METHODS: For each of 53 county-based spatial units in Jiangsu province, we calculated annual death counts for all-site cancer and 23 site-specific cancers. Using a validated high-resolution PM2.5 grid dataset, long-term PM2.5 exposure of a spatial unit within a given year was evaluated as the average of population-weighted annual concentrations during recent 10 years. Conditional Poisson regression models were employed to evaluate exposure-response associations adjusting for spatial and temporal variables, seasonal temperatures, relative humidity, and gross domestic product (GDP). RESULTS: During the study period, we identified 947,337 adult cancer deaths in Jiangsu province. Each 1 µg/m3 increment in PM2.5 exposure was significantly associated with a 2.7% increase in the risk of all-site cancer mortality. PM2.5-mortality associations were also observed in cancer of lip, oral cavity and pharynx, stomach, colorectum, pancreas, lung, bone and joints, ovary, prostate, and lymphoma (all adjusted P < 0.05), with the relative risks ranging from 1.028 (95% confidence interval [CI]: 1.011, 1.046) for stomach cancer to 1.201 (95% CI: 1.120, 1.308) for bone and joints cancers. Exposure-response curves showed that these associations were close to linearity, though most of them had increasing slopes at high exposure levels. Overall, women and subjects in low GDP regions were more vulnerable to PM2.5 exposures. CONCLUSIONS: Long-term exposure to ambient PM2.5 contributes to a higher risk of mortality from multiple site-specific cancers.

Heat wave exposure and semen quality in sperm donation volunteers: A retrospective longitudinal study in south China.

BACKGROUND: Previous studies have suggested an association between non-optimum ambient temperature and decreased semen quality. However, the effect of exposure to heat waves on semen quality remains unclear. METHODS: Volunteers who intended to donate sperm in Guangdong provincial human sperm bank enrolled. Heat waves were defined by temperature threshold and duration, with a total of 9 definitions were employed, specifying daily mean temperature exceeding the 85th, 90th, or 95th percentile for at least 2, 3, or 4 consecutive days. Residential exposure to heat waves during 0-90 days before ejaculation was evaluated using a validated gridded dataset on ambient temperature. Association and potential windows of susceptibility were evaluated and identified using linear mixed models and distributed lag non-linear models. RESULTS: A total of 2183 sperm donation volunteers underwent 8632 semen analyses from 2018 to 2019. Exposure to heat wave defined as daily mean temperature exceeding the 95th percentile for at least 4 consecutive days (P95-D4) was significantly associated with a 0.11 (95% confidence interval [CI]: 0.03, 0.18) ml, 3.36 (1.35, 5.38) × 106/ml, 16.93 (7.95, 25.91) × 106, and 2.11% (1.4%, 2.83%) reduction in semen volume, sperm concentration, total sperm number, and normal forms, respectively; whereas exposure to heat wave defined as P90-D4 was significantly associated with a 1.98% (1.47%, 2.48%) and 2.08% (1.57%, 2.58%) reduction in total motility and progressive motility, respectively. Sperm count and morphology were susceptible to heat wave exposure during the early stage of spermatogenesis, while sperm motility was susceptible to exposure during the late stage. CONCLUSION: Heat wave exposure was significantly associated with a reduction in semen quality. The windows of susceptibility during 0-90 days before ejaculation varied across sperm count, motility, and morphology. Our findings suggest that reducing heat wave exposure before ejaculation may benefit sperm donation volunteers and those attempting to conceive.

Association between thermal stress and cardiovascular mortality in the subtropics.

Hazardous thermal conditions resulting from climate change may play a role in cardiovascular disease development. We chose the Universal Thermal Climate Index (UTCI) as the exposure metric to evaluate the relationship between thermal conditions and cardiovascular mortality in Shenzhen, China. We applied quasi-Poisson regression non-linear distributed lag models to evaluate the exposure-response associations. The findings suggest that cardiovascular mortality risks were significantly increased under heat and cold stress, and the adverse effects of cold stress were stronger than heat stress. Referencing the 50th percentile of UTCI (25.4°C), the cumulative risk of cardiovascular mortality was 75% (RRlag0-21 =1.75, 95%CI: 1.32, 2.32) higher in the 1st percentile (3.5°C), and 40% (RRlag0-21=1.40, 95%CI: 1.09, 1.80) higher in the 99th percentile (34.1°C). We observed that individuals older than 65 years were more vulnerable to both cold and heat stress, and females were identified as more susceptible to heat stress than males. Moreover, increased mortality risks of hypertensive disease and cerebrovascular disease were observed under cold stress, while heat stress was related to higher risks of mortality for hypertensive disease and ischemic heart disease. We also observed a stronger relationship between cold stress and ischemic heart disease mortality during the cold season, as well as a significant impact of heat stress on cerebrovascular disease mortality in the warm season when compared to the analysis of the entire year. These results confirm the significant relationship between thermal stress and cardiovascular mortality, with age and sex as potential effect modifiers of this association. Providing affordable air conditioning equipment, increasing the amount of vegetation, and establishing comprehensive early warning systems that take human thermoregulation into account could all help to safeguard the well-being of the public, particularly vulnerable populations, in the event of future extreme weather.

The effects of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells.

Emerging evidence suggests that selenium plays an essential role in sperm maturation. However, the specific signaling pathway by which selenium exerts effect has not been elucidated. To evaluate the effect of selenium on GPX4-mediated lipid peroxidation and apoptosis in germ cells, selenium deficiency was modeled by culturing GC2-spd cells in serum-free medium. Treatment with 0.5-µM sodium selenite (NaSe) or 5.0-µM selenomethionine (SeMet) significantly improved the proliferation rate and GPX4 protein expression after selenium deficiency. Moreover, NaSe and SeMet decreased the MDA content and lipid peroxidation. When adenovirus was used to knockdown the expression of the GPX4 gene (shRNA-GPX4), the early apoptosis rate of the shRNA-GPX4 cells was significantly higher than that of the EGFP cells. Increased expression of Caspase3 and Bax, as well as MDA content were observed in the shRNA-GPX4 cells compared with EGFP cells. In further, overexpression of the GPX4 gene (ORF-GPX4) cells exhibited increased cell proliferation and decreased MDA content. However, there was no significant difference in 12/15-lox expression both in ORF-GPX4 cells and shRNA-GPX4 cells. Conclusively, GPX4 was involved in the regulation of lipid peroxidation and apoptosis in GC2-spd cells. Selenium played a role in promoting cell proliferation by mediating GPX4. The regulation of GPX4 may occur independently of 12/15-Lox. These findings confirmed the effect of selenium on spermatogenesis and offered a potential target for treating abnormal semen quality in men.

Short-term exposure to nitrogen dioxide and ischemic stroke incidence in Shenzhen, China: Modification effects by season and temperature.

BACKGROUND AND OBJECTIVES: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO2) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO2 on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature. METHODS: A time-stratified case-crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 µg/m3 increment in NO2. RESULTS: NO2 was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0-5, with 1.81% (95% confidence interval (CI) was 0.86-2.76%) over the full year, 2.75% (1.48-4.03%) in the cold season, and 3.04% (1.74-4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals. CONCLUSIONS: Our findings provide evidence that reductions in NO2 levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO2 modified by season and temperature.

Associations of multiple plasma metals with the risk of metabolic syndrome: A cross-sectional study in the mid-aged and older population of China.

BACKGROUND: Metal exposures have been reported to be related to the progress of metabolic syndrome (MetS), however, the currents results were still controversial, and the evidence about the effect of multi-metal exposure on MetS were limited. In this study, we intended to evaluate the relationships between metal mixture exposure and the prevalence of MetS in a mid-aged and older population of China. METHODS: The plasma levels of 13 metals (aluminum, magnesium, calcium, iron, manganese, cobalt, copper, arsenic, zinc, selenium, cadmium, molybdenum and thallium) were detected by inductively coupled plasma mass spectrometry (ICP-MS) in 1277 adults recruited from the Eighth Affiliated Hospital of Sun Yat-Sen University (Shenzhen, China). Logistic regression, the adaptive least absolute shrinkage and selectionator operator (LASSO) penalized regression analysis and restricted cubic spline (RCS) analysis were used to explore the associations and dose-response relationships of plasma metals with MetS. To evaluate the cumulative effect of metals, the Bayesian Kernel Machine Regression (BKMR) model was applied. RESULTS: The concentrations of magnesium and molybdenum were lower in the MetS group (p < 0.05). In the single-metal model, the adjusted ORs (95%CI) in the highest quartiles were 0.44 (0.35, 0.76) for magnesium and 0.30 (0.17, 0.51) for molybdenum compared with the lowest quartile. The negative associations and dose-dependent relationships of magnesium and molybdenum with MetS were further validated by the stepwise model, adaptive LASSO penalized regression and RCS analysis. The BKMR models showed that the metal mixture were associated with decreased MetS when the chemical mixtures were≥ 25th percentile compared to their medians, and Mg, Mo were the major contributors to the combined effect. Moreover, concentrations of magnesium were significantly related to blood glucose, and molybdenum was related with BMI, blood glucose and blood pressure. CONCLUSIONS: Elevated levels of plasma magnesium and molybdenum were associated with decreased prevalence of MetS. Further investigations in larger perspective cohorts are needed to confirm our findings.

Associations between plasma metal levels and mild renal impairment in the general population of Southern China.

BACKGROUND: Metal exposure were assumed to be closely related with declined renal function, but the conclusions were controversial. We employed diverse statistical models and assessed the association between metal mixture exposure and mild renal impairment. METHODS: A total of 13 plasma metals were measured in 896 general population from Southern China. Subjects with estimated glomerular filtration rate within 60-89 ml/min/1.73 m2 and urinary albumin-creatinine ratio <30 mg/g creatinine were defined as mild renal impairment (MRI). RESULTS: About 31.47 % participants showed MRI. In the multivariate logistic regression models, compared with the first quartile, high levels of arsenic and molybdenum (the fourth quartile) were both associated with MRI, and the ORs (95 % CI) were 1.68 (1.05, 2.68) and 2.21 (1.40, 3.48), respectively. Their predominant roles were identified by the weighted quantile regression (WQS). Besides, restricted cubic spline analysis verified the relationship between molybdenum level and increased MRI risk in a linear and dose-response manner. CONCLUSION: High levels of arsenic and molybdenum might be independent risk factors of MRI, and they showed combined effect. Our findings might provide vigorous evidence in preventing mild decline in renal function.

Role of Essential Amino Acids in Age-Induced Bone Loss.

Age-induced osteoporosis is a global problem. Essential amino acids (EAAs) work as an energy source and a molecular pathway modulator in bone, but their functions have not been systematically reviewed in aging bone. This study aimed to discuss the contribution of EAAs on aging bone from in vitro, in vivo, and human investigations. In aged people with osteoporosis, serum EAAs were detected changing up and down, without a well-established conclusion. The supply of EAAs in aged people either rescued or did not affect bone mineral density (BMD) and bone volume. In most signaling studies, EAAs were proven to increase bone mass. Lysine, threonine, methionine, tryptophan, and isoleucine can increase osteoblast proliferation, activation, and differentiation, and decrease osteoclast activity. Oxidized L-tryptophan promotes bone marrow stem cells (BMSCs) differentiating into osteoblasts. However, the oxidation product of tryptophan called kynurenine increases osteoclast activity, and enhances the differentiation of adipocytes from BMSCs. Taken together, in terms of bone minerals and volume, more views consider EAAs to have a positive effect on aging bone, but the function of EAAs in bone metabolism has not been fully demonstrated and more studies are needed in this area in the future.

Rapid detection of human origin colistin-resistance genes mcr-1, mcr-3, mcr-8, mcr-10 in clinical fecal samples.

Plasmid-mediated colistin-resistance genes have been reported in human origin clinical samples worldwide which raises its threats to human infections. Notably, mcr-1, mcr-3, mcr-8, and mcr-10 have been reported isolated directly from clinical samples which creates more seriously threaten to human health than other mcr gene types. A multiplex polymerase chain reaction (Multi-PCR) protocol was developed to detect and genotype mobile colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes. We first designed four pairs of new primers for the amplification of mcr-1, mcr-3, mcr-8, and mcr-10 gene respectively to achieve stepwise separation of amplicons between 216 and 241 bp, and complete this Multi-PCR system with the assistance of another pair of universal primer. Among which the forward primers for mcr-8 and mcr-10 amplicons were identical. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella from human origin, each well characterized and prospectively validated. The Multi-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The assay could detect all variants of the various mcr alleles described. The Multi-PCR assay successfully genotyped of mcr alleles described in one test.

Determination of carbapenems in water samples by UHPLC-MS/MS.

A rapid and reliable method for the detection of five carbapenems (biapenem, imipenem, doripenem, meropenem, and faropenem) in water was developed and validated. After acidification of water samples with acetic acid, carbapenems were isolated using a Bond Elut PPL cartridge. The target compounds were separated using ultra high performance liquid chromatography with a chromatographic run time of 5 min and detected on a triple quadrupole mass spectrometer operated in positive electrospray ionization and multiple reaction monitoring mode. Mean recoveries were in the range of 76.6-106.5%, with satisfactory intraday and interday relative standard deviations lower than 10.0 and 10.8%, respectively. The limits of detection and quantification were in the ranges of 0.05-0.2 µg/L and 0.1-0.5 µg/L, respectively, depending on the analyte. The proposed method was applied to the analysis of river samples and wastewater samples from swine farms, and no carbapenems were detected in the collected samples.

Proteomics study unveils ROS balance in acid-adapted Salmonella Enteritidis.

Salmonella Enteritidis is a major cause of foodborne gastroenteritis and is thus a persistent threat to global public health. The acid adaptation response helps Salmonella survive exposure to gastric environment during ingestion. In a previous study we highlighted the damage caused to cell membrane and the regulation of intracellular reactive oxygen species (ROS) in S. Enteritidis. In this study, we applied both physiologic and iTRAQ analyses to explore the regulatory mechanism of acid resistance in Salmonella. It was found that after S. Enteritidis was subject to a 1 h period of acid adaptation at pH 5.5, an additional 1 h period of acid shock stress at pH 3.0 caused less Salmonella cell death than in non-acid adapted Salmonella cells. Although there were no significant differences between adapted and non-adapted cells in terms of cell membrane damage (e.g., membrane permeability or lipid peroxidation) after 30 min, intracellular ROS level in acid adapted cells was dramatically reduced compared to that in non-acid adapted cells, indicating that acid adaption promoted less ROS generation or increased the ability of ROS scavenging with little reduction in the integrity of the cell membrane. These findings were confirmed via an iTRAQ analysis. The adapted cells were shown to trigger incorporation of exogenous long-chain fatty acids into the cellular membrane, resulting in a different membrane lipid profile and promoting survival rate under acid stress. S. Enteritidis experiences oxidative damage and iron deficiency under acid stress, but after acid adaption S. Enteritidis cells were able to balance their concentrations of intracellular ROS. Specifically, SodAB consumed the free protons responsible for forming reactive oxygen intermediates (ROIs) and KatE protected cells from the toxic effects of ROIs. Additionally, acid-labile proteins released free unbound iron promoting ferroptotic metabolism, and NADH reduced GSSH to G-SH, protecting cells from acid/oxidative stress.

miR-129-2-3p directly targets SYK gene and associates with the risk of ischaemic stroke in a Chinese population.

Spleen tyrosine kinase (SYK) gene has been identified as novel susceptibility locus for ischaemic stroke (IS) previously. However, regulation of SYK gene remains unknown in IS. In this study, we aimed to identify miRNAs that might be involved in the development of IS by targeting SYK gene. miRNAs were firstly screened by bioinformatics predicting tool. The expression levels of SYK gene were detected by qRT-PCR and western blotting, respectively, after miRNA transfection. Luciferase reporter assay was applied to investigate the direct binding between miRNAs and target gene. miRNA levels were detected by miRNA TaqMan assays in the blood cells of 270 IS patients and 270 control volunteers. Results suggest that SYK gene might be a direct target of miR-129-2-3p. The blood level of miR-129-2-3p was significantly lower in IS patients (P < 0.05), and negatively associated with the risk of IS (adjusted OR: 0.88; 95% CI: 0.80-0.98; P = 0.021) by multivariable logistic regression analysis. The blood levels of SYK gene were significantly higher in IS patients, and miR-129-2-3p expression was negatively correlated with mean platelet volume. In summary, our study suggests that miR-129-2-3p might be involved in the pathogenesis of IS through interrupting SYK expression and the platelet function, and further investigation is needed to explore the underlying mechanism.

Emerging erm(B)-Mediated Macrolide Resistance Associated with Novel Multidrug Resistance Genomic Islands in Campylobacter.

The rapid dissemination of the macrolide resistance gene erm(B) will likely compromise the efficacy of macrolides as the treatment of choice for campylobacteriosis. More importantly, erm(B) is always associated with several multidrug resistance genomic islands (MDRGIs), which confer resistance to multiple other antimicrobials. Continuous monitoring of the emergence of erm(B) and analysis of its associated genetic environments are crucial for our understanding of macrolide resistance in Campylobacter In this study, 290 Campylobacter isolates (216 Campylobacter coli isolates and 74 Campylobacter jejuni isolates) were obtained from 1,039 fecal samples collected in 2016 from pigs and chickens from three regions of China (344 samples from Guangdong, 335 samples from Shanghai, and 360 samples from Shandong). Overall, 74 isolates (72 C. coli isolates and 2 C. jejuni isolates) were PCR positive for erm(B). Combined with data from previous years, we observed a trend of increasing prevalence of erm(B) in C. coli Pulsed-field gel electrophoresis analyses suggested that both clonal expansion and horizontal transmission were involved in the dissemination of erm(B) in C. coli, and three novel types of erm(B)-associated MDRGIs were identified among the isolates. Furthermore, 2 erm(B)-harboring C. jejuni isolates also contained an aminoglycoside resistance genomic island and a multidrug-resistance-enhancing efflux pump, encoded by RE-cmeABC Antimicrobial susceptibility testing showed that most of the isolates were resistant to all clinically important antimicrobial agents used for the treatment of campylobacteriosis. These findings suggest that the increasing prevalence of erm(B)-associated MDRGIs might further limit treatment options for campylobacteriosis.

Different effects of titanium dioxide nanoparticles instillation in young and adult mice on DNA methylation related with lung inflammation and fibrosis.

Wide use of titanium dioxide nanoparticles (TiO2 NPs) as white pigments induces unintentionally release in environment which increases concerns about their adverse health effects on respiratory system. So it is crucial to get a deep understanding of the disease process and molecular mechanism. Epigenetic mechanisms, such as DNA methylation, have been found to play a role in the development of lung diseases by affecting expression of key genes. In addition, there could be potential different toxic effects of TiO2 NPs between young and adult. Thus, the comparative toxicity of TiO2 NPs in 5-week (young) and 10-week (adult) old NIH mice is investigated in this study following nasal inhalation of TiO2 NPs at dose of 20 mg/kg (body weight)/day for 30 days. Global DNA methylation and hydroxymethylation in lung were measured. Promoter methylation of inflammatory genes (IFN-γ and TNF-α) and tissue fibrosis gene (Thy-1) were determined. Additional, RNA-sequencing runs were performed on the pulmonic libraries. We found the induced pulmonary inflammation and fibrosis were more severe in young mice. Decreased global methylation and hydroxymethylation were only found in the young group. The altered methylation in promoter of TNF-α and Thy-1 were found to play a role in the inflammatory response and fibration. RNA-sequencing showed that in pathways in cancer expression of 197 genes was up-regulated in the young mice more that in the adult mice. All these results suggested that the young ages are more sensitive to TiO2 NP exposure and the potential of abnormal DNA methylation might be used as biomarkers of both exposure and disease development.

Association between whole grain intake and breast cancer risk: a systematic review and meta-analysis of observational studies.

BACKGROUND: Epidemiological studies have found that high whole grain intake may be associated with a reduced risk of breast cancer. However, the evidence has not been consistent. We conducted a meta-analysis to quantitatively assess the association between whole grain intake and breast cancer risk. METHODS: Relevant observational studies were identified by searching PubMed, Embase, Cochrane library databases, and Google Scholar through April 2017. Summary relative risk (RR) estimates were calculated using random-effects meta-analysis. RESULTS: A total of 11 studies, including 4 cohort and 7 case-control studies and involving 131,151 participants and 11,589 breast cancer cases, were included in the current meta-analysis. The pooled RR of breast cancer for those with high versus low whole grain intake was 0.84 (95% confidence interval [CI]: 0.74 to 0.96, p = 0.009; I2 = 63.8%, p for heterogeneity = 0.002). Subgroup analysis by study design found a significant inverse association in the case-control studies (RR: 0.69; 95% CI: 0.56 to 0.87, p = 0.001; I2 = 58.2%, p for heterogeneity = 0.026), but not in the cohort studies (RR, 0.96; 95% CI: 0.82 to 1.14, p = 0.69; I2 = 66.7%, p for heterogeneity = 0.029). In addition, stratified analysis suggested that sample size could be a potential source of heterogeneity. CONCLUSIONS: Results of the current meta-analysis suggest that high intake of whole grains might be inversely associated with a reduced risk of breast cancer, and the inverse association was only observed in case-control but not cohort studies. More large-scale cohort studies are needed to confirm the inverse association observed.

A Genetic Variant in Pre-miR-146a (rs2910164 C>G) Is Associated with the Decreased Risk of Acute Coronary Syndrome in a Chinese Population.

MicroRNAs (miRNAs) can contribute to the development of cardiovascular diseases, and single nucleotide polymorphisms (SNPs) in miRNA genes may influence disease susceptibility by altering mature miRNA expression levels. However, the effect of SNPs located in miR-146a and miR-196a2 genes on risk of acute coronary syndrome (ACS) has not been reported in the Chinese population. Two miRNA polymorphisms located in miRNA genes (miR-146a rs2910164 C>G and miR-196a2 rs11614913 T>C) were genotyped in 722 ACS patients and 721 control subjects. The CG genotype of rs2910164 was significantly associated with decreased risk of ACS [CG vs. CC, odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.55-0.95, P = 0.020; dominant model, OR = 0.77, 95% CI: 0.60-0.99, P = 0.044]. We did not find any association of rs11614913 with the risk of ACS. Stratification analysis showed that the rs2910164 CG genotype was associated with decreased risk of ACS (dominant model) in males, subjects with body mass index more than 24 kg/m(2), and in hypertensive subjects. Significant combined effects were also observed between rs2910164 and blood lipids or C-reactive protein levels. In summary, this study provides the first evidence that the CG genotype of miR-146a rs2910164 is associated with a significantly decreased risk of ACS in a Chinese population. Moreover, rs2910164 and blood lipids or an inflammatory marker may have a combined effect on the onset of ACS. These findings indicate that miR-146a rs2910164 may act as a novel molecular marker for ACS susceptibility.