Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome.

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1ß and IL-18 levels and repressed hepatic IL-1ß, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.

Exploration of water-nitrogen coupling effects in paddy field based on ORYZA (v3) model.

BACKGROUND: Nitrogen and water are two major factors in rice production. Due to the lack of ample evidence and much uncertainty in field experiments, the coupling effects of water and nitrogen in paddy fields have remained debatable over recent years. RESULTS: A fine-calibrated ORYZA (v3) model was applied to simulate rice growth and development under different nitrogen (N) rates and irrigation regimes for a double rice-cropping system in South China. We designed a numerical experiment of 504 treatments, consisting of seven nitrogen rates (0-300 kg ha-1 ), eight irrigation thresholds (30-100%, presented as the percentage of saturated soil water content) and nine irrigation quotas (20-100 mm), and each treatment was simulated for 30 years. Yield varied greatly with different water-nitrogen conditions, particularly in the scenario of frequently alternate wetting and drying irrigation and low-N rates. The coupling effects had a negligible influence on water input and water loss, which were found to be sensitive only to the irrigation regime and rainfall distribution. Based on the results, the N fertilizer for early rice growing in the wet season is suggested as 150-200 kg ha-1 , and 200-250 kg ha-1 for late rice growing in the dry season. The irrigating threshold and irrigation quota for early rice are suggested as lower than 70% and 30-40 mm, respectively, and, for late rice, 70-80% and 40-60 mm. CONCLUSION: Remarkable water-nitrogen coupling effects were found in the paddy field, and integrative water-nitrogen management strategies were suggested for both early rice and late rice in South China. © 2021 Society of Chemical Industry.

Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1α/GSTA1 expression via JNK signaling pathway.

Drug-induced liver injury (DILI) is a serious and frequently occurring issue in drug development. The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in many diseases; hepatocyte nuclear factor-1α (HNF-1α) and glutathione S-transferase A1 (GSTA1) are important in regulating liver-specific genes expressions and affecting drug metabolism. Oltipraz is used to treat liver cirrhosis by improving liver function, and C2-ceramide is a pro-apoptotic lipid that regulates multiple signaling pathways. In this study, we investigated the function of the JNK signaling pathway with HNF-1α and GSTA1 in a cellular model of DILI and whether oltipraz and C2-ceramide exert effects via the JNK pathway. The results showed that inhibiting JNK could ameliorate APAP-induced hepatocyte injury, reduced oxidative stress, suppressed JNK and c-Jun activation, and hepatocyte apoptosis. Meanwhile, the mRNA and protein expressions of HNF-1α and GSTA1 were increased significantly compared to control conditions. The effect of oltipraz (8 µmol/L) was similar to a JNK inhibitor and significantly increased HNF-1α/GSTA1 expression, but oltipraz combined with JNK inhibitor did not show a synergistic effect. Although C2-ceramide (8 µmol/L) aggravated hepatocyte injury and apoptosis, exacerbated oxidative stress, increased phosphorylation of JNK and c-Jun, and markedly decreased HNF-1α/GSTA1 expression, C2-ceramide combined with JNK inhibitor could partially alleviate these alterations. These results demonstrated that the JNK signaling pathway with HNF-1α/GSTA1 are involved in the process of DILI. Inhibiting JNK up-regulated HNF-1α and GSTA1 expressions which could attenuate hepatocyte injury. Oltipraz and C2-ceramide might affect the expression of HNF-1α/GSTA1 though JNK signaling.

Dihydromyricetin attenuates Escherichia coli lipopolysaccharide-induced ileum injury in chickens by inhibiting NLRP3 inflammasome and TLR4/NF-κB signalling pathway.

Lipopolysaccharide (LPS) as a major component of Escherichia coli cell wall can cause inflammation and cell death. Dihydromyricetin (ampelopsin, DHM) is a natural flavonoid compound with anti-inflammatory, anti-oxidant and anti-bacterial effects. The preventive effects of DHM against ileum injury remain unclear. Here, we explored the protective role of DHM against LPS-induced ileum injury in chickens. In this study, DHM significantly attenuated LPS-induced alteration in diamine oxidase, malondialdehyde, reduced glutathione, glutathione peroxidase and superoxide dismutase levels in chicken plasma and ileum. Histology evaluation showed that the structure of blood vessels in ileum was seriously fragmented and presence of necrotic tissue in the lumen in the LPS group. Scanning electron microscopic observation revealed that the surface of the villi was rough and uneven, the structure was chaotic, and the normal finger shape was lost in the LPS group. In contrast, 0.05% and 0.1% DHM treatment partially alleviated the abnormal morphology. Additionally, DHM maintained the barrier function by restoring the protein expression of occludin, claudin-1 and zonula occludens protein-1. DHM inhibited apoptosis through the reduction of the expression of bax and caspase-3 and restored the expression of bcl-2. Importantly, DHM could reduce ileum NLR family pyrin domain-containing 3 (NLRP3), caspase-1, interleukin (IL)-1ß and IL-18 expression to protect tissues from pyroptosis and inhibited toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathway. In summary, DHM attenuated the ileum mucosal damage, oxidative stress and apoptosis, maintained barrier function, inhibited NLRP3 inflammasome and TLR4/NF-κB signalling pathway activation triggered by Escherichia coli LPS.

Acetaminophen-induced reduction in glutathione-S-transferase A1 in hepatocytes: A role for hepatic nuclear factor 1α and its response element.

The role of hepatic nuclear factor 1α (HNF-1α) and its response element in the expression of glutathione S-transferase A1 (GSTA1) was investigated in hepatocytes cells injury induced by acetaminophen (APAP). Treatment of hepatocytes with C2-ceramide exacerbated cells injury with GSTA1 mRNA level reducing. Contrastingly, administration of oltipraz alleviated cells damage with GSTA1 mRNA level elevating relative to hepatotoxicity induced by APAP. Western blot analysis showed that C2-ceramide decreased the translocation of HNF-1α and expression of GSTA1 protein, while oltipraz increased nuclear HNF-1α level and transactivation of GSTA1. The role of HNF-1α on GSTA1 expression was confirmed by transfection experiment and dual-luciferase reporter assay system. In the cells transfected with pGSTA1-1298-LUC vector in which HNF-1 response element (HRE) was contained, the luciferase activity decreased with reduction of nuclear HNF-1α and increased with elevation of nuclear HNF-1α. However, the luciferase activity had no change with the variation of nuclear HNF-1α when the cells transfected with the plasmid of pGSTA1-ΔHNF1-LUC in which the HRE was mutated. In conclusion, HNF-1α could affect the transcription of GSTA1 and HNF-1 response element in the GSTA1 promoter region, which is functionally active for the GSTA1 transcription.

Acetaminophen-induced hepatocyte injury: C2-ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S-transferase A1 changes.

Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with drug-induced hepatic injury. C2-ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. Glutathione S-transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF-1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2-ceramide and oltipraz on APAP-induced hepatocyte injury and the changes of HNF-1 and GSTA1. Results showed that C2-ceramide (6 µmol/L) exacerbated APAP-induced hepatocyte injury and caused a significant decrease (P < .01) in HNF-1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased (P < .01). In contrast, oltipraz (8 µmol/L) reduced the injury and significantly elevated (P < .01) HNF-1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased (P < .01). In conclusion, these findings revealed that C2-ceramide inhibited HNF-1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF-1 and GSTA1 expression. Additionally, the changes in HNF-1 and GSTA1 were related to APAP-induced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination.

A novel environmental exposure index and its interaction with familial susceptibility on oral cancer in non-smokers and non-drinkers: a case-control study.

The objective of this study was to explore the collective effect of environmental factors and its interaction with familial susceptibility on oral cancer among non-smokers and non-drinkers (NSND). A hospital-based case-control study, including 319 oral cancer patients and 994 frequency-matched controls, was conducted in Fujian, China. We raised a weighed environmental exposure index according to nine significant environmental factors obtained from multivariable logistic regression model. And then, the index was classified into three categories according to the tertiles of controls (<1.34, 1.34-2.43, and >2.43). Multiplicative and additive interactions were evaluated between environmental exposure index and family cancer history. Our results showed that environmental exposure index was associated with an increased risk of oral cancer especially for those with family cancer history. Compared to subjects with low environmental exposure index and without family cancer history, those with high index and family cancer history showed the highest magnitude of OR in oral cancer risk (OR 10.40, 95% CI 5.46-19.80). Moreover, there was a multiplicative interaction between environmental exposure index and family cancer history for the risk of oral cancer (P < 0.001). This study puts forward a novel environmental exposure index, which enables a comprehensive evaluation on the overall effect of environmental risk factors on oral cancer among NSND and may interact with family cancer history. Further studies are warranted to explore the underlying mechanisms.

Glutathione S-transferase A1 (GSTA1) as a marker of acetaminophen-induced hepatocyte injury in vitro.

Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p < .05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p < .05) at 8 h after APAP exposure, 2 h later than GSTA1. Furthermore, GSTA1 increased in a dose-dependent manner with APAP treatment. GSTA1 increased significantly (p < .05) at a concentration of 5.0 mmol/L APAP, while the marked changes in ALT, AST and other indexes were undetectable until the concentration of APAP reached 7.5 mmol/L. These results suggest that increased GSTA1 can be more sensitive than ALT and other indexes as a marker of APAP-induced hepatic injury, which provide novel diagnostic index for APAP-induced hepatic injury and supply valuable information to further understand the pathogenesis of liver damage.

[Effects of dietary factors on the incidence of tongue cancer in smoking and non-smoking population].

OBJECTIVE: To evaluate the effects of dietary factors on tongue cancer in smoking and non-smoking population. METHODS: A case-control study was performed including 251 tongue cancer patients with pathologically confirmed in a hospital in Fuzhou and 1382 healthy community controls from December 2011 to March 2016. Face-to-face interviews were used to collect the information about demographics characteristics, dietary habits, smoking, drinking, etc. Unconditional logistic regression analysis was used to calculate the odds ratios( ORs) and 95% confidence intervals( 95% CI) to examine thedietary factors related to tongue cancer and to assess multiplicative interactions. RESULTS: Intake of fish ≥3 times/week, seafood ≥1 times/week, milk and dairy products ≥1times/week, green vegetables ≥1 times/day, non-green leafy vegetables ≥ 1 times/day and fruits ≥3 times/week were all associated with decreased risk of tongue cancer. When stratified by smoking, the protective effects of fish, seafood, green vegetables and nongreen leafy vegetables on tongue cancer were more obvious in smokers. And the statistically significant association between daily intake of meat ≥3 times/week and tongue cancer was only emerged in smokers( adjusted OR = 1. 55, 95% CI 1. 02- 2. 34). Moreover, there is a positive multiplicative interaction between smoking and meat intake( OR multiplicative = 2. 08, 95% CI1. 43-3. 03). CONCLUSION: Moderate intake of fresh fruits and vegetables, fish and seafood, milk and dairy products, and low intake of meat( especially for smokers) may reduce tongue cancer risk to a certain extent.

[Association between oral hygiene, chronic diseases, and oral squamous cell carcinoma].

OBJECTIVE: To investigate the association between oral hygiene, chronic diseases, and oral squamous cell carcinoma. METHODS: We performed a case-control study with 414 cases and 870 controls in Fujian during September 2010 to January 2015. Patients were newly diagnosed oral squamous cell carcinoma cases according to the pathologic diagnoses, control subjects were enrolled from community population. Epidemiological data were collected by in-person interviews using a standard questionnaire. The contents of the questionnaire included demography character, history of tobacco smoking and alcohol drinking, dietary habits, oral hygiene status, family history of cancer, etc. Using unconditional logistic regression analysis to estimate adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI) for oral hygiene and chronic diseases. We also stratified by sex, smoking and drinking to explore possible difference in association between subgroups. RESULTS: The multivariate logistic regression analysis indicated that number of teeth (20-27 and < 20), bad prosthesis, recurrent oral ulceration were the risk factors of oral squamous cell carcinoma, the adjusted OR (95% CI) values were 2.01 (1.49-2.73), 3.51 (2.39-5.15), 2.33 (1.79-3.04), 3.96 (2.11-7.44), respectively; brushing tooth once per bay, brushing tooth more than once per day, regular oral health examination at least 5 years per time were the protective factors of oral squamous cell carcinoma, the adjusted OR (95% CI) values were 0.24 (0.13-0.43), 0.13 (0.07-0.24), 0.37 (0.26-0.53), respectively. The stratification analysis indicated that recurrent oral ulceration could increase the risk of oral squamous cell carcinoma for non-smokers and non-drinking, the adjusted OR (95% CI) value was 5.21 (2.42-11.18) and 4.71 (2.37-9.36); and a risky effect of hypertension on risk of oral squamous cell carcinoma was observed for non-smokers and non-drinking, the adjusted OR (95% CI) values were 1.70 (1.10-2.61) and 1.58 (1.07-2.34). CONCLUSIONS: Oral hygiene and chronic diseases could affect the incidence of oral squamous cell carcinoma.

[Effect of tea on oral cancer in nonsmokers and nondrinkers: a case-control study].

UNLABELLED: OBJECTIVE To investigate the effect of tea on oral cancer in nonsmokers and nondrinkers. METHODS: A case-control study were performed between September 2010 and January 2015 including 203 oral cancer cases in nonsmokers and nondrinkers with pathologically confirmed and 572 community controls. The related information included socio-demographic characteristics, detailed information on tobacco smoking and alcohol and tea consumption, personal medical history, family history of cancer, and occupational history were collected from all subjects. Unconditional logistic regression analysis was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI) to examine the effect of tea on oral cancer and to assess multiplicative interactions between tea and passive smoking. We also stratified by age, sex, residence, and passive smoking to explore possible difference in association between subgroups. Additive interactions between tea and passive smoking were assessed using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: Compared with non-tea drinkers, tea consumption (OR = 0.52, 95% CI: 0.34-0.81), age of tea drinking initiation (years) ≥ 18 (OR = 0.54, 95% CI: 0.34-0.85), duration of tea consumption (years) < 20 (OR = 0.49, 95% CI: 0.27-0.90), duration of tea consumption (years) ≥ 20 (OR = 0.55, 95% CI: 0.32-0.95), average daily tea consumed < 700 ml (OR = 0.52, 95% CI: 0.32-0.86), moderate concentration of tea consumed (OR = 0.56, 95% CI: 0.32-0.96), weak concentration of tea consumed (OR = 0.35, 95% CI: 0.16-0.77), drinking green-tea (OR = 0.48, 95% CI: 0.28-0.82) and drinking moderate temperature of tea (OR = 0.55, 95% CI: 0.31-0.98) could reduce the risk of oral cancer; Stratified analysis indicated the protective effects of tea drinking on female (OR = 0.53, 95% CI: 0.30-0.94), age < 60 years old (OR = 0.53, 95% CI: 0.29-0.97), live in the urban (OR = 0.38, 95% CI: 0.20-0.69) and no passive smoking (OR = 0.47, 95% CI: 0.25-0.86) population with nonsmoking and nondrinking was more obvious; Crossover analysis showed tea and passive smoking did not exist multiplication interaction relationship (OR = 0.95, 95% CI: 0.41-2.20) and addition interaction relationship (RERI = -0.15, 95% CI: -0.92-0.62;AP = -0.16, 95% CI: -1.06-0.73; SI = -0.18, 95% CI: -1.44-0.87). CONCLUSION: Tea consumption, age of tea drinking initiation, duration of tea consumption, average daily tea consumed, concentration of tea consumed, types of tea and temperature of tea might have impact on the incidence of oral cancer in nonsmokers and nondrinkers to a certain extent.

[Influencing factors for oral-maxillofacial benign tumors: a case-control study].

OBJECTIVE: To investigate the clinical influence factors of oral-maxillofacial benign tumors. METHODS: We conducted a case-control study with 113 cases newly diagnosed primary oral-maxillofacial benign tumors and 584 cases controls from a hospital in Fujian from September 2010 to January 2015. Epidemiological data were collected by in-person interviews using a standard questionnaire. The contents of the questionnaire included demography character, history of tobacco smoking and alcohol drinking, dietary habits, oral hygiene status, family history of cancer, etc. Unconditional logistic regression was used to research the relationship between the factors and oral-maxillofacial benign tumors. RESULTS: Multivariable analysis showed that risk factors of oral-maxillofacial benign tumors included: cigarette smoking index above 1 000, passive smoking before the age of 18, age of wearing bad prosthesis between 33 to 55 years old and high blood pressure; the corresponding OR (95% CI) values were 14.63 (3.88-55.13), 2.34 (1.19-4.62), 2.35 (1.17-4.73), 3.46 (1.71-7.00), respectively; Protective factors included: regularly intake of meat above 1 time/day, fruits, health care products and vitamin tablets, brushing teeth above 1 time per day and oral examination above 5 years/time, the corresponding OR (95% CI) values were 0.22 (0.07-0.70), 0.18 (0.08-0.41), 0.32 (0.11-0.88), 0.22 (0.07-0.73), 0.28 (0.16-0.48), 0.28 (0.13-0.60), respectively. CONCLUSION: Abstinence from tobacco smoking, reduce passive smoking before the age of 18, regularly intake of meat, fruits, health care products and vitamin tablets, and oral examination at regular time might have impact on the incidence of oral-maxillofacial benign tumors to a certain extent.

Ginkgolide C inhibits ROS-mediated activation of NLRP3 inflammasome in chondrocytes to ameliorate osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba, as the most widely available medicinal plant worldwide, has been frequently utilized for treat cardiovascular, cerebrovascular, diabetic and other diseases. Due to its distinct pharmacological effects, it has been broadly applications in pharmaceuticals, health products, dietary supplements, and so on. Ginkgolide C (GC), a prominent extract of Ginkgo biloba, possesses potential in anti-inflammatory and anti-oxidant efficacy. AIMS OF THE STUDY: To determine whether GC mitigated the progressive degeneration of articular cartilage in a Monosodium Iodoacetate (MIA)-induced osteoarthritis (OA) rat model by inhibiting the activation of the NLRP3 inflammasome, and the specific underlying mechanisms. MATERIALS AND METHODS: In vivo, an OA rat model was established by intra-articular injection of MIA. The protective effect of GC (10 mg/kg) on articular cartilage was evaluated. Application of ATDC5 cells to elucidate the mechanism of the protective effect of GC on articular cartilage. Specifically, the expression levels of molecules associated with cartilage ECM degrading enzymes, OS, ERS, and NLRP3 inflammasome activation were analyzed. RESULTS: In vivo, GC ameliorated MIA-induced OA rat joint pain, and exhibited remarkable anti-inflammatory and anti- ECM degradation effects via inhibition of the activation of NLRP3 inflammasome, the release of inflammatory factors, and the expression of matrix-degrading enzymes in cartilage. Mechanically, GC inhibited the activation of NLRP3 inflammasome by restraining ROS-mediated p-IRE1α and activating Nrf2/NQO1 signal path, thereby alleviating OA. The ROS scavenger NAC was as effective as GC in reducing ROS production and inhibiting the activation of NLRP3 inflammasome. CONCLUSIONS: GC have exerted chondroprotective effects by inhibiting the activation of NLRP3 inflammasome.

Expression of cytochrome P450 2A5 in a C57BL/6J mouse model of nonalcoholic fatty liver disease.

Cytochrome P450 2A5 (CYP2A5) expression is induced during the hepatotoxicity caused by various hepatotoxins and hepatitis. However, CYP2A5 expression during nonalcoholic fatty liver disease (NAFLD) is still unknown. In this study, serum biochemical parameters and liver histopathological analyses found that NAFLD had developed in C57BL/6J mice via administration of a high-fat diet continuously for 8 weeks. Subsequently, CYP2A5 expression was probed in the mice diagnosed with NAFLD that were treated with or without pyrazole, the inducer of chemical liver injury. It is shown that hepatic CYP2A5 mRNA, protein expression and coumarin 7-hydroxylase activity are enhanced with high-fat feed, and that pyrazole is able to further increase CYP2A5 expression and activity in mice with NAFLD. These results revealed that CYP2A5 is elevated during NAFLD and suggested that pyrazole and NAFLD act synergistically to induce the expression of CYP2A5 via an unclear mechanism.

Integrated 16S and metabolomics revealed the mechanism of drought resistance and nitrogen uptake in rice at the heading stage under different nitrogen levels.

The normal methods of agricultural production worldwide have been strongly affected by the frequent occurrence of drought. Rice rhizosphere microorganisms have been significantly affected by drought stress. To provide a hypothetical basis for improving the drought resistance and N utilization efficiency of rice, the study adopted a barrel planting method at the heading stage, treating rice with no drought or drought stress and three different nitrogen (N) levels. Untargeted metabolomics and 16S rRNA gene sequencing technology were used to study the changes in microorganisms in roots and the differential metabolites (DMs) in rhizosphere soil. The results showed that under the same N application rate, the dry matter mass, N content and N accumulation in rice plants increased to different degrees under drought stress. The root soluble protein, nitrate reductase and soil urease activities were improved over those of the no-drought treatment. Proteobacteria, Bacteroidota, Nitrospirota and Zixibacteria were the dominant flora related to N absorption. A total of 184 DMs (98 upregulated and 86 downregulated) were identified between low N with no drought (LN) and normal N with no drought (NN); 139 DMs (83 upregulated and 56 downregulated) were identified between high N with no drought (HN) and NN; 166 DMs (103 upregulated and 63 downregulated) were identified between low N with drought stress (LND) and normal N with drought stress (NND); and 124 DMs (71 upregulated and 53 downregulated) were identified between high N with drought stress (HND) and NND. Fatty acyl was the metabolite with the highest proportion. KEGG analysis showed that energy metabolism pathways, such as D-alanine metabolism and the phosphotransferase system (PTS), were enriched. We conclude that N-metabolism enzymes with higher activity and higher bacterial diversity have a significant effect on drought tolerance and nitrogen uptake in rice.

Analysis of Related Metabolites Affecting Taste Values in Rice under Different Nitrogen Fertilizer Amounts and Planting Densities.

The aim of this study was to explore the differences in metabolites related to rice quality formation under different nitrogen (N) fertilizers and planting densities. In this study, Yangnongxiang 28 was used as the experimental material with the following conditions: high nitrogen and low density (HNLD; high nitrogen: 360 kg·hm-2, low density: the row spacing of rice plants was 16 cm × 30 cm), medium nitrogen and medium density (MNMD; medium nitrogen: 270 kg·hm-2, medium density: the row spacing of rice plants was 13 cm × 30 cm), and low nitrogen and high density (LNHD; low nitrogen: 270 kg·hm-2, high density: the row spacing of rice plants was 10 cm × 30 cm). The rice quality indexes, including the processing quality, amylose content, and taste value, were compared under different treatments, and we analyzed their relationship with the metabolites. The results show that the milled rice rate of HNLD was 13.85% and was 1.89% higher than that of LNHD and MNMD, respectively. The head milled rice rate of HNLD was 32.45% and 6.39% higher than that of LNHD and MNMD, respectively. The milled rice rate and head milled rice rate of HNLD and MNMD were significantly higher than those of LNHD. This study identified 22 differential metabolites (DMs) in HNLD and LNHD, 38 DMs in HNLD and MNMD, and 23 DMs in LNHD and MNMD. Most of the identified differential metabolites were lipid metabolites, which were mainly enriched in the lipid metabolic pathways and amino acid metabolic pathways. The correlation analysis showed that the lipid metabolite physapubescin was significantly negatively correlated with the taste value. The lipid metabolites 2-undecen-1-ol, lucidenic acid F, and 8-deoxy-11,13-dihydroxygrosheimin were significantly positively correlated with the taste value. Lipids may be important substances that lead to differences in taste under different nitrogen fertilizer and density treatments.

Can ensemble machine learning be used to predict the groundwater level dynamics of farmland under future climate: a 10-year study on Huaibei Plain.

Accurate and simple prediction of farmland groundwater level (GWL) is an important aspect of agricultural water management. A farmland GWL prediction model, GWPRE, was developed that integrates four machine learning (ML) models (support vector machine regression, random forest, multiple perceptions, and the stacking ensemble model) with weather forecasts. Based on the GWL and meteorological data of five monitoring wells (N1, N2, N3, N4, and N5) in Huaibei plain from 2010 to 2020, the feasibility of predicting GWL by meteorological factors and ML algorithm was tested. In addition, the stacking ensemble model and future meteorological data after Bayesian model averaging were introduced for the first time to predict GWL under future climate conditions. The results showed that GWL showed an increasing trend in the past decade, but it will decrease in the future. The performance of the stacking ensemble model was better than that of any single ML model, with RMSE reduced by 4.26 ~ 96.97% and the running time reduced by 49.25 ~ 99.40%. GWL was most sensitive to rainfall, and the sensitivity index ranged from 0.2547 to 0.4039. The fluctuation range of GWL of N1, N2, and N3 was 1.5 ~ 2.5 m in the next decade. Due to the possible high rainfall, the GWL decreased in 2024 under RCP 2.6 and 2026 under RCP 8.5. It is worth noting that although the stacking ensemble model can improve the accuracy, it is not always the best among ML models in terms of portability. Nevertheless, the stacking ensemble model was recommended for GWL prediction under climate change.

Hematologic and biochemical reference intervals for 1-month-old specific-pathogen-free Landrace pigs.

BACKGROUND: Hematologic and biochemical reference intervals (RIs) provide valuable data for the nutritional status and clinical diagnosis of animals. However, the specific hematologic and biochemical RIs for specific-pathogen-free (SPF) Landrace pigs has not been determined. OBJECTIVE: The present study was designed to establish the hematologic and biochemical RIs for SPF 1-month-old Landrace pigs. METHODS: Blood samples were collected from the jugular vein of 105 SPF 1-month-old Landrace pigs (50 males and 55 females), and complete blood counts and biochemical examinations were performed. The mean, RI, and 90% confidence interval were calculated for each variable, and gender differences were analyzed. RESULTS: Reference intervals for SPF 1-month-old Landrace pigs were generated. The results revealed that there was generally no significant difference between male and female hematologic and serum biochemical variables (P > .05). However, a significant difference was noted in serum triglyceride concentrations between male and female pigs (P < .05). CONCLUSIONS: This study provides hematologic and biochemical RIs for SPF 1-month-old Landrace pigs and provides basic data for the research and application of SPF Landrace pigs as a laboratory animal.

Improved test to determine design parameters for optimization of free surface flow constructed wetlands.

Orthogonal tests were performed to assess the effect of design parameters on hydraulic and treatment performances of constructed wetlands. The results showed that water depth, layout of in- and outlet, flow rate, and aspect ratio mainly affected hydraulic performance, and water depth, plant spacing, and layout of in- and outlet mainly affected treatment performance. Optimal integrated performance was achieved with combination of 20-30 cm water depth, five evenly distributed inlets and one middle outlet, a flow rate of 0.4-0.55 m3/h, 20-cm plant spacing, a 1.125:1 aspect ratio, and planted with Scripus tabernaemontani. The average treatment performances of 27.2%, 16.3%, and 30.7% removal rates were received for total nitrogen, total phosphorus, and total suspended solid, respectively. The design parameters that significantly influenced hydraulic performance did not significantly influence treatment performance. Various hydraulic and purification indicators displayed extremely significant correlations. There was a significant correlation between hydraulic performance and mass removal capacity.

JNK Signaling Pathway Mediates Acetaminophen-Induced Hepatotoxicity Accompanied by Changes of Glutathione S-Transferase A1 Content and Expression.

Acetaminophen (APAP) is an analgesic-antipyretic drug and widely used in clinics. Its overdose may cause serious liver damage. Here, we examined the mechanistic role of c-Jun N-terminal kinase (JNK) signaling pathway in liver injury induced by different doses of APAP. Male mice were treated with APAP (150 and 175 mg·kg-1), and meanwhile JNK inhibitor SP600125 was used to interfere APAP-induced liver damage. The results showed that JNK signaling pathway was activated by APAP in a dose-dependent manner. C-Jun N-terminal kinase inhibitor decreased JNK and c-Jun activation significantly (P < 0.01) at 175 mg·kg-1 APAP dose, and phosphorylation levels of upstream proteins of JNK were also decreased markedly (P < 0.05). In addition, serum aminotransferases activities and hepatic oxidative stress increased in a dose-dependent manner with APAP treatment, but the levels of aminotransferases and oxidative stress decreased in mice treated with JNK inhibitor, which implied that JNK inhibition ameliorated APAP-induced liver damage. It was observed that apoptosis was increased in APAP-induced liver injury, and SP600125 can attenuate apoptosis through the inhibition of JNK phosphorylation. Meanwhile, glutathione S-transferases A1 (GSTA1) content in serum was enhanced, while GSTA1 content and expression in liver reduced significantly with administration of APAP (150 and 175 mg·kg-1). After inhibiting JNK, GSTA1 content in serum decreased significantly (P < 0.01); meanwhile, GSTA1 content and expression in liver enhanced. These findings suggested that JNK signaling pathway mediated APAP-induced hepatic injury, which was accompanied by varying GSTA1 content and expression in liver and serum.