GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.

Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1ß expression levels and interleukin-1ß (IL-1ß) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor-/- Nlrp3-/- double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1ß transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.

Effect of repetitive transcranial magnetic stimulation-assisted training on lower limb motor function in children with hemiplegic cerebral palsy.

OBJECTIVE: To explore the effect of repetitive transcranial magnetic stimulation (rTMS)-assisted training on lower limb motor function in children with hemiplegic cerebral palsy (HCP). METHOD: Thirty-one children with HCP who met the inclusion criteria were selected and randomly divided into a control group (n = 16) and an experimental group (n = 15). The control group received routine rehabilitation treatment for 30 min each time, twice a day, 5 days a week for 4 weeks. Based on the control group, the experimental group received rTMS for 20 min each time, once a day, 5 days a week for 4 weeks. The outcome measures included a 10-metre walk test (10MWT), a 6-minute walk distance (6MWD) test, D- and E-zone gross motor function measurements (GMFM), the symmetry ratio of the step length and stance time and the muscle tone of the triceps surae and the hamstrings (evaluated according to the modified Ashworth scale), which were obtained in both groups of children before and after treatment. RESULTS: After training, the 10MWT (P < 0.05), 6MWD (P < 0.01), GMFM (P < 0.001) and the symmetry ratio of the step length and stance time of the two groups were significantly improved (P < 0.05), there was more of an improvement in the experimental group compared with the control group. There was no significant change in the muscle tone of the hamstrings between the two groups before and after treatment (P > 0.05). After treatment, the muscle tone of the triceps surae in the experimental group was significantly reduced (P < 0.05), but there was no significant change in the control group (P > 0.05). CONCLUSION: Repetitive TMS-assisted training can improve lower limb motor function in children with HCP.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study.

BACKGROUND: The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI. METHODS: The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings. RESULTS: The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP. CONCLUSION: Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.

Interpretable machine learning models for early prediction of acute kidney injury after cardiac surgery.

OBJECTIVE: Postoperative acute kidney injury (PO-AKI) is a common complication after cardiac surgery. We aimed to evaluate whether machine learning algorithms could significantly improve the risk prediction of PO-AKI. METHODS: The retrospective cohort study included 2310 adult patients undergoing cardiac surgery in a tertiary teaching hospital, China. Postoperative AKI and severe AKI were identified by the modified KDIGO definition. The sample was randomly divided into a derivation set and a validation set based on a ratio of 4:1. Exploiting conventional logistic regression (LR) and five ML algorithms including decision tree, random forest, gradient boosting classifier (GBC), Gaussian Naive Bayes and multilayer perceptron, we developed and validated the prediction models of PO-AKI. We implemented the interpretation of models using SHapley Additive exPlanation (SHAP) analysis. RESULTS: Postoperative AKI and severe AKI occurred in 1020 (44.2%) and 286 (12.4%) patients, respectively. Compared with the five ML models, LR model for PO-AKI exhibited the largest AUC (0.812, 95%CI: 0.756, 0.860, all P < 0.05), sensitivity (0.774, 95%CI: 0.719, 0.813), accuracy (0.753, 95%CI: 0.719, 0.781) and Youden index (0.513, 95%CI: 0.451, 0.573). Regarding severe AKI, GBC algorithm showed a significantly higher AUC than the other four ML models (all P < 0.05). Although no significant difference (P = 0.173) was observed in AUCs between GBC (0.86, 95%CI: 0.808, 0.902) and conventional logistic regression (0.803, 95%CI: 0.746, 0.852), GBC achieved greater sensitivity, accuracy and Youden index than conventional LR. Notably, SHAP analyses showed that preoperative serum creatinine, hyperlipidemia, lipid-lowering agents and assisted ventilation time were consistently among the top five important predictors for both postoperative AKI and severe AKI. CONCLUSION: Logistic regression and GBC algorithm demonstrated moderate to good discrimination and superior performance in predicting PO-AKI and severe AKI, respectively. Interpretation of the models identified the key contributors to the predictions, which could potentially inform clinical interventions.

Optical fractal in cryogenic environments based on distributed feedback Bragg photonic crystals.

We studied the optical fractal effect of the one-dimensional distributed feedback Bragg photonic crystals formed by semiconductor GaAs and dielectric TiO2. Light wave is transmitted in the intermediate dielectric slab and reflected back by the periodic photonic crystals at both ends, forming multiple fractal resonance output. The transmission channels expand exponentially by thickening the bulk in a cryogenic environment. The quality factor of each fractal resonant state improves with a greater periodic number of crystals. Furthermore, central wave of resonance has a blue-shift as the external pressure increases, while the influence of environment temperature on the fractal resonance could be ignored. It is hoped that our study can highlight the potential of these findings for designing multi-channel communication filters in cryogenic environments.

Coexistence of Multiple Functional Variants and Genes Underlies Genetic Risk Locus 11p11.2 of Alzheimer's Disease.

BACKGROUND: Genome-wide association studies have identified dozens of genetic risk loci for Alzheimer's disease (AD), yet the underlying causal variants and biological mechanisms remain elusive, especially for loci with complex linkage disequilibrium and regulation. METHODS: To fully untangle the causal signal at a single locus, we performed a functional genomic study of 11p11.2 (the CELF1/SPI1 locus). Genome-wide association study signals at 11p11.2 were integrated with datasets of histone modification, open chromatin, and transcription factor binding to distill potentially functional variants (fVars). Their allelic regulatory activities were confirmed by allele imbalance, reporter assays, and base editing. Expressional quantitative trait loci and chromatin interaction data were incorporated to assign target genes to fVars. The relevance of these genes to AD was assessed by convergent functional genomics using bulk brain and single-cell transcriptomic, epigenomic, and proteomic datasets of patients with AD and control individuals, followed by cellular assays. RESULTS: We found that 24 potential fVars, rather than a single variant, were responsible for the risk of 11p11.2. These fVars modulated transcription factor binding and regulated multiple genes by long-range chromatin interactions. Besides SPI1, convergent evidence indicated that 6 target genes (MTCH2, ACP2, NDUFS3, PSMC3, C1QTNF4, and MADD) of fVars were likely to be involved in AD development. Disruption of each gene led to cellular amyloid-ß and phosphorylated tau changes, supporting the existence of multiple likely causal genes at 11p11.2. CONCLUSIONS: Multiple variants and genes at 11p11.2 may contribute to AD risk. This finding provides new insights into the mechanistic and therapeutic challenges of AD.

Combining controlled-release urea with potassium chloride to reduce soil N/K leaching and promote growth of Italian ryegrass.

Nitrogen (N) and potassium (K) are essential nutrients for Italian ryegrass (Lolium multiflorum L.) growth. A 2-year field experiment with a split-plot design was conducted to study the effect of N fertilizer type combined with different K fertilizer rates on the soil mineral N and K availability, and growth characteristics of Italian ryegrass. The main plots were assigned to two N fertilizer types, controlled-release urea (CRU) and common urea. While low, moderate and high potassium chloride (KCl) rates (150, 300 and 450 kg ha-1, respectively) were assigned to the subplots. Compared with the common urea treatments, the CRU significantly increased the SPAD value, plant height, leaf area, and photosynthetic index of Italian ryegrass, which significantly prolonged the green stage of Italian ryegrass and prevented premature senescence. Moreover, the dry yields of the CRU increased by 4.5-12.5% in 2019 and 10.9-25.3% in 2020 compared with the urea, respectively. At the same time, compared with the KCl150 and KCl450 treatments, the KCl300 treatment resulted in better plant growth. Overall, the CRU × KCl300 maximized the soil inorganic N and different soil K forms, and reduced the soil N/K leaching. The root length, volume, surface area, average diameter, tips and branches were also improved, and there was a significant N × K interaction effect on the tips. The CRU combined with 300 kg ha-1 KCl fertilization enhanced crop growth by improving leaf photosynthesis, soil fertility, and yield and should be recommended as the best fertilizer ratio for Italian ryegrass production.

Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States. METHODS: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). RESULTS: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. CONCLUSION: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Effect of Persulfate Activation by Electrogenerated H2O2 and Anodic Oxidation on the Color Removal of Dye Solutions at Pt and BDD Anodes.

In this study, tartrazine solutions were oxidized using innovative electrochemical advanced oxidation processes (EAOPs) that combined persulfate (PS) activation with electrogenerated H2O2, cathodic reduction and anodic oxidation at Pt and BDD anodes, and graphite cathode in an undivided stirred reactor. For the Pt anode, SO4·- was generated from a reduction reaction at the cathode and a reaction between the PS and electrogenerated H2O2. For the BDD anode, SO4·- was generated from a reduction reaction at the cathode, an oxidation reaction at the anode, and a reaction between PS and electrogenerated H2O2. Among these activation methods, the activation efficiency of PS by electrogenerated H2O2 is much better than other methods. The effects of PS concentration up to 36 mM, applied current density between 6 to 15 mA cm-2, and temperatures between 25 to 45 °C were investigated. For the electro-Fenton process with Pt anode (Pt-H2O2/PS process), the best result for oxidizing 250 mg L-1 tartrazine solution was obtained with 37.5 mM Na2SO4 + 9.0 mM Na2S2O8, applied current density at 12 mA cm-2 and 45 °C, acquiring total color removal after 30 min reaction. For the electro-Fenton process with BDD anode (BDD-H2O2/PS process), the best result for oxidizing 250 mg L-1 tartrazine solution was obtained with 25 mM Na2SO4 + 18 mM Na2S2O8, applied current density at 12 mA cm-2 and 45 °C, yielding 100% color removal after 30 min reaction. The main oxidizing agents are SO4·- and OH· in the anodic oxidation process with PS and the electro-Fenton process with PS. It is concluded that the additions of PS tremendously improve the oxidation power of electro-Fenton processes with PS, especially the Pt-H2O2/PS process.

Chronic Anti-Coagulation Therapy Reduced Mortality In Patients With High Cardiovascular Risk Early In COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviate these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients during the early phase of the pandemic in the United States. Methods: A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous therapeutic AC for a least 30 days prior to or after their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR). Results: We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events. Conclusion: AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Influence of Potamogeton crispus harvesting on phosphorus composition of Lake Yimeng.

Harvesting is an important method used to control the overproduction of Potamogeton crispus in lakes. A three-year comparative field study was performed in a eutrophic lake (harvested area) and its connected lake (non-harvested area) to determine the effects of harvesting on the phosphorus (P) composition and environmental factors in the water and sediment. Results revealed that harvesting significantly reduced the dissolved total P and dissolved organic P (DOP) and increased the alkaline phosphatase activity and particulate P (PP) in the water. No significant differences were detected in the water total P (TP), soluble reactive P, chlorophyll-a, pH, and dissolved oxygen between the harvested and non-harvested areas. Sediment TP and organic P (OP) were significantly reduced in the harvested area. Harvesting changed the P composition in the water. In the non-harvested area, P was mainly formed by DOP (40%) in the water body, while in the harvested area, PP was the main water component (47%). Harvesting increased the proportion of inorganic P (IP) in the sediment and decreased the proportion of OP. In the water, the IP to TP ratio in the non-harvested and harvested areas were 58.26% and 63.51%, respectively. Our results showed that harvesting changed the P composition in the water and sediment. In the harvesting of submerged vegetation, our results can serve as a reference for the management of vegetation-rich lakes.

GSNOR deficiency attenuates MPTP-induced neurotoxicity and autophagy by facilitating CDK5 S-nitrosation in a mouse model of Parkinson's disease.

The S-nitrosoglutathione reductase (GSNOR) is a key denitrosating enzyme that regulates protein S-nitrosation, a process which has been found to be involved in the pathogenesis of Parkinson's disease (PD). However, the physiological function of GSNOR in PD remains unknown. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, we found that GSNOR expression was significantly increased and accompanied by autophagy mediated by MPTP-induced cyclin dependent kinase 5 (CDK5), behavioral dyskinesias and dopaminergic neuron loss. Whereas, knockout of GSNOR, or treatment with the GSNOR inhibitor N6022, alleviated MPTP-induced PD-like pathology and neurotoxicity. Mechanistically, deficiency of GSNOR inhibited MPTP-induced CDK5 kinase activity and CDK5-mediated autophagy by increasing S-nitrosation of CDK5 at Cys83. Our study indicated that GSNOR is a key regulator of CDK5 S-nitrosation and is actively involved in CDK5-mediated autophagy induced by MPTP.

Effects of robotic-assisted gait training on motor function and walking ability in children with thoracolumbar incomplete spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) results in neurological dysfunction of the spinal cord below the injury. OBJECTIVE: To explore the immediate and long-term effects of robotic-assisted gait training (RAGT) on the recovery of motor function and walking ability in children with thoracolumbar incomplete SCI. METHODS: Twenty-one children with thoracolumbar incomplete SCI were randomly divided into the experimental (n = 11) and control groups (n = 10). The control group received 60 min of conventional physical therapy, and the experimental group received 30 min of RAGT based on 30 minutes of conventional physical therapy. Changes in walking speed and distance, physiological cost index (PCI), lower extremity motor score (LEMS), SCI walking index and centre-of-pressure (COP) envelope area score were observed in both groups of children before and after eight weeks of training. The primary outcome measures were the 10-metre walk test (10MWT) and six-minute walk distance (6MWD) at preferred and maximal speeds. In addition, several other measures were assessed, such as postural control and balance, lower limb strength and energy expenditure. RESULTS: Compared with control group, the self-selected walk speed (SWS), maximum walking speed (MWS), 6MWD, PCI, LEMS, COP, and Walking Index for Spinal Cord injury II (WISCI II) of experimental group were improved after treatment. The 6MWD, PCI, COP, and WISCI II after eight weeks of treatment were improved in experimental group. All indicators were not identical at three different time points when compared between two groups. Pairwise comparisons in experimental group suggested that the SWS, MWS, 6MWD, PCI, LEMS, COP, and WISCI II after treatment were higher than those before treatment. The 6MWD, LEMS, COP, and WISCI II after treatment were higher than at the one-month follow-up appointment. The SWS, PCI, LEMS, COP, and WISCI II at the eight-week follow-up appointment were improved. CONCLUSION: Robotic-assisted gait training may significantly improve the immediate motor function and walking ability of children with thoracolumbar incomplete SCI.

[Research status and prospect of cardiac arrest early warning scoring system].

Cardiac arrest is the fourth stage of sudden cardiac death, which is characterized by the cessation of electrical activity in the heart, rapid circulatory and respiratory failure, and the prognosis is often poor. How to effectively predict cardiac arrest is the key and difficult point in the diagnosis and treatment process. In recent years, the research on the application of early warning scoring system in cardiac arrest has made continuous breakthroughs, from initially formulating a traditional scoring system containing only basic vital signs indicators according to a certain number of samples to continuously increasing and changing indicators, increasing the sample size, and formulating an improved scoring system with better sensitivity and specificity. Nowadays, with the continuous development of electronic information technology, machine learning technology is introduced into the formulation of scoring system, which breaks through the limitations of previous scoring system and has achieved good results in clinic. This article analyzes and compares the relevant research and cutting-edge progress of different early warning scoring systems at home and abroad, and summarizes the research results, gaps and shortcomings. Finally, combined with the relevant policies of graded diagnosis and treatment in China, this paper discusses the development and application direction of cardiac arrest early warning scoring system in the future.

Relationship between the coprecipitation of phosphorus-on-calcite by submerged macrophytes and the phosphorus cycle in water.

To assess potential phosphorus removal, we utilized Potamogeton crispus to determine the effects of calcium addition on phosphorus removal. Plastic film was used to block material exchange between the overlying water and the sediment, and we compared the experimental results with long-term monitoring results of Yimeng Lake, which contained a dense population of P. crispus. The results revealed that the first 10-40 days constituted a period of rapid P decrease, as P. crispus could effectively remove the phosphorus in the water through coprecipitation of CaCO3-P. The treatment groups indicated that P. crispus released calcium into the overlying water, and after the addition of calcium ions, P. crispus showed increased phosphorus removal efficiency in the water. Total phosphorus (TP) and P/Ca content increased with increasing pH in the treatment groups, and the TP and pH declined as the calcium content increased in the treatment groups. Long-term field observations showed that the calcium-to-phosphorus ratio in the coprecipitates was dependent on the pH during the crystallization process. Thus, water calcium driven by P. crispus plays an important role in the phosphorus cycle of water, due to P. crispus assisted precipitation. This study revealed the effect of P. crispus on the water purification, the migration and transformation of Ca and P in sediment and overlying water under the condition of sediment calcium addition, so as to provide a theoretical basis for the ecological restoration of shallow lakes eutrophication.

Application of mixotrophic acidophiles for the bioremediation of cadmium-contaminated soils elevates cadmium removal, soil nutrient availability, and rice growth.

A major challenge in radically alleviating the threats posed by Cd-contaminated paddy fields to human health is to reduce the Cd levels in both soils and rice grains. In this study, the microbial extraction (ME) treatment using a mixotrophic acidophilic consortium was used for the bioremediation of Cd-contaminated soils. The results showed that the ME treatment enhanced the total Cd (40%) and diethylenetriamine pentaacetic acid-soluble Cd (DTPA-Cd, 64%) removal efficiencies in contaminated soils. In addition, ME treatment decreased the levels of Cd acid-soluble and reducible fractions and thereby reduced Cd uptake in rice tissues. Microbial community analysis indicated that the indigenous soil microbial diversity and composition were not changed after the ME treatment, but the relative abundance of functional microbes associated with Cd removal was improved. Notably, soil available nutrient levels were elevated upon inoculation with mixotrophic acidophiles, resulting in an increase in rice growth and grain weight. This study provides a scientific basis for the potential application and evaluation of ME treatment in the field for remediating Cd-contaminated paddy soils.

Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has been a great threat to global public health since 2020. Although the advance on vaccine development has been largely achieved, a strategy to alleviate immune overactivation in severe COVID-19 patients is still needed. The NLRP3 inflammasome is activated upon SARS-CoV-2 infection and associated with COVID-19 severity. However, the processes by which the NLRP3 inflammasome is involved in COVID-19 disease remain unclear. METHODS: We infected THP-1 derived macrophages, NLRP3 knockout mice, and human ACE2 transgenic mice with live SARS-CoV-2 in Biosafety Level 3 (BSL-3) laboratory. We performed quantitative real-time PCR for targeted viral or host genes from SARS-CoV-2 infected mouse tissues, conducted histological or immunofluorescence analysis in SARS-CoV-2 infected mouse tissues. We also injected intranasally AAV-hACE2 or intraperitoneally NLRP3 inflammasome inhibitor MCC950 before SARS-CoV-2 infection in mice as indicated. FINDINGS: We have provided multiple lines of evidence that the NLRP3 inflammasome plays an important role in the host immune response to SARS-CoV-2 invasion of the lungs. Inhibition of the NLRP3 inflammasome attenuated the release of COVID-19 related pro-inflammatory cytokines in cell cultures and mice. The severe pathology induced by SARS-CoV-2 in lung tissues was reduced in Nlrp3-/- mice compared to wild-type C57BL/6 mice. Finally, specific inhibition of the NLRP3 inflammasome by MCC950 alleviated excessive lung inflammation and thus COVID-19 like pathology in human ACE2 transgenic mice. INTERPRETATION: Inflammatory activation induced by SARS-CoV-2 is an important stimulator of COVID-19 related immunopathology. Targeting the NLRP3 inflammasome is a promising immune intervention against severe COVID-19 disease. FUNDING: This work was supported by grants from the Bureau of Frontier Sciences and Education, CAS (grant no. QYZDJ-SSW-SMC005 to Y.G.Y.), the key project of the CAS "Light of West China" Program (to D.Y.) and Yunnan Province (202001AS070023 to D.Y.).

Divergences of soil carbon turnover and regulation in alpine steppes and meadows on the Tibetan Plateau.

The grasslands of the Tibetan Plateau store approximately 2.5% of global soil organic carbon (SOC) and considerable soil inorganic carbon (SIC) and have the potential to become a vast carbon source or sink as climate change progresses. However, the soil carbon (C) sequestration mechanisms that occur across large-scale natural gradients remain unclear. Here, humic substances (HS) were utilized to trace soil C turnover at 0-20 cm, and we compared divergences among three main grassland types (alpine meadow, alpine steppe, and artificial plantation) using structural equation modeling (SEM). The results showed that the alpine meadows sequestered the most soil C (63.99 ± 4.41 g kg-1 SOC and 4.11 ± 0.63 g kg-1 SIC), sequestering 2-3 times more than the alpine steppe ecosystems (19.78 ± 1.98 g kg-1 SOC and 9.21 ± 0.66 g kg-1 SIC). The alpine steppe and artificial plantation regions have strong C sink potential due to their low C/N ratios (P < 0.05). Importantly, SIC played an important role in the alpine steppes, accounting for nearly 26-37% of soil C. The ratios of recalcitrant HS to SOC were estimated as 46.50%, 65.09%, and 78.17% in the alpine meadow, alpine steppe, and artificial plantation ecosystems, respectively, indicating that SOC in the alpine meadow was the most sensitive to climate change. Fulvic acid (FA) accounted for 50.86% of SOC in the 0-20-cm interval, contributing most to the formation of SOC in all vegetation types. In addition, in contrast to climatic controls on soil C turnover in the alpine meadow, climate conditions rarely controlled C turnover in the alpine steppe. Moreover, sand and silt were the main soil minerals involved in C turnover in alpine meadow and alpine steppe ecosystems, respectively. Our study improves understanding of the mechanism by which soil C sinks form on the Tibetan Plateau under warming and wetting conditions.

Watershed runoff modeling through a multi-time scale approach by multivariate empirical mode decomposition (MEMD).

Accurate runoff modeling has an important role in water resource management. Attributable to the effects of climate variability and vegetation dynamics, runoff time series is nonstationary, resulting in the difficulty of runoff modeling. Detecting the temporal features of runoff and its potential influencing factors can help to increase the modeling accuracy. Selecting the Yihe watershed in the rocky mountainous area of northern China as a case study, multivariate empirical mode decomposition (MEMD) was adopted to analyze the time scales of the monthly runoff and its influencing factors, i.e., precipitation (P), normalized difference vegetation index (NDVI), temperature (T), relative humidity (RH), and potential evapotranspiration (PE). Using the MEMD technique, the original monthly runoff and its influencing factors were decomposed into six orthogonal and bandlimited functions, i.e., intrinsic mode functions (IMF1-6) and one residue, respectively. Each IMF is a counterpart of the simple harmonic function and represents a simple but general oscillatory mode in the original time series data. The results of the IMF contribution rate showed that the annual cycle had the most important role in runoff, P, NDVI, T and PE change. The contribution of quarterly oscillation was the largest contribution for the month RH variability. The monotonic residue showed that the predominant trends of runoff, P, NDVI, T, RH, and PE were decreasing from 2006 to 2015. Stepwise multiple linear regression (SMLR) was chosen to simulate the runoff IMFs and residue. The modeling results using the IMFs and residue of the potential influencing factors as input variables (R2 ranges from 0.53 to 1.0) were better than those using the original time series of influencing factors as input variables (R2 ranges from 0.17 to 0.6). By summing all the modeled IMFs and residues, the monthly runoff model was obtained, which increased the R2 value by 24.2% compared with the SMLR model using the original time series of influencing factors as input. The results indicated that MEMD was efficient for improving the accuracy of nonstationary runoff modeling.