Spatial and temporal distribution characteristics and risk assessment of heavy metals in groundwater of Pingshuo mining area.

Groundwater pollution in the Pingshuo mining area is strongly associated with mining activities, with heavy metals (HMs) representing predominant pollutants. To obtain accurate information about the pollution status and health risks of groundwater, 189 groups of samples were collected from four types of groundwater, during three periods of the year, and analyzed for HMs. The results showed that the concentration of HMs in groundwater was higher near the open pit, waste slag pile, riverfront area, and human settlements. Except for Ordovician groundwater, excessive HMs were found in all investigated groundwater of the mining area, as compared with the standard thresholds. Fe exceeded the threshold in 13-75% of the groundwater samples. Three sources of HMs were identified and quantified by Pearson's correlation analysis and the PMF model, including coal mining activities (68.22%), industrial, agricultural, and residential chemicals residue and leakage (16.91%), and natural sources (14.87%). The Nemerow pollution index revealed that 7.58% and 100% of Quaternary groundwater and mine water samples were polluted. The health risk index for HMs in groundwater showed that the non-carcinogenic health risk ranged from 0.18 to 0.42 for adults, indicating an acceptable level. Additionally, high carcinogenic risks were identified in Quaternary groundwater (95.45%), coal series groundwater (91.67%), and Ordovician groundwater (26.67%). Both carcinogenic and non-carcinogenic risks were greater for children than adults, highlighting their increased vulnerability to HMs in groundwater. This study provides a scientific foundation for managing groundwater quality and ensuring drinking water safety in mining areas.

The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy.

BACKGROUND: Malignant tumours seriously threaten human life and health, and effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance and inhibit tumour growth has been increasingly studied, but its dynamic role in the tumour cell cycle and corresponding effects leading to mitotic catastrophe and DNA damage have rarely been studied. RESULTS: In this paper, we found that the nucleoprotein SHCBP1 exhibits dynamic spatiotemporal expression during the tumour cell cycle, and SHCBP1 knockdown slowed cell cycle progression by inducing spindle disorder, as reflected by premature mitotic entry and multipolar spindle formation. This dysfunction was caused by G2/M checkpoint impairment mediated by downregulated WEE1 kinase and NEK7 (a member of the mammalian NIMA-related kinase family) expression and upregulated centromere/kinetochore protein Zeste White 10 (ZW10) expression. Moreover, both in vivo and in vitro experiments confirmed the significant inhibitory effects of SHCBP1 knockdown on tumour growth. Based on these findings, SHCBP1 knockdown in combination with low-dose DNA-damaging agents had synergistic tumouricidal effects on tumour cells. In response to this treatment, tumour cells were forced into the mitotic phase with considerable unrepaired DNA lesions, inducing mitotic catastrophe. These synergistic effects were attributed not only to the abrogation of the G2/M checkpoint and disrupted spindle function but also to the impairment of the DNA damage repair system, as demonstrated by mass spectrometry-based proteomic and western blotting analyses. Consistently, patients with low SHCBP1 expression in tumour tissue were more sensitive to radiotherapy. However, SHCBP1 knockdown combined with tubulin-toxic drugs weakened the killing effect of the drugs on tumour cells, which may guide the choice of chemotherapeutic agents in clinical practice. CONCLUSION: In summary, we elucidated the role of the nucleoprotein SHCBP1 in tumour cell cycle progression and described a novel mechanism by which SHCBP1 regulates tumour progression and through which targeting SHCBP1 increases sensitivity to DNA-damaging agent therapy, indicating its potential as a cancer treatment.

Comparison of different treatment regimens and analysis of prognostic factors in secondary hemophagocytic lymphohistiocytosis in adults: A single-center retrospective study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by immune hyperactivation. The overall survival (OS) of adults with secondary HLH remains suboptimal and new treatment strategies are needed. OBJECTIVES: This study aimed to compare the efficacy of different regimens in the treatment of secondary HLH in adults and analyze the prognostic factors affecting patient survival. MATERIAL AND METHODS: The clinical data of 245 adults with secondary HLH admitted to our hospital from January 2016 to October 2021 were analyzed retrospectively. The patients were divided into 3 groups according to different treatment regimens: corticosteroids therapy + chemotherapy + supportive treatment group (JHZ group), chemotherapy + supportive treatment group (HZ group) and corticosteroids therapy + supportive treatment group (JZ group). The clinical efficacy was compared among the 3 groups after treatment, and progression-free survival (PFS) and overall survival (OS) were calculated. Additionally, risk factors associated with prognosis were also analyzed with Cox regression analysis. RESULTS: The objective response rate (ORR) in the JHZ group was higher than that in the HZ group and JZ group, but there was no significant difference between the 3 groups. Also, the patients in the JHZ group had the longest OS and median PFS. Further Cox regression analysis suggested that hyperbilirubinemia was an independent risk factor for OS in secondary HLH patients. CONCLUSIONS: A combination of corticosteroids therapy, chemotherapy and supportive therapy is superior to the other 2 regimens in the clinical benefit in the treatment of secondary HLH in adults, and thus may be a preferred and feasible treatment regimen. Moreover, hyperbilirubinemia was a risk factor for prognosis that has crucial guiding significance for clinical treatment of patients with secondary HLH.

Characterization and drivers of water and carbon fluxes dynamics in dune ecosystems of the Horqin Sandy Land.

Sandy regions constitute pivotal components of terrestrial ecosystems, exerting significant influences on global ecological equilibrium and security. This study meticulously explored water and carbon fluxes dynamics within a dune ecosystem in the Horqin Sandy Land throughout the growing seasons from 2013 to 2022 by employing an advanced eddy covariance system. The dynamic characteristics of these fluxes and their underlying driving forces were extensively analyzed, with a particular focus on the impact of precipitation. The main results are as follows: (1) During the growing seasons of 2015 and 2016, the dune ecosystem acted as a modest carbon source, while in 2013, 2014, and 2017- 2022, it transformed into a net carbon sink. Notably, the annual mean values of water use efficiency (WUE) and evapotranspiration (ET) were 5.16 gC·kg-1H2O and 255.4 mm, respectively. (2) The intensity, frequency, and temporal distribution of precipitation were found to significantly influence the carbon and water fluxes dynamics. Isolated minor precipitation events did not trigger substantial fluctuations, but substantial and prolonged precipitation events spanning multiple days or consecutive minor precipitation events resulted in notable assimilation delays. (3) Air temperature, soil temperature, and fractional vegetation cover (FVC) were found to be key factors influencing the carbon and water fluxes. Specifically, FVC exhibited a negative logarithmic correlation with net ecosystem CO2 exchange (NEE) and a power function relationship with WUE. (4) The interaction between carbon and water fluxes is exhibited by exponential increases in ecosystem respiration (Reco) and gross primary productivity (GPP) with WUE, while NEE displayed an exponential decrease in relation to WUE. These findings are of high significance in predicting the potential ramifications of climate change on the intricate carbon and water cycles, and enhance our understanding of ecosystem dynamics in sandy environments.

Occurrence, source apportionment, and ecological risk of legacy and emerging per- and poly-fluoroalkyl substances (PFASs) in the Dahei river basin of a typical arid region in China.

Per- and poly-fluoroalkyl substances (PFASs) are artificial chemicals with broad commercial and industrial applications. Many studies about PFASs have been conducted in densely industrial and populated regions. However, fewer studies have focused on the PFASs' status in a typical arid region. Here, we investigated 30 legacy and emerging PFASs in surface water from the mainstream and tributaries of the Dahei River. Our results revealed that total PFASs concentrations (∑30PFASs) in water ranged from 3.13 to 289.1 ng/L (mean: 25.40 ng/L). Perfluorooctanoic acid (PFOA) had the highest mean concentration of 2.44 ng/L with a 100% detection frequency (DF), followed by perfluorohexanoic acid (PFHxA) (mean concentration: 1.34 ng/L, DF: 59.26%). Also, perfluorohexane sulfonate (DF: 44.44%), perfluorobutane sulfonate (DF: 88.89%), and perfluorooctane sulfonate (PFOS) (DF: 92.59%) had mean concentrations of 12.94, 2.00, and 1.05 ng/L, respectively. Source apportionment through ratio analysis and principal component analysis-multiple linear regression analysis showed that treated or untreated sewage, aqueous film-forming foam, degradation of precursors, and fluoropolymer production were the primary sources. The PFOS alternatives were more prevalent than those of PFOA. Conductivity, total phosphorus, and chlorophyll a positively correlated with Σ30PFASs and total perfluoroalkane sulfonates concentrations. Furthermore, ecological risk assessment showed that more attention should be paid to perfluorooctadecanoic acid, perfluorohexadecanoic acid, perfluorooctane sulfonate, perfluorohexane sulfonate, and (6:2 and 6:2/8:2) polyfluoroalkyl phosphate mono- and di-esters. The mass load of PFASs to the Yellow River was 1.28 kg/year due to the low annual runoff in the Dahei River in the arid region. This study provides baseline data for PFASs in the Dahei River that can aid in the development of effective management strategies for controlling PFASs pollution in typical arid regions in China.

[Relationship Between Precipitation, River Water, and Groundwater Conversion in the Upper Reaches of Xilin River During the Rainy Season].

To deeply understand the hydrological cycle process and the transformation mechanism of different water bodies in the grassland inland river basin, the atmospheric precipitation, river water, and groundwater in the Xilin River Basin were taken as the research objects, the hydrogen and oxygen stable isotopes were analyzed, and the multi-scale spatio-temporal characteristics were analyzed to explore the quantitative transformation relationship between different water bodies in the basin. The results showed that:① the Xilin River Basin had an obvious inland semi-arid climate, the atmospheric precipitation was the main source of recharge for the river water and groundwater, and the groundwater and river water experienced different degrees of non-equilibrium evaporation at the same time. ② The isotopic composition of the river water showed the characteristics of depletion in spring and autumn and enrichment in summer and showed a trend of increasing from upstream to downstream in space. The variation in δ18O in shallow and deep groundwater during the growing season was basically the same, and the main difference between the two occurred at the end of the growing season, that is, the former tended to be stable, whereas the latter showed an upward trend, which reflected that the deep groundwater had a lagged response to the infiltration and recharge of atmospheric precipitation and surface water, and both of them were depleted gradually from southeast to northwest in space. ③ Based on the estimation results of the endmember mixing model, the average recharge ratio of atmospheric precipitation and shallow groundwater to river water in summer was 52.69% and 47.31%, respectively, indicating that shallow groundwater was an important recharge source of river water in the inland river basin even during the rainy season. The results of this study provide theoretical guidance for water resource regulation and ecological environment protection in a typical semi-arid grassland inland river basin.

Deciphering spatio-seasonal patterns, driving forces, and human health risks of nitrate and fluoride enriched water bodies in the Inner Mongolia Reaches of the Yellow River Basin, China.

The ecology and environment of the Yellow River Basin is threatened by fluoride and nitrate contamination induced by anthropogenic activity and geogenic factors. As a result, deciphering the spatio-temporal variability of fluoride and nitrate contamination in this area remains a challenge. Three hundred eighty-six samples of surface water and groundwater from the Inner Mongolia Reaches of the Yellow River Basin were taken for this investigation. According to the results of the multivariate statistical and geostatistical analyses, the fluoride pollution was primarily discovered in the middle and lower reaches of the study area and was determined to be more severe during the dry season. In contrast, nitrate contamination was found to be more severe during the wet season while being widely distributed in groundwater and concentrated in areas with intensive agricultural activities. The primary mechanisms governing the spatial-seasonal patterns of NO3- and F- pollution were shown by the principal component analysis, isotopic, and hydrochemical diagrams. The water-rock interaction or evaporation was crucial in the enrichment of F-. The human inputs (e.g., fertilizer or sewage) dominated fluoride and nitrate contamination. Additionally, the alkaline environment played a role in the generation of NO3- and F-. The health risk assessment concluded that the threat of fluoride contamination was greater than that of nitrate contamination. Children faced the greatest health risks, followed by females and males. These findings would serve as a guide for water management and pollution control in the Yellow River Basin.

[Water Chemical Isotope Characteristics and Water Transformation Relationship in Mongolian Section of the Yellow River Basin].

The Yellow River in Inner Mongolia was selected as the study area in this study. In July (wet season) and October (dry season) of 2021, the acquisition of seasonal rivers, the Yellow River tributaries and precipitation, the Yellow River, Wuliangsuhai, Lake Hasuhai, Lake Daihai, an irrigation canal system, and underground water and sea water samples were collected to test the water chemical composition and hydrogen and oxygen isotopic values of different water types. Using the Piper triplot, Gibbs plot, ion ratio, and MixSIAR model methods, the evolution of water chemistry in the Mongolian section of the Yellow River Basin was analyzed, and the transformation relationship between precipitation, surface water, and groundwater was revealed. The results showed that both groundwater and surface water in the study area were slightly alkaline; the dominant anion in water was Cl-, and the dominant cation was Na+. The main hydrochemical types of surface water were Cl·SO4-Na·Mg and SO4·HCO3-Na·Mg, whereas those of groundwater were Cl·SO4-Na·Mg and SO4·HCO3-Na·Ca. Groundwater Ca2+ and Mg2+ were primarily derived from the dissolution of silicate and evaporite, and surface water Ca2+ and Mg2+ were primarily derived from carbonate karst dissolution and carbonate and sulfuric acid in water participating in the dissolution process of carbonate and sulfide minerals. Na+ and Cl- in different water bodies were all affected by anthropogenic pollution sources. Owing to the seasonal effect, δD and δ18O of surface water and groundwater were higher in the wet season than in the dry season. The results showed that surface water was affected by evaporative fractionation after receiving precipitation recharge, and the groundwater recharge sources were complex. The MixSIAR model revealed that surface water was the main recharge source of groundwater, accounting for 52.4%-62.2% of the total recharge, and atmospheric precipitation was the main recharge source of surface water, accounting for 85.4%-97.1% of the total recharge.

Spatiotemporal variations of ecosystem security pattern in Horqin sandy dune meadow alternating area, China.

The natural and geographical environment of ecologically fragile areas in northern China is complex. Due to heavy human disturbance and impacts of climate change, the sustainable development of ecosystems is facing serious challenges. Constructing ecological security pattern can provide decision-making basis for ecological environment protection in desertification areas. Based on land use change data of Horqin dune-meadow interphase area from 1985 to 2021, we identified ecological sources with the importance of ecosystem services and ecological sensitivity, and constructed the ecological security pattern using the minimum cumulative resistance model. We further analyzed the ecological security pattern and its development trend in 1985, 1995, 2005, 2015 and 2021, and explored the ecological spatial layout adjustment strategy. The results showed that the proportion of source area in the ecological security pattern of the study area was always small and scattered from 1985 to 2021, the network of ecological corridors was low, and the connectivity between ecological patches was lacking. The ecological security pattern had experienced a trend of deterioration first and then gradually improving. Ecological policies such as returning farmland to forest and grassland and afforestation had significantly improved the environmental security. We optimized the study area by combining the cultivated land suitability evaluation method. The ecological security pattern showed a spatial trend of 'dual-core, scattered and semi-surrounded'. The results could provide references for the construction of county-scale ecological security pattern in ecologically fragile areas and the ecological management of Horqin sands.

Large-scale surface water-groundwater origins and connectivity in the Ordos Basin, China: Insight from hydrogen and oxygen isotopes.

The sustainability of water resources is a major challenge for the Ordos Basin and Loess Plateau of China. The basis of effective water management is an understanding of the water cycle process. This study investigated the surface water-groundwater origins and connectivity using stable isotopes (δD and δ18O) of surface water and groundwater in 11 river basins in the Ordos Basin. It was found that the surface water-groundwater origins and hydraulic connection were characterized by regional differences, mainly induced by climatic characteristics, hydrogeological conditions and human activities. Specifically, the impact of thick loess deposits caused surface water and groundwater to take long time to produce a hydraulic connection. In contrast, areas with thin loess deposits and frequent human activities showed a good connectivity between surface water and groundwater. As for water origins, summer precipitation was a common source of surface water and groundwater in the study area, and groundwater discharge was another source of surface water. However, surface water and groundwater were subjected to different degrees of evaporation during receiving precipitation recharge. Notably, thick loess deposits had an impact on groundwater evaporation because both the recharge of precipitation to groundwater and the discharge of groundwater to surface water took a long time. In addition, it was found that frequent human activities (mining, irrigation and urban construction) could weaken the impact of evaporation. This large-scale analysis provided new insights into the origins and connectivity of surface water and groundwater in areas with thick unsaturated zones for water resources management.

Study on spatio-temporal simulation and prediction of regional deep soil moisture using machine learning.

Deep soil moisture (SM) plays a crucial role in vegetation restoration, particularly in semi-arid areas. However, current SM products have limited access and do not meet the spatio-temporal scale and soil depth requirements in eco-hydrological research. Thus, this study constructs a random forest prediction model for SM at different depths by identifying driving factors and quantifying the correlation effect of vertical SM based on the international SM network dataset. Subsequently, the SMAP product is integrated into the model to expand SM from point scale to regional scale, yielding an SM data product with a suitable scale and continuous time and space. The results indicate that the correlation between precipitation and SM changes into the interaction between adjacent SM layers as the depth increases. The lag time of SM in the shallow surface layer (0-3 cm) to precipitation was 1 day, and there was no delay on the daily scale in the 3-20 cm layers of the three underlying surface types. The response time of 50 cm SM to 20 cm SM was 1-2 days in cropland and grassland and 2 days in forest. Slope, land use type, clay proportion, leaf area index, potential evapotranspiration, and land surface temperature were the key driving factors of SM in the Shandian River region. The random forest model established in this study demonstrated good prediction performance for SM at both site and regional scales. The obtained daily products had higher spatial fineness than CLDAS products and could describe the SM characteristics of different underlying surfaces. This study offers new ideas and technical support for acquiring deep SM data in arid and semi-arid areas of northern China.

Clinical value of soluble fms-like tyrosine kinase 1 (sFlt-1) in adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a syndrome characterized by an excessive systemic inflammatory response, manifested by multiple organ dysfunction, lacking reliable immune biomarkers for predicting their inflammatory status and prognosis. Soluble fms-like tyrosine kinase 1 (sFlt-1) is associated with various inflammation-related diseases, including sepsis and severe organ failure. METHODS: This study retrospectively included 32 adult sHLH patients diagnosed from January 2020 to December 2021. The expression of Flt-1 in peripheral blood CD14 + monocytes was detected by flow cytometry, and the level of plasma sFlt-1 was detected by ELISA. RESULTS: In our study, the results of flow cytometry reveal that the Flt-1 expression on CD14 + monocytes of peripheral blood from sHLH patients was higher than that in normal control. In plasma samples of sHLH patients, sFlt-1 levels were 677.8 (463.2-929.7) pg/mL, significantly higher than in normal controls 377.18 (350.4-424.6) pg/mL and sepsis group 378.3 (257.0-499.1) pg/mL. Besides, a positive correlation was found between sFlt-1 and IL-6 in sHLH patients. The analysis of univariate Cox regression indicated that sFlt-1 >681.5 pg/mL demonstrated unfavorable overall survival ( p = 0.022). Multivariate analysis demonstrated that sFlt-1 >681.5 pg/mL was an independent factor associated with OS ( p = 0.041) after adjustment for confounders. Restricted cubic spline confirmed a linear and positive association between sFlt-1 and mortality risk. CONCLUSION: Retrospective analysis showed that sFlt-1 was a promising prognostic factor.

Prognostic value of the albumin-bilirubin score in patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare life-threatening systemic disease. This study aimed to assess the prognostic value of pretreatment albumin-bilirubin (ALBI). We retrospectively analyzed 168 non-Hodgkin lymphoma-associated secondary hemophagocytic lymphohistiocytosis (NHL-sHLH) patients with hepatic injuries. Multivariable logistic/Cox models and restricted cubic spline models were conducted to evaluate the relationships between the ALBI score and short- and long-term survival. Among 168 adult NHL-sHLH patients, 82 (48.8%) patients died within 30 days after admission, and 144 (85.7%) patients died during the follow-up period. Multivariable logistic/Cox regression model indicated that ALBI grade could be an independent risk factor for predicting the prognosis of patients with 30-day mortality and overall survival (odds ratios [OR]30 days 5.37, 95% confidence interval 2.41-12.64, P < 0.001; hazard ratios [HR]OS 1.52, 95% confidence interval 1.06-2.18, P = 0.023), respectively. The restricted cubic spline curve displayed a linear and positive relationship between the ALBI score and risk of mortality (P for nonlinearity =0.503). Furthermore, receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for predicting mortality by integrative analysis of the ALBI score and ferritin was significantly improved compared to the ALBI score (AUC 30 days: 0.820 vs 0.693, P = 0.001; AUC1 year: 0.754 vs 0.681, P = 0.043) or ferritin (AUC30 days: 0.820 vs 0.724, P = 0.005; AUC1 year: 0.754 vs 0.658, P = 0.031) alone. The ALBI score could be a useful indicator of short and long-term survival for NHL-sHLH patients with hepatic injuries.

Prognostic value of lipid profile in adult hemophagocytic lymphohistiocytosis.

Background: Adult secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare clinical syndrome with a high mortality rate. Currently, there are no feasible prognostic factors to clinically predict untreated sHLH patients' prognosis. Our objective was to characterize the lipid profile of adult sHLH patients and to determine the relationship with overall survival. Methods: We retrospectively analyzed 247 patients with newly diagnosed sHLH from January 2017 to January 2022 according to the HLH-2004 criteria. Multivariate Cox regression analyses and restricted cubic splines were conducted to evaluate the prognostic value of the lipid profile. Results: The median age of all patients was 52 years, and the commonest cause of sHLH in our cohort was malignancy. During a median follow-up of 88 (interquartile ranges, 22-490) days, 154 deaths occurred. The univariate analysis confirmed total cholesterol (TC) ≤ 3 mmol/L, triglycerides (TG) > 3.08 mmol/L, high-density lipoprotein cholesterol (HDL-c) ≤ 0.52 mmol/L, and low-density lipoprotein cholesterol (LDL-c) ≤ 2.17 mmol/L were associated with an inferior survival. In a multivariate model, HDL-c, hemoglobin, platelet, fibrinogen, and soluble interleukin-2 receptor were considered as independent factors. Additionally, the restricted cubic spline analyses indicated an inverse linear association between HDL-c and the risk of mortality in sHLH. Conclusion: Lipid profiles, which were low-cost and readily available promising biomarkers, were strongly associated with the overall survival in adult sHLH patients.

Genome-Wide Splicing Quantitative Expression Locus Analysis Identifies Causal Risk Variants for Non-Small Cell Lung Cancer.

Alternative RNA splicing is an essential mechanism linking genetic variation to human diseases. While the signals from genome-wide association studies (GWAS) have been linked to expression quantitative trait loci (eQTL) in previous studies, further work is needed to better elucidate the relationship to other genetic regulatory mechanisms, such as splicing QTLs (sQTL). Here, we performed a genome-wide sQTL analysis to identify variants that might affect RNA splicing in 1,010 non-small cell lung cancer (NSCLC) samples from The Cancer Genome Atlas. The identified sQTLs were largely independent of eQTLs and were predominantly enriched in exonic regions, genetic regulatory elements, RNA-binding protein (RBP) binding sites, and known NSCLC risk loci. In addition, target genes affected by sQTLs (sGenes) were involved in multiple processes in cancer, including cell growth, apoptosis, metabolism, immune infiltration, and drug responses, and sGenes were frequently altered genetically in NSCLC. Systematic screening of sQTLs associated with NSCLC risk using GWAS data from 15,474 cases and 12,375 controls identified an sQTL variant rs156697-G allele that was significantly associated with an increased risk of NSCLC. The association between the rs156697-G variant and NSCLC risk was further validated in two additional large population cohorts. The risk variant promoted inclusion of GSTO2 alternative exon 5 and led to higher expression of the GSTO2 full-length isoform (GSTO2-V1) and lower expression of the truncated GSTO2 isoform (GSTO2-V2), which was induced by RBP quaking (QKI). Mechanistically, compared with GSTO2-V1, GSTO2-V2 inhibited NSCLC cells proliferation by increasing S-glutathionylation of AKT1 and thereby functionally blocking AKT1 phosphorylation and activation. Overall, this study provides a comprehensive view of splicing variants linked to NSCLC risk and provides a set of genetic targets with therapeutic potential. SIGNIFICANCE: Analysis of sQTL reveals the role of genetically driven mRNA splicing alterations in NSCLC risk and elucidates that rs156697 variant impacts risk by altering GSTO2 splicing.

Employment intentions among rural order-oriented medical students in inner mongolia autonomous region, China.

BACKGROUND: The program of the "Free Training of Chinese Rural Order-Oriented Medical Students" is a plan to train general practitioners who can work at rural medical institutions. However, many students have been unwilling to fulfill their commitments and actually work in their assigned locations. OBJECTIVE: This study aimed to provide some explanation by exploring factors influencing the employment intentions of rural order-oriented medical students in Inner Mongolia Autonomous Region of China to provide a basis for formulating relevant supporting policies to help increase the fulfillment rate of medical students. METHODS: We conducted a cross-sectional study with a stratified cluster sampling method at four medical universities in Inner Mongolia using a survey questionnaire. Multivariate logistic regression was used to identify factors that were significantly associated with employment intentions. RESULTS: Approximately 67% of students were willing to work in rural areas, whereas 33% were not. Order-oriented medical students who were dissatisfied with, or indifferent to, training, were unclear about policy, were of Han ethnicity, or came from an urban area, had lower intentions to accept employment in rural areas. The training satisfaction in particular had the greatest predictive effect. CONCLUSION: The implementation of the program "Free Training of Chinese Rural Order-Oriented Medical Students" has been affected by the low actual employment intentions. This study may provide a useful basis on which medical educators and health policy makers can formulate relevant supporting policies and develop strategies to increase the number of order-oriented medical students who working in rural areas where they are most needed.

Nanopore membrane chip-based isolation method for metabolomic analysis of plasma small extracellular vesicles from COVID-19 survivors.

Multiple studies showed that metabolic disorders play a critical role in respiratory infectious diseases, including COVID-19. Metabolites contained in small extracellular vesicles (sEVs) are different from those in plasma at the acute stage, while the metabolic features of plasma sEVs of COVID-19 survivors remain unknown. Here, we used a nanopore membrane-based microfluidic chip for plasma sEVs separation, termed ExoSEC, and compared the sEVs obtained by UC, REG, and ExoSEC in terms the time, cost, purity, and metabolic features. The results indicated the ExoSEC was much less costly, provided higher purity by particles/proteins ratio, and achieved 205-fold and 2-fold higher sEVs yield, than UC and REG, respectively. Moreover, more metabolites were identified and several signaling pathways were significantly enriched in ExoSEC-sEVs compared to UC-sEVs and REG-sEVs. Furthermore, we detected 306 metabolites in plasma sEVs using ExoSEC from recovered asymptomatic (RA), moderate (RM), and severe/critical COVID-19 (RS) patients without underlying diseases 3 months after discharge. Our study demonstrated that COVID-19 survivors, especially RS, experienced significant metabolic alteration and the dysregulated pathways mainly involved fatty acid biosynthesis, phenylalanine metabolism, etc. Metabolites of the fatty acid biosynthesis pathway bore a significantly negative association with red blood cell counts and hemoglobin, which might be ascribed to hypoxia or respiratory failure in RM and RS but not in RA at the acute stage. Our study confirmed that ExoSEC could provide a practical and economical alternative for high throughput sEVs metabolomic study.

Hydrochemical and isotopic fingerprints of groundwater origin and evolution in the Urangulan River basin, China's Loess Plateau.

The origin and evolution of groundwater in the Urangulan River basin area under growing concern as its situated in an economically and ecologically crucial area of China. In the present study, a combination of different methods (i.e. self-organizing maps (SOM), piper diagrams, ionic ratios, multiple isotopic analyses and Bayesian isotope mixing model) provided an efficient way for analysing groundwater origin and evolution. The hydrochemical type was found to be Ca-HCO3 in low TDS and Na + K-Cl or Na + K-SO4 in high TDS groundwater. According to the δ2H and δ18Owater values, groundwater in the study area mainly originated from atmospheric precipitation and was influenced by evaporation. In addition, the rock weathering in conjunction with the cation exchange completely dominated the geochemical evolution process. The dual SO42- isotope and Bayesian isotope mixing model showed that gypsum dissolution, fertilizer input and sewage input were the main sources of SO42- in the study area, accounting for an average of 30.2 %, 28.5 %, and 17.3 % of SO42- in the groundwater, respectively. Other than water-rock interactions, human activity (mining and irrigation) distributed throughout the study area in combination with the spatial characteristics was the dominant factor controlling the hydrochemical evolution. The results of this study provided a basis for understanding groundwater origin and evolution while facilitating the effective management and utilization of groundwater.

Exploring the spatiotemporal variations in regional rainwater harvesting potential resilience and actual available rainwater using a proposed method framework.

Rainwater harvesting potential provides a basis for alleviating regional drought and water shortages. The resilience of rainwater harvesting potential is directly related to the sustainable level of actual available rainwater. Thus, SWAT model was combined with the proposed rainwater harvesting potential evaluation model to quantify rainwater harvesting potential, its resilience and actual available rainwater in the study area. The results showed that: (1) restoration of forest and grass increased the rainwater resource potential in the study area by 12.41 %, especially in the northeast, central and southwest of the study area. Although the surface runoff increased slightly in the past 20 years, it remained stable at 28.62 % of rainwater harvesting potential, which was benefited from the rainwater harvesting potential resilience to maintain the component stability; (2) rainwater harvesting potential resilience in the study area increased from class II to class III, which was closely related to the 17.93 % increase in the resilience intensity of the study area to resist external interference; and (3) surface runoff and net soil moisture content were the main components affecting the spatiotemporal variation of actual available rainwater, and lateral flow was also the main component affecting the spatial variation of actual available rainwater. In the past 20 years, the actual available rainwater has been increasing, and its conversion rate exceeded 89 %. The high level of actual available rainwater has been expanding to the western region with dense grassland coverage. This study provides a scientific basis for clarifying the sustainable utilization level of rainwater.

Defective iron based metal-organic frameworks derived from zero-valent iron for highly efficient fenton-like catalysis.

Introducing crystal defects into iron based metal-organic frameworks (Fe-MOFs) is regarded as a promising strategy to enhance Fenton-like performance. However, developing a facile and effective strategy to construct defective Fe-MOFs as highly efficient Fenton-like catalyst is still a challenge. Herein, MIL-100(Fe) (Def-MIL-100(Fe)) with missing ligands defects was synthesized by a simple heterogeneous reaction using zero-valent iron. The bisphenol A degradation efficiency in the Def-MIL-100(Fe)/H2O2 system reached up to 91.26% within 10 min at pH 4 with a low catalyst dosage of 0.05 g/L, while the perfect MIL-100(Fe) has almost no Fenton-like performance. It was observed that missing ligands defects in the Def-MIL-100(Fe) play a key role in the Fenton-like reaction. The missing ligands defects could increase the Lewis acidity for fast H2O2 adsorption and accelerate the electron transfer between FeII and FeIII cycling, leading to faster and more·OH generation. Moreover, the missing ligands defects could promote the mass transfer for improving·OH utilization efficiency. This work provides a novel strategy to construct defective Fe-MOFs as highly efficient Fenton-like catalyst to degrade organic pollutants in water.