Effectiveness of enterovirus A71 vaccine against pediatric HFMD and disease profile of post-vaccination infection.

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.

Incorporating environmental capacity considerations to prioritize control factors for the management of heavy metals in soil.

Heavy metals (HMs) pollution threatens food security and human health. While previous studies have evaluated source-oriented health risk assessments, a comprehensive integration of environmental capacity risk assessments with pollution source analysis to prioritize control factors for soil contamination is still lacking. Herein, we collected 837 surface soil samples from agricultural land in the Nansha District of China in 2019. We developed an improved integrated assessment model to analyze the pollution sources, health risks, and environmental capacities of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn. The model graded pollution source impact on environmental capacity risk to prioritize control measures for soil HMs. All HMs except Pb exceeded background values and were sourced primarily from natural, transportation, and industrial activities (31.26%). Approximately 98.92% (children), 97.87% (adult females), and 97.41% (adult males) of carcinogenic values exceeded the acceptable threshold of 1E-6. HM pollution was classified as medium capacity (3.41 kg/hm2) with mild risk (PI = 0.52). Mixed sources of natural backgrounds, transportation, and industrial sources were identified as priority sources, and As a priority element. These findings will help prioritize control factors for soil HMs and direct resources to the most critical pollutants and sources of contamination, particularly when resources are limited.

Prioritization of control factors for heavy metals in groundwater based on a source-oriented health risk assessment model.

Heavy metals (HMs) in groundwater seriously threaten ecological safety and human health. To facilitate the effective management of groundwater contamination, priority control factors of HMs in groundwater need to be categorized. A total of 86 groundwater samples were collected from the Huangpi district of Wuhan city, China, during the dry and wet seasons. To determine priority control factors, a source-oriented health risk assessment model was applied to compare the pollution sources and health risks of seven HMs (Cu, Pb, Zn, Cr, Ni, As, and Fe). The results showed that the groundwater had higher As and Fe contents. The sources of HM pollution during the wet period were mainly industrial and agricultural activities and natural sources. During the dry period, origins were more complex due to the addition of domestic discharges, such as sewage wastewater. Industrial activities (74.10% during the wet period), agricultural activities (53.84% during the dry period), and As were identified as the priority control factors for groundwater HMs. The results provide valuable insights for policymakers to coordinate targeted management of HM pollution in groundwater and reduce the cost of HM pollution mitigation.

Association of B vitamin intake and total homocysteine levels with all-cause and cause-specific mortality in central obesity.

OBJECTIVES: Future primary prevention strategies may benefit from understanding the connection between mortality in individuals with central obesity and modifiable lifestyle factors like dietary intake. This study sought to determine whether there was a separate relationship between folate, vitamin B6, and vitamin B12 intake and all-cause and cause-specific mortality in the US population with central obesity. METHODS: The study analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2016. Using the Cox proportional hazards model, the association between dietary intake of B vitamins and all-cause and cause-specific mortality was examined. A total of 7718 adults with central obesity were enrolled, with a mean age of 49.87 (SD = 0.25) y at baseline. RESULTS: Folate intake was independently associated with a decreased incidence of all-cause mortality (adjusted hazard ratio = 0.71; 95% CI, 0.58-0.87). Furthermore, higher intake of vitamin B6 and vitamin B12 was inversely correlated with cardiovascular disease mortality (adjusted hazard ratio = 0.63; 95% CI, 0.40-0.98; and adjusted hazard ratio = 0.44; 95% CI, 0.29-0.65, respectively) and the finding reveal an interaction between homocysteine and vitamin B12 and folate on All-cause mortality CONCLUSIONS: The findings of this study suggest that vitamin B12 and folate intake may be protective factors in individuals with central obesity. It is important to consider both their total homocysteine level and body mass index in conjunction with these nutrients. Further research is needed to validate these findings.

Assessment of groundwater hydrochemistry, water quality, and health risk in Hainan Island, China.

Groundwater is an important source of water for human sustenance. The determination of groundwater quality at island sites is an urgent priority in China, but there are lacking systematic reports relating to them. Here, 63 groups of groundwater samples were collected and analyzed of Hainan Island. The groundwater in the study area is weakly alkaline, mainly comprising hard and soft freshwater. The predominant anions and cations are HCO3-, and Ca2+ and Na+, respectively, and the main water chemistry types are HCO3-Cl-Na and HCO3-Cl-Na-Ca. The chemical evolution of groundwater is mainly affected by water-rock interactions, cation exchange, and human activity. The groundwater is mostly of high quality and, in most areas, is suitable for drinking and irrigation. Contrastingly, the water quality in the west of the island is relatively poor. The spatial distribution of the risk coefficient (HQ) is consistent with the spatial variation in the NO3- concentrations in the groundwater. Notably, there are unacceptable health risks for different groups of people, with infants having the greatest level of impact, followed by children, teenagers, and adults. This study provides a valuable reference for the development and utilization of groundwater resources, as well as the improvement of aquatic ecological conditions on Hainan Island and other island areas worldwide.

Priority control factors for heavy metal groundwater contamination in peninsula regions based on source-oriented health risk assessment.

Peninsula regions in China face serious environmental issues, such as heavy metal (HM) groundwater contamination. However, attempts to investigate the pollution sources and health risks of HM contamination in such regions require considerable resources and costs. Moreover, the priority control factors for groundwater HMs remain unclear. In this study, absolute principal component score/multiple linear regression (APCS/MLR) was used to quantify the groundwater pollution sources of typical peninsular areas in China, and a health risk assessment (HRA) was performed to assess the health risks caused by different sources. The results showed that the concentrations of Mn and Fe were higher than those of other HMs, and HM pollution was high in shallow groundwater. The dominant source of HMs in groundwater was agricultural activities (31.12 %), followed by natural sources (26.33 %), industrial activities (22.47 %), and atmospheric deposition (20.09 %). The non-carcinogenic risks to residents were acceptable, whereas the carcinogenic risks were high. Agricultural sources, atmospheric deposition sources, and Cr and As were identified as the priority control factors for HM groundwater contamination. This study has implications for improving the control of groundwater HM contamination in peninsula regions and ensuring sustainable groundwater development.

Birthweight, genetic risk, and gastrointestinal cancer incidence: a prospective cohort study.

BACKGROUND: The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. The study aimed to prospectively assess the interactions and joint effects of birthweight and genetic risk levels on gastrointestinal cancer incidence in adulthood. METHODS: A total of 254,997 participants were included in the UK Biobank study. We used multivariate restricted cubic splines and Cox regression models to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the association between birthweight and gastrointestinal cancer risk, then constructed a polygenic risk score (PRS) to assess its interaction and joint effect with birthweight on the development of gastrointestinal cancer. RESULTS: We documented 2512 incident cases during a median follow-up of 8.88 years. Compare with participants reporting a normal birthweight (2.5-4.5 kg), multivariable-adjusted HR of gastrointestinal cancer incidence for participants with high birthweight (≥4.5 kg) was 1.17 (95%CI: 1.01-1.36). Such association was remarkably observed in pancreatic cancer, with an HR of 1.82 (95%CI: 1.26-2.64). No statistically significant association was observed between low birth weight and gastrointestinal cancers. Participants with high birthweight and high PRS had the highest risk of gastrointestinal cancer (HR: 2.95, 95%CI: 2.19-3.96). CONCLUSION: Our findings highlight that high birthweight is associated with a higher incidence of gastrointestinal cancer, especially for pancreatic cancer. Benefits would be obtained from birthweight control, particularly for individuals with a high genetic risk.KEY MESSAGESThe epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce.This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer.Our data suggests a possible effect of in utero or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk.

Molecular epidemiology and clinical features of hand, foot and mouth disease requiring hospitalization after the use of enterovirus A71 inactivated vaccine in chengdu, China, 2017-2022: a descriptive study.

Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.

Health Risk Assessment of Heavy Metals in Groundwater of Hainan Island Using the Monte Carlo Simulation Coupled with the APCS/MLR Model.

Groundwater is a significant component of water resources, but drinking groundwater with excessive heavy metals (HMs) is harmful to human health. Currently, quantitative source apportionment and probabilistic health risk assessment of HMs in groundwater are relatively limited. In this study, 60 groundwater samples containing seven HMs were collected from Hainan Island and analyzed by the coupled absolute principal component scores/multiple linear regression (APCS/MLR), the health risk assessment (HRA) and the Monte Carlo simulation (MCS) to quantify the pollution sources of HMs and the health risks. The results show that the high-pollution-value areas of HMs are mainly located in the industry-oriented western region, but the pollution level by HMs in the groundwater in the study area is generally low. The main sources of HMs in the groundwater are found to be the mixed sources of agricultural activities and traffic emissions (39.16%), industrial activities (25.57%) and natural sources (35.27%). Although the non-carcinogenic risks for adults and children are negligible, the carcinogenic risks are at a high level. Through analyzing the relationship between HMs, pollution sources, and health risks, natural sources contribute the most to the health risks, and Cr is determined as the priority control HM. This study emphasizes the importance of quantitative evaluation of the HM pollution sources and probabilistic health risk assessment, which provides an essential basis for water pollution prevention and control in Hainan Island.

Relationship between meteorological factors, air pollutants and hand, foot and mouth disease from 2014 to 2020.

BACKGROUND: Meteorological factors and air pollutants have been reported to be associated with hand, foot, and mouth disease (HFMD) epidemics before the introduction of vaccine. However, there is limited evidence for studies with long-term dimensions. METHODS: We collected the daily HFMD counts, weather and air pollution data from 2014 to 2020 in Chengdu. Distributed lag non-linear models (DLNM) were used to assess the associations of meteorological factors and air pollutants on HFMD cases. RESULTS: From 2014-2020, high relative humidity and precipitation and extremely high and low levels of PM10, O3, SO2 and CO increased the risk of HFMD. In pre-vaccination period, extreme high and low temperatures, PM10 and NO2, low precipitation and high concentrations of PM2.5 and O3 significantly increase the risk of HFMD; In post-vaccination period, high relative humidity and low level of CO can significantly increase the incidence of HFMD; During the period of COVID-19, only low temperature will significantly increase the risk of HFMD; Low concentration of air pollutants has the greatest impact on the 6-14 age group, while the high concentration of air pollutants has the greatest impact on the 0-1 age group. CONCLUSIONS: Our study suggest that high relative humidity and precipitation and extremely high and low levels of PM10, O3, SO2 and CO increased the risk of HFMD from 2014 to 2020. The results of this study provide a reference for local authorities to formulate intervention measures and establish an environment-based disease early warning system.

Time-Space Simulation, Health Risk Warning and Policy Recommendations of Environmental Capacity for Heavy Metals in the Pearl River Basin, China.

In China, the environmental capacity problem of heavy metals has long been hidden in the Pearl River Basin creating a contradiction between the economic development and environmental health. Thus, this research calculated the environmental capacity of heavy metals in the agricultural land of the urban agglomeration in the Pearl River Basin, evaluated the health risk warning capacity using a comprehensive index. The results showed that the static capacity order of heavy metals in the study area was As > Pb > Zn > Cr > Hg > Cu > Ni > Cd. The dynamic capacity showed an upward trend, and it fluctuated in some cities. The remaining capacity of Cr and Ni was relatively poor, and the comprehensive soil quality index of the Pearl River Basin was 0.64. The pollution level was of grade IV, which belongs to the medium capacity, but the soil pollution risk still existed, which threaten the health of local resident. In this regard, this study also put forward some countermeasures for pollution control. Thus, studying the soil heavy metal environmental capacity can provide a reference for heavy metal pollution control and health risk early warning in the Pearl River Basin.

Dynamic changes of viral load and the duration of viral shedding in patients with hand, foot and mouth disease: a protocol for longitudinal study.

BACKGROUND: The duration of virus shedding is necessary for determining the infectious period. But there were few quantitative studies on the changes of viral load and the law of the viral shedding in hand foot and mouth disease (HFMD) patients has not yet been clarified. METHODS: This study will prospectively recruit coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) infected inpatients from January 2022 to December 2022. A series of samples and questionnaire information will be collected regularly to establish the dynamic function relationship between time and viral load changes and a Bayesian multilevel model will be constructed to clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in patients with HFMD. DISCUSSION: The results of this study is expected to further clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in HFMD patients under the influence of related factors. It can also provide important evidence for the scientific definition of the infectious period and isolation period of HFMD in China.

Evaluation of Resources and Environment Carrying Capacity Based on Support Pressure Coupling Mechanism: A Case Study of the Yangtze River Economic Belt.

Resource and environmental carrying capacity (RECC) is an important basis for achieving sustainable urban development, and analysis of the relationship between regional resources and human activities is of great significance for sustainable regional development. Taking the Yangtze River Economic Belt (YREB) as the study area, this study establishes a framework for analyzing RECC based on the resource and environmental support capacity (RES) and the pressure on the resource and environment (REP), calculates the RES and REP of 110 cities in the YREB from 2009 to 2018, and analyzes the main constraints on RECC. The results show that (1) there are inter-regional imbalances in RECC within the study area, with cities that are more economically developed or at a higher administrative level usually having more severe problems with RECC. (2) The RES and REP indices of cities in the YREB show an overall increasing trend, but the relative growth rates of the RES and REP indices of cities at different levels differ. (3) The built-up area, green space in built-up areas, total gas supply, and length of sewage pipes are hindering factors for most cities to improve their RES. This study contributes to a comprehensive understanding of the current situation and changing trends of RECC in the YREB and can provide a reference for decision-making on sustainable development of the region's large river basin.

[Hydrochemical Characteristics and Controlling Factors of Groundwater in the Leizhou Peninsula].

Groundwater resources in the Leizhou Peninsula provide a strong support for the economic and social development. Therefore, understanding the chemical characteristics and formation mechanism of groundwater in this area is necessary for the rational exploitation and sustainable utilization of water resources. In this study, 43 groundwater samples were collected, and the hydrochemical characteristics and controlling factors were analyzed by descriptive statistical analysis, Piper triangular diagrams, ArcGIS spatial interpolation, Gibbs diagram, and ion ratios. The results showed that:① The anions and cations of the groundwater in the study area were mainly HCO3-, Ca2+, and Na+, and the hydrochemical types were mainly HCO3-Cl-Na-Ca, HCO3-Cl-Na-Ca-Mg, HCO3-Cl-Na-Mg, and HCO3-Na. The contents of Cl-, SO42-, and Na+were higher in the west of Leizhou City compared to other areas. The sites with higher contents of HCO3-, NO3-, Ca2+, Mg2+, and K+ were mainly concentrated in the southwest and eastern coastal areas. ② The chemical evolution of groundwater was mainly affected by water-rock interaction, cation alternating adsorption, and anthropogenic activities. The sources of Na+ and K+ were mainly from evaporative and silicate rocks, Ca2+ and Mg2+ were mainly from carbonate karstification, while NO3- originated from anthropogenic activities.

Corrigendum to "SOX4 contributions to TGF-ß-induced endothelial-mesenchymal transition and stem cell characteristics of gastric cancer cells" [Genes & Diseases 5 (2018) 49-61].

[This corrects the article DOI: 10.1016/j.gendis.2017.12.005.].

[Source Analysis and Health Risk Assessment of Heavy Metals in Groundwater of Leizhou Peninsula].

Source identification and health risk assessment of heavy metals in groundwater is one of the key issues in China's new era of environmental management. In order to reveal the status, sources, and health risk of pollutants in groundwater of the Leizhou Peninsula, 44 groundwater samples were collected, and the concentrations and spatial distribution of Cr, Mn, Cu, Zn, As, Cd, Hg, and Pb were measured and analyzed. The sources of heavy metals in groundwater were then determined through correlation coefficient and principal component analysis. Finally, the health risk model was used to evaluate the different health risks associated with these heavy metals. The results showed that the average value of heavy metal elements in groundwater of the Leizhou Peninsula does not inferior to the class Ⅱ water quality standard(GB/T 14848-2017). However, As, Mn, and Cd do not meet the standard. The overall spatial distribution indicated obvious spatial differences, with higher values in the south than in the north. Heavy metal sources can be identified as three principal components (PCs). PC1 (Cu, Zn, Cd, and Pb) metals mainly originate from industrial, agricultural, and traffic sources. PC2 (Cr, Mn, and As) sources can be both natural and man-made, and PC3 (Hg) sources are primarily man-made. For the groundwater of the Leizhou Peninsula, the health risks of 8 metals are with the acceptable range, the carcinogenic risk of adults is higher than that of children, and the risk of drinking exposure is higher than that of skin exposure. The study shows that the environmental protection department should encourage the rational exploitation of groundwater resources and control the sources of pollution to reduce health risks.

The dietary carcinogen PhIP activates p53-dependent DNA damage response in the colon of CYP1A-humanized mice.

Species differences in the metabolism of xenobiotics by cytochrome P450 are critical in evaluating the use of experimental animals in studying toxic compounds relevant to human diseases. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which is produced by high-temperature cooking of fish and meat, is activated to become a carcinogen by cytochrome P4501A2 (CYP1A2) through N2 -hydroxylation in humans, but is detoxified by Cyp1a2 through 4'-hydroxylation in mice. CYP1A-humanized (hCYP1A) mice, in which mouse Cyp1a is replaced with human CYP1A, show constitutive human xenobiotic metabolism by hCYP1A, thereby serving as a suitable model for studying PhIP. Previous studies have demonstrated that oral administration of PhIP induces colon tumors in hCYP1A mice; however, these studies used a super-high dose, raising concerns regarding the relevance of the mechanism to human cancer. Herein, we systematically investigated PhIP-induced colon carcinogenesis in hCYP1A mice treated with lower doses. We found that a dose 2000 times lower than that used previously, which is comparable to human daily intake levels, could induce colon tumors, albeit at a lower incidence rate. We further investigated the transcriptome changes in the colon of hCYP1A mice treated with PhIP and identified that PhIP treatment increased the expression of Bax, Btg2, Ccng1, Cdkn1a, and Trp53inp1 and decreased the expression of Igf1 and Ccnd1. Since these genes are key components of the p53-dependent DNA damage response, the altered expression patterns indicated PhIP-induced DNA damage in hCYP1A mice. Together, these results prove that hCYP1A mice are suitable for studying PhIP-induced carcinogenesis and show that PhIP is an important colorectal cancer carcinogen in human diet.

A New Type of MgFe2O4@CuS-APTES Nanocarrier for Magnetic Targeting and Light-Microwave Dual Controlled Drug Release.

INTRODUCTION: Cancer is a major health problem worldwide, and the most extensive treatment can be obtained by using chemotherapy in the clinic. However, due to the low selectivity of cancer cells, chemotherapy drugs produce a series of grievous side effects on normal cells. METHODS: In this research, we developed novel nanocarriers for magnetically targeted near-infrared (NIR) light-electromagnetic wave dual controlled drug delivery based on MgFe2O4@CuS nanoparticles (NPs) modified with aminopropyltriethoxysilane (APTES) in response to magnetic, NIR light, and electromagnetic wave irradiation. Synthesis and characterization of MgFe2O4@CuS-APTES NPs was carried out using X-ray diffraction measurements, scanning electron microscopy, transmission electron microscopy, photoluminescence emission spectra, UV-1800 spectrophotometer, N5230A vector network analyzer, MDS-6 microwave sample preparation system, and superconducting quantum interference device. In addition to that mentioned above, we also explored many other sides, such as the drug-loading, drug-controlled release efficiency, elect99omagnetic wave thermal effect and photo-thermal effect. RESULTS: The results showed that APTES-modified MgFe2O4@CuS NPs had 37% high drug-loading capacity and high electromagnetic wave thermal conversion ability and NIR-light thermal conversion ability. In addition, ibuprofen (IBU) release from the MgFe2O4@CuS-APTES-IBU depends on the electromagnetic wave (2.45 GHz) and 1060 nm NIR light irradiation. After five cycles, the drug-release percentage was 90% and 66% separately, and could be adjusted by the time and cycles times of electromagnetic wave and NIR light irritation. Electromagnetic wave irradiation compared with NIR light irradiation, has a higher drug release rate and better penetration. Therefore, choosing different stimulation methods according to the treatment needs of the disease, we can achieve accurate personalized treatment of the disease. DISCUSSION: Our findings indicate that multifunctional APTES modified MgFe2O4@CuS NPs could be used for the first time as a new drug carrier for "location-timing-quantification" drug release with magnetic targeting and dual control of NIR light-electromagnetic waves.

Eight Elements in Soils from a Typical Light Industrial City, China: Spatial Distribution, Ecological Assessment, and the Source Apportionment.

Contamination with the eight elements, Hg, As, Cr, Cu, Ni, Pb, Zn, and Cd, is a serious concern in Zhongshan, which is a typical light industrial city, China. 60 surface soil samples were collected to investigate the concentrations, spatial distribution, human health risk, and sources of these elements in the soils in Zhongshan. The concentrations of the eight elements were analyzed while using ordinary kriging analysis, pollution load index (PLI), potential ecological risk index (RI), human health risk, correlation analysis, and factor analysis. The mean concentrations of the tested elements, excluding Pb and As, were higher than the soil background values in the Pearl River Delta. The spatial distribution of the tested elements revealed a zonal distribution pattern and high values in several areas. The mean PLI and RI indicated slight and moderate risk levels. Health risk assessment demonstrates that both children and adults were more exposed to Cu than to Cr, As, and Cd. However, the associated carcinogenic risk is acceptable. Hg that originated from human activities; As, Cr, Cu, Ni, and Cd originated from industrial activities; and, Pb and Zn originated from transportation activities. Cd was the main pollutant in the study area and it was present at higher concentrations when compared with those of the other elements. Therefore, Zhongshan should encourage enterprises to conduct industrial transformation to control the ecological risk.

SOX4 contributes to TGF-ß-induced epithelial-mesenchymal transition and stem cell characteristics of gastric cancer cells.

SOX4 is highly expressed in gastric cancer (GC) and is associated with tumor grade, metastasis and prognosis, however the mechanism is not clear. We report herein that SOX4 was upregulated and overexpression of SOX4 was associated with increased expression of the markers of Epithelial-mesenchymal transition (EMT) and stemness in clinic patient samples. In vitro, overexpression of SOX4 promoted the invasion as showed by Transwell assay and stemness of GC cells as assessed by sphere formation assay, which was suppressed by silencing SOX4 with shRNA. Further studies showed that SOX4 up-regulated the expression of EMT transcription factors Twist1, snail1 and zeb1 and stemness transcription factors SOX2 and OCT4, and promoted the nuclear translocation of ß-catenin. Moreover, we revealed that TGF-ß treatment significantly up-regulated the expression of SOX4 and silencing SOX4 reversed TGF-ß induced invasion and sphere formation ability of GC cells. Finally, we showed that SOX4 promoted the lung metastasis and tumor formation ability of gastric cancer cells in nude mice. Our results suggest that SOX4 is a target TGF-ß signaling and mediates TGF-ß-induced EMT and stem cell characteristics of GC cells, revealing a novel role of TGF-ß/SOX4 axis in the regulation of malignant behavior of GC.