Combined pollution of heavy metals and polycyclic aromatic hydrocarbons in the soil in Shenfu Region, China: a case of three different cities.

It is a challenging issue to investigate the combined pollution of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in urban soils. The purpose of this study was to determine the concentrations of these two pollutants in soils in Shenyang, Fushun, and Fushun New District, to analyze their distribution, their interaction, and co-contamination levels. The concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry (ICP-MS), while the concentrations of 21 kinds of PAH were analyzed by gas chromatography-mass spectrometry (GC-MS). Based on the analysis of pollution concentrations and distribution patterns, the intrinsic links between heavy metals and PAHs in three different cities were assessed using a variety of multivariate analysis methods. Compared to Shenfu New District, the concentration of pollutants in Shenyang and Fushun shows a higher level. Moreover, the results of redundancy analysis (RDA) of samples may quantify the possibility of combined pollution of different heavy metal elements and PAHs. This study also affirms the important role of multivariate analysis in being used to reveal the complex interactions and spatial distribution of different pollutants.

Coxsackievirus A6 was the most common enterovirus serotype causing hand, foot, and mouth disease in Shiyan City, central China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) has become one of the most common infectious diseases in China. Before 2016, the primary causal serotypes were enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Following the introduction of EV-A71 vaccines in China since 2016, the situation could change. CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China. However, the epidemiological characteristics of central China remain unknown. AIM: To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City, central China, in recent years. METHODS: The epidemiological, clinical, and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed. 196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020. To detect and genotype enteroviruses, real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used. In Shiyan, 168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes. Based on the logistic regression model, the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan. RESULTS: From 2016 to 2020, 35840 HFMD cases were reported in Shiyan. The number of cases decreased by 48.4% from 2016 to 2017. Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year, respectively. In 2020, a decrease of about 85.5% was reported when compared to 2019. The most common serotypes shifted from EV-A71 and CV-A16 (about 60%-80% in 2016 and 2018) to others (more than 80.0% in 2017, 2019, and 2020). EV-A71 lost its dominance in 2017 in Shiyan. Among 196 confirmed HFMD cases, 85.7% tested positive for enterovirus, with CV-A6 being the most common serotype (121/168, 72.0%). The positive rates for CV-A16 and CV-A10 were 4.8% and 3.0%, respectively. There was no EV-A71 discovered. Infection with CV-A6 was linked to fever, myocardial damage, increased creatine kinase MB isoenzyme, and lactate dehydrogenase levels. CONCLUSION: CV-A6 was the most common enterovirus serotype in Shiyan City, replacing EV-A71 and CV-A16 as the HFMD pathogen. Developing vaccines against CV-A6 or multiple pathogens, as well as rising CV-A6 surveillance, will help prevent HFMD in central China.

[Effects of resistance training on mitochondrial function in skeletal muscle of aging rats].

Objective: To investigate the effects of resistance exercise on mitochondrial function in skeletal muscle of aging rats. Methods: Forty male Sprague-Dawley rats were randomly assigned to 4 groups, 2-month sedentary control group (C1; n=10), 2-month with resistance training group (R1; n=10), 6-month sedentary control group (C2; n=10), 6-month with resistance training group (R2; n =10 ). Rats in R1 and R2 groups were arranged for resistance training for 8 weeks. This program consisted of interval running on a treadmill, speed 15 m·min-1, 35° incline, duration 15 s, interval 30 s, 4 times/group, 3 groups/cycle, 2 cycles per day, 6 days per week, a total of 8 weeks. The expressions of mitochondrial fusion protein 2(Mfn2) and dynamin-related protein 1(DRP1) in rat quadriceps were detected by Western blot, and the changes of mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and Ca2+ concentration were measured by flow cytometry. Results: ①Compared with C1 group, the expression of DRP1 protein in R1 group was increased (P＜0. 01), and the Mfn2 protein in R1 group had no significant difference, both DRP1 and Mfn2 protein in C2 group were decreased (P＜0. 01);compared with C2 group, the DRP1 and Mfn2 protein in R2 group were similarly increased (P＜0. 01, P＜0. 05);compared with R1 group, the DRP1 and Mfn2 protein in R2 group were both decreased (P＜0. 01). ② Compared with C1 group, the Ca2+ content of R1 group was decreased (P＜0. 01) and the Ca2+ content of C2 group was increased (P＜0. 01);Compared with C2 group, the content of Ca2+ in R2 group was decreased (P＜0. 01);compared with R1 group, the Ca2+ content in R2 group was increased (P＜0. 01). ③ Compared with C1 group, the ROS content in R1 group was increased, but there was no significant difference, while the ROS content in C2 group was increased (P＜0. 01);compared with C2 group, ROS content in R2 group was decreased (P＜0. 01); compared with R1 group, the ROS content in R2 group was increased (P＜0. 01). ④ Compared with group C1, the levels of ΔΨm in C2 group was decreased (P＜0. 01);Compared with C2 group, The ΔΨm of R2 group was increased(P＜0. 01); Compared with group R1, the ΔΨm of R2 group was decreased, but there was no statistical difference. Conclusion: During the aging process of rats, mitochondria of quadriceps femoral muscle showed Ca2+ accumulation, increased reactive oxygen species, decreased mitochondrial membrane potential, decreased fusion protein and other phenomena, and resistance training could effectively improve these changes.

Fumonisin B1 Affects the Biophysical Properties, Migration and Cytoskeletal Structure of Human Umbilical Vein Endothelial Cells.

Fumonisin B1 (FB1) is an important mycotoxin in nature and is a serious threat to human and animal health, but its specific target and molecular mechanism of the toxicity and potential carcinogenicity remain unclear. In this study, we first detected the effects of FB1 on the cell viability, biophysical properties, migration ability, and reactive oxygen species (ROS) of human umbilical vein endothelial cells (HUVECs). Subsequently, changes in the cytoskeletal structure and its binding proteins were analyzed by immunofluorescence and real-time PCR, respectively. The results showed that FB1 could inhibit the viability of HUVECs in a dose-dependent manner. After treatment of HUVECs with FB1, the hypotonic resistance, cell surface charges, cell membrane fluidity, and migration ability were weakened, whereas the ROS levels were significantly increased. Moreover, the cytoskeletal structure of the HUVECs was significantly changed, and the mRNA expression of some important actin-binding proteins was altered. Therefore, this study revealed that FB1 can affect the migration and cytoskeletal structure of HUVECs, which provides a new perspective for further understanding the molecular mechanisms of FB1 toxicity.

Reversible promoter methylation determines fluctuating expression of acute phase proteins.

Acute phase reactants (APRs) are secretory proteins exhibiting large expression changes in response to proinflammatory cytokines. Here we show that the expression pattern of a major human APR, that is C-reactive protein (CRP), is casually determined by DNMT3A and TET2-tuned promoter methylation status. CRP features a CpG-poor promoter with its CpG motifs located in binding sites of STAT3, C/EBP-ß and NF-κB. These motifs are highly methylated at the resting state, but undergo STAT3- and NF-κB-dependent demethylation upon cytokine stimulation, leading to markedly enhanced recruitment of C/EBP-ß that boosts CRP expression. Withdrawal of cytokines, by contrast, results in a rapid recovery of promoter methylation and termination of CRP induction. Further analysis suggests that reversible methylation also regulates the expression of highly inducible genes carrying CpG-poor promoters with APRs as representatives. Therefore, these CpG-poor promoters may evolve CpG-containing TF binding sites to harness dynamic methylation for prompt and reversible responses.

[Vertical Distribution Characteristics of PAHs in Soils with Different Land Use Types During Rapid Urbanization].

To study the vertical distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in the soils from different land use types during urbanization, three land use types (urban land, cultivated land, and woodland) were selected in the eastern part of Shenyang, where urbanization is occurring rapidly. In each case, five soil samples were obtained from different depths (0-1 m). Change in the concentrations of PAHs, vertical migration factors, and the distribution and sources of PAHs were analyzed in the vertical soil profiles. Total concentrations of PAHs in the different soil type were ordered as follows:city 1 (513.19-12689.04 µg·kg-1); dry field (36.18-7196.10 µg·kg-1); paddy field (70.92-747.53 µg·kg-1); city 2 (19.39-636.47 µg·kg-1); and woodland (4.79-349.24 µg·kg-1). PAHs were mainly trapped in shallow soils in urban and forest land, but can migrate deeper into the soil profile in cultivated land. High-ring PAHs were abundant at depths of 0-30 cm, while low-ring PAHs were abundant deeper in the soil profiles. SOM had a significant effect on the vertical distribution of PAHs, and the physical and chemical properties of PAHs had a significant influence on their migration ability. However, combustion sources from industrial activities and transportation in the region are still considered the main sources of PAHs despite the fact that some low-ring PAHs derive from petroleum product inputs.

Clinical Implications of Tumor-Infiltrating Immune Cells in Breast Cancer.

The immune infiltration of tumors is closely related to clinical outcomes. The composition of tumor-infiltrating immune cells (TIICs) can serve as biomarkers for predicting response to treatment and survival in different patient subgroups in terms of chemotherapy and immunotherapy. This study is focused on investigating the clinical implications of TIICs in breast cancer patients. We performed several in silico analyses of gene expression profiles in 2976 nonmetastatic tumor samples. CIBERSORT was used to estimate the proportion of 22 immune cell types to analyze their correlation with overall survival (OS) and disease-free survival (DFS) in different breast cancer subtypes and stages. Our results showed that a higher fraction of plasma cells in estrogen receptor (ER)-positive breast cancer patients indicated an increase in DFS (hazard ratio [HR]=0.66, 95% confidence interval [CI] 0.54~0.82, p<0.01), while a decreased OS was correlated with a greater number of M0 macrophages (HR=2.02, 95% CI 1.27~3.30, p=0.01) and regulatory T cells (HR=1.90, 95% CI 1.20~3.02, p=0.02). In ER-negative or progesterone receptor (PR)-negative subtypes or in a combined subtype, the increase in activated memory CD4+ T cells was correlated with increased DFS (HR=0.46, 95% CI 0.33~0.63, p<0.01). In all breast cancer patients, a higher proportion of M0 macrophages indicated a decreased DFS (HR=1.67, 95% CI 1.22~2.27, p<0.01), while increased OS was associated with relatively larger fractions of resting memory CD4+ T cells (HR=0.70, 95% CI 0.55~0.90, p=0.02) and γδ T cells (HR=0.66, 95% CI 0.51~0.85, p<0.01). Therefore, this study revealed that the composition of TIICs is different in patients with various subtypes of breast cancer and is directly related to prognosis, suggesting that TIICs are important participants in tumor progression and may, potentially be used for future diagnosis and treatment.

A Mathematical Modelling of Initiation of Dendritic Cells-Induced T Cell Immune Response.

Dendritic cells (DCs) are the most potent specialized antigen-presenting cells as now known, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Immunologically, the motilities and T cell activation capabilities of DCs are closely related to the resulting immune responses. However, due to the complexity of the immune system, the dynamic changes in the number of cells during the peripheral tissue (e.g. skin and mucosa) immune response induced by DCs are still poorly understood. Therefore, this study simulated dynamic number changes of DCs and T cells in this process by constructing several ordinary differential equations and setting the initial conditions of the functions and parameters. The results showed that these equations could simulate dynamic numerical changes of DCs and T cells in peripheral tissue and lymph node, which was in accordance with the physiological conditions such as the duration of immune response, the proliferation rates and the motilities of DCs and T cells. This model provided a theoretical reference for studying the immunologic functions of DCs and practical guidance for the clinical DCs-based therapy against immune-related diseases.

[Pollution Characteristic and Risk Assessment of Polycyclic Aromatic Hydrocarbons in the Groundwater of Shen-Fu New City in the Hunhe River Basin].

To protect the safety of water used by the residents in Shen-Fu New City, which is undergoing the process of urbanization, 49 groundwater samples were collected along the Hunhe River Basin and 16 US EPA priority control polycyclic aromatic hydrocarbons (PAHs) were analyzed. The occurrence, distribution characteristics, sources, and potential health risk of drinking the groundwater were also assessed in this study. The results show that PAHs were detected in all samples. The concentration of PAHs ranges from 4.38 to 2005.02 ng·L-1, with an average value of (414.64±526.13) ng·L-1. Based on the comparison of the concentration level with that of other regions, the results in this study indicate a higher pollution level. The 3-4 ring PAHs are dominant; the average value was (190.93±238.96) ng·L-1 and (140.01±234.69) ng·L-1, respectively, accounting for 80% of the total PAHs. The distribution of PAHs in the groundwater is affected by the land use types. The concentration of PAHs is higher when the land use type is cultivated land, while it is lower when it is forest land. The source of PAHs was identified using Principal Component Analysis-Multiple Linear Regression (PCA-MLR). It was revealed that 36.26% of the PAHs are due to incomplete combustion of petroleum and gas, 32.72% are due to coal combustion, 28.17% originate from petroleum spills, and 2.87% are due to traffic emissions. The cancer risk levels releated to drinking the groundwater range from 5.55×10-10 to 5.65×10-6 and 13.60% of the values is in the range of 10-6-10-4. The levels are higher than the baseline of the acceptable risk, indicating the potential cancer risk. More attention should be paid to the quality of the groundwater.

[Sources and Risk Assessment of Polycyclic Aromatic Hydrocarbons from the Urbanization Process of Topsoil].

To study the effects of urbanization on concentration, sources, and health risks of polycyclic aromatic hydrocarbons (PAHs), 95 topsoil samples were collected from Liaoning Province. For this assessment, 21 PAHs were analyzed via gas chromatography-mass spectrometry and discussed. The results show the total concentrations of the 21 PAHs in background, Shen-Fu, Shen-Yang, and Fu-Shun were 1496.76 µg·kg-1, 3000.50 µg·kg-1, 8705.11 µg·kg-1, and 8178.90 µg·kg-1, respectively, which is positively correlated with the urbanization levels. Diagnostic ratios and PMF modal analysis indicate that the sources of the PAHs in soils were most likely coal combustion and traffic combustion (petroleum combustion). The main sources of PAHs in the four areas were petrochemical combustion (41.0%), coal combustion (64.4%), traffic combustion (67.5%), and traffic combustion (62.0%), that is, with the urbanization process, human activity (mainly traffic combustion) gradually become the major contributor of PAHs to the environment. Health risk assessment showed that the risk of cancer exposure through soil digestion and skin exposure was higher. There is a higher health risk from PAHs in urban soils, and the health risks associated with children and adolescents are greater than with other residents, requiring more attention.

[Concentration, Sources and Ecological Risks of PAHs of Different Land Use Types in Shenfu New City].

The concentration level of polycyclic aromatic hydrocarbon (PAHs) in topsoil from Shenfu New City in urbanization was studied. 54 topsoil samples were collected from Shenfu New City and 4 different land uses (urban land, rural land, forest land, cultivated land) were included. The concentration of PAHs in different land uses was analyzed, the sources of soil PAHs were analyzed by using diagnostic ratios and principal component analysis, and the ecological risks were calculated using toxic equivalency concentrations of BaP and the incremental lifetime cancer risk(ILCR)model. Results indicated that the concentrations of ∑PAHs in urban land, cultivated land, rural land and forest land were in the range of 184-18276, 230-14102, 151-3205, 303-2980 µg·kg-1, respectively. Four land uses had similar sources, the main sources were coal combustion and traffic emission. According to the calculation of ecological risks, there were potential health risks for residents in Shenfu New City, especially urban land, meanwhile, residents were easily exposed to soil PAHs through dermal contact.

TREM-1 expression in craniopharyngioma and Rathke's cleft cyst: its possible implication for controversial pathology.

Whether a mixed type of craniopharyngioma (CP) exists and whether papillary craniopharyngioma (pCP) is on a histopathological continuum with Rathke's cleft cyst (RCC) remain controversial. Herein, we examined the expression and localization of ß-catenin, BRAF p.V600E (V600E), and triggering receptor expressed on myeloid cells-1 (TREM-1) in 58 samples including 20 pCPs, 26 adamantinomatous craniopharyngiomas (aCP), and 12 RCCs. Five aCPs were diagnosed with mixed type CPs and the remaining 21 cases were pure aCPs. Four of the 12 RCCs presented with significant squamous epithelium (SE). V600E immunoreactivity was observed in all pCPs in the cytoplasm, but not in the nuclei. aCPs and RCCs, including mixed type CP, did not express V600E. Nuclear ß-catenin translocation was detected exclusively in aCPs. TREM-1 was expressed in pCPs. Additionally, TREM-1 expression was detected in the SE of 5 "mixed type" CPs, while it was absent in pure aCPs. TREM-1 was expressed in 4 RCCs with SE, but not in the remaining 8 RCCs. TREM-1 mRNA levels were compared in cultured pCP and aCP cells. TREM-1 mRNA level was significantly (p < 0.001; up to 4.045 fold) higher in pCPs than in aCPs. Western blotting revealed a significantly (p < 0.001; up to 7.19 fold) lower level of TREM-1 expression in aCP cells compared to that in pCP cells. Our findings further supported that RCC and pCP may represent two ends of a morphological spectrum. A variant showing overlapping histological features of aCP and pCP should not be considered as a mixed type.

K(+) accumulation in the cytoplasm and nucleus of the salt gland cells of Limonium bicolor accompanies increased rates of salt secretion under NaCl treatment using NanoSIMS.

Recretohalophytes with specialized salt-secreting structures (salt glands) can secrete excess salts from plant, while discriminating between Na(+) and K(+). K(+)/Na(+) ratio plays an important role in plant salt tolerance, but the distribution and role of K(+) in the salt gland cells is poorly understood. In this article, the in situ subcellular localization of K and Na in the salt gland of the recretohalophyte Limonium bicolor Kuntze is described. Samples were prepared by high-pressure freezing (HPF), freeze substitution (FS) and analyzed using NanoSIMS. The salt gland of L. bicolor consists of sixteen cells. Higher signal strength of Na(+) was located in the apoplast of salt gland cells. Compared with control, 200 mM NaCl treatment led to higher signal strength of K(+) and Na(+) in both cytoplasm and nucleus of salt gland cells although K(+)/Na(+) ratio in both cytoplasm and nucleus were slightly reduced by NaCl. Moreover, the rate of Na(+) secretion per salt gland of L. bicolor treated with 200 mM NaCl was five times that of controls. These results suggest that K(+) accumulation both in the cytoplasm and nucleus of salt gland cells under salinity may play an important role in salt secretion, although the exact mechanism is unknown.

Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.

In situ IR, pulse reaction and TPD-ITD study of catalytic performance of room-temperature carbon monoxide oxidation on supported gold catalysts.

With in situ IR, two different CO adsorption bands were detected on various chemical state gold catalysts. One band is attributed to the linear CO on an oxidized gold catalyst(2100 cm-1), the other one is ascribed to the bridged CO on metallic gold (2085 cm-1), CO pulse reaction showed that Au/Fe2O3 catalyst had a room-temperature activity even in the presence of moisture. The produced CO2 was detained and more easily desorbed from supported gold catalyst than support oxide. TPD-IDT results indicated that the O2- superoxide ions are the possible active oxygen species.