Subacute exposure to dechlorane 602 dysregulates gene expression and immunity in the gut of mice.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)- 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study.

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: A population-based case-control study.

BACKGROUND: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. METHODS: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. RESULTS: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). CONCLUSIONS: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Past and Recent Salted Fish and Preserved Food Intakes Are Weakly Associated with Nasopharyngeal Carcinoma Risk in Adults in Southern China.

BACKGROUND: Chinese-style salted fish intake in early life is considered an established risk factor for nasopharyngeal carcinoma (NPC). However, results for adult intakes of salted fish and preserved foods are inconsistent. OBJECTIVE: The aim of this study was to ascertain the relations of Chinese-style hard and soft salted fish and preserved food intakes with NPC risk. METHODS: We conducted a population-based case-control study in southern China with 2554 NPC cases identified through a rapid case ascertainment system and 2648 healthy controls, frequency-matched on age, sex, and area. Subjects (aged 20-74 y) were interviewed via a food-frequency questionnaire, including information on portion size. Data were also collected on alcohol consumption and potential confounders. Food intake was grouped into 3-5 energy-adjusted intake levels during adulthood (10 y prior) and adolescence (16-18 y). For childhood (at age 10 y), intake frequency of selected food items was collected. Multivariate-adjusted ORs with 95% CIs were estimated via logistic regression. RESULTS: We found no association between NPC and intake of hard Chinese-style salted fish during adulthood, and an increased risk at the highest level of intake during adolescence (OR: 1.19; 95% CI: 1.03, 1.39). In contrast, we found a decreased risk for the middle intake level of soft salted fish during adulthood (OR: 0.68; 95% CI: 0.57, 0.81) and adolescence (OR: 0.71; 95% CI: 0.59, 0.85). Preserved foods showed contrasting risk profiles, e.g., the highest adult intake level of salted egg (OR: 1.51; 95% CI: 1.22, 1.87) and fermented black beans (OR: 0.67; 95% CI: 0.56, 0.80). Associations with NPC were weaker than previously reported, e.g., for weekly childhood intake of salted fish (OR: 1.56; 95% CI: 1.24, 1.97). CONCLUSIONS: Hard and soft salted fish have different risk profiles. Salted fish and other preserved foods were at most weak risk factors for NPC in all periods and may play a smaller role in NPC occurrence than previously thought.

Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.

Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear-nose-throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2,532 persons with NPC and 2,597 controls, aged 20-74 years, from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically nonsignificant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related medication use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related medications cannot be excluded.

Nrf2 Signaling Pathway Mediates the Antioxidative Effects of Taurine Against Corticosterone-Induced Cell Death in HUMAN SK-N-SH Cells.

Substantial evidence has shown that elevated circulating corticosteroids or chronic stress contributes to neuronal cell death, cognitive and mental disorders. However, the underlying mechanism is still unclear. Taurine is considered to protect neuronal cells from apoptotic cell death in neurodegenerative diseases and neuropsychiatric disorders. In the present study, the protective effects of taurine against corticosterone (CORT)-induced oxidative damage in SK-N-SH neuronal cells were investigated. The results showed that CORT significantly induced cell death, which was blocked by pretreatment with taurine. Similarly, pretreatment with taurine suppressed CORT-induced apoptotic cell death decreasing the levels of intracellular reactive oxygen species and improving mitochondrial function. Pretreatment with taurine increased the expression of phosphorylated extracellular regulated protein kinases (ERK) as well as the nuclear translocation of nuclear factor (erythroid 2-derived)-like 2 (Nrf2) in the CORT rich environment. Furthermore, administration of the ERK inhibitor U0126 or transient (siRNA) silencing of Nrf2 blocked the protective effects of taurine on cell viability and expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the CORT model of neuronal damage. These results suggest that the Nrf2 signaling pathway may play a role in the protection mechanism of taurine against CORT-induced neuronal oxidative damage.

Cadmium immobilization in river sediment using stabilized nanoscale zero-valent iron with enhanced transport by polysaccharide coating.

Proper management of metal-contaminated sediment plays a key role in sediment recovery and reuse. This study synthesized two kinds of stabilized nanoscale zero-valent iron (nZVI) with starch (S-nZVI) and carboxymethyl cellulose (C-nZVI) for the in situ immobilization of Cd(II) in river sediment and investigated their transport in porous media. Experimental data showed that when the sediment sample was treated with C-nZVI for 56 days at a dosage ranging from 5 to 10 mg/g-sediment as Fe0, the TCLP (toxicity characteristic leaching procedure) leachability of Cd(II) in the sediment decreased by 93.75-96.43%, and the PBET (physiologically-based extraction test) bioaccessibility of Cd(II) decreased by 22.79-71.32%. Additionally, the acid soluble fraction of Cd(II) was partially transformed to a residual fraction, resulting in a 32.4-33.1% decrease of acid soluble Cd(II) and a 125.4-205.6% increase of the residual-Cd(II) fraction. Surface complexation with iron oxyhydroxide minerals might be the main mechanism of Cd(II) immobilization in sediment. Column experiments indicate that starch or carboxymethyl cellulose (CMC) could extend the travel distance of nZVI, but inherent site physical and chemical heterogeneities still posed challenges for nanoparticle transport. Over all, this study verifies the effectiveness of stabilized nZVI for Cd(II) immobilization in sediment and discusses the potential immobilization mechanism.

Active and Passive Smoking and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers.

Quantification of familial risk of nasopharyngeal carcinoma in a high-incidence area.

BACKGROUND: To the authors' knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations. METHODS: The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC. RESULTS: Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls. CONCLUSIONS: Individuals with a family history of NPC have a substantially higher risk of NPC. These relative and cumulative risk estimates can guide the development of strategies for early detection and clinical consultation in populations with a high incidence of NPC. Cancer 2017;123:2716-25. © 2017 American Cancer Society.

SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons.

It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity.

Characteristics of airborne Staphylococcus aureus (including MRSA) in Chinese public buildings.

The aim of this study was to evaluate the concentration and size distribution of airborne culturable Staphylococcus aureus (S. aureus) (including MRSA) in Chinese public buildings. Air samples were collected, using six-stage Andersen sampler from five different public buildings in one large Chinese community. The mean indoor concentrations of the total and respirable airborne S. aureus were 72 and 50 CFU/m3 in the general hospital, 72 and 49 CFU/m3 in the kindergarten, 76 and 52 CFU/m3 in the hotel, 84 and 57 CFU/m3 in the movie theater, and 55 and 40 CFU/m3 in the university classroom. Respirable S. aureus amounted to approximately 57-73 % of the total S. aureus concentrations. Mean total and respirable concentrations of airborne MRSA were 32 and 20 CFU/m3 in the general hospital, 20 and 13 CFU/m3 in the kindergarten, 23 and 16 CFU/m3 in the hotel, 33 and 20 CFU/m3 in the movie theater, and 24 and 17 CFU/m3 in the university classroom. Respirable MRSA amounted to approximately 61-72 % of the total MRSA concentrations. The ratios of indoor and outdoor concentration for airborne S. aureus and MRSA were more than 1.0 in all the investigated public buildings. The size distribution results showed relatively high collection rates on stage 4 (2.1-3.3 µm) for both airborne culturable S. aureus and MRSA regardless of the type of public buildings.

Excellent temperature performance of spherical LiFePO4/C composites modified with composite carbon and metal oxides.

Nanosized spherical LiFePO4/C composite was synthesized from nanosized spherical FePO4 ·2H2O, Li2C2O4, aluminum oxide, titanium oxide, oxalic acid, and sucrose by binary sintering process. The phases and morphologies of LiFePO4/C were characterized using SEM, TEM, CV, EIS, EDS, and EDX as well as charging and discharging measurements. The results showed that the as-prepared LiFePO4/C composite with good conductive webs from nanosized spherical FePO4 ·2H2O exhibits excellent electrochemical performances, delivering an initial discharge capacity of 161.7 mAh·g(-1) at a 0.1 C rate, 152.4 mAh·g(-1) at a 1 C rate and 131.7 mAh·g(-1) at a 5 C rate, and the capacity retention of 99.1%, 98.7%, and 95.8%, respectively, after 50 cycles. Meanwhile, the high and low temperature performance is excellent for 18650 battery, maintaining capacity retention of 101.7%, 95.0%, 88.3%, and 79.3% at 55°C, 0°C, -10°C, and -20°C by comparison withthat of room temperature (25°C) at the 0.5 C rate over a voltage range of 2.2 V to 3.6 V, respectively.

Temporal dynamic effects of meteorological factors and air quality on the physical health of the older adults in Shenzhen, China.

Introduction: Meteorological and environmental factors can affect people's lives and health, which is crucial among the older adults. However, it is currently unclear how they specifically affect the physical condition of older adults people. Methods: We collected and analyzed the basic physical examination indicators of 41 older adults people for two consecutive years (2021 and 2022), and correlated them with meteorological and environmental factors. Partial correlation was also conducted to exclude unrelated factors as well. Results: We found that among the physical examination indicators of the older adults for two consecutive years, five indicators (HB, WBC, HbAlc, CB, LDL-C) showed significant differences across the population, and they had significantly different dynamic correlation patterns with six meteorological (air pressure, temperature, humidity, precipitation, wind speed, and sunshine duration) and seven air quality factors (NO2, SO2, PM10, O3-1h, O3-8h, CO, PM2.5). Discussion: Our study has discovered for the first time the dynamic correlation between indicators in normal basic physical examinations and meteorological factors and air quality indicators, which will provide guidance for the future development of policies that care for the healthy life of the older adults.

Biotransformation and Gut Microbiota-Mediated Bioactivity of Flavonols.

Consumption of fruits and vegetables has been associated with a reduced risk of multiple diseases, such as metabolic disorders. Flavonols are the most ubiquitous flavonoids in fruits and vegetables. However, dietary flavonols exhibit a general low oral bioavailability for their extensive biotransformation mediated by phase II enzymes in enterocytes and liver as well as by microbiota in the gut lumen. In this context, flavonols have brought attention to a paradox between low bioavailability and health-promoting effects. Flavonols are often transformed prior to absorption, which could change their biological activity. Compared to their parent compounds, the corresponding metabolites of flavonols in vivo might exhibit similar or higher intrinsic bioactivities, or perhaps a decreased efficacious effectiveness. Indeed, a growing body of evidence from biological function studies of metabolites supports the positive and significant contribution of in vivo metabolic processes, particularly conversion mediated by gut microbiota, to the health-promoting benefits of flavonols. As such, further understanding of the metabolic fate of flavonols and biological activities of their metabolites as well as the possible impact of microbiota-mediated conversion on the bioactivity is of great significance to guide a rational diet with flavonol-rich fruits and vegetables and/or flavonol-containing functional foods.

A Study on Parents' Attitudes towards Middle School Students' Online Learning Based on Statistical Analysis.

Based on the role separation scenario in which students need parental support, this paper explores the effect of parents' attitude on secondary school students' online learning. Through structural equation model analysis and regression analysis of 745 valid responses to a questionnaire, the data results show that parents' subjective dimension includes perceived gain and perceived loss, and social factor dimension includes teachers' influence and online comments. Perceived value is the key influencing factor of parents' attitude towards secondary school students in online learning platform. Perceived usefulness and platform information influence parents' attitude positively and significantly, while perceived risk influences parents' attitude negatively and significantly. In the dimension of social factors, teachers' influence positively influences parents' attitude, and online comments modulate the influence of perceived value on parents' attitude.

SARS-CoV-2 Aerosol Transmission Through Vertical Sanitary Drains in High-Rise Buildings - Shenzhen, Guangdong Province, China, March 2022.

What is already known about this topic?: Aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via sanitary pipelines in high-rise buildings is possible, however, there is a lack of experimental evidence. What is added by this report?: The field simulation experiment confirmed the existence of a vertical aerosol transmission pathway from toilet flush-soil stack-floor drains without water seal. This report provided experimental evidence for vertical aerosol transmission of clustered outbreaks on 18 floors of a 33-story residential building. What are the implications for public health practice?: The water seal on floor drains is a necessary barrier to prevent the risk of vertical aerosol transmission of infectious disease pathogens in buildings. It is necessary not only to have a U-shaped trap in the drainage pipe, but also to be filled with water regularly.

Subacute effects of the chlorinated flame retardant dechlorane 602 on intestinal microenvironment in mice.

BACKGROUND: Chlorinated flame retardant Dechlorane 602 (Dec 602) has been detected in daily food, indicating that it may pose a risk to intestinal health. The intestinal microenvironment plays an important role in intestinal health. Intestinal microbiota and metabolites are two important factors for maintaining the microenvironment. However, little is known about the effects of Dec 602 on intestinal microbiota and metabolites. OBJECTIVES: We aimed to probe the effects of Dec 602 on the intestine by revealing the changes that Dec 602 caused to the intestinal microbiota and metabolites. METHODS: Adult female C57BL/6 mice were exposed to Dec 602 (low/high doses: 1.0/10.0 µg/kg body weight per day) orally for 7 consecutive days, and sacrificed after 7 days of recovery. The composition of colonic microbiota was measured by 16S rRNA gene sequencing, and the colonic metabolites were determined by LC-ESI-MS/MS. Finally, the effects of Dec 602 on the colon were validated by histopathological analysis. RESULTS: The intestinal microbiota composition was altered toward a pro-inflammatory status after exposure to Dec 602. Dec 602 exposure also up-regulated oxidative metabolites (glutathione disulfide, taurine and retinoic acid) and pro-inflammatory metabolites (prostaglandin E2). On the other hand, antioxidative metabolites (s-adenosylmethionine and 11-cis-retinol) and anti-inflammatory metabolites (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) were down-regulated after exposure to Dec 602. Infiltration of lymphocytes in the colonic lamina propria was observed in the mice treated with Dec 602 for 7 days, and it was not recovered after another 7 days without further treatment. CONCLUSION: Dec 602 interfered with the colonic microbiota and metabolome, and exhibited inflammatory features. Histopathological studies confirmed that Dec 602 exposure did induce colonic inflammation.

HIF-1alpha/VEGF pathway mediates 1,3,6,8-tetrabromo-9 H-carbazole-induced angiogenesis: a potential vascular toxicity of an emerging contaminant.

The dioxin-like substances polyhalogenated carbazoles (PHCZs) may trigger the aryl hydrocarbon receptor (AhR) signaling pathway. Although the crosstalk between AhR and the hypoxia inducible factor-1 (HIF-1) pathways is generally believed to occur, the exact mechanisms of the HIF-1 pathway in PHCZ toxicity have not been determined. We aimed to elucidate the effect of PHCZs on the HIF-1 pathway and its involvement in the regulation of target genes of HIF-1. Herein, we employed human HepG2 cells transiently transfected with a hypoxia response element (HRE) luciferase reporter to identify PHCZs that could influence HIF-1 pathway. We found that exposure to one of the four selected PHCZs, specifically 1,3,6,8-tetrabromo-9 H-carbazole (1368-BCZ), induced a significant enhancement of the activity of HRE activity. In silico data supported 1368-BCZ-induced HIF-1α activity preferentially. Moreover, 1368-BCZ significantly upregulated the expression of HIF-1 target genes, including endothelial growth factor (VEGF) and erythropoietin. Importantly, the stimulated secretion of VEGF by 1368-BCZ promoted the angiogenesis in human umbilical vein endothelial cells. Therefore, the present experimental and computational studies provide new and direct evidence of 1368-BCZ - HIF-1 interaction, which sheds light on the HIF-mediated cardiovascular toxicity and allows a knowledge-based risk assessment of emerging pollutants.

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

BACKGROUND: Metal exposures are suspected to associate with the risk of hyperuricemia (HUA), but the current results are still conflicting. OBJECTIVE: To investigate the associations between multiple plasma metal exposures and HUA risk. METHODS: A cross-sectional study was conducted in 1406 Chinese Han adults who underwent routine physical examination in the Eighth Affiliated Hospital of Sun Yat-Sen University in Shenzhen. The plasma levels of 13 metals were measured by the inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic, linear regression models, least absolute shrinkage and selection operator (LASSO) penalized regression analysis, and restricted cubic spline (RCS) models were applied to assess the associations. RESULTS: The median plasma uric acid concentration in HUA group (434 µmol/L) was significantly higher than that in non-HUA group (305 µmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 1.62(1.08-2.43) for magnesium, 1.61(1.05-2.47) for copper, 1.62(1.06-2.49) for zinc, 1.87(1.26-2.81) for arsenic, 1.50(1.01-2.23) for selenium, and 1.70(1.16-2.49) for thallium based on the single-metal logistic regression models, comparing the highest versus the lowest quartile of metal levels. Further multi-metal logistic, linear regression models and the LASSO analysis all indicated positive associations of zinc, arsenic with HUA risk or uric acid levels. RCS model indicated an inverted V-shaped positive association between zinc levels and HUA risk (p for non-linearity = 0.048, p for overall association = 0.022), while arsenic levels showed a positive and linear dose-response relationship with HUA risk (p for non-linearity = 0.892, p for overall association<0.001). CONCLUSIONS: Higher plasma levels of zinc and arsenic might increase HUA risk and showed positive dose-response relationships. Further cohort studies in larger population are required to testify our findings.

Non-Structural Protein 3 of Duck Tembusu Virus Induces Autophagy via the ERK and PI3K-AKT-mTOR Signaling Pathways.

Despite autophagy's pivotal role in the replication of viruses such as duck Tembusu virus (DTMUV), which has caused massive economic losses to the poultry industry in the world, the specific relationships between DTMUV and cellular autophagy remain largely unknown. In response, we investigated the interactions between autophagy and DTMUV, the effects of the structural and non-structural proteins of DTMUV on autophagy, and the autophagy-related signaling pathways induced by DTMUV. Among the results, DTMUV increased the autophagy flux in duck embryo fibroblasts (DEF) and BHK-21 cells, while autophagy facilitated viral replication. After we pharmacologically induced autophagy with rapamycin (RAPA), the replication of DTMUV increased by 15.23-fold compared with the control group of DEF cells. To identify which DTMUV protein primarily induced autophagy, all three structural proteins and seven non-structural proteins of DTMUV were transfected into cells, and the results showed that non-structural protein 3 (NS3) induced significant autophagy in DEF cells. By means of Western blot, immunofluorescence, and transmission electron microscopy, we confirmed that NS3 protein could significantly induce autophagy and autophagy flux. Furthermore, we showed that NS3 induced autophagy in DEF cells through extracellular signal-regulated kinase 2 (ERK2) and phosphatidylinositol-3-kinase (PI3K)/AKT and the mammalian target of rapamycin (mTOR) signaling pathways using specific inhibitors and RNA interference assays. Finally, autophagy induced by NS3 promoted DTMUV replication. These results provide novel insight into the relationship between DTMUV and autophagy, broadening the current understanding of the molecular pathogenesis of DTMUV.