Different "nongrain" activities affect the accumulation of heavy metals and their source-oriented health risks on cultivated lands.

"Nongrain" production on cultivated land is one of the primary environmental issues in China. Different "nongrain" activities may introduce different pollution sources to the local environment, leading to variations in heavy metal contents in soil, which can profoundly impact national food security. In this study, three typical "nongrain" regions (Nanxun (NX), Xiaoshan (XS) and Lin'an (LA)) with intensive aquaculture, tea planting and flower (seedling) growth on cultivated land around the Hangzhou metropolitan area were selected to address the spatial heterogeneity of accumulation levels, sources and source-oriented health risks of heavy metals in soil. The results showed that Hg was the main pollutant in NX and XS, while Cd and As were the major contaminants in LA. Aquiculture and sericultural industries (37.43%), natural sources (23.59%) and industrial activities (38.99%) were the major sources in NX; atmospheric deposition (37.73%), flower and seedling planting (23.49%) and metal-related industries (35.16%) were the major sources in XS; and atmospheric deposition (28.06%), excessive application of fertilizers and pesticides during tea planting (43.47%) and natural sources (28.47%) were the major sources in LA. The major risk population, area, exposure route and hazardous elements were children, LA, ingestion and As and Cr, respectively. From the perspective of source-based health risk assessment, in addition to natural sources that are difficult to intervene in, industrial activities, especially leather and wood process industries, metal-related industries and excessive fertilizer and pesticide application during tea planting contributed the most to the total health risk, which explained 67%, 41% and 42%, respectively, of the total risk in NX, XS and LA. High health risks are present in sources with heavy loadings of hazardous heavy metals (As and Cr); thus, to protect human health, the corresponding high-risk anthropogenic pollution sources in different "nongrain" areas need to be controlled.

Salmonid alphavirus non-structural protein 2 is a key protein that activates the NF-κB signaling pathway to mediate inflammatory responses.

Salmonid alphavirus (SAV) infection of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) causes pancreas disease (PD) with typical inflammatory responses, such as necrosis of the exocrine pancreas, cardiomyopathy and skeletal myopathy. However, the pathogenic mechanism underlying SAV infection is still unclear. Inflammation may cause damage to the body, but it is a defense response against infection by pathogenic microorganisms, of which nuclear factor-kappa B (NF-κB) is the main regulator. This study revealed that SAV can activate NF-κB, of which the viral nonstructural protein Nsp2 is the major activating protein. SAV activates the NF-κB signaling pathway by simultaneously up-regulating TLR3, 7, 8 and then the expression of the signaling molecule myeloid differentiation factor 88 (Myd88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). We found that Nsp2 can induce IκB degradation and p65 phosphorylation and transnucleation, and activate NF-κB downstream inflammatory cytokines. Nsp2 may simultaneously activate NF-κB through TLR3,7,8-dependent signaling pathways. Overexpression of Nsp2 can up-regulate mitochondrial antiviral signaling protein (MAVS) and then promote the expression of IFNa1 and antiviral protein Mx, which inhibits viral replication. This study shows that Nsp2 acts as a key activator protein for the NF-κB signaling pathway, which induces inflammation post-SAV infection. This study systematically analyzes the molecular mechanism of SAV activation of the NF-κB signaling pathway, and provides a theoretical basis for revealing the mechanism of innate immune response and inflammatory injury caused by SAV.

Staging Surgery for The Treatment of Aortic Arch Aneurysm Combined with Aberrant Bilateral Subclavian Artery, Persistent Left Superior Vena Cava and Airway Compression: A Case Report.

BACKGROUND: To describe staging surgery for the treatment of a patient with aortic arch aneurysm combined with aberrant bilateral subclavian artery, persistent left superior vena cava (PLSVC), and airway compression. CASE REPORT: A 42-year-old female was hospitalized for aortic arch aneurysm involving aberrant bilateral subclavian artery, PLSVC, and airway compression. The patient's aneurysm was successfully treated by stage I surgery, including total aortic arch replacement and stented elephant trunk procedure and stage II surgery, including tracheal stenting and tracheotomy. Aortic CTA examination showed an unobstructed lumen and a good stent position without tracheal stent migration. Regular postoperative follow-up showed no complications, such as dyspnea, cough, and sputum, or other discomfort symptoms. CONCLUSIONS: Total aortic arch replacement, elephant trunk surgery, and second-stage tracheal stent surgery are effective and safe for the treatment of aortic arch aneurysm combined with aberrant bilateral subclavian artery, PLSVC, and airway compression.

The association between heavy metal soil pollution and stomach cancer: a case study in Hangzhou City, China.

Stomach cancer (SC) is a severe health burden, with nearly half of the world's cases found in China. Noticeably, the emissions of heavy metals into the environment have increased alongside rapid urbanization and industrialization in China. However, as regards carcinogenic associations, the relationship between heavy metals and SC is yet unclear. Based on 9378 newly diagnosed SC cases in Hangzhou City from 2009 to 2012, this work is concerned with the quantitative characterization of the spatial distribution pattern of SC incidence and its geographical association with soil heavy metals by means of a novel geographical model. The results show that (a) Cd is one of the severe soil pollutants in Hangzhou; (b) higher SC incidence clusters are in central Hangzhou, whereas lower clusters are found in the northeast and southwest with a male to female incidence ratio about 2.2:1; (c) although when considered separately, the heavy metals in this work do not have a considerable impact on the distribution of SC incidence in Hangzhou City, nevertheless, the joint effects of multiple heavy metals have significant impacts on SC risk. The present work calls for a rigorous quantitative assessment of the integrated heavy metal soil pollution and its effects on SC incidence.

Processing toxic metal source proxies appropriately for better spatial heterogeneity source apportionment.

Soil toxic metals have strong spatial heterogeneity, and their sources vary among regions. Thus, this study integrated the Catreg and geographically weighted regression (GWR) models to quantitatively extract the main source proxies (numerical and categorical variables were analyzed simultaneously) for different toxic metals and analyze the spatial heterogeneity of the distributions of these sources. Pb, Cd and Hg were the predominant toxic metals in soil. Of the samples with Pb, Cd and Hg, 84.12 %, 68.03 % and 41.57 % exceeded the background values, and 5.36 %, 6.42 % and 5.43 % were moderately contaminated according to the geoaccmulation index, respectively. Industrial activities, with relative importance values of 17.82 %, 31.54 % and 26.51 % for Cd, Hg and Pb, respectively, were the predominant source of these metals especially, in their high-content cluster areas (central urban areas). Soil available phosphorus was another important factor (relative importance values of 13.03 %, 13.41 % and 25.55 % for Cd, Hg and Pb, respectively), and agricultural activities (especially the overuse of phosphoric fertilizers) were identified as an anthropogenic source of these toxic metals. Soil parent material had the greatest influence on As and Cr, with relative importance values of 19.88 % and 19.09 %, respectively, especially in their high-content accumulation area (the eastern coastal area), indicating that these toxic metals mainly come from natural sources. Slope had important impacts on toxic metal accumulation (relative importance values of 17.48 %, 21.22 %, 12.40 % and 16.13 % for Cd, Hg, Cr and As, respectively) by influencing industrial distribution and pollutant migration. By changing the soil adsorption capacity, soil organic matter (explaining 13.01 % of Pb) and soil pH (explaining 14.58 % of As and 12.40 % of Cr) strongly influenced toxic metal accumulation. This study highlights the benefits of the integrated Catreg-GWR model for analyzing multiple spatially heterogeneous environmental data types (numerical and categorical variables), providing a potential foundation for local pollution prevention.

Pollution threshold assessment and risk area delineation of heavy metals in soils through the finite mixture distribution model and Bayesian maximum entropy theory.

Pollution threshold and high-risk area determination for heavy metals is important for effectively developing pollution control strategies. Based on heavy metal contents in 3627 dense samples, an integrated framework combining the finite mixture distribution model and Bayesian maximum entropy (BME) theory was proposed to assess pollution thresholds, contamination levels and risk areas in an uncertain environment for soil heavy metals. The results showed that the average heavy metal contents were in the order Zn > Cr > Pb > Cu > Ni > As > Cd > Hg, with strong/moderate variation, and the corresponding pollution thresholds were 158.39, 84.29, 47.84, 49.75, 28.95, 18.01, 0.49 and 0.16 mg/kg, respectively. The thresholds were consistently greater than the Zhejiang Province backgrounds but lower than the national risk screening values, except for Cd. Approximately 27.9% of the samples were classified as contaminated at various levels, and they were distributed in the northern, northwestern and eastern regions of the study area. Additionally, 3.73%, 5.34% and 8.22% of the total area were classified as at-risk areas under confidence levels of 95%, 90% and 75%, respectively, through BME theory. The findings provide a reasonable classification system and suggestions for heavy metal pollution management and control.

Contamination assessment, health risk evaluation, and source identification of heavy metals in the soil-rice system of typical agricultural regions on the southeast coast of China.

To quantitatively assess heavy metal accumulation and potential ecological and human health risks as well as analyze the sources of metals in a typical soil-rice system located on the southeast coast of China, 120 topsoil samples and corresponding rice grain samples were collected across the study area. The concentrations of As, Cd, Pb, Cr, Hg, Zn, Cu, and Ni were analyzed. The results revealed that Hg, Cd, and Cu were the main pollutants in soils. Besides, according to geo-accumulation value of Hg, 18.3% of samples were at or above moderate contamination levels. Additionally, the soil was in moderate ecological risk from combined heavy metal pollution, and 49.7% and 27.0% of this risk could be attributed to Hg and Cd pollution, respectively, due to their high toxic-response factors. For the rice samples, Cd content showed the highest biological accumulation coefficient value (40.8%) in rice grains and was slightly greater than its maximum allowable value (MAV) (0.2 mg/kg) in 7.5% of samples, whereas the other metals were all lower than their corresponding MAVs. Heavy metal exposure (especially As exposure) via rice consumption causes significant carcinogenic and non-carcinogenic risks to adults, and non-carcinogenic risk to children, while the carcinogenic risk to children was at tolerable level. Greater rice consumption might be responsible for the greater health risk to adults than children. Natural sources (loaded heavily with Cr and Ni) such as lithogenic components and soil parent materials, agricultural activities (loaded heavily with Cd, Cu, and Zn), especially excessive use of pesticides and fertilizers, and industrial activities (loaded heavily with Hg, Pb, and As) including vehicle emissions, coal combustion, and those of the textile and chemical industries were identified as the main sources. Effective regulations should be enforced to guarantee the safety of farm produce and protect ecological and human health in the study area.

Contamination assessment and source apportionment of heavy metals in agricultural soil through the synthesis of PMF and GeogDetector models.

Heavy metal pollution in soils has attracted great attention worldwide in recent decades. Selecting Hangzhou as a case study location, this research proposed the synthesis application of positive matrix factorization (PMF) and GeogDetector models for quantitative analysis of pollution sources, which is the basis for subsequent soil pollution prevention and remediation. In total, 2150 surface soil samples were collected across the study area. Although the mean concentrations of As, Cd, Cr, Hg, and Pb in the soils were lower than the National Environmental Quality Standards for Soils in China, the mean contents of As and Cd were higher than their corresponding local background values by approximately 1.31 and 1.59 times, respectively, indicating that heavy metals have been enriched in topsoil. Agricultural activities, industrial activities, and soil parent materials were the main sources of heavy metal pollution in the soils, accounting for 63.4%, 19.8%, and 16.8% of the total heavy metal accumulation, respectively. Cr was derived mainly from soil parent materials (80.72%). Cd was closely associated with agricultural activities (73.68%), such as sewage irrigation and application of fertilizer. Mercury was mainly attributed to industrial activities (92.38%), such as coal mining and smelting. As was related to agricultural (57.83%) and natural (35.56%) sources, and Pb was associated with industrial (42.42%) and natural (41.83%) sources. The new synthesis models are useful for estimating the source apportionment of heavy metals in soils.

Improved heavy metal mapping and pollution source apportionment in Shanghai City soils using auxiliary information.

Soil heavy metal pollution can be a serious threat to human health and the environment. The accurate mapping of the spatial distribution of soil heavy metal pollutant concentrations enables the detection of high pollution areas and facilitates pollution source apportionment and control. To make full use of auxiliary soil properties information and show that they can improve mapping, a synthesis of the Bayesian Maximum Entropy (BME) theory and the Geographically Weighted Regression (GWR) model is proposed and implemented in the study of the Shanghai City soils (China). The results showed that, compared to traditional techniques, the proposed BME-GWR synthesis has certain important advantages: (a) it integrates heavy metal measurements and auxiliary information on a sound theoretical basis, and (b) it performs better in terms of both prediction accuracy and implementation flexibility (including the assimilation of multiple data sources). Based on the heavy metal concentration maps generated by BME-GWR, we found that the As, Cr and Pb concentration levels are high in the eastern part of Shanghai, whereas high Cd concentration levels were observed in the northwestern part of the city. Organic carbon and pH were significantly correlated with most of the heavy metals in Shanghai soils. We concluded that Cd pollution is mainly the result of agricultural activities, and that the Cr pollution is attributed to natural sources, whereas Pb and As have compound pollution sources. Future studies should investigate the implementation of BME-GWR in the case of space-time heavy metal mapping and its ability to integrate human activity information and soil category variables.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

Molecular mechanism of Gd@C82(OH)22 increasing collagen expression: Implication for encaging tumor.

Gadolinium-containing fullerenol Gd@C82(OH)22 has demonstrated low-toxicity and highly therapeutic efficacy in inhibiting tumor growth and metastasis through new strategy of encaging cancer, however, little is known about the mechanisms how this nanoparticle regulates fibroblast cells to prison (instead of poison) cancer cells. Here, we report that Gd@C82(OH)22 promote the binding activity of tumor necrosis factor (TNFα) to tumor necrosis factor receptors 2 (TNFR2), activate TNFR2/p38 MAPK signaling pathway to increase cellular collagen expression in fibrosarcoma cells and human primary lung cancer associated fibroblasts isolated from patients. We also employ molecular dynamics simulations to study the atomic-scale mechanisms that dictate how Gd@C82(OH)22 mediates interactions between TNFα and TNFRs. Our data suggest that Gd@C82(OH)22 might enhance the association between TNFα and TNFR2 through a "bridge-like" mode of interaction; by contrast, the fullerenol appears to inhibit TNFα-TNFR1 association by binding to two of the receptor's cysteine-rich domains. In concert, our results uncover a sequential, systemic process by which Gd@C82(OH)22 acts to prison tumor cells, providing new insights into principles of designs of cancer therapeutics.

Pulmonary Function and Retrobulbar Hemodynamics in Subjects With Type 2 Diabetes Mellitus.

BACKGROUND: The primary goals of this study were to evaluate early changes in pulmonary function and retrobulbar hemodynamics and to examine the correlation between these parameters in patients with type 2 diabetes during the preclinical stages of diabetic retinopathy. METHODS: For the single-time point measurements, 63 subjects with type 2 diabetes without diabetic retinopathy (diabetes group) and 32 healthy subjects (control group) were selected to evaluate any early changes in pulmonary function and retrobulbar hemodynamics and to examine the correlation between these parameters. In the longitudinal follow-up study, 32 subjects who were newly diagnosed with type 2 diabetes were divided into 2 groups according to their resistivity index (≤0.7 and >0.7). Early changes in pulmonary function and retrobulbar hemodynamics were studied in these groups and compared with the previous values. RESULTS: For the single-time point measurements, the fasting plasma glucose, 2-h postprandial blood glucose, glycosylated hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels as well as the pulmonary function parameters were significantly higher in the diabetes group than in the control group. The pulmonary function parameters were negatively and significantly correlated with glycosylated hemoglobin A1c and the duration of diabetes. The retrobulbar hemodynamics were positively correlated with glycosylated hemoglobin A1c and diabetes duration; in contrast, the correlation between retrobulbar hemodynamics and glycosylated hemoglobin A1c. In the longitudinal follow-up study, the pulmonary function of the 2 groups categorized by their resistivity index levels indicated that subjects with resistivity index levels ≤0.7 showed significantly better pulmonary function, and the pulmonary function of this group showed improvement and a significantly smaller decrease. The incidence of diabetic retinopathy in the group with resistivity index levels ≤0.7 (9 of 22, 40.9%) was significantly lower than that in the group with resistivity index levels >0.7. CONCLUSIONS: Pulmonary function and retrobulbar hemodynamics changed during the preclinical stages of diabetic retinopathy. Regulating glycemia may improve retrobulbar hemodynamics in the retrobulbar arteries (ie, central retinal artery, posterior ciliary artery, and arteria ophthalmica). By detecting the retrobulbar resistivity index and the levels of glycosylated hemoglobin A1c, we could predict future changes in pulmonary function during the preclinical stages of diabetic retinopathy as well as the degree of retinopathy. (ClinicalTrials.gov registration NCT02774733.).

Soil organic carbon of an intensively reclaimed region in China: Current status and carbon sequestration potential.

Land reclamation has been highly intensive in China, resulting in a large amount of soil organic carbon (SOC) loss to the atmosphere. Evaluating the factors which drive SOC dynamics and carbon sequestration potential in reclaimed land is critical for improving soil fertility and mitigating global warming. This study aims to determine the current status and factors important to the SOC density in a typical reclaimed land located in Eastern China, where land reclamation has been undergoing for centuries. A total of 4746 topsoil samples were collected from 2007 to 2010. The SOC density of the reclaimed land (3.18±0.05kgCm(-2); mean±standard error) is significantly lower than that of the adjacent non-reclaimed land (5.71±0.04kgCm(-2)) (p<0.05). A Random Forest model is developed and it captures the relationships between the SOC density and the environmental/anthropogenic factors (R(2)=0.59). The soil pH, land use, and elevation are the most important factors for determining SOC dynamics. In contrast, the effect of the reclamation age on the SOC density is negligible, where SOC content in the land reclaimed during years 1047-1724 is as low as that reclaimed during years 1945-2004. The scenario analysis results indicate that the carbon sequestration potential of the reclaimed lands may achieve a maximum of 5.80±1.81kgCO2m(-2) (mean±SD) when dryland is converted to flooded land with vegetable-rice cropping system and soil pH of ~5.9. Note that in some scenarios the methane emission substantially offsets the carbon sequestration potential, especially for continuous rice cropping system. With the optimal setting for carbon sequestration, it is estimated that the dryland reclaimed in the last 50years in China is able to sequester 0.12milliontons CO2 equivalent per year.

Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells.

Infection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells.

Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infections.

Coronaviruses belong to the family Coronaviridae, which primarily cause infection of the upper respiratory and gastrointestinal tract of hosts. Transmissible gastroenteritis virus (TGEV) is an economically significant coronavirus that can cause severe diarrhea in pigs. Silver nanomaterials (Ag NMs) have attracted great interests in recent years due to their excellent anti-microorganism properties. Herein, four representative Ag NMs including spherical Ag nanoparticles (Ag NPs, NM-300), two kinds of silver nanowires (XFJ011) and silver colloids (XFJ04) were selected to study their inhibitory effect on TGEV-induced host cell infection in vitro. Ag NPs were uniformly distributed, with particle sizes less than 20 nm by characterization of environmental scanning electron microscope and transmission electron microscope. Two types of silver nanowires were 60 nm and 400 nm in diameter, respectively. The average diameter of the silver colloids was approximately 10 nm. TGEV infection induced the occurring of apoptosis in swine testicle (ST) cells, down-regulated the expression of Bcl-2, up-regulated the expression of Bax, altered mitochondrial membrane potential, activated p38 MAPK signal pathway, and increased expression of p53 as evidenced by immunofluorescence assays, real-time PCR, flow cytometry and Western blot. Under non-toxic concentrations, Ag NPs and silver nanowires significantly diminished the infectivity of TGEV in ST cells. Moreover, further results showed that Ag NPs and silver nanowires decreased the number of apoptotic cells induced by TGEV through regulating p38/mitochondria-caspase-3 signaling pathway. Our data indicate that Ag NMs are effective in prevention of TGEV-mediated cell infection as a virucidal agent or as an inhibitor of viral entry and the present findings may provide new insights into antiviral therapy of coronaviruses.

25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma.

Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from regulating calcium homeostasis and bone function, its levels also associate with the presence of development of adenocarcinoma. VitD can interact with VitD receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then induces transcription of proteins that function in cell proliferation, differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes and their associated polymorphisms involved in the correlation between development of adenocarcinoma and VitD deficiency to highlight how VitD may be instrumental in cancerization. Furthermore, pilot epidemiological data show that the detection of 25-hydroxy-Vitamin D3 ((36.5±10.7 nmol/L, n=129) vs (81.4±19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this review, we suggest that 25-hydroxy-Vitamin D3 can act as an indicator and/or risk assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma.

A monoclonal antibody against transmissible gastroenteritis virus generated via immunization of a DNA plasmid bearing TGEV S1 gene.

Transmissible gastroenteritis virus (TGEV) is a member of the coronaviruses. The viral spike (S) protein of TGEV mediates interaction between TGEV and its susceptible cells. Herein, DNA plasmid bearing TGEV S1 gene (the N terminal half of TGEV S gene) was used to immunize BALB/c mice followed by generation of a monoclonal antibody (MAb) using the hybridoma technique. The generated MAb (1H4) was identified by ELISA. Immunofluorescence assays showed that MAb 1H4 was able to detect infection of cells with TGEV. The MAb 1H4 distinguished TGEV from other control viruses. Additionally, although the type of MAb 1H4 was IgM, it could reduce cell infection by TGEV in a dose-dependent manner.