Progress in phosphorylation of natural products.

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.

Robust (hydrogen) phosphate sensing based on reversible redox of cobalt(II) hydroxide.

Response mechanism of the electrode is elucidated in terms of (hydrogen) phosphate accelerating oxidation of CoII to CoIII for the first time. Cyclic voltammetric techniques in conjunction with XRD, XPS and Raman characterizations have demonstrated unambiguously the response of cobalt (II) hydroxide electrode involves a phosphate and hydrogen ion dependent charge transfer process. Phosphate ions induce Co(OH)2 transformed into CoOOH within interlayer adsorption and restored the initial state after reduction. Meanwhile, the in common structural between Co(OH)2 and CoOOH prevents extensive structural convertibility upon cycling, result in the advantage of reversibility in phase transformation. Demonstrated sustainable technique offered the determination of phosphate with robust reproducibility (1000 cycles), long storage stability (6 months) and selectivity (potential interference: Cl-, NO3-, SO42- and HCO3-), achieving a detection limit of 5 × 10-8 M over a wide linear range up to 1.28 mM. Presented work provided insights into the unique selectivity towards phosphate in cobalt based sensors, which may inspire the rational design of Co(OH)2-based electrodes with superior electrochemical performance or extended applications.

Driving factors for decoupling water resources ecological footprint and economic growth in water-deficient cities dominated by agriculture.

To explore the key factors and specific thresholds of water resources limiting economic development, and to provide technical support for water resources management in cities dominated by agriculture similar to Zhangjiakou. We used the Tapio elastic decoupling method to quantitatively evaluate the decoupling relationship between the water resources ecological footprint (WEF) and economic growth. Then the logarithmic mean Divisia index (LMDI) and mathematical statistics are used to identify the key factors and threshold effects. The results show a significant decreasing trend in the WEF and obvious spatial differences in Zhangjiakou between 2006 and 2015, with agricultural ecological footprint dominating all districts and counties (77.54 ± 14.35%). The changes in technological effect are a contributing factor to the decoupling between the WEF and the economy in Zhangjiakou, while the economic effect is the main restricting factor. In particular, there is a high correlation between the WEF and the number of water-saving irrigation machines and the total power of agricultural machinery. According to the findings, for water-scarce cities such as Zhangjiakou, where agriculture is the primary focus, it is suggested that increasing the number of agricultural machinery can effectively alleviate the problem of water scarcity constraining economic development.

Noisy Label Learning With Provable Consistency for a Wider Family of Losses.

Deep models have achieved state-of-the-art performance on a broad range of visual recognition tasks. Nevertheless, the generalization ability of deep models is seriously affected by noisy labels. Though deep learning packages have different losses, this is not transparent for users to choose consistent losses. This paper addresses the problem of how to use abundant loss functions designed for the traditional classification problem in the presence of label noise. We present a dynamic label learning (DLL) algorithm for noisy label learning and then prove that any surrogate loss function can be used for classification with noisy labels by using our proposed algorithm, with a consistency guarantee that the label noise does not ultimately hinder the search for the optimal classifier of the noise-free sample. In addition, we provide a depth theoretical analysis of our algorithm to verify the justifies' correctness and explain the powerful robustness. Finally, experimental results on synthetic and real datasets confirm the efficiency of our algorithm and the correctness of our justifies and show that our proposed algorithm significantly outperforms or is comparable to current state-of-the-art counterparts.

PGC7 regulates H3K27me3 modification by inhibiting the interaction of YY1 with PRC2.

Primordial germ cell 7 (PGC7)(Dppa3 or Stella) is a small inherently disordered protein that is mainly expressed in oocytes and plays a vital role in the regulation of DNA methylation reprogramming in imprinted loci through interaction with other proteins. Most of PGC7-deficient zygotes are blocked at two-cell stage with an increased tri-methylation at lysine 27 of histone H3 (H3K27me3) level in the nucleus. Our previous work has indicated that PGC7 interacts with yin-yang1 (YY1) that is essential for the recruitment of enhancer of zeste homolog 2 (EZH2)-containing Polycomb repressive complex 2 (PRC2) to H3K27me3 modification sites. Here, we found that the presence of PGC7 weakened the interaction between YY1 and PRC2 without disrupting the assembly of core subunits of the PRC2 complex. In addition, PGC7 promoted AKT to phosphorylate serine 21 of EZH2, resulting in inhibition of EZH2 activity and the dissociation of EZH2 from YY1, thereby decreasing H3K27me3 level. In zygotes, the PGC7-deficient and AKT inhibitor MK2206 both promoted EZH2 to enter the pronuclei but without disturbing the subcellular localization of YY1 and caused an increase in the level of H3K27me3 in the pronuclei, as well as inhibition of the expression of zygote-activating genes regulated by H3K27me3 in two-cell embryos. In summary, PGC7 could affect zygotic genome activation during early embryonic development by regulating the level of H3K27me3 through regulation of PRC2 recruitment, EZH2 activity, and subcellular localization.NEW & NOTEWORTHY PGC7 and YY1 interaction inhibits recruitment of PRC2 by YY1. PGC7 promotes AKT and EZH2 interaction to increase pEZH2-S21 level, which weakens YY1 and EZH2 interaction, thereby decreasing H3K27me3 level. In zygotes, the PGC7-deficient and AKT inhibitor MK2206 promote EZH2 to enter the pronuclei, and increase H3K27me3 level in the pronuclei, as well as inhibition of the expression of zygote-activating genes regulated by H3K27me3 in two-cell embryos, which ultimately affects early embryo development.

Optimal allocation of agricultural water resources in Yanghe watershed considering blue water to green water ratio.

BACKGROUND: Yanghe Watershed has low annual rainfall, uneven spatial and temporal distribution, extreme shortage of water resources in some areas. The contradiction between supply and demand of water for agricultural production is prominent and the expected production value cannot be achieved. Therefore, it is necessary to investigate the supply and demand of agricultural water resources and the impact of green water on agricultural crops in Yanghe Watershed. RESULTS: This article proposes a new crop economic model for increasing the green-water footprint to blue-water footprint ratio (GWF:BWF) in accordance with the regional characteristics, alleviating agricultural water shortage in irrigation areas, optimizing water resource allocation, and achieving sustainable agricultural development. The proposition is based on a study of five crops in eight districts and counties in the Yanghe River watershed. By combining the economic model F with a crop water production function, we achieved 89.3%, 88.9%, 97.1%, 81.5%, and 87.0% of the optimal water demands of the five crops, respectively, and effectively improved the underground irrigation of crops and the water resource utilization efficiency. CONCLUSION: The GWF:BWF threshold interval was subsequently selected based on the temporal changes in the BWF and GWF in the study area. This enabled significant reduction of the planting area of blue-water crops and increase in the proportion of green-water crops, while also improving the agricultural economy of the Yanghe Watershed. The proposed model promises to afford enhanced management of agricultural irrigation areas that experience rainfall shortage. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Sediment nitrogen contents controlled by microbial community in a eutrophic tributary in Three Gorges Reservoir, China.

Nitrogen pollution caused serious environmental problems in reservoir ecosystems. Reducing nitrogen pollution by enhancing nitrogen removal in river sediments deserved intensive research. Distributions of nitrogen contents in sediment-water interface were characterized along the Xiangxi bay (XXB), a eutrophic tributary in Three Gorges Reservoir, China. More than 47% of total Kjeldahl nitrogen (TKN) and 67% of total organic nitrogen (TON) were degraded during burial. Higher TN, TON and NH4+ consuming at downstream sites indicated stronger nitrogen mineralization and release due to higher turbulence of the overlying density currents. Nitrifying bacteria, denitrifying bacteria, anaerobic ammonium oxidizing (anammox) bacteria and nitrite/nitrate-dependent anaerobic methane oxidation (N-DAMO) bacteria were detected in nitrate-ammonium transition zone. Nitrogen contents transitions were responded to microbial stakeholders indicated microbially mediated nitrogen cycling in sediments. The dissolved oxygen and nitrate availabilities were the key limits of denitrification and associated reactions. These results suggested microbial mediated nitrogen cycling processes in sediments were critical for nitrogen removal in aquatic ecosystems, and replenishing dissolved oxygen and nitrate was expected to enhance sediment denitrification and strengthen potential environmental self-purification.

A Convergence Path to Deep Learning on Noisy Labels.

In many real-world machine learning classification applications, the model performance based on deep neural networks (DNNs) oftentimes suffers from label noise. Various methods have been proposed in the literature to address this issue, primarily by focusing on designing noise-tolerant loss functions, cleaning label noise, and correcting the objective loss. However, the noise-tolerant loss functions face challenges when the noise level increases. This article aims to reveal a convergence path of a trained model in the presence of label noise, and here, the convergence path depicts the evolution of a trained model over epochs. We first propose a theorem to demonstrate that any surrogate loss function can be used to learn DNNs from noisy labels. Next, theories on the general convergence path for the deep models under label noise are presented and verified through a series of experiments. In addition, we design an algorithm based on the proposed theorems that make efficient corrections on the noisy labels and achieve strong robustness in the DNN models. We designed several experiments using benchmark datasets to assess noise tolerance and verify the theorems presented in this article. The comprehensive experimental results firmly confirm our theoretical results and also clearly validate the effectiveness of our method under various levels of label noise.

Estimating the Carbon Emission of Construction Waste Recycling Using Grey Model and Life Cycle Assessment: A Case Study of Shanghai.

Great efforts have been exerted in reducing carbon emissions in design, construction and operation stages. However, little attention is paid to the quantification of carbon emissions in construction waste recycling at the end-of-life stage. This study aims to quantitatively analyze the carbon emission of construction waste in Shanghai City, PR China. A grey model is used to forecast the generation amount of construction waste, and a life cycle assessment is performed to estimate the carbon emission of construction waste. In this study, both the carbon emission of recycling activities (environmental costs), and the equivalent amount of carbon generated from alternative materials (environmental benefit) are considered. Here, recycling 1 ton (t) of construction waste in Shanghai can save 100.4 kg CO2-e. The total carbon-emission-saving potential can be increased from 0.31 million t CO2-e (2022) to 0.35 million t CO2-e (2031). The carbon emission of recycling concrete, brick, steel, wood and mortar, identified as the key components of construction waste, is investigated. This research can help to reduce carbon emissions and further achieve carbon neutrality for Shanghai City. The proposed methods can also be applied to other regions, especially when the data for construction waste are insufficient.

Oyster (Crassostrea gigas) Polysaccharide Ameliorates High-Fat-Diet-Induced Oxidative Stress and Inflammation in the Liver via the Bile Acid-FXR-AMPKα Pathway.

Oyster polysaccharides (OPS) have a variety of biological activities. In this study, we aimed to investigate the potential mechanisms of OPS to ameliorate hepatic oxidative stress and inflammation in mice induced by a high-fat diet (HFD). The results showed that OPS reduced the HFD-induced increases in serum transaminase levels and alleviated hepatic oxidative stress and inflammation. Moreover, OPS regulated bile acid metabolism and increased bile acid content in the liver, serum, and feces. Serum bile acid profile results indicated that OPS reduced levels of chenodeoxycholic acid, deoxycholic acid, and lithocholic acid associated with high-affinity agonists of Farnesol X receptor (FXR). Western blot analysis showed that OPS accelerated bile acid metabolism by downregulating hepatic FXR expression and promoting its downstream CYP7A1, CYP27A1, and CYP8B1 protein expression. Meanwhile, OPS ameliorated oxidative stress and inflammation in the liver by modulating FXR-AMPKα-Nrf2/NF-κB signaling to reduce p-IκBα/IκBα, p-NF-κB p65/NF-κB p65, IL-1ß, and TNF-α expression and increase p-Nrf2/Nrf2, HO-1, and NQO-1 expression. This study was the first to explore the possible mechanism of OPS in improving liver oxidative stress and inflammation from the perspective of bile acid metabolism, providing a theoretical basis for OPS as a new source of functional food.

Transfer of microplastics in sludge upon Fe(II)-persulfate conditioning and mechanical dewatering.

Sewage treatment plants act as both sinks and sources of microplastics with elevated concentrations of microplastics accumulating in the sludge. Consequently, the effects of sludge conditioning and dewatering processes on the fate of microplastics need to be clarified. Microplastic characteristics in sludge, before and after advanced oxidation Fe(II)-activated persulfate conditioning were studied using a microplastics dynamic flotation separator (MDFS). In the unconditioned sludge (no dewatering), white and transparent microplastics dominated and seven types of plastic polymer were detected with polyethylene (30.3%) and polypropylene (23.9%) being the main ones. Pellet microplastics were found to be the dominant morphology, accounting for 67.0% of the total number of microplastics. The abundance of microplastics extracted using the MDFS device from the unconditioned (no dewatering) sludge was 320 ± 3 particles g-1 dried sludge, which was greater by 37% than extracted using microplastics static flotation separation. Due to the release of the adsorbed microplastics from the destroyed sludge flocs after conditioning, the abundance of extractable microplastics increased by 19 ± 2% as compared to the unconditioned sludge (both with no dewatering). After filter presses (plate-frame filter, vacuum filter) and centrifuge dewatering, 81-90% of the microplastics were present in the filter cake, of which microplastics <500 µm accounted for more than 80% of the total number. The abundance of microplastics per unit volume of filtrate after filter press dewatering was significantly smaller than after centrifuge dewatering (3.2-4.4 × 103 cf 13.0 × 103 particles L-1, respectively). The difference increments in relative abundance of <10 µm microplastics in the centrifuge filtrate was about twice that of the filter presses. The surface morphology of the microplastics did not change in the conditioning process. This study highlights the need to assess the application of advanced oxidation conditioning which has significant influence on the microplastics distribution via the subsequent sludge dewatering.

Mechanism of a Herbal Formula Associated with Prognosis and Immune Infiltration in LIHC: Transcriptomics Analysis and Molecular Dynamics Simulations.

Background: The aim of this study is to explore the interactions between effective monomers of herbal formulas and their therapeutic targets using systems biology approaches which may be a promising approach to unraveling their underlying mechanisms. Shentao Ruangan decoction (STRGD), which has been experimentally, clinically demonstrated to be effective in treating liver hepatocellular carcinoma (LIHC), was selected. Methods: Bioactive ingredients and drug targets of STRGD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform and BATMAN-TCM databases. LIHC-related differentially expressed genes (DEGs) and key modules were identified by a weighted gene coexpression network analysis using The Cancer Genome Atlas data. The Kaplan-Meier analysis was used to investigate the relationship between STRGD tumor targets and patients survival. The CIBERSORT deconvolution algorithm was used to analyze the correlation between STRGD tumor targets and infiltrating immune cells. Enrichment analysis was used to analyze biological functions. Interactions between STRGD compounds and LIHC-immune-related genes were investigated using molecular docking and MDS. Results: We identified 24 STRGD tumor targets, which were found to be correlated with survival and the level of immune cell infiltration in LIHC patients. Immune infiltration, gene set enrichment, and Kyoto Encyclopedia of Genes and Genomes analyses highlighted the roles of T and B cell subsets, which were both related to activator protein 1 (AP1), in STRGD action. Docking studies and HPLC indicated that tanshinone IIA is the main compound of STRGD in LIHC treatment, and MDS showed that the potential LIHC-immune-related targets 1FOS and 1JUN firmly bind to tanshinone IIA. Conclusions: The mechanisms of STRGD in improving the immune and survival status of LIHC patients include interactions between STRGD compounds and LIHC-immune-related targets. The findings of this study can guide research studies on the potential usefulness of tanshinone IIA in the development of drugs targeting 1JUN and 1FOS for the treatment of LIHC.

Influence of the In-Stream Structure on Solute Transport in the Hyporheic Zone.

The hyporheic zone (HZ) plays an important role in the river ecosystem, and hyporheic exchange and solute transport in the HZ are important ecological functions. However, the relationship between the design parameters of river structure and solute transport is still poorly understood. In this study, we combined flume experiments and numerical simulations to systematically evaluate how in-stream structures impact the solute transport depth (DP), hyporheic vertical exchange flux (Q), and solute flux (Qs). The results showed that the in-stream structure had a significant influence on solute transport in the HZ and could obviously increase the intensity of hyporheic exchange and promote solute transport. Model results indicated that DP, Q, and Qs increased with the ratio of ground height to underground height of structure (H/D) and structure number (N), while Q, DP, and Qs increased with the structural spacing (S) to begin with; then, Q remained constant, and DP and Qs decreased as S continued to increase. This study deepened our understanding of the influence of in-stream structural design parameters on HZ solute transport, which is helpful to provide a theoretical basis for ecological restoration projects in the river HZ.

Targets and Potential Mechanism of Scutellaria baicalensis in Treatment of Primary Hepatocellular Carcinoma Based on Bioinformatics Analysis.

OBJECTIVE: To analyze the target and potential mechanism of Scutellaria baicalensis (SB) in the treatment of HCC based on bioinformatics, so as to provide suggestions for the diagnosis, treatment, and drug development of hepatocellular carcinoma (HCC). METHODS: The regulated gene targets of SB were screened by gene expression pattern clustering and differential analysis of gene expression data of HepG2 cells treated with SB at 0 h, 1 h, 3 h, 6 h, 12 h, and 24 h. The module genes related to HCC were identified by the weighted gene coexpression network analysis (WGCNA). KEGG and GO enrichment were used to analyze the molecular function and structure of the module, and GSEA was used to evaluate the different functional pathways between normal people and patients with HCC. Then, the module gene was used for univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model. The protein-protein interaction network (PPI) was used to analyze the core genes regulated by SB (CGRSB) of the module, and the survival curve revealed the CGRSB impact on patient survival. The CIBERSORT algorithm combined with correlation analysis to explore the relationship between CGRSB and immune infiltration. Finally, the single-cell sequencing technique was used to analyze the distribution of CGRSB at the cellular level. RESULTS: SB could regulate 903 genes, of which 234 were related to the occurrence of HCC. The prognosis model constructed by these genes has a good effect in evaluating the survival of patients. KEGG and GO enrichment analysis showed that the regulation of SB on HCC mainly focused on some cell proliferation, apoptosis, and immune-related functions. GSEA enrichment analysis showed that these functions are related to the occurrence of HCC. A total of 24 CGRSB were obtained after screening, of which 13 were significantly related to survival, and most of them were unfavorable factors for patient survival. The correlation analysis of gene expression showed that most of CGRSB was significantly correlated with T cells, macrophages, and other functions. The results of single-cell analysis showed that the distribution of CGRSB in macrophages was the most. CONCLUSION: SB has high credibility in the treatment of HCC, such as CDK2, AURKB, RRM2, CENPE, ESR1, and PRIM2. These targets can be used as potential biomarkers for clinical diagnosis. The research also shows that the p53 signal pathway, MAPK signal pathway, apoptosis pathway, T cell receptor pathway, and macrophage-mediated tumor immunity play the most important role in the mechanism of SB in treating HCC.

The influence of hydraulic characteristics on algal bloom in three gorges reservoir, China: A combination of cultural experiments and field monitoring.

It is essential to understand the mechanism of algal bloom and develop effect measures to control the hazard in aquatic environment, such as large reservoirs. In this study, a series of experiments, along with field observation from 2007 to 2016, were carried out to identify the hydrodynamic parameters that drive the algal bloom in the Three Gorges Reservoir (TGR), China, and their threshold values were determined. The results show that algae concentration was markedly diluted with a short retention time, and the threshold value of the retention time to avoid algal bloom was approximately less than 3 days. With strong stratification, the algae concentration was able to approach to the level of algal bloom in 10 days, even when the water temperature is lower than 12 °C. The ratio of mixing depth to euphotic depth (Zm/Ze) had significant negative correlations with both algae concentration and algae specific growth rate (SGR). The field monitoring data indicated that Zm/Ze is an important hydrodynamic parameter which sensitively affects algae growth and concentration. This study made the first attempt to determine Zm/Ze >2.8 to restrain algal bloom in the TGR. Our findings shed light on the influence of critical depth on the algal bloom in the TGR, and the results can serve to control algal bloom in reservoirs through discharge operation.

Improved growth of bait microalgae Isochrysis and aquacultural wastewater treatment with mixotrophic culture.

This research of mixotrophic microalgae Isochrysis 3011 with glycerol was combined with the treatment of aqua-cultural wastewater, different initial concentrations, and optimized light intensities. The algae growth rate, removal efficiencies of total nitrogen (TN) and total phosphorus (TP) were determined. Results showed that the suitable initial concentration was 0.4 g L-1, and the optimum light intensity was 60 µmol m-2 s-1. The growth of the mixotrophic group was better than that of the autotrophic culture. The biomass yield of the mixotrophic group with glycerol was 0.17 g L-1 d-1, and the removal rates of TN and TP were 73.39% and 95.61%, respectively. The content of total lipid and total protein in mixotrophic group were higher than the values of the autotrophic group. This indicates that aquaculture wastewater treatment with mixotrophic bait microalgae can obtain superior micro-algal biomass, which is also a potential technology for wastewater utilization and ecological protection.

Adaptability of organic matter and solid content to Fe2+/persulfate and skeleton builder conditioner for waste activated sludge dewatering.

Sludge conditioning is important for improved dewatering, with the sludge characteristics impacting the effect of conditioning. A composite conditioner, Fe2+-activated sodium persulfate (Fe2+/SPS) combined with phosphogypsum (PG), was used to examine its impact on sludges with different organic contents (34.6-43.8%) or different solid contents (2.8-5.9%). Response surface optimization analysis shows that when the best conditioning is achieved, the reduction of the specific resistance to filtration (SRF) is not sensitive to organic matter content, but the dewatering performance of the sludge is greatly affected by the solid content. The oxidation role of Fe2+/SPS and the skeleton builder role of PG together affect the conditioning, oxidation playing a major role in conditioning, especially for greater organic matter content. The organic content (maximum ηSOL value was 0.32) also affects the effectiveness of the skeleton builder more than the solid content (Maximum ηSOL value was 0.25). Changes in PG significantly impacts the optimal molar ratio and dosage of Fe2+/SPS. Sludge with greater solid content requires greater Fe2+/SPS dosage to provide stronger oxidation to destroy flocs, and the maximum Fe2+:SPS molar ratio was 1.14 with solid content of 5.9 wt%. The composite conditioning decreases the content of extracellular polymeric substances and proteins/polysaccharides. This study provides new insight into the relationship between the oxidation role of Fe2+/SPS and the skeleton builder role of PG for sludge conditioning strategies according to the optimal conditions.

Spatial and temporal variability of dissolved methane concentrations and diffusive emissions in the Three Gorges Reservoir.

Methane (CH4) emissions from freshwater aquatic systems such as rivers and reservoirs are an important component of the global methane budget. However, the estimation can be largely affected by the spatial and temporal resolutions of measurements. Especially, the lack of high-resolution studies in the Three Gorges Reservoir (TGR), one of the largest reservoirs in the world, has led to a longstanding debate on its CH4 emissions. In this study, the spatial distribution and seasonal variations of dissolved CH4 concentrations were measured using a fast-response automated gas equilibrator in the TGR. We observed large spatiotemporal variations of dissolved CH4 (mean ± SD: 0.26 ± 0.19 µM in summer and 0.24 ± 0.17 µM in winter). Higher concentrations with stronger variations were found in the upstream than in the section close to the Three Gorges Dam. The dissolved CH4 concentration in the TGR was mainly influenced by sewage discharge, sedimentation, topographical conditions, tributaries, and spatial and seasonal variations in hydrodynamics. Regression analyses suggest that the concentration can be characterized by sewage discharge, water depth, and electrical conductivity to a certain extent. Mean diffusive CH4 fluxes from the TGR in summer and winter were 16.2 mg m-2 d-1 and 3.1 mg m-2 d-1, respectively. Downsampling simulations show that scaling dissolved CH4 in the TGR from one site likely involves large errors, and at least ∼38 sites and ∼52-58 sites are needed to achieve an accurate estimate in summer and winter, respectively. Due to the large spatial and temporal heterogeneity, high-resolution measurements are key to improving the reliability of CH4 estimates and assessing the contribution of the TGR to regional and global CH4 budgets.

Effect of Berberine on Hyperuricemia and Kidney Injury: A Network Pharmacology Analysis and Experimental Validation in a Mouse Model.

PURPOSE: Berberine (BBR) is an active component of Phellodendri Cortex (PC), which is a traditional Chinese medicine that has been prescribed clinically for hyperuricemia (HUA) for hundreds of years. Many studies reported the anti-inflammatory and nephroprotective properties of BBR and PC; however, the therapeutic effects of BBR on HUA have not been explored. This study aims to investigate the efficacy and mechanism of BBR for treating HUA. METHODS: The mechanism of BBR in the treatment of HUA were predicted by network pharmacology. A mouse model of HUA established by potassium oxonate and hypoxanthine was used to verify the prediction. The levels of serum uric acid (UA), urea nitrogen (BUN) and creatinine (CRE) were determined by biochemical test kits. Hematoxylin and eosin staining of kidney tissues was used to observe the kidney damage. ELISA kits were applied to detect the levels of interleukin (IL)-1ß and IL-18 in serum and kidney tissues. Quantitative real-time PCR and Western blotting were adopted to analyze the expression of NLRP3, ASC, Caspase1, IL-1ß and URAT1. The expressions of URAT1 in the kidney tubules were visualized by immunohistochemical staining. Molecular docking was used to assess the interaction between URAT1 and BBR. RESULTS: The network pharmacology screened out 82 genes and several inflammation-related signaling pathways related to the anti-hyperuricemia effect of BBR. In the in vivo experiment, BBR substantially decreased the level of UA, BUN and CRE, and alleviated the kidney damage in mice with HUA. BBR reduced IL-1ß and IL-18, and downregulated expressions of NLRP3, ASC, Caspase1 and IL-1ß. BBR also inhibited expression of URAT1 and exhibited strong affinity with this target in silico docking. CONCLUSION: BBR exerts anti-HUA and nephroprotective effects via inhibiting activation of NLRP3 inflammasome and correcting the aberrant expression of URAT1 in kidney. BBR might be a novel therapeutic agent for treating HUA.