Pan-cancer analysis reveals the pro-oncogenic role of N6-methyladenosine (m6A)-regulated NTMT1 in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is a common and fatal tumor with a bleak prognosis, posing a significant threat to human health. N6-methyladenosine (m6A) modification regulates tumor progression by modulating gene expression post-transcriptionally. Nevertheless, the specific function of m6A-modified tumor drivers in HNSC remains largely uncharted. In this study, we revealed the pro-oncogenic role of m6A-regulated NTMT1 in HNSC through comprehensive pan-cancer analysis and experimental validation. By scrutinizing the prognostic and expression profiles of NTMT1 across over 30 cancer types, we observed a significant association between NTMT1 and patient overall survival in ACC, HNSC, LAML, LGG, KIRC, and STAD. Moreover, we find a close correlation between NTMT1 and disease-free survival in ACC, HNSC, LUSC, UVM, KIRC, and STAD. NTMT1 exhibited dysregulation in 15 cancers, including CESC, CHOL, COAD, DLBC, GBM, HNSC, LGG, LIHC, PAAD, READ, SKCM, THYM, UCS, LAML, and TGCT. Integrated data underscored the critical involvement of NTMT1 in HNSC. Furthermore, the expression of NTMT1 was closely associated with tumor stage and immune infiltration in HNSC. Functionally, NTMT1 deficiency was demonstrated to significantly impede cell proliferation and cell-cycle progression in HNSC. Mechanistically, METTL3 was elucidated to mediate the epigenetic upregulation of NTMT1 in HNSC in an m6A-dependent manner, and the overexpression of METTL3 was shown to alleviate the inhibitory impact of downregulated NTMT1 on HNSC proliferation. In conclusion, our findings enhance our understanding of NTMT1's role across various cancer types and offer a rationale for clinically targeting NTMT1 as a therapeutic approach for HNSC.

[Hydrochemical Characteristics and Formation Causes of Ground Karst Water Systems in Gudui Spring Catchment].

As one of the famous karst springs in Shanxi Province, the Gudui spring is the only medium-low temperature hot spring, with a long history of development and a rich cultural accumulation. The karst groundwater in the Gudui spring catchment was taken as the research object. Through systematic sample collection and isotope analysis, hydrochemistry (Durov map, ion ratio, Gibbs map, and hydrogen and oxygen isotope) methods were comprehensively used to analyze groundwater hydrochemistry and groundwater system runoff characteristics. The87Sr/86Sr value of karst groundwater in the Gudui spring catchment was 0.709 to 0.717, and the Mg/(Mg+Ca) value was 0.27 to 0.74. By analyzing the Sr isotope composition and Mg/(Mg+Ca) and 1/Sr variation characteristics, it was concluded that the karst groundwater in the Gudui spring catchment was a mixture of deep hot water and shallow cold water. The karst water subsystem of Nanliang spring presented the characteristics of carbonate stratum runoff. The karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin exhibited the runoff characteristics of carbonate rock and igneous rock strata. The karst water subsystem of Taiershan Jiuyuanshan Gudui spring presented the runoff characteristics of carbonate rock and ancient silicoaluminate strata. The δ18O value in karst groundwater of Guodui spring area ranged from -11.46‰ to -7.81‰, and the average value was -10.08‰. The range of the δD value was -83.7‰ to -60.8‰, and the average value was -73.6‰. This showed that karst groundwater in the spring area was the result of mixing of various types of water. Through comparative analysis of hydrogen and oxygen isotopes of 2014 and 2021 sampling points at the same location, it was concluded that the change in water samples at the Guduiquan resulted from the gradual accumulation of water supplied by Sanquan Reservoir. The change in Sanquan Reservoir was due to the influence of Yellow River diversion. The karst groundwater in the spring area were characterized by large calcium ion, magnesium ion, and sodium ion values; a small potassium ion value; a large sulfate value; and a small chloride value. The hydrochemical types of karst groundwater in Gudui spring catchment could be divided into SO4-Na, SO4-Ca, HCO3-Na, HCO3-Mg, HCO3-Ca, and Cl-Na. The hydrochemical types of karst groundwater showed evident hydrochemical composition zoning from HCO3-Ca·Mg→HCO3·SO4-Ca·Mg→SO4·HCO3-Na·Ca→SO4·Cl-Na·Ca. According to the comprehensive analysis of hydrochemical isotope and hydrogeological conditions, the karst water subsystem of Nanliang spring was primarily recharged by rainfall infiltration in the exposed limestone area and river infiltration, and its karst groundwater was recharged by runoff from south to north to the karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin. The karst water subsystem of Taier Jiuyuan Mountain Gudui spring received rainfall infiltration supplement and upstream runoff supplement from the exposed limestone area. Its karst groundwater flowed from north to south and received the supply of Sanquan Reservoir from Yellow River water in the natural discharge area of Gudui spring.

Analysis of changes in the spatiotemporal characteristics of impervious surfaces and their influencing factors in the Central Plains Urban Agglomeration of China from 2000 to 2018.

The change of the impervious surface area (ISA) is an important feature of urban spatial expansion. Understanding the spatial and temporal change characteristics of urban impervious surfaces and their influencing factors is of great significance to the planning, management, and urbanization development of cities. This paper adopts a global artificial impervious surface dataset, with a resolution of 30 m, calculates and processes the data based on the ArcGIS platform, adopts the MK trend test method, introduces the dynamic degree, qualitatively and quantitatively analyses the changing characteristics of the ISA in the Central Plains Urban Agglomeration (CPUA), and analyzes the influencing factors of ISA changes using GeoDetector. The results show that the ISA dynamic degree was significantly enhanced from 2000 to 2018, which increased 1.86 times, indicating the accelerated outward expansion of the CPUA and the rapid level of urban development during that period. The explanatory power of the greenery coverage area on the change of the ISA in the CPUA during 2000-2018 was the strongest; the same factor has different explanatory powers for the ISA in different periods. The influencing factors have an enhanced relationship between two and two, including two-factor enhancement and nonlinear enhancement, in 2000-2009, during which the interaction level of the greenery coverage area and the GDP per capita was strong, while from 2009 to 2018, the interaction between transportation and other factors was significantly strong.

The Effects of COVID-19 Lockdown on Air Pollutant Concentrations across China: A Google Earth Engine-Based Analysis.

To overcome the spread of the severe COVID-19 outbreak, various lockdown measures have been taken worldwide. China imposed the strictest home-quarantine measures during the COVID-19 outbreak in the year 2020. This provides a valuable opportunity to study the impact of anthropogenic emission reductions on air quality. Based on the GEE platform and satellite imagery, this study analyzed the changes in the concentrations of NO2, O3, CO, and SO2 in the same season (1 February-1 May) before and after the epidemic control (2019-2021) for 16 typical representative cities of China. The results showed that NO2 concentrations significantly decreased by around 20-24% for different types of metropolises, whereas O3 increased for most of the studied metropolises, including approximately 7% in megacities and other major cities. Additionally, the concentrations of CO and SO2 showed no statistically significant changes during the study intervals. The study also indicated strong variations in air pollutants among different geographic regions. In addition to the methods in this study, it is essential to include the differences in meteorological impact factors in the study to identify future references for air pollution reduction measures.

[Hydrochemical and Isotopic Characteristics in the Surface Water of the Fenhe River Basin and Influence Factors].

The Fenhe River Basin is the mother river of Shanxi Province. Due to the over-exploitation of water resources and the impact of social and economic development, the ecological environment has deteriorated. After a series of treatment and protection measures, the water quality has since been improved. Mathematical statistics, Piper diagrams, Gibbs model, hydrogen and oxygen isotopes, and other methods were used to analyze the characteristics and sources of hydrochemistry in the surface water of the Fenhe River basin, which revealed the evolution process of surface water quality of the Fenhe River basin. The results showed that the content of the main hydrochemical components in the main stream surface water of Fenhe River basin increased gradually along the runoff path. The hydrochemical types of surface water of Fenhe River basin were mainly HCO3·SO4·Cl-Ca·Na·Mg and SO4·HCO3·Cl-Ca·Na·Mg. There were great differences in hydrochemical components of tributaries and karst water in the basin. There were also great differences in hydrochemical components of tributaries in the basin. The hydrochemical types of surface water of karst water were mainly SO4·HCO3-Ca·Mg. The hydrochemical composition of surface water in Fenhe River basin was mainly affected by rock weathering and evaporation crystallization, whereas rainfall had little effect. Na+ and K+ mainly came from the dissolution of evaporated salt rocks with Na in the surrounding loess. Ca2+, Mg2+, and HCO3- mainly came from the dissolution of carbonate rocks. SO42- may have also come from the dissolution of sulfide minerals in the loess layer around Fenhe River in addition to the dissolution of gypsum. The values of δD and δ18O of Fenhe River surface water were gradually enriched from upstream to downstream. The characteristics of hydrogen and oxygen isotopes further showed that the surface water was mainly affected by evaporation. The results of this study can provide evidence for ecological restoration and protection and ecological civilization construction in the Fenhe River basin.

Three-dimensional mapping of carbon, nitrogen, and phosphorus in soil microbial biomass and their stoichiometry at the global scale.

Soil microbial biomass and microbial stoichiometric ratios are important for understanding carbon and nutrient cycling in terrestrial ecosystems. Here, we compiled data from 12245 observations of soil microbial biomass from 1626 published studies to map global patterns of microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial biomass phosphorus (MBP), and their stoichiometry using a random forest model. Concentrations of MBC, MBN, and MBP were most closely linked to soil organic carbon, while climatic factors were most important for stoichiometry in microbial biomass ratios. Modeled seasonal MBC concentrations peaked in summer in tundra and in boreal forests, but in autumn in subtropical and in tropical biomes. The global mean MBC/MBN, MBC/MBP, and MBN/MBP ratios were estimated to be 10, 48, and 6.7, respectively, at 0-30 cm soil depth. The highest concentrations, stocks, and microbial C/N/P ratios were found at high latitudes in tundra and boreal forests, probably due to the higher soil organic matter content, greater fungal abundance, and lower nutrient availability in colder than in warmer biomes. At 30-100 cm soil depth, concentrations of MBC, MBN, and MBP were highest in temperate forests. The MBC/MBP ratio showed greater flexibility at the global scale than did the MBC/MBN ratio, possibly reflecting physiological adaptations and microbial community shifts with latitude. The results of this study are important for understanding C, N, and P cycling at the global scale, as well as for developing soil C-cycling models including soil microbial C, N, and P as important parameters.

[Distribution Characteristics and Health Risk Assessment of Metal Elements in Groundwater of Longzici Spring Area].

Longzici Spring is an important water source for industry, agriculture, and urban life in Linfen City. With the improvements in public environmental health awareness, it is particularly necessary to study the health risk of posed by metal elements in groundwater. In this study, 43 groundwater samples from Longzici Spring area were analyzed for ten metal elements (As, Cd, Hg, Al, Pb, Co, Mn, Fe, Cu, and Ni). The distribution and health risk of these metal elements in the groundwater were studied using multivariate statistical analysis and a health risk assessment model. The results show that metal elements can be ranked, from high to low, by their average concentrations in groundwater in the following order: Fe, Al, Mn, Ni, As, Cu, Co, Pb, Hg, and Cd. The concentration of Al, Mn, Fe, and As exceed the limit for class Ⅲ water, as defined in the quality standard for groundwater (GB/T 14848-2017). Different types of groundwater in the spring area showed different metal contents. The quality of karst spring water was good, reaching the standard for drinking water, while mine drainage water exceeded the standard for drinking water, with the highest metal concentration (60%) and the worst water quality. Multivariate statistical results show that Pb, Ni, Co, Cd, Mn, and Cu concentrations were mainly affected by the geochemical background, while Al, Fe, Hg, and As concentrations were closely related to human mining activities under the unique geological background of Shanxi Province. The health risk assessment showed that the different types of groundwater could be ranked by the annual total health risks, posed by metal elements to adults and children through drinking water and skin infiltration, as follows: karst well > non-karst spring > non-karst well > karst spring. The health risks mainly came from drinking water, while health risks through skin infiltration would not cause obvious harm to the human body. The metal element causing the greatest health risk in spring groundwater was As, which should therefore be controlled in the utilization of water resources, especially in children's drinking water.

Theoretical study on the noncovalent interactions involving triplet diphenylcarbene.

The properties of some types of noncovalent interactions formed by triplet diphenylcarbene (DPC3) have been investigated by means of density functional theory (DFT) calculations and quantum theory of atoms in molecule (QTAIM) studies. The DPC3···LA (LA = AlF3, SiF4, PF5, SF2, ClF) complexes have been analyzed from their equilibrium geometries, binding energies, and properties of electron density. The triel bond in the DPC3···AlF3 complex exhibits a partially covalent nature, with the binding energy - 65.7 kJ/mol. The tetrel bond, pnicogen bond, chalcogen bond, and halogen bond in the DPC3···LA (LA = SiF4, PF5, SF2, ClF) complexes show the character of a weak closed-shell noncovalent interaction. Polarization plays an important role in the formation of the studied complexes. The strength of intermolecular interaction decreases in the order LA = AlF3 > ClF > SF2 > SiF4 > PF5. The electron spin density transfers from the radical DPC3 to ClF and SF2 in the formation of halogen bond and chalcogen bond, but for the DPC3···AlF3/SiF4/PF5 complexes, the transfer of electron spin density is minimal.

[Chemical Characteristics and Causes of Groups Water in Niangziguan Spring].

Discharge in Niangziguan Spring is 7.19 m3·s-1, which is the main water supply source for Yangquan City and Pingding County. Every year, Yangquan municipal government take water from the mouth of Niangziguan Spring to supply drinking water to urban residents at a rate of approximately 1.7 m3·s-1. It is of great significance to determine the characteristics and causes of variations in spring water flow conditions for the appropriate utilization of water resources and pollution prevention. Here, sample collection and hydrochemical isotope analyses were undertaken for the Niangziguan Spring area to chemically characterize the water environment and genesis. The pH of the karst spring is 7.2-7.5 with an average of 7.36; the calcium content of the water is 112.1-135.2 mg·L-1 with a mean value of 131.4 mg·L-1; the concentration of magnesium ions is 34.8-42.3 mg·L-1 with an average of 40.8 mg·L-1; the concentration of K++Na- ions is 41.6-46.7 mg·L-1 with an average of 45.2 mg·L-1; and the sulfate ion concentration is 185.6-271.8 mg·L-1 with a mean value of 255.4 mg·L-1. The hydrochemical type of the aquifer is classified as HCO3·SO4-Ca·Mg. The spring water is characterized by high Ca2+, Mg2+, and SO42- concentrations, and low Na+, K+, and Cl- concentrations. The supply path of Chengxi Spring is shortest followed by Wulong Spring. The supply paths of the remaining five spring are much longer. The Niangziguan Spring water environment is characterized by increasing pollution from coal mine acid drainage alongside decreasing inputs from domestic sewage. Environmental isotope tracing shows that sulfate in Chengxi Spring mainly derives from precipitation and gypsum dissolution, and the concentrations of sulfate in Wulong Spring are increasing. These changes are mainly driven by the amount of coal mine acid water pollution in the area.

Drought alters the carbon footprint of trees in soils-tracking the spatio-temporal fate of 13 C-labelled assimilates in the soil of an old-growth pine forest.

Above and belowground compartments in ecosystems are closely coupled on daily to annual timescales. In mature forests, this interlinkage and how it is impacted by drought is still poorly understood. Here, we pulse-labelled 100-year-old trees with 13 CO2 within a 15-year-long irrigation experiment in a naturally dry pine forest to quantify how drought regime affects the transfer and use of assimilates from trees to the rhizosphere and associated microbial communities. It took 4 days until new 13 C-labelled assimilates were allocated to the rhizosphere. One year later, the 13 C signal of the 3-h long pulse labelling was still detectable in stem and soil respiration, which provides evidence that parts of the assimilates are stored in trees before they are used for metabolic processes in the rhizosphere. Irrigation removing the natural water stress reduced the mean C residence time from canopy uptake until soil respiration from 89 to 40 days. Moreover, irrigation increased the amount of assimilates transferred to and respired in the soil within the first 10 days by 370%. A small precipitation event rewetting surface soils altered this pattern rapidly and reduced the effect size to +35%. Microbial biomass incorporated 46 ± 5% and 31 ± 7% of the C used in the rhizosphere in the dry control and irrigation treatment respectively. Mapping the spatial distribution of soil-respired 13 CO2 around the 10 pulse-labelled trees showed that tree rhizospheres extended laterally 2.8 times beyond tree canopies, implying that there is a strong overlap of the rhizosphere among adjacent trees. Irrigation increased the rhizosphere area by 60%, which gives evidence of a long-term acclimation of trees and their rhizosphere to the drought regime. The moisture-sensitive transfer and use of C in the rhizosphere has consequences for C allocation within trees, soil microbial communities and soil carbon storage.

Improved model simulation of soil carbon cycling by representing the microbially derived organic carbon pool.

During the decomposition process of soil organic carbon (SOC), microbial products such as microbial necromass and microbial metabolites may form an important stable carbon (C) pool, called microbially derived C, which has different decomposition patterns from plant-derived C. However, current Earth System Models do not simulate this microbially derived C pool separately. Here, we incorporated the microbial necromass pool to the first-order kinetic model and the Michaelis-Menten model, respectively, and validated model behaviors against previous observation data from the decomposition experiments of 13C-labeled necromass. Our models showed better performance than existing models and the Michaelis-Menten model was better than the first-order kinetic model. Microbial necromass C was estimated to be 10-27% of total SOC in the study soils by our models and therefore should not be ignored. This study provides a novel modification to process-based models for better simulation of soil organic C under the context of global changes.

Spatiotemporal Analysis of AIDS Incidence and Its Influencing Factors on the Chinese Mainland, 2005-2017.

Acquired Immune Deficiency Syndrome (AIDS) has become one of the most severe public health issues and nowadays around 38 million people are living with the human immunodeficiency virus (HIV). Ensuring healthy lives and promoting well-being is one of 17 United Nations Sustainable Development Goals. Here, we used the Markov chain matrix and geospatial clustering to comprehensively quantify the trends of the AIDS epidemic at the provincial administrate level in the mainland of China from 2005 to 2017. The Geographically Weighted Regression (GWR) model was further adopted to explore four groups of potential influencing factors (i.e., economy, traffic and transportation, medical care, and education) of the AIDS incidence rate in 2017 and their spatially distributed patterns. Results showed that the AIDS prevalence in southeastern China had been dominant and become prevalent in the past decade. The AIDS intensity level had been increasing between 2008 and 2011 but been gradually decreasing afterward. The analysis of the Markov chain matrix indicated that the AIDS epidemic has been generally in control on the Chinese mainland. The economic development was closely related to the rate of AIDS incidence on the Chinese mainland. The GWR result further suggested that medical care and the education effects on AIDS incidence rate can vary with different regions, but significant conclusions cannot be directly demonstrated. Our findings contribute an analytical framework of understanding AIDS epidemic trends and spatial variability of potential underlying factors throughout a complex extent to customize scientific prevention.

Maternal oral contraceptive pill use and the risk of atopic diseases in the offspring: A systematic review and meta-analysis.

Studies of maternal oral contraceptive pill (OCP) exposure and the offspring's risk of atopic diseases are of current interest due to concerns about widespread use of OCP before or during pregnancy.We evaluated whether maternal OCP exposure is associated with an increased risk of atopic diseases by reviewing the literature and performing a meta-analysis. The PubMed and Embase databases were searched to identify potential studies for inclusion. Three common atopic outcomes were included: asthma, eczema, and rhinitis.We found 693 titles, abstracts, and citations, and 6 studies were included in this analysis. A meta-analysis revealed that maternal OCP exposure was associated with higher odds of asthma (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.02-1.19; P = .014), rhinitis (OR 1.34; 95% CI 1.07-1.68; P = .011) during childhood, whereas there was no association with eczema (OR 1.17; 95% CI 0.81-1.68; P = .383). This analysis was limited by the small number of studies included and the limited adjustments for the possible confounders in the studies.Current evidence suggests that maternal OCP exposure increases the risk for respiratory allergic diseases (asthma and rhinitis) in the offspring, but not for eczema. Given the few studies included, future larger, prospective studies that control for important confounders are needed to verify our findings.

Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study.

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient= -0.101, OR = 0.904), and albumin (ALB) (coefficient= -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma.

As documented, the expression, biological roles, and prognostic significance of FKBP10 in stomach adenocarcinoma (STAD) have not been investigated till now. This drives us to detect the biological roles and clinical significance of FKBP10 in STAD. The expression level of FKBP10 was measured based on the data obtained from the TCGA, ONCOMINE, and GEPIA databases, and STAD cell lines. Through in vitro experiments, cell behaviors were investigated to evaluate the effects of FKBP10 on STAD. Moreover, the PI3K-AKT signaling pathway was measured. Relying on the data of TCGA, ONCOMINE, and GEPIA databases, and cancer cell lines, FKBP10 was up-regulated in STAD when compared with normals. The patients with low expression of FKBP10 had higher survival rate than those with high FKBP10 expression. After knockdown of FKBP10 in AGS cells, cell vitality, colony formation ability, and the migratory and invasive potential were inhibited. Western blotting analysis exhibited that knockdown of FKBP10 significantly reduced the expression level of p-AKT, and p-PI3K, but it did not influence the total expression level of AKT, and PI3K. FKBP10 might serve as a crucial player in gastric cancer, and targeting FKBP10 might provide clinical utility in gastric cancer in future.

Different pathways for 4-n-nonylphenol biodegradation by two Aspergillus strains derived from estuary sediment: Evidence from metabolites determination and key-gene identification.

Nonylphenols (NPs) are known as Endocrine Disputing Chemicals (ECDs) and Persistent Organic Pollutants (POPs) and have attracted continuous attention. Biodegradation is one of the effective ways for pollutant removal in aquatic, sedimentary and soil environments. In this study, two estuarine derived fungi strains, NPF2 and NPF3, were screened from Moshui river estuarine sediment and identified as genus Aspergillus. The growth curves of the two strains as well as the removal and degradation rates for 4-n-NP in Potato Dextrose(PD)medium were used to evaluate their degradation ability. Both strains showed high efficiency for 4-n-NP degradation with 86.03% and 98.76% removal rates in 3 days for NPF2 and NPF3, respectively. Determination of degradation intermediates by LC-MS suggested that the mechanisms for 4-n-NP biodegradation by NPF2 and NPF3 are quite different. Some key functional genes for the two strains also provided supplementary evidences for the different biodegradation mechanism. On strain NPF2, with participation of Cox1, 2 and 3, 4-n-NP degradation starts from reaction at the terminal of the long alkyl chain. The chain reduces one carbon atom once within a cycle of hydroxylation, subsequent oxidation at α-C position and decarboxylation. However, on NPF3, with involvement of sMO, Cel7A, Cel7B and ATEG-00639, 4-n-NP degradation starts from benzene ring, converting into fatty acids. The latter bio-pathway was the first time reported for NPs degradation on fungi.

Carvedilol Attenuates the Progression of Hepatic Fibrosis Induced by Bile Duct Ligation.

Background. The sympathetic nervous system (SNS) is responsible for hepatic stellate cells (HSCs) activation and the accumulation of collagen that occurs in hepatic fibrogenesis. Carvedilol has been widely used for the complication of hepatic cirrhosis in the clinic. Furthermore, it has powerful antioxidant properties. We assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may further enhance its clinical benefits. Methods. Using a bile duct ligation rat model of hepatic fibrosis, we studied the effects of carvedilol on the fibrosis, collagen deposition, and oxidative stress based on histology, immunohistochemistry, western blot, and RT-PCR analyses. Results. Carvedilol attenuated liver fibrosis, as evidenced by reduced hydroxyproline content and the accumulation of collagen, downregulated TIMP-1 and TIMP-2, and upregulated MMP-13. MMP-2 was an exception, which was decreased after carvedilol treatment for 2 weeks and upregulated after carvedilol treatment for 4 weeks. Carvedilol reduced the activation of HSCs, decreased the induction of collagen, transforming growth factor-ß1, and MDA content, and strengthened the SOD activity. The antifibrotic effects were augmented as dosages increased. Conclusions. The study indicates that carvedilol attenuated hepatic fibrosis in a dose-dependent manner. It can decrease collagen accumulation and HSCs activation by the amelioration of oxidative stress.

Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy.

Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B'-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B'-infected individuals with longer infection length. However, subtype B'-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo.

BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor. MATERIALS AND METHODS: We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil. RESULTS: The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice without weight loss. With virus replication, oHSV2 not only resulted in a reduction of myeloid-derived suppressor cells and regulatory T cells in the spleen, but also increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4+T and CD8+T-cells in the tumor microenvironment. CONCLUSION: Our study provides the first evidence that oHSV2 induces cell death in CRC in vitro and in vivo. These findings indicate that oHSV2 is an effective therapeutic cancer candidate that causes an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, thus providing a potential therapeutic tool for treatment of CRC.

Groundwater level prediction using a SOM-aided stepwise cluster inference model.

Accurate groundwater level (GWL) prediction can contribute to sustaining reliable water supply to domestic, agricultural and industrial uses as well as ecological services, especially in arid and semi-arid areas. In this paper, a regional GWL modeling framework was first presented through coupling both spatial and temporal clustering techniques. Specifically, the self-organizing map (SOM) was applied to identify spatially homogeneous clusters of GWL piezometers, while GWL time series forecasting was performed through developing a stepwise cluster multisite inference model with various predictors including climate conditions, well extractions, surface runoffs, reservoir operations and GWL measurements at previous steps. The proposed modeling approach was then demonstrated by a case of an arid irrigation district in the western Hexi Corridor, northwest China. Spatial clustering analysis identified 6 regionally representative central piezometers out of 30, for which sensitivity and uncertainty analysis were carried out regarding GWL predictions. As the stepwise cluster tree provided uncertain predictions, we added an AR(1) error model to the mean prediction to forecast GWL 1 month ahead. Model performance indicators suggest that the modeling system is a useful tool to aid decision-making for informed groundwater resource management in arid areas, and would have a great potential to extend its applications to more areas or regions in the future.