A General Strategy toward Self-assembled Nanovaccine Based on Cationic Lentinan to Induce Potent Humoral and Cellular Immune Responses.

Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.

Physiologically Based Pharmacokinetic Modeling: The Reversible Metabolism and Tissue-Specific Partitioning of Methylprednisolone and Methylprednisone in Rats.

The pharmacokinetics (PK) of methylprednisolone (MPL) exhibited tissue-specific saturable binding and reversible conversion with its metabolite, methylprednisone (MPN). Blood and 11 tissues were collected in male rats after intravenous (i.v.) bolus doses of 50 mg/kg MPL and 20 mg/kg MPN and upon i.v. infusion of MPL and MPN at 0.3, 3, and 10 mg/h per kg. The concentrations of MPL and MPN were simultaneously measured. A comprehensive physiologically based pharmacokinetic (PBPK) model was applied to describe the plasma and tissue profiles and estimate PK parameters of the MPL/MPN interconversion system. Both dosed and formed MPL and MPN were in rapid equilibrium or achieved steady-state rapidly in plasma and tissues. MPL tissue partitioning was nonlinear, with highest capacity in liver (322.9 ng/ml) followed by kidney, heart, intestine, skin, spleen, bone, brain, muscle, and lowest in adipose (2.74 ng/ml) and displaying high penetration in lung. The tissue partition coefficient of MPN was linear but widely variable (0.15∼5.38) across most tissues, with nonlinear binding in liver and kidney. The conversion of MPL to MPN occurred in kidney, lung, and intestine with total clearance of 429 ml/h, and the back conversion occurred in liver and kidney at 1342 ml/h. The irreversible elimination clearance of MPL was 789 ml/h from liver and that of MPN was 2758 ml/h with liver accounting for 44%, lung 35%, and kidney 21%. The reversible metabolism elevated MPL exposure in rats by 13%. This highly complex PBPK model provided unique and comprehensive insights into the disposition of a major corticosteroid. SIGNIFICANCE STATEMENT: Our dual physiologically based pharmacokinetic (PBPK) study and model of methylprednisolone/methylprednisone (MPL/MPN) with multiple complexities reasonably characterized and parameterized their disposition, and provided greater insights into the interpretation of their pharmacodynamics in rats. Drug knowledge gained in this study may be translatable to higher-order species to appreciate the clinical utility of MPL. The complex model itself is instructive for advanced PBPK analysis of drugs with reversible metabolism and/or nonlinear tissue partitioning features.

The relationship between male and female endogenous reproductive hormones levels and subjective cognitive decline score: A cross-sectional analysis of the Pingyin cohort study.

OBJECTIVE: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score. DESIGN, PATIENTS AND MEASUREMENTS: A cross-sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45-70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9-item subjective cognitive decline questionnaire (SCD-Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used. RESULTS: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01-2.05). Men with a high level of testosterone (0.59, 0.35-0.98) and high testosterone/E2 ratio (0.55, 0.33-0.90) were related to decreased chances of having SCD. Each one-unit increase of testosterone was linked to reduced SCD score in males [(ß: -.029, 95% CI (-0.052, -0.007)]. CONCLUSION: There was sex-specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation.

LncRNA H19 Participates in Leukemia Inhibitory Factor Mediated Stemness Promotion in Colorectal Cancer Cells.

Colorectal cancer (CRC) is a common human malignancy and the third leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) were considered to play important roles in the genesis and development of many tumors. In recent years, it has been observed that leukemia inhibitory factor (LIF) might be involved in the regulation of stemness in cancer cells. In this study, we observed that LIF could increase the spheroid formation and stemness marker expression (inculding Nanog and SOX2) in CRC cell lines, such as HCT116 and Caco2 cells. Meanwhile, we also observed that LIF could upregulate LncRNA H19 expression via PI3K/AKT pathway. Knockdown of the expression of LncRNA H19 could decrease the spheroid formation and SOX2 expression in LIF-treated HCT116 and Caco2 cells, and thereby LncRNA H19 knockdown could compensate for the stemness enhancement effects induced by LIF. Our results indicated that LncRNA H19 might participate in the stemness promotion of LIF in CRC cells.

Tracing spatial patterns of lacustrine groundwater discharge in a closed inland lake using stable isotopes.

Tracing lacustrine groundwater discharge (LGD) is essential for understanding the hydrological cycle and water chemistry behaviour of lakes. LGD usually exhibits large spatial variability, but there are few reports on quantitatively revealing the spatial patterns of LGD at the whole lake scale. This study investigated the spatial patterns of LGD in Daihai Lake, a typical closed inland lake in northern China, based on the stable isotopes (δ2H and δ18O) of groundwater, surface water, and sediment pore water (SPW). The results showed that there were significant differences between the δ2H and δ18O values of different water bodies in the Daihai Lake Basin: groundwater < SPW < lake water. The LGD through SPW was found to be an important recharge pathway for the lake. Accordingly, stable isotopes of SPW showed that LGD in the northeastern and northwestern of Daihai Lake was significantly greater both horizontally and vertically than that in the other regions, and the proportions of groundwater in SPW in these two regions were 55.53% and 29.84%, respectively. Additionally, the proportion of groundwater in SPW showed a significant increase with profile depth, and the proportion reached 100% at 50 cm below the sediment surface in the northeastern of the lake where the LGD intensity was strongest. The total LGD to Daihai Lake was 1.47 × 107 m3/a, while the LGD in the northeastern and northwestern of the lake exceeded 1.9 × 106 m3/a. This study provides new insights into assessing the spatial patterns of LGD and water resource management in lakes.

Water-soluble brown carbon in atmospheric aerosols from the resource-dependent cities: Optical properties, chemical compositions and sources.

As a vital type of light-absorbing aerosol, brown carbon (BrC) presents inherent associations with atmospheric photochemistry and climate change. However, the understanding of the chemical and optical properties of BrC is limited, especially in some resource-dependent cities with long heating periods in northwest China. This study showed that the annual average abundances of Water-soluble BrC (WS-BrC) were 9.33±7.42 and 8.69±6.29 µg/m3 in Baotou and Wuhai and the concentrations, absorption coefficient (Abs365), and mass absorption efficiency (MAE365) of WS-BrC presented significant seasonal patterns, with high values in the heating season and low values in the non-heating season; while showing opposite seasonal trends for the Absorption Ångström exponent (AAE300-400). Comparatively, the levels of WS-BrC in developing regions (such as cities in Asia) were higher than those in developed regions (such as cities in Europe and Australia), indicating the significant differences in energy consumption in these regions. By combining fluorescence excitation-emission matrix (EEM) spectra with the parallel factor (PARAFAC) model, humic-like (C1 and C2) and protein-like (C3) substances were identified, and accounted for 61.40%±4.66% and 38.6%±3.78% at Baotou, and 60.33%±6.29% and 39.67%±4.17% at Wuhai, respectively. The results of source apportionment suggested that the potential source regions of WS-BrC varied in heating vs. non-heating seasons and that the properties of WS-BrC significantly depended on primary emissions (e.g., combustion emissions) and secondary formation.

Hydrochemical variations and driving mechanisms in a large linked river-irrigation-lake system.

A linked river-irrigation-lake system exhibits intricate and dynamic hydrochemical variations, closely related to changes in natural conditions and anthropogenic activities. However, little is known about the sources, migration and transformation of hydrochemical composition, and the driving mechanisms, in such systems. In this study, the hydrochemical characteristics and processes in the linked Yellow River-Hetao Irrigation District-Lake Ulansuhai system were studied, based on a comprehensive hydrochemical and stable isotope analysis of water samples collected during spring, summer, and autumn. The results showed that the water bodies in the system were weakly alkaline with a pH range of 8.05-8.49. The concentrations of hydrochemical ions showed an increasing trend in the water flow direction. Total dissolved solids (TDS) were less than 1000 mg/L (freshwater) in the Yellow River and the irrigation canals, and increased to more than 1800 mg/L (saltwater) in the drainage ditches and Lake Ulansuhai. The dominant hydrochemical types varied from SO4•Cl-Ca•Mg and HCO3-Ca•Mg types in the Yellow River and the irrigation canals to Cl-Na type in the drainage ditches and Lake Ulansuhai. The ion concentrations in the Yellow River, the irrigation canals, and the drainage ditches were highest during summer, while ion concentrations in Lake Ulansuhai were highest during spring. The hydrochemistry of the Yellow River and the irrigation canals was mainly affected by rock weathering, while evaporation was the principal controlling factor in the drainage ditches and Lake Ulansuhai. Water-rock interactions including the dissolution of evaporites and silicates, the precipitation of carbonates, and cation exchange were the main sources of hydrochemical compositions in this system. Anthropogenic inputs had a low impact on the hydrochemistry. Therefore, greater attention should be paid in future to hydrochemical variations, especially salt ions, in the management of linked river-irrigation-lake system water resources.

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.

Fluxes in CO2 and CH4 and influencing factors at the sediment-water interface in a eutrophic saline lake.

Although saline aquatic ecosystems are significant emitters of greenhouse gases (GHGs), dynamic changes in GHGs at the sediment-water interface remain unclear. The present investigation carried out a total of four sampling campaigns in Daihai Lake, which is a eutrophic saline lake situated in a semi-arid area of northern China. The aim of this study was to investigate the spatio-temporal dynamics of carbon dioxide (CO2) and methane (CH4) fluxes at the sediment-water interface and the influencing factors. The mean concentrations of porewater CO2 and CH4 were 44.98 ± 117.99 µmol L-1 and 124.36 ± 97.00 µmol L-1, far exceeding those in water column of 11.14 ± 2.16 µmol L-1 and 0.33 ± 0.23 µmol L-1, respectively. The CO2 and CH4 fluxes at the sediment-water interface (FS-WCO2 and FS-WCH4) exhibited significant spatial and temporal variations, with mean values of 9.24 ± 13.84 µmol m-2 d-1 and 3.53 ± 4.36 µmol m-2 d-1, respectively, indicating that sediment is the source of CO2 and CH4 in the water column. However, CO2 and CH4 fluxes were much lower than those measured at the water-air interface in a companion study (17.54 ± 14.54 mmol m-2d-1 and 0.50 ± 0.50 mmol m-2d-1, respectively), indicating that the diffusive flux of gases at the sediment-water interface was not the primary source of CO2 and CH4 emissions to the atmosphere. Regression and correlation analyses revealed that salinity (Sal) and nutrients were the most influential factors on porewater gas concentrations, and that gas fluxes increased with increasing gas concentrations and porosity. The microbial activity of sediment is greatly affected by nutrients and Sal. Additionally, Sal has the ability to regulate biogeochemical processes, thereby regulating GHG emissions. The present investigation addresses the research gap concerning GHG emissions from sediments of eutrophic saline lakes. The study suggests that controlling the eutrophication and salinization of lakes could be a viable strategy for reducing carbon emissions from lakes. However, further investigations are required to establish more conclusive results.

Significant methane ebullition from large shallow eutrophic lakes of the semi-arid region of northern China.

Eutrophic lakes are a major source of the atmospheric greenhouse gas methane (CH4), and CH4 ebullition emissions from inland lakes have important implications for the carbon cycle. However, the spatio-temporal heterogeneity of CH4 ebullition emission and its influencing factors in shallow eutrophic lakes of arid and semi-arid regions remain unclear. This study aimed to determine the mechanism of CH4 emission via eutrophication in Lake Ulansuhai, a large shallow eutrophic lake in a semi-arid region of China.To this end, monthly field surveys were conducted from May to October 2021, and gas chromatography was applied using the headspace equilibrium technique with an inverted funnel arrangement. The total CH4 fluxes ranged from 0.102 mmol m-2 d-1 to 59.296 mmol m-2 d-1 with an average value of 4.984 ± 1.82 mmol m-2 d-1. CH4 ebullition emissions showed significant temporal and spatial variations. The highest CH4 ebullition emission was observed in July with a grand mean of 9.299 mmol m-2 d-1, and the lowest CH4 ebullition emissions occurred in October with an average of 0.235 mmol m-2 d-1. Among seven sites (S1-S7), the maximum (3.657 mmol m-2 d-1) and minimum (1.297 mmol m-2 d-1). CH4 ebullition emissions were observed at S2 and S7, respectively. As the main route of CH4 emission to the atmosphere in Lake Ulansuhai, the CH4 ebullition flux during May to October accounted for 69% of the total CH4 flux. Statistical analysis showed that CH4 ebullition was positively correlated with temperature (R = 0.391, P < 0.01) and negatively correlated with air pressure (R = 0.286, P < 0.00). Temperature and air pressure were found to strongly regulate the production and oxidation of CH4. Moreover, nutritional status indicators such as TP and NH4+-N significantly affect CH4 ebullition emissions (R = 0.232, P < 0.01; R = -0.241, P < 0.01). This study reveals the influencing factors of CH4 ebullition emission in Lake Ulansuhai, and provides theoretical reference and data support for carbon emission from eutrophic lakes. Nevertheless, research on eutrophic shallow lakes needs to be further strengthened. Future research should incorporate improved flux measurement techniques with process-based models to improve the accuracy from regional to large-scale estimation of CH4 emissions and clarify the carbon budget of aquatic ecosystems. In this manner, the understanding and predictability of CH4 ebullition emission from shallow lakes can be improved.

Interactions of Tofacitinib and Dexamethasone on Lymphocyte Proliferation.

PURPOSES: Lymphocyte proliferation is a major factor determining the magnitude of the immune response. Both dexamethasone (DEX) and tofacitinib (TOF) exert marked immunosuppressive effects and are mainstay drugs in the treatment of rheumatoid arthritis (RA). This study was aimed to explore the single and combined anti-proliferative action of DEX and TOF on lymphocytes and their sex differences. METHODS: The single-drug effects and dual-drug interactions of TOF and DEX were assessed on the in vitro concanavalin A-stimulated proliferation of lymphocytes isolated from male and female rat and human peripheral blood. RESULTS: DEX was more potent than TOF across species and sex. DEX showed greater inhibition on rat lymphocytes compared to those from humans, which was reflected in both Imax and IC50. The antiproliferative action of TOF was comparable in rats and humans with exception of a higher IC50 in male rats. Both sex- and species-related differences were detected in DEX/TOF interactions with synergistic effects in male lymphocytes, and additive and antagonistic effect for females in humans and rats. CONCLUSION: TOF has a promising steroid-sparing potential with the beneficial effects of the combination therapy more likely in males than females.

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion.

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration-time curve of vitamin K1 was fit to a linear equation following PCSII (R2  = 0.9599 ± 0.0096). Then, half-time (T1/2 ), apparent volume of distribution (Vd ), and clearance rate (CL) were estimated successively. T1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and Vd was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T1/2 and mean residence time (MRTINF ) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T1/2 of vitamin K1 was obviously different from MRT-equated half-time (T1/2,MRT )(P < .05). Vd and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration-time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T1/2 and a relatively large Vd following PCSII.

Spatiotemporal variability of phytoplankton functional groups in a shallow eutrophic lake from cold, arid regions.

In the shallow eutrophic lakes in cold, arid regions, the phytoplankton functional groups and the factors that drive their spatiotemporal variabilities remain unclear. Samples were collected from Lake Ulansuhai in April, August, and October 2017 (wet season) and January 2018 (dry season). Based on the functional group classification method, 23 phytoplankton functional groups with 5 major ones were identified. During the wet season, high amounts of nutrients, elevated temperatures, and heavy rainfall produced spatiotemporal variabilities in phytoplankton communities, whereas during the dry season, the frozen period was the critical factor that determined the spatiotemporal variabilities in the phytoplankton communities. Through redundancy analyses, total nitrogen and total phosphorus concentrations were observed to directly affect the phytoplankton growth; algal growth affected the chemical oxygen demand, and pH and environmental factors interacted with the phytoplankton growth. These results highlight the complex feedbacks of shallow eutrophic lake ecosystems in arid regions. Group TC (represented by Lyngbya) was correlated with Huangtai algae. In August, a Huangtai algal bloom resulted in a relatively stable water column, which was conducive to group TC growth. Therefore, the presence of certain phytoplankton functional groups can indicate the current lake conditions by identifying the coverage of Huangtai algae, which provides a scientific basis for an early warning of a potential algal bloom.

Non-IgE-mediated hypersensitivity induced by multivitamins containing Tween-80.

Multivitamins have been widely used for years. Adverse reactions, especially hypersensitivity, to multivitamins are becoming noteworthy. However, the classification of hypersensitivity is confusing, and the trigger is unknown. Multivitamins consist of two vials labelled vial 1 containing Tween-80 and vial 2. Multivitamins without Tween-80 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea-pigs were investigated by observation, ELISA and sphygmomanometer, and degranulation and apoptotic of RBL-2H3 cells were assayed by spectrophotometry and flow cytometry. The results showed that dogs suffered from multiorgan anaphylactoid symptoms, and dramatically decreased blood pressure, and high plasma concentrations of histamine after the first administration of multivitamins and multivitamins vial 1, which contains Tween-80, compared to the control, multivitamins vial 2 or multivitamins without Tween-80. In anaphylaxis assay, guinea-pigs did not display any anaphylaxis symptoms and there were no changes in plasma histamine and IgE concentrations in the multivitamins and multivitamins vial 1 groups or in the multivitamins vial 2 and multivitamins without Tween-80 groups except ovalbumin. Compared to the control, the release of ß-hexosaminidase and histamine, and the apoptosis of non-antigen-sensitized RBL-2H3 cells significantly increased in the Tween-80 and multivitamins and multivitamins vial 1 groups in a concentration-dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween-80 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin-induced release of inflammatory factors is triggered by Tween-80 through a non-IgE-mediated pathway.

Discovery of novel 3-benzylquinazolin-4(3H)-ones as potent vasodilative agents.

In the present study, a series of 3-benzylquinazolin-4(3H)-ones were synthesized and characterized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60mM KCl. The SAR of target compounds was discussed preliminarily. Among these compounds, 2a and 2c displayed potent vasodilatation action and could compete significantly the rat mesenteric arterial rings induced contraction with phenylephrine. Compounds 2a and 2c were further tested for their antihypertensive effects in SHR by oral administration. The results indicated that 2a and 2c could reduce significantly both diastolic and systolic blood pressure. Moreover, 2c displayed antihypertensive effect in a dose dependent manner, and could maintain the effects for 6h at a dosage of 4.0mg/kg. These findings suggest that the title compounds are novel vasodilative agents, representing a novel series of promising antihypertensive agents.

Association and prediction of Life's Essential 8 score, genetic susceptibility with MCI, dementia, and MRI indices: A prospective cohort study.

BACKGROUND: To examine the associations of Life's Essential 8 (LE8) and its predictive performance with mild cognitive impairment (MCI), dementia and brain MRI indices. METHODS: We used cohort data from UK Biobank. LE8 was categorized into low (<50 score), moderate (50-79 score), and high (≥80 score) levels. Cox regression models considering death as a competing risk were used to estimate the hazard ratios (HRs) and 95%CI on the association between LE8 and MCI and dementia. Multivariable linear regression models were used to analyze LE8 every 10-score increase and brain MRI indices. Area under the curve (AUC) was used to measure the predictive performances of LE8. RESULTS: We included 126,785 participants with a mean (SD) age of 56.0 (8.0) years and 53.5 % were female. The median follow-up was 13.0 years. Compared to individuals with a low LE8 score, those with a high LE8 score were associated with decreased risk of MCI (0.49, 95%CI: 0.40-0.62), all-cause dementia (0.60, 0.44-0.80), vascular dementia (VD, 0.44, 0.21-0.94), and non-Alzheimer non-vascular dementia (NAVD, 0.55, 0.35-0.84). High LE8 score was associated with increased total brain volume, hippocampus volume, grey matter volume, and grey matter in hippocampus volume (p all ≤0.001). LE8 combined age and sex had good performance for predicting all-cause dementia (AUC: 84.1 %), AD (85.4 %), VD (87.6 %), NAVD (81.4 %), and MCI (75.3 %). LIMITATIONS: Our findings only reflect the characteristics of UKB participants. CONCLUSIONS: High LE8 score was associated with reduced risk of MCI and dementia. It was also linked to brain MRI indices. LE8 score had good predicting performance for future risk of MCI and dementia.

Anthropogenic processes drive spatiotemporal variability of sulfate in groundwater from a multi-aquifer system: Dilution caused by mine drainage.

The water quality evolution of surface and groundwater caused by mining activities and mine drainage is a grave public concern worldwide. To explore the effect of mine drainage on sulfate evolution, a multi-aquifer system in a typical coal mine in Northwest China was investigated using multi-isotopes (δ34SSO4, δ18OSO4, δD, and δ18Owater) and Positive Matrix Factorization (PMF) model. Before mining, the Jurassic aquifer was dominated by gypsum dissolution, accompanied by cation exchange and bacterial sulfate reduction, and the phreatic aquifers and surface water were dominated by carbonate dissolution. Significant increase in sulfate in phreatic aquifers due to mine drainage during the early stages of coal mining. However, in contrast to common mining activities that result in sulfate contamination from pyrite oxidation, mine drainage in this mining area resulted in accelerated groundwater flow and enhanced hydraulic connections between the phreatic and confined aquifers. Dilution caused by the altered groundwater flow system controlled the evolution of sulphate, leading to different degrees of sulfate decrease in all aquifers and surface water. As the hydrogeochemical characteristic of Jurassic aquifer evolved toward phreatic aquifer, this factor should be considered to avoid misjudgment in determining the source of mine water intrusion. The study reveals the hydrogeochemical evolution induced by mine drainage, which could benefit to the management of groundwater resources in mining areas.

The fate of Arsenic associated with the transformation of iron oxides in soils: The mineralogical evidence.

The influence of iron (oxyhydr)oxides on the transformation and migration of arsenic(As) has garnered significant attention. Previous work has largely focused on the transformation of iron oxides related to As fate at molecular and mechanistic levels. However, studies examining the interplay between As concentration and iron oxides transformation within complex soil system are sparse. This study investigates the transformation of iron oxides in soils with varying As concentration during microbial dissimilatory iron reduction (DIR), employing humic acid (HA) as electron shuttle and assesses the impact on As speciation transformation. Comparative analyses indicate that in soils with high As concentration (>1000 mg/kg), the secondary transformation of iron (oxyhydr)oxides to other forms, such as the conversion of ferrihydrite to goethite and lepidocrocite, or schwertmannite to goethite, is impeded. Consequently, the formation of goethite and lepidocrocite, which would typically re-stabilize As, is inhibited, leading to elevated release of As(III). On the other hand, an increase in magnetite formation in soils with low As concentration (<100 mg/kg) appears to re-stabilize As effectively. Furthermore, the formation of new secondary iron (oxyhydr)oxides in soils with As concentration <200 mg/kg enhances fraction F5, which subsequently contributes to the re-immobilization of As, sequestering it within the soil matrix. This process results in a lower release of As(III) from soils with As concentration below 200 mg/kg. These findings enhance the understanding of the interdependent relationship between the transformation of iron oxides and the fate of As in complex soil systems.

Bubbles dominated the significant spatiotemporal variability and accumulation of methane concentrations in an ice-covered reservoir.

Climate-sensitive ice-covered reservoirs are critical components of methane (CH4) release. However, the mechanisms that influence CH4 dynamics during ice-covered periods remain poorly studied. To investigate the effects of bubbles on CH4 dynamics, we conducted intensive field and incubation experiments in an ice-covered reservoir (ice growth, stability, and melt period) in Northeast China. We found that the mean dissolved CH4 concentrations in the ice (625.9 ± 2419.7 nmol L-1) and underlying water (1218.9 ± 2678.9 nmol L-1) were high, making them atmosphere CH4 sources. The visible bubble bands (bubble area) in the riverine zone and the vertical profile of the CH4 concentration in the ice reflect the distribution of trapped bubbles. The mean CH4 concentration in the ice of the bubble area (1674.8 ± 3926.8 nmol L-1) was 2 orders of magnitude higher than that of no-bubble area (53.7 ± 9.2 nmol L-1). Moreover, a large amount of CH4 accumulated under the ice in the bubble area. These findings suggest that bubbles determine the CH4 storage in ice and CH4 accumulation in the underlying water. Ice growth increases CH4 storage in ice and the underlying water because of the entrapment and re-dissolution of CH4 bubbles. However, ice melting releases the CH4 accumulated in the ice and underlying water. A comparison of the field and incubation experiments indicated that the deep-water environment of the reservoir had a CH4 burial effect. Stepwise regression analysis revealed that higher sediment organic matter content, median particle size, and porosity increased the production and release of CH4 bubbles, trapping more CH4 bubbles in ice. Overall, this study improves the mechanistic understanding of CH4 dynamics and predictability of CH4 emissions during ice-covered periods.

Investigating the regional ecological environment stability and its feedback effect on interference using a novel vegetation resilience assessment model.

Vegetation resilience is critical for understanding the dynamic feedback effect of regional ecological environment stability against interferences. Thus, based on quantify the interferences of climate dryness and vegetation water deficit affecting vegetation growth function, incorporate mechanical Hooke's law to develop a vegetation resilience assessment model by quantitatively expressing vegetation growth function maintenance ability, to reveal the ecological environment stability and its feedback effect on interferences in the study area. The essential discoveries of the study are as follows: (1) with the increase of precipitation and the improvement of afforestation on soil erosion, the interferences intensity of climate dryness and vegetation water deficit in the ecological environment decreased by 5.88 % and 4.92 % respectively, the regional vegetation growth function loss was improved, especially in the southern region; (2) the decrease of vegetation growth function loss promoted the vegetation resilience level fluctuated from class II to class IV, with the average annual vegetation resilience increased by 7.02 %, reflecting that the regional ecological environment stability increased from difficult to rapid recovery after disturbance, and the benefit was especially noticeable in the eastern and southern forested areas; (3) the contribution rates of climate dryness and vegetation water deficit to the variation of vegetation resilience caused by vegetation restoration were -1.38 % and 4.73 %, respectively, and the prominent positive feedback effect of increasing vegetation resilience with decreasing vegetation water deficit degree in forest restoration area, indicating that the vegetation water deficit greatly impacts ecological environment stability in the study area, and forest restoration constantly improves regional ecological environment stability more than grassland restoration. This research has crucial guiding implications for supporting the sustainable development of regional ecological environments.