MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells.

Gastric cancer is histologically classified into the intestinal subtype, which forms tubular structures, and the aggressive diffuse subtype, characterized by rapid invasion and poor prognosis. The variety and quantity of miRNA isoforms between different histological subtypes of gastric cancer were unknown. Through systematic filtering, we found that more diverse miR-30a-5p isoforms was present in the diffuse subtype of gastric cancer, and was associated with patients' worse survival independent of tumor stage based on the TCGA miRNA-seq data. Among all nine isoforms of miR-30a-5p, miR-30a-5p -1|1 was more abundant than the archetype of miR-30a-5p. Higher expression of miR-30a-5p -1|1 was observed in patients with advanced tumor stage and poor survival. Furthermore, miR-30a-5p -1|1 could promote the metastasis of gastric cancer cells both in vitro and in vivo by down-regulating TMEM66. In clinical samples, decreased expression of TMEM66 was characteristic of gastric cancer, and the low level of TMEM66 correlated with deceased CD8 positive cells in the tumor microenvironment probably due to decreased cytokines production. In conclusion, the variety of miR-30a-5p isoforms correlates with worse survival in gastric cancer patients. Moreover, miR-30a-5p -1|1 could promote gastric cancer metastasis by inhibiting TMEM66 and the infiltration of intratumoral CD8 positive cells.

From lake to fisheries: Interactive effect of climate and landuse changes hit on lake fish catch?

Global warming and unpredictable nature possess a negative impact on fisheries and the daily activities of other habitats. GIS and remote sensing approach is an effective tool to determine the morphological characteristics of the lake. The present study addresses the interactive effect of climate and landuse changes hit on fish catch in lake fisheries. We used a combination of the landscape disturbance index, vulnerability index, and loss index to construct a complete ecological risk assessment framework based on the landscape structure of regional ecosystems. The results indicate an increase from around 45%-76% in the percentage of land susceptible to moderate to ecological severe risk in the landscape from 2004 to 2023. Since 1950, temperature changes have increased by 0.4%, precipitation has decreased by 6%, and water levels have decreased by 4.2%, based on the results. The results indicate that landuse, water temperature, precipitation, and water depth significantly impact the aquaculture system. The findings strongly suggest integrating possible consequences of environmental change on fish yield for governance modeling techniques to minimize their effects.

Mitochondria-associated endoplasmic reticulum membranes involve in oxidative stress-induced intestinal barrier injury and mitochondrial dysfunction under diquat exposing.

Many factors induced by environmental toxicants have made oxidative stress a risk factor for the intestinal barrier injury and growth restriction, which is serious health threat for human and livestock and induces significant economic loss. It is well-known that diquat-induced oxidative stress is implicated in the intestinal barrier injury. Although some studies have shown that mitochondria are the primary target organelle of diquat, the underlying mechanism remains incompletely understood. Recently, mitochondria-associated endoplasmic reticulum membranes (MAMs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and signal transduction. In this study, we investigated whether MAMs involved in intestinal barrier injury and mitochondrial dysfunction induced by diquat-induced oxidative stress in piglets and porcine intestinal epithelial cells (IPEC-J2 cells). The results showed that diquat induced growth restriction and impaired intestinal barrier. The mitochondrial reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased following diquat exposure. The ultrastructure of mitochondria and MAMs was also disturbed. Meanwhile, diquat upregulated endoplasmic reticulum stress marker protein and activated PERK pathway. Furthermore, loosening MAMs alleviated intestinal barrier injury, decrease of antioxidant enzyme activity and mitochondrial dysfunction induced by diquat in IPEC-J2 cells, while tightening MAMs exacerbated diquat-induced mitochondrial dysfunction. These results suggested that MAMs may be associated with the intestinal barrier injury and mitochondrial dysfunction induced by diquat in the jejunum of piglets.

Research on machine learning hybrid framework by coupling grid-based runoff generation model and runoff process vectorization for flood forecasting.

One of the important non-engineering measures for flood forecasting and disaster reduction in watersheds is the application of machine learning flood prediction models, with Long Short-Term Memory (LSTM) being one of the most representative time series prediction models. However, the LSTM model has issues of underestimating peak flows and poor robustness in flood forecasting applications. Therefore, based on a thorough analysis of complex underlying surface attributes, this study proposes a framework for distinguishing runoff models and integrates a Grid-based Runoff Generation Model (GRGM). Simultaneously considering the time series characteristics of runoff processes, including rising, peak, and recession, a runoff process vectorization (RPV) method is proposed. In this study, a hybrid deep learning flood forecasting framework, GRGM-RPV-LSTM, is constructed by coupling the GRGM, RPV, and LSTM neural network models. Taking the Jialu River in the Zhongmu station control basin as an example, the model is validated using 18 instances of measured floods and compared with the LSTM and GRGM-LSTM models. The study shows that the GRGM model has a relative error and average coefficient of determination for simulating runoff of 8.41% and 0.976, respectively, indicating that considering the spatial distribution of runoff patterns leads to more accurate runoff calculations. Under the same lead time conditions, the GRGM-RPV-LSTM hybrid forecasting model has a Nash efficiency coefficient greater than 0.9, demonstrating better simulation performance compared to the GRGM-LSTM and LSTM models. As the lead time increases, the GRGM-RPV-LSTM model provides more accurate peak flow predictions and exhibits better robustness. The research findings can provide scientific basis for coordinated management of flood control and disaster reduction in watersheds.

Study on the response analysis of LID hydrological process to rainfall pattern based on framework for dynamic simulation of urban floods.

An in-depth analysis of the urban flood disaster level in response to different rainfall characteristics and Low Impact Development (LID) measures is of significant importance for addressing unfavorable management conditions and implementing effective flood control measures. This study proposes a dynamic urban flood simulation framework based on the Storm Water Management Model (SWMM) and Geographic Information System (GIS) spatial analysis, incorporating an active inundation seed search algorithm. The framework is calibrated and validated using nine historical urban flood events. Subsequently, the impact of rainfall patterns on urban inundation under LID measures is analyzed based on the dynamic urban flood simulation framework. The results show that the urban flood simulation framework exhibits good applicability, with Nash-Sutcliffe Efficiency (NSE) values of 0.825 and 0.763 during the calibration and validation periods, respectively. The extent of inundation shows little variation for rainfall events with a return period greater than 20 years, and the location of flooding is minimally affected by rainfall patterns. LID measures have a decreasing effect on urban inundation control as the return period of rainfall increases, and there are variations in hydrological responses to different rainfall patterns under the same return period. For single-peak rainfall events with the same return period, the control rates of inundation volume, flow, and infiltration decrease as the rainfall peak coefficient increases, indicating a weakening effect of LID measures on flood control with increasing rainfall peak coefficient. Under the same return period conditions, LID measures exhibit the best runoff control effect for uniform rainfall, while their effectiveness is lower for double-peak rainfall events and single-peak rainfall events with an r = 0.75 coefficient. The findings of this study provide a theoretical basis for urban flood warning and management of Low Impact Development measures.

Research on runoff process vectorization and integration of deep learning algorithms for flood forecasting.

Accurate multi-step ahead flood forecasting is crucial for flood prevention and mitigation efforts as well as optimizing water resource management. In this study, we propose a Runoff Process Vectorization (RPV) method and integrate it with three Deep Learning (DL) models, namely Long Short-Term Memory (LSTM), Temporal Convolutional Network (TCN), and Transformer, to develop a series of RPV-DL flood forecasting models, namely RPV-LSTM, RPV-TCN, and RPV-Transformer models. The models are evaluated using observed flood runoff data from nine typical basins in the middle Yellow River region. The key findings are as follows: Under the same lead time conditions, the RPV-DL models outperform the DL models in terms of Nash-Sutcliffe efficiency coefficient, root mean square error, and relative error for peak flows in the nine typical basins of the middle Yellow River region. Based on the comprehensive evaluation results of the train and test periods, the RPV-DL model outperforms the DL model by an average of 2.82%-22.21% in terms of NSE across nine basins, with RMSE and RE reductions of 10.86-28.81% and 36.14%-51.35%, respectively. The vectorization method significantly improves the accuracy of DL flood forecasting, and the RPV-DL models exhibit better predictive performance, particularly when the lead time is 4h-6h. When the lead time is 4-6h, the percentage improvement in NSE is 9.77%, 15.07%, and 17.94%. The RPV-TCN model shows superior performance in overcoming forecast errors among the nine basins. The research findings provide scientific evidence for flood prevention and mitigation efforts in river basins.

Interpretable baseflow segmentation and prediction based on numerical experiments and deep learning.

Baseflow is a crucial water source in the inland river basins of high-cold mountainous region, playing a significant role in maintaining runoff stability. It is challenging to select the most suitable baseflow separation method in data-scarce high-cold mountainous region and to evaluate effects of climate factors and underlying surface changes on baseflow variability and seasonal distribution characteristics. Here we attempt to address how meteorological factors and underlying surface changes affect baseflow using the Grey Wolf Optimizer Digital Filter Method (GWO-DFM) for rapid baseflow separation and the Long Short-Term Memory (LSTM) neural network model for baseflow prediction, clarifying interpretability of the LSTM model in baseflow forecasting. The proposed method was successfully implemented using a 63-year time series (1958-2020) of flow data from the Tai Lan River (TLR) basin in the high-cold mountainous region, along with 21 years of ERA5-land meteorological data and MODIS data (2000-2020). The results indicate that: (1) GWO-DFM can rapidly identify the optimal filtering parameters. It employs the arithmetic average of three methods, namely Chapman, Chapman-Maxwell and Eckhardt filter, as the best baseflow separation approach for the TLR basin. Additionally, the baseflow significantly increases after the second mutation of the baseflow rate. (2) Baseflow sources are mainly influenced by precipitation infiltration, glacier frozen soil layers, and seasonal ponding. (3) Solar radiation, temperature, precipitation, and NDVI are the primary factors influencing baseflow changes, with Nash-Sutcliffe efficiency coefficients exceeding 0.78 in both the LSTM model training and prediction periods. (4) Changes in baseflow are most influenced by solar radiation, temperature, and NDVI. This study systematically analyzes the changes in baseflow and response mechanisms in high-cold mountainous region, contributing to the management of water resources in mountainous basins under changing environmental conditions.

Effects of low protein diets on acid-base balance, electrolyte balance, intestinal structure, and amino acid transport in piglets.

Reducing the dietary crude protein (CP) could effectively reduce pressure on protein ingredient supplies. However, few data have been reported about the extent to which CP can be reduced and whether limiting the use of soybean meal leads to electrolyte imbalance. In this experiment, using the low protein (LP) diet [2% lower than NRC (2012)], seventy-two piglets (35 days old) were randomly divided into 2 groups with 6 replicates of 6 piglets each: CON group (CP = 18.5%) and LP group (CP = 16.5%), to investigate the effect of the LP diet on electrolyte balance, acid-base balance, intestinal structure and amino acid transport in piglets. The results revealed that the LP diet decreased the average daily gain and dietary CP digestibility, and damaged the villi structure of the small intestine. Compared with the CON diet, the potassium content decreased and the chlorine content increased in the LP diet, and similar trends were shown in piglet serum. The arterial pH, pCO2, HCO3 -, and base excess of piglets in the LP group were lower than those in the CON group, while pO2 was higher than those in the CON group. Interestingly, the LP diet significantly increased the lysine content in piglet serum and significantly decreased the levels of arginine, leucine, and glutamic acid. Furthermore, the LP diet significantly affected the expression of some amino acid transport vectors (B0AT1, EAAC1, and y+LAT1). In summary, these findings suggested that the LP diet leads to acid-base imbalance, amino acid transport disorder and amino acids imbalance in piglets, and the dietary electrolyte may be a key factor in the impact of the LP diet on piglet growth performance and intestinal health.

The role of self-esteem and emotion regulation in the associations between childhood trauma and mental health in adulthood: a moderated mediation model.

BACKGROUND: High levels of childhood trauma (CT) have been observed in adults with mental health problems. Herein, we investigated whether self-esteem (SE) and emotion regulation strategies (cognitive reappraisal (CR) and expressive suppression (ES)) affect the association between CT and mental health in adulthood, including depression and anxiety symptoms. METHODS: We performed a cross-sectional study of 6057 individuals (39.99% women, median age = 34 y), recruited across China via the internet, who completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Childhood Trauma Questionnaire (CTQ), Self-esteem Scale (SES), and Emotion Regulation Questionnaire (ERQ). Multivariate linear regression analysis and bias-corrected percentile bootstrap methodologies were used to assess the mediating effect of SE, and hierarchical regression analysis and subgroup approach were performed to examine the moderating effects of emotion regulation strategies. RESULTS: After controlling for age and sex, we found that (1) SE mediated the associations between CT and depression symptoms in adulthood (indirect effect = 0.05, 95% confidence interval [CI]: 0.04-0.05, 36.2% mediated), and CT and anxiety symptoms in adulthood (indirect effect = 0.03, 95% CI: 0.03-0.04, 32.0% mediated); (2) CR moderated the association between CT and SE; and (3) ES moderated the association between of CT and mental health in adulthood via SE, and such that both the CT-SE and SE-mental health pathways were stronger when ES is high rather than low, resulting the indirect effect was stronger for high ES than for low ES. CONCLUSIONS: These findings suggested that SE plays a partially mediating role in the association between CT and mental health in adulthood. Furthermore, ES aggravated the negative effect of CT on mental health in adulthood via SE. Interventions such as emotional expression training may help reduce the detrimental effects of CT on mental health. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn/index.aspx and the registration number was ChiCTR2200059155.

BK-SWMM flood simulation framework is being proposed for urban storm flood modeling based on uncertainty parameter crowdsourcing data from a single functional region.

In recent years, urban flood disasters caused by sudden heavy rains have become increasingly severe, posing a serious threat to urban public infrastructure and the life and property safety of residents. Rapid simulation and prediction of urban rain-flood events can provide timely decision-making reference for urban flood control and disaster reduction. The complex and arduous calibration process of urban rain-flood models has been identified as a major obstacle affecting the efficiency and accuracy of simulation and prediction. This study proposes a multi-scale urban rain-flood model rapid construction method framework, BK-SWMM, focusing on urban rain-flood model parameters and based on the basic architecture of Storm Water Management Model (SWMM). The framework comprises two main components: 1) constructing a SWMM uncertainty parameter sample crowdsourcing dataset and coupling Bayesian Information Criterion (BIC) and K-means clustering machine learning algorithm to discover clustering patterns of SWMM model uncertainty parameters in urban functional areas; 2) coupling BIC and K-means with SWMM model to form BK-SWMM flood simulation framework. The applicability of the proposed framework is validated by modeling three different spatial scales in the study regions based on observed rainfall-runoff data. The research findings indicate that the distribution pattern of uncertainty parameters, such as depression storage, surface Manning coefficient, infiltration rate, and attenuation coefficient. The distribution patterns of these seven parameters in urban functional zones indicate that the values are highest in the Industrial and Commercial Areas (ICA), followed by Residential Areas (RA), and lowest in Public Areas (PA). All three spatial scales' REQ, NSEQ, and RD2 indices were superior to the SWMM and less than 10%, greater than 0.80, and greater than 0.85, respectively. However, when the study area's geographical scale expands, the simulation's accuracy will decline. Further research is required on the scale dependency of urban storm flood models.

Potential of circulating lncRNA CASC2 as a biomarker in reflecting the inflammatory cytokines, multi-organ dysfunction, disease severity, and mortality in sepsis patients.

BACKGROUND: Long noncoding RNA (lncRNA) cancer susceptibility candidate gene 2 (CASC2) inhibits inflammation and multi-organ dysfunction in various ways. The present study was intended to explore the potency of blood lncRNA CASC2 as a biomarker for sepsis management. METHODS: Totally, 184 sepsis patients and 30 healthy controls were enrolled. The reverse transcription-quantitative polymerase chain reaction was used to detect lncRNA CASC2 expression in peripheral blood mononuclear cell samples from the subjects. Mortality during 28 days was recorded in sepsis patients. RESULTS: LncRNA CASC2 was decreased in sepsis patients [median (interquartile range [IQR]): 0.473 (0.241-0.773)] by comparison to healthy controls [median (IQR): 1.019 (0.676-1.685)] (p < 0.001). In sepsis patients, lncRNA CASC2 was negatively correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) (p = 0.001), Sequential Organ Failure Assessment (SOFA) (p < 0.001), SOFA-respiratory system (p = 0.010), SOFA-coagulation (p = 0.020), SOFA-liver (p = 0.019), and SOFA-renal (p = 0.010) scores, but was not related to SOFA-nervous (p = 0.466) and SOFA-cardio vascular system (p = 0.059) scores. Additionally, lncRNA CASC2 was negatively related to tumor necrosis factor-α (p = 0.024), interleukin (IL)-1ß (p = 0.013), and IL-17A (p = 0.002), but was not linked to IL-6 (p = 0.112) or IL-10 (p = 0.074). Furthermore, lncRNA CASC2 was lower in sepsis deaths [median (IQR): 0.286 (0.166-0.475)] than in survivors [median (IQR): 0.534 (0.296-0.811)] (p < 0.001). Simultaneously, Kaplan-Meier (KM) curve analysis also observed that lncRNA CASC2 was inversely related to accumulating mortality in sepsis patients (p = 0.003). While lncRNA CASC2 could independently predict lower mortality risk. CONCLUSION: Circulating lncRNA CASC2 inadequacy indicates the release of inflammatory cytokines, severe multi-organ injuries, and increased mortality in sepsis patients.

Efficacy of atezolizumab to treat non-small-cell lung cancer: a meta-analysis based on randomized clinical trials.

Purpose: Atezolizumab, an immunoglobulin G1 monoclonal antibody against PD-L1, is accepted to treat advanced non-small-cell lung cancer (NSCLC). Our systematic review aims to evaluate survival efficacy of atezolizumab, overall and in subgroups defined by PD-L1 expression. Materials and Methods: Search the trials on efficacy of atezolizumab in advanced NSCLC based on online electronic databases from their dates of inception up to June 2019, including PubMed, Embase and Cochrane library databases. After rigorous reviewing of quality, the data of the PFS and OS were measured as outcomes. Results: Six trials including seven researches were included. Overall, 4722 subjects involving 2488 patients received atezolizumab and 2234 patients received investigator's choice chemotherapy were retrieved. For the intention-to-treat (ITT) population, the pooled ORs for overall survival (OS) was 0.81 (95 % confidence interval [CI] 0.75-0.87; P<0.00001) and progression-free survival benefit (PFS) was 0.65 (95 % CI 0.59-0.73; P<0.00001), respectively. For the subgroups PD-L1 expression (negative and high), there were benefits both observed in the PFS and OS in two sub-groups with atezolizumab (P 0.05). However, in the low expression of PD-L1 group, the subjects who received atezolizumab achieved PFS (OR 0.70; 95% CI: 0.58-0.84, P=0.0002) advantage but OS advantage (OR 0.91; 95% CI: 0.62-1.33, P=0.62). Conclusion: In low expression of PD-L1 subgroups, a benefit was observed for PFS but OS. However, the status of PD-L1 expression cannot be recommend as prognostic biomarker to support the decision who will benefit from atezolizumab.

Dietary copper/zinc-loaded montmorillonite improved growth performance and intestinal barrier and changed gut microbiota in weaned piglets.

The effects of copper/zinc-loaded montmorillonite (Cu/Zn-Mt) on growth performance, intestinal barrier and gut microbiota of weaned pigs were investigated in the present study. A total of 108 piglets (Duroc × Landrace × Yorkshire; 6.36 kg; weaned at 21 ± 1 d age) were used in this experiment. The pigs were randomly assigned to three treatments with six replicates, six pigs in each replicate. The three treatments were as follows: (1) control group: basal diet; (2) Cu/Zn-Mt group: basal diet supplemented with 39 mg/kg Cu and 75 mg/kg Zn as Cu/Zn-Mt; and (3) Cu +Zn +Mt group: basal diet supplemented with the mixture of copper sulphate, zinc sulphate and montmorillonite (equivalent to the copper and zinc in the Cu/Zn-Mt treatment). The results indicated that, compared with the pigs from control group, average daily gain and gain: feed ratio were increased and the faecal score on days 7 and 14 after weaning was decreased by supplementation of Cu/Zn-Mt; intestinal transepithelial electrical resistance (TER) and expressions of tight junction protein claudin-1 and zonula occludens-1 were increased, and intestinal permeability of fluorescein isothiocyanate-dextran 4 kDa was decreased by supplementation with Cu/Zn-Mt. According to the Illumina-based sequencing results, Cu/Zn-Mt supplementation increased the relative abundance of core bacteria (Lactococcus, Bacillus) at genus level and decreased the potentially pathogenic bacteria (Streptococcus and Pseudomonas) in colon of weaned piglets. However, the piglets fed with the mixture of copper sulphate, zinc sulphate and montmorillonite showed no effects in above parameters in comparison with the pigs from control group. In conclusion, dietary Cu/Zn-Mt could improve growth performance, decrease the diarrhoea and improve intestinal barrier and bacterial communities of weaned pigs. The results indicated that 'loading' of montmorillonite with Zn and Cu changed not only its chemical but also its nutritional properties.

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis-related interstitial lung diseases via TLR9-miR-7-Smad2 pathway.

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR-7 expression was down-regulated in lung tissue of PM group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were up-regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM-related ILD, and TLR9-miR-7-Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.

Clinicopathological evidence of hepatitis B virus infection in the development of gastric adenocarcinoma.

Gastric cancer (GC) is one of the infection-related cancers. Helicobacter pylori and Epstein-Barr virus (EBV) were established risk factors for GC. Recently, there are several reports showing the inconsistent association between hepatitis B virus (HBV) infection and the development of GC. To explore the relationship between HBV infection and the development of GC, we designed a meta-analysis of previous epidemiological studies, a hospital-based case-control study, followed by an immunohistochemistry (IHC) assay of HBV-exposed GC samples. We found that HBV infection was associated with an increased risk of GC based on the meta-analysis. No significant association between HBV infection and GC was detected according to our hospital-based case-control study. Histological examination showed that the gastric epithelium positive for HBx demonstrated a higher nuclear-cytoplasmic ratio compared to those HBx-negative cells. HBx and HBcAg were expressed more in tumors than those in normal counterparts in HBV-exposed subjects, and PD-L1 was lower in GC tissues from HBV carriers than those in HBV clearances. In conclusion, HBV infection may contribute to a higher risk for GC based on the meta-analysis and to the morphological atypia of gastric epithelium by the histological assessment, and GC patients among HBV carriers showed lower expression of PD-L1 may lose the chance for immune checkpoint blockade therapy.

ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism.

Previously we reported that ErbB4 played a protective role in chronic liver injury and hepatocellular carcinoma. Herein, we examined the role of ErbB4 in the development of colitis-associated cancer (CAC) in ErbB4 knockout mice models, in vitro cell lines and clinical samples. We found that ErbB4 deficiency may lead to more severe inflammation, slower recovery and the development of CAC. Further, loss of ErbB4 could activate Kras by upregulating rate-limiting enzymes in cholesterol metabolism pathway through interacting with the transcription factor Srebf1. In clinic samples, ErbB4 is downregulated in colonic tissues from patients with Crohn's disease. And data from The Cancer Genome Atlas also showed significant negative correlation between ErbB4 and several cholesterol metabolic enzymes. In summary, our study uncovers ErbB4 as a protector in the development of CAC, for its loss could activate Kras by upregulating cholesterol metabolism.

Copper-Containing Nitrite Reductase Employing Proton-Coupled Spin-Exchanged Electron-Transfer and Multiproton Synchronized Transfer to Reduce Nitrite.

The possible catalytic mechanism of the reduction of nitrite by copper-containing nitrite reductases (CuNiRs) is examined by using the M06 function according to two copper models, which include type-one copper (T1Cu) and type-two copper (T2Cu) sites. Examinations confirm that the protonation of two residues, His255 and Asp98, near the T2Cu site, can modulate the redox states of T1Cu and T2Cu, but cannot directly cause electron transfer from T1Cu to T2Cu. The electron hole remains at the T2Cu site when only one residue, His255 or Asp98, is protonated. However, the hole resides at the T1Cu site when both His255 and Asp98 are protonated. Then, the first protonation of nitrite takes place through indirect proton transfer from protonated His255 through the bridging H2 O and Asp98 with three protons moving together, which cannot cause the cleavage of the HO-NO bond. Subsequently, the substrate is required to obtain another proton from reprotonated His255 through the bridging H2 O. The reprotonation of nitrite induces the generation of nitric oxide (NO) and H2 O at the T2Cu site through a special double-proton-coupled spin-exchanged electron-transfer mechanism with indirect proton transfer from His255 to the substrate, a beta-electron of T2CuI shift to the NO cation, and the remaining alpha-electron changing spin direction at the same time. These results may provide useful information to better understand detailed proton-/electron-transfer reactions for the catalytic processes of CuNiR.

Whey protein concentrate enhances intestinal integrity and influences transforming growth factor-ß1 and mitogen-activated protein kinase signalling pathways in piglets after lipopolysaccharide challenge.

Whey protein concentrate (WPC) has been reported to have protective effects on the intestinal barrier. However, the molecular mechanisms involved are not fully elucidated. Transforming growth factor-ß1 (TGF-ß1) is an important component in the WPC, but whether TGF-ß1 plays a role in these processes is not clear. The aim of this study was to investigate the protective effects of WPC on the intestinal epithelial barrier as well as whether TGF-ß1 is involved in these protection processes in a piglet model after lipopolysaccharide (LPS) challenge. In total, eighteen weanling pigs were randomly allocated to one of the following three treatment groups: (1) non-challenged control and control diet; (2) LPS-challenged control and control diet; (3) LPS+5 %WPC diet. After 19 d of feeding with control or 5 %WPC diets, pigs were injected with LPS or saline. At 4 h after injection, pigs were killed to harvest jejunal samples. The results showed that WPC improved (P<0·05) intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, which was reflected by increased transepithelial electrical resistance and decreased mucosal-to-serosal paracellular flux of dextran (4 kDa), compared with the LPS group. Moreover, WPC prevented the LPS-induced decrease (P<0·05) in claudin-1, occludin and zonula occludens-1 expressions in the jejunal mucosae. WPC also attenuated intestinal inflammation, indicated by decreased (P<0·05) mRNA expressions of TNF-α, IL-6, IL-8 and IL-1ß. Supplementation with WPC also increased (P<0·05) TGF-ß1 protein, phosphorylated-Smad2 expression and Smad4 and Smad7 mRNA expressions and decreased (P<0·05) the ratios of the phosphorylated to total c-jun N-terminal kinase (JNK) and p38 (phospho-JNK:JNK and p-p38:p38), whereas it increased (P<0·05) the ratio of extracellular signal-regulated kinase (ERK) (phospho-ERK:ERK). Collectively, these results suggest that dietary inclusion of WPC attenuates the LPS-induced intestinal injury by improving mucosal barrier function, alleviating intestinal inflammation and influencing TGF-ß1 canonical Smad and mitogen-activated protein kinase signalling pathways.

An ecological compensation standard based on emergy theory for the Xiao Honghe River Basin.

The calculation of an ecological compensation standard is an important, but also difficult aspect of current ecological compensation research. In this paper, the factors affecting the ecological-economic system in the Xiao Honghe River Basin, China, including the flow of energy, materials, and money, were calculated using the emergy analysis method. A consideration of the relationships between the ecological-economic value of water resources and ecological compensation allowed the ecological-economic value to be calculated. On this basis, the amount of water needed for dilution was used to develop a calculation model for the ecological compensation standard of the basin. Using the Xiao Honghe River Basin as an example, the value of water resources and the ecological compensation standard were calculated using this model according to the emission levels of the main pollutant in the basin, chemical oxygen demand. The compensation standards calculated for the research areas in Xipin, Shangcai, Pingyu, and Xincai were 34.91 yuan/m3, 32.97 yuan/m3, 35.99 yuan/m3, and 34.70 yuan/m3, respectively, and such research output would help to generate and support new approaches to the long-term ecological protection of the basin and improvement of the ecological compensation system.