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Abstract Oral tolerance is essential for intestinal homeostasis and systemic immune function. However, our understanding of how oral tolerance is maintained is inadequate. Here we report that food-derived nucleic acids promote oral tolerance through innate sensing pathways. We find that dietary nucleic acids, but not microbiota, expand the natural intraepithelial lymphocyte (IEL) pool, specifically in the small intestine. TGF-β1, produced by natural IELs, then promotes activation of gut CD103+ dendritic cells to support the induction of antigen-specific Treg cells in a mouse model of OVA-induced oral tolerance. Mechanistically, MAVS and STING are redundantly required for sensing dietary RNAs and DNAs to activate downstream TBK1 signalling to induce IL-15 production, which results in the accumulation of natural IELs. Thus, our study demonstrates a key role of food-triggered innate sensing pathways in the maintenance of natural IELs and oral tolerance.

Abstract Background Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. Methods We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model’s prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. Results We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we’ve discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. Conclusion As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.

Abstract Congenital heart defects (CHDs) represent one of the most prevalent categories of neonatal defects, and maternal dietary patterns have been linked to the risk of these conditions. Branched‐chain amino acids (BCAAs), particularly leucine, are essential for various metabolic and physiological processes involved in heart development. In this study, we examined the molecular mechanisms through which elevated levels of leucine induce defects in cardiac microvascular endothelial cells. We collected plasma samples from healthy controls and neonatal patients with CHDs, employed a high‐leucine diet for pregnant female mice, and applied high‐leucine treatment in human cardiac microvascular endothelial cells (HCMECs). The impacts of high‐leucine levels on WD Repeat Containing Planar Cell Polarity Effector (WDPCP)/MAPK signaling axis were investigated in the cell and animal models. We reported heightened plasma leucine levels in neonatal patients with CHDs and observed that a high‐leucine diet in pregnant mice was associated with reduced expression of WDPCP and attenuated MAPK/ERK signaling. High‐leucine treatment in HCMECs impaired epithelial‐mesenchymal transition (EMT) and cell migration; however, overexpression of WDPCP or activation of MAPK exhibited a rescue effect. The upregulation of endomucin (EMCN) under high‐leucine conditions contributed to the impaired EMT and migratory capacity of HCMECs, and the WDPCP/MAPK signaling axis regulated EMCN overexpression in response to high‐leucine treatment. High levels of leucine in neonatal patients with CHDs may inhibit the WDPCP/MAPK axis, leading to an increase in EMCN expression that undermines the function of cardiac microvascular endothelial cells. These findings suggest the potential of targeting the WDPCP/MAPK axis as an intervention strategy for neonatal CHDs.

Abstract Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven’t been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ − 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child–Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child–Pugh classification.

Owing to the high hydrocarbon content and photosynthetic efficiency of phytoplankton, planktonic microalgae account for the main source of petroleum hydrocarbons in marine and continental petroliferous basins. Therefore, the presence of algal residues in such basins is considered an important indicator of high-quality hydrocarbon source rocks. The southwestern region of the Qaidam Basin, characterized by lacustrine deposits from the Paleogene, has substantial petroleum resources. However, studies on the development of source rocks and the mechanisms involved in their organic matter enrichment are insufficient, thus hampering ongoing shale oil exploration efforts. Herein, abundant Botryococcus fossils were discovered in the main source rocks of the upper member of Xiaganchaigou Formation of Paleogene in Southwest Qaidam, accounting for >50 % of the total organic matter content. The palynofacies assemblages reflected relatively distal and oxygen-rich sedimentary environments. The algae-rich rocks usually exhibited distinctive laminated structures alternately composed of quartz-feldspathic, clay and carbonate laminae, indicating periodic climate fluctuations. The Botryococcus, which was mainly preserved in the coarse-grain quartz-feldspathic laminae, probably reflected heavy precipitation conditions and subsequently high nutrient inputs. Finally, the oxygen-rich, low salinity and eutrophic water was likely taking form which benefit the growth of these hydrobiontic algae. These algal-rich shales exhibited typically high hydrogen index (IH) and total organic carbon (TOC) values, indicating their high hydrocarbon-generation potential. Thus, they are important marker beds for high-quality source rocks in petroliferous basins. Concurrently, the coarse-grained detrital mineral laminae displayed excellent reservoir physical properties, probably providing sufficient reservoir space for planktonic algae-derived liquid hydrocarbon. Therefore, these Botryococcus-rich source rocks might represent important targets for ongoing shale oil exploration.

The refinement of embryo culture media is essential in improving embryo viability and in vitro production efficiency. Our previous work demonstrated that the nutrients (carbohydrates, amino acids, and vitamins) in traditional culture media far exceed the need for an embryo and producing developmentally competent embryos in a reduced nutrient environment is feasible. Here, we aim to evaluate the impact of exogenous lipid and l-carnitine supplementation on bovine blastocyst development and refine our RN condition further. Zygotes were cultured in the control medium (100% nutrients) and reduced nutrient media containing 6.25% of the standard nutrient concentrations supplemented with l-carnitine and lipid-free or lipid-rich BSA. Increased blastocyst development was observed in the reduced nutrient lipid-rich medium compared to the other two groups. However, in both reduced nutrient conditions, blastocyst cell numbers were lower than those obtained in the control condition. We then examined the expression level of 18 transcripts correlated with lipid metabolism, glucose metabolism, redox balance, and embryo quality, along with mitochondrial DNA copy numbers, ATP productions, and lipid profile. The results indicated that lipid metabolism, embryo quality, and redox enzyme-related genes were upregulated while the glucose-related gene was downregulated in embryos derived from reduced nutrient lipid-rich condition. Finally, we identified that the lipid-rich BSA has enriched linoleic, stearic, oleic, palmitic, and alpha-linoleic fatty acids, a lipid profile that may contribute to the increased lipid metabolism and improved blastocyst development of the bovine embryos under the reduced nutrient condition.

Tidal creeks play a crucial role in lateral transport of carbon and nutrients from tidal salt marshes. However, the specific impact of tidal creek development on carbon and nutrient distribution within the marsh remains poorly understood. The objective of this study is to assess the influence of lateral tidal flooding through the tidal creeks on the spatial distribution of carbon and nitrogen fractions in the soils of a Chinese temperate salt marsh. We conducted a comprehensive analysis of the relative variations in different carbon and nitrogen fractions, along with soil physicochemical and microbial indicators, between the bank soil of the tidal creek and its lateral inland soils across high, middle, and low flats. Our findings highlight that tidal creek development significantly affects the middle flat, leading to substantial variations in organic carbon and total nitrogen. The low flat mainly experiences changes in dissolved inorganic carbon levels. Furthermore, a lateral increase in microbial biomass is observed in the middle flat, indicating that the significantly lower SOC in the middle flat might be ascribed to enhanced microbial decomposition. The lateral enrichment of dissolved inorganic carbon in the low flat is possibly related to the nearshore location and/or abiotic adsorption in inorganic carbon sequestration. Overall, this study demonstrates the critical role of tidal creek development in shaping the distribution patterns of carbon and nitrogen fractions in tidal salt marshes.

Abstract Photocatalytic CO2 reduction plays an important role in solar energy storage and carbon balance. GaN as an III‐V semiconductor material has received extensive attention in the field of photocatalysis. In this study, the porous indium‐doped GaN (In/GaN) micro‐rods are synthesized successfully by a facile hydrothermal method and subsequent controlled atmosphere heat treatment. Photocatalytic CO2 reduction performance of In/GaN is higher than that of pure GaN due to the In doping improves the light absorption efficiency. The primary products are CO and CH4. Among the samples, 3%‐In/GaN exhibits the highest catalytic activity as well as stability and reusability. The yield rates of CO and CH4 can be reached 50.2 and 14.6 µmol · g−1 · h−1, respectively. Furthermore, density functional theory (DFT) calculations reveal that the bandgap is narrowed and the adsorption energy of CO2 molecules is improved by In doping. Moreover, the N‐vacancy detected by electron paramagnetic resonance (EPR) increases with the In doping, resulting in an increase in the number of unpaired electrons, which is conducive to carrier transport. This work provides a new study In/GaN prepared by simple method for the light‐driven photocatalytic conversion of CO2 to high‐value‐added products.

This study focuses on the optimization of consequence management actions in the urban water distribution network. The EPANET simulation model is employed in combination with the multi-objective modified seagull optimization algorithm (MOMSOA) based on archives for a more efficient optimization process. Two objective functions are developed: minimizing reactive activities (cost reduction) and minimizing consumed pollution mass. The utilization of shut-off valves and hydrants for isolating the network and discharging pollution is explored. Without consequence management, 84.5 kg of pollution is consumed. With 18 reactive activities, pollution consumption was reduced to 59.8 kg. Also, to compare the proposed method with other algorithms, the interaction curve between reactive activities and the amount of pollutant mass consumed was obtained using other methods, including MOSOA, NSGA-II, MOPSO, and MOSMA. According to the obtained curve, the proposed method performed better in reducing the mass of consumed pollution. Extracting optimal activities using MOMSOA and a maximum of 18 activities takes about 80 min. The MOMSOA with archive technique significantly shortens this time for real-time consequence management. The proposed approach demonstrates that increasing the archive population decreases the extraction time of interaction curves between objectives by up to 60 %. A small archive capacity slightly increases the time required to extract optimal activities due to searching for similar solutions. However, utilizing the archive capacity enables real-time optimization and consequence management in the network.

Abstract Effect of microstructure on the formability of the stainless sheet metals is a major concern for engineers in sheet industries. In the case of austenitic steels, existence of strain-induced martensite ( $${\alpha }^{^{\prime}}$$ α ′ -martensite) in their micro structure causes considerable hardening and formability reduction. In the present study, we aim to evaluate the formability of AISI 316 steels with different intensities of martensite via experimental and artificial intelligence methods. In the first step, AISI 316 grade steels with 2 mm initial thicknesses are annealed and cold rolled to various thicknesses. Subsequently, the relative area of strain-induced martensite are measured using metallography tests. Formability of the rolled sheets are determined using hemisphere punch test to obtain forming limit diagrams (FLDs). The data obtained from experiments were further utilized to train and validate an artificial neural fuzzy interfere system (ANFIS). After training the ANFIS, predicted major strains by the neural network are compared to a new set experimental results. The results indicate that cold rolling has unfavorable effects on the formability of this type of stainless steels while significantly strengthens the sheets. Moreover, the ANFIS exhibits satisfactory results in comparison to the experimental measurements.

Background and purposeDiabetes mellitus (DM) is a well-established cardiovascular risk factor for atherosclerotic disease; however, its effect on the risk of rupture of intracranial aneurysms remains controversial. Herein, we aimed to perform a case–control study to investigate the relationship between DM and aneurysmal subarachnoid hemorrhage (aSAH).MethodsWe retrospectively reviewed the data of patients with ruptured or unruptured aneurysms who were treated between 2013 and 2023. Univariate and multivariate analyses were performed. Propensity score matching (PSM) analysis was conducted to evaluate the relationship between DM and risk of aSAH.ResultsA total of 4,787 patients with 5,768 intracranial aneurysms were included. Among them, 2,957 (61.8%) were females, 1765 (36.9%) had ruptured aneurysms, and 531 (11.1%) presented with DM. Female sex, current drinking, and hypercholesterolemia were associated with a higher risk of aSAH, whereas old age, former smoking, and DM were associated with a lower risk of aSAH in multivariate analysis (p

Summary: ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.

Seed dispersal is a key process in the conservation of coastal wetland vegetation. In this study, we selected a typical plant of the Yellow River Delta, namely, Suaeda salsa, to explore its dispersal process and environmental impact factors. The seed flow of S. salsa gradually increased along the direction from the sea to the inland, and the seed flow in the supratidal zone was significantly greater than that in the intertidal and subtidal zones. Seed germination in the subtidal zone was the smallest, whereas the intertidal zone was the largest. Different tidal zones also had significant effects on seed germination. In addition, by analyzing the relationship among tidal inundation frequency, inundation depth, distance from the tidal channel, elevation, soil water and salinity, and seed flow and germination, the influence of tides was more significant than microtopography as well as soil water and salinity. In coastal wetlands, tides were the key factor affecting seed dispersal. In particular, seed flow and germination decreased with the increase of tidal inundation frequency and depth, but they were inhibited by the strengthening of tides within a certain range. Overall, different tidal zones should be selected for the recovery of different stages of seed dispersal and germination, while also taking tidal characteristics into account.

The invasion of Spartina alterniflora has threatened and damaged coastal wetlands in China, therefore, control and removal of this severe invasive plant are urgently needed. Green chemical control is an effective and low-cost method that can be used for large-scale removal of invasive specie. To study the control effect of imazapyr on S. alterniflora and evaluate its impact on other species and the wetland environment, a control experiment was set up in the Yellow River Delta Reserve in Shandong Province in May 2021. A total of 9 treatments were set up in the experiment: 25 % (W) imazapyr water (main agent), three treatments with dose gradients of 3.0, 6.0, and 9.0 L/acre, and the main agent at a dose of 6.0 L/acre with six treatments of AGE 809 (adjuvant A) and AGE 852 (adjuvant B) with dose gradients of 1.3, 2.6, and 5.2 L/acre, respectively. The results showed that after 60 days of application, the control efficiency of Spartina alterniflora was over 90 %, and the residual amount was small in the plots with the main agent additive

Smooth cordgrass (Spartina alterniflora) introduced to China in 1970 s for coastline stabilization threatening the habitat range of native Phragmites australis and even become more adaptive than P. australis. Thus, we used electronic universal testing machine and Van Soest method to compare the morphological and biomechanical responses of these two species to wave interference in the Yellow River Delta, east China. Our study showed that the morphological response of P. australis was more sensitive to waves with shorter individuals in wave zones but larger stem diameter and higher biomass than those in none-wave zones, while S. alterniflora did not exhibit such variations. In wave zones, S. alterniflora invaded P. australis’ habitat regardless higher stem-bending resistance of P. australis with excessive energy allocated in stem growth while decreasing reproduction and fitness. Compared with the none-wave zones, S. alterniflora allocated excessive energy in the stem to resist wind interference, and they are less fitted than P. australis. Thus, economic energy allocation to wave mechanical interference contributed to the successful invasion of S. alterniflora to landward in estuaries. S. alterniflora continued to expand landward in a semi-saline area but the community pattern may maintain the status quo for areas with low salinity and high wave interference.

BackgroundAnastomotic leakage is a life-threatening complication. Improvement of the anastomosis technique is needed, especially in patients with an inflamed edematous intestine. The aim of our study was to evaluate the safety and efficacy of an asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis in pediatric patients.MethodsA total of 23 patients underwent intestinal anastomosis at the Department of Pediatric Surgery of Binzhou Medical University Hospital. Demographic characteristics, laboratory parameters, anastomosis time, duration of nasogastric tube placement, day of first postoperative bowel movement, complications, and length of hospital stay were statistically analyzed. The follow-up was conducted for 3–6 months after discharge.ResultsPatients were divided into two groups: the single-layer asymmetric figure-of-eight suture technique (group 1) and the traditional suture technique (group 2). Body mass index in group 1 was lower than in group 2 (14.43 ± 3.23 vs. 19.38 ± 6.74; P = 0.036). The mean intestine anastomosis time in group 1 (18.83 ± 0.83 min) was less than that in group 2 (22.70 ± 4.11 min; P = 0.005). Patients in group 1 had an earlier first postoperative bowel movement (2.17 ± 0.72 vs. 2.80 ± 0.42; P = 0.023). The duration of nasogastric tube placement in group 1 was shorter than that in group 2 (4.12 ± 1.42 vs. 5.60 ± 1.57; P = 0.043). There was no significant difference in laboratory variables, complication occurrence, and length of hospital stay between the two groups.ConclusionThe asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis was feasible and effective. More studies are needed to compare the novel technique with the traditional single-layer suture.

Abstract Dopamine (DA) and uric acid (UA) are biomolecules of great consideration that coexist in human body. It is essential and challenging to detect them simultaneously with high sensitivity. This paper reports a novel electrochemical biosensor based on the nanocomposites of cobalt phthalocyanine (CoPc) anchored with graphene quantum dots (GQDs) for DA and UA detection. The GQDs incorporation on CoPc nanorods with partial end stretching significantly enhances the electrocatalytic activity and promotes the electron transfer rate. Low detection limits of 21 nm for DA and 145 nm for UA have been successfully achieved for the fabricated CoPc/GQDs biosensor. The density‐functional theory proves the enhanced conductivity of CoPc/GQDs and the biomolecule's interaction with the electrode surface. Furthermore, the proposed sensor shows remarkable reproducibility, repeatability, and stability. The fabricated sensor is applied for the simultaneous detections of DA and UA in human urine samples. The excellent performance suggests that the CoPc/GQDs could be a promising and potential candidate for electrochemical sensors to detect DA and UA selectively.

Alterations in root hydraulics in response to varying moisture conditions remain a subject of debate. In our investigation, we subjected common reeds (Phragmites australis) to a 45-day treatment with four distinct soil moisture levels. The findings unveiled that, in response to drought stress, the total root length, surface area, volume, and average diameter exhibited varying degrees of reduction. Anatomically, drought caused a reduction in root diameter (RD), cortex thickness (CT), vessel diameter (VD), and root cross-sectional area (RCA). A decrease in soil moisture significantly reduced both whole- and single-root hydraulic conductivity (Lpwr, Lpsr). The total length, surface area, volume, and average diameter of the reed root system were significantly correlated with Lpwr, while RD, CT, and RCA were significantly correlated with Lpsr. A decrease in soil moisture content significantly influenced root morphological and anatomical characteristics, which, in turn, altered Lpr, and the transcriptome results suggest that this may be associated with the variation in the expression of abscisic acid (ABA) and aquaporins (AQPs) genes. Our initial findings address a gap in our understanding of reed hydraulics, offering fresh theoretical insights into how herbaceous plants respond to external stressors.

Precipitation is considered the most effective way to remove particulate matter from the leaves of plants. Changes in rainfall characteristics can affect the scavenging processes of particulate matter from leaves. In order to better understand the dynamics of PM scavenging during rainfall, especially the water-soluble ions components, leaves from the 11 plant species (trees, shrubs, terrestrial herbs, wetland plants) from the Olympic park were sampled and used in indoor experiments. During the experiments, the rainfall intensity was set at 30 mm/h, 45 mm/h, and 60 mm/h, and the duration was divided into 0–20 min, 20–40 min, and 40–60 min. The sampled plant leaves were set in the experiments at 1 m and 3 m height from the ground. Concentrations and compositions of nine water-soluble ions of rainfall samples were analyzed in this experiment. The results revealed that SO42-, Ca2+, and Na+ were the most abundant ionic species removed from the leaves, and NO3- ranked fourth, followed by Cl-, Mg2+ K+, NH4+, and F-. The ions concentration of rainfall samples decreased when the rain intensity increased from 30 to 45 mm/h and when the rain intensity increased to 60 mm/h. The efficiency of scavenging during different rainfall durations depends on the ionic species. Na+, Mg2+, Ca2+, and SO42- concentrations increased with the increase in rainfall duration, whereas those of NH4+, K+, and Cl- decreased. The effect of leaf height on ions concentration of rainfall samples was also different among the ionic species: Na+, Mg2+, Ca2+, NO3-, and F- concentrations were significantly higher at 1 m compared with 3 m. The principal component analysis of ions in rainfall samples revealed two main sources of particulate matter in our study. One is from vehicle exhaust and industrial and agricultural pollution. The other is agricultural combustion and ground dust sources. The results of the above study can provide a basis and theoretical support for the establishment of urban cleaning systems and the prevention of air pollution.

Three-point shooting plays an important role in determining the outcomes of basketball games and could be relevant for player selection. However, there has been little research into the relationship between basketball players’ physical capacities, metabolic capacities, and three-point shooting accuracy, particularly among female players. The aim of this study was to examine the relationship between physical capacities, metabolic capacities, and dynamic three-point shooting accuracy in female professional basketball players. Twelve female professional basketball players from the Women’s Chinese Basketball Association (WCBA) league (age: 19.04 ± 1.31 years, height: 181.33 ± 4.90 cm, playing experience: 7.83 ± 1.7 years) were recruited for this study. Pearson correlations and multiple linear regression analysis were run to assess the relationship between physical capacities, metabolic capacities, and dynamic three-point shooting. Results showed that coordination, balance, core strength, and relative average power were positively correlated with three-point shooting accuracy (r > 0.58, p < 0.05), while no other variables showed significant correlations. The current study suggests that coaching staff should consider coordination, balance, core strength, and anaerobic capacities when selecting players as well as in their training periodization if three-point shooting accuracy is considered relevant.

Assessment of soil quality in different vegetation types of wetland ecosystems is essential for soil functioning, such as nutrient cycling and vegetation growth, particularly the maintenance of wetland ecosystem sustainability. Wetland degradation can extremely influence soil quality. However, prediction of soil quality in terms of soil quality index in wetland soils remains obscure. In this study with the fundamental goal to assess soil quality, we have intended to assemble a range of soil quality indicators to characterize the soil quality index (SQI). The minimum data set (MDS) from the Principal component analysis (PCA) was used to determine the SQI. With such objectives, three vegetation types: Robinia pseudoacacia community (tree), Tamarix chinensis community (bush), and Suaeda salsa community (grass) were selected in the Yellow River Delta wetland, eastern of China. A total of 108 soil samples [3 sites (tree, bush and grass)—3 field plots—3 replicates—4 soil depth layers: 0–10 cm, 10–20 cm, 20–40 cm, and 40–60 cm] were collected for laboratory analyses. This study showed that there were high variations in soil physical and chemical properties among the three sites. Soil organic carbon (SOC), silt, clay, and pH at tree site, total soil porosity (TSP), soil organic carbon (SOC), pH, and soil bulk density (SBD) at bush site, and total soil porosity (TSP), silt, and soil electronic conductivity (SEC) at grass site were retained in the MDS. SOC and TSP were the key soil quality indicators. The values of the SQI at 0–10 cm soil depth at all three sites (2.236, 0.895, and 2.573 respectively) were the highest compared with other soil depths, indicating the best soil quality in the upper soil layers (0–10 cm). The values of the SQI at 0–10 cm soil depth at both tree site and grass site were similar, and they were higher than those at bush site. At tree site, the values of the SQI decreased with increasing soil depth, which indicated that soil quality became worse with depth. At bush site, the values of the SQI decreased with increasing soil depth (0–40 cm), while the values increased at 40–60 cm depth, indicating better soil quality in the deeper soil layers (40–60 cm). At grass site, the values of the SQI at 10–20 cm and 40–60 cm soil depth were lower than those at 20–40 cm soil depth, indicating better soil quality at 20–40 cm soil depth. It is concluded that the SQI can be compared more accurately in different vegetation types of wetland ecosystems based on its simplicity and quantitative flexibility. These findings are of importance because the assessment of the SQI allows to quantify different vegetation effects on soil quality.

Abstract Background Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear. Methods Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed. Results HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg. Conclusion Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment. Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530 .

Background: In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported. Methods: A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion. Results: The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r = 0.094, P = 0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC = 0.821). Conclusions: The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.

Abstract Background Nucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal. Methods/design The study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5 mg per day for consolidation therapy for 96 weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5 mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial. Conclusion This study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population. Trial registration Chinese Clinical Trial Registry No. ChiCTR1900021232 . Registered on February 2, 2019

ABSTRACT It is widely recognized that plant-symbiotic fungi are supported by photosynthates; however, little is known about the molecular mechanisms underlying the utilization of plant-derived sugars by rhizospheric fungi. In the insect-pathogenic and plant-symbiotic fungus Metarhizium robertsii, we previously showed that the utilization of oligosaccharides by the transporter MRT (Metarhizium raffinose transporter) is important for rhizosphere competency. In this study, we identified a novel monosaccharide transporter (MST1) that is involved in the colonization of the rhizoplane and acts additively with MRT to colonize the rhizosphere. MST1 is not involved in infection of insects by M. robertsii. MST1 is an H+ symporter and is able to transport a broad spectrum of monosaccharides, including glucose, sorbose, mannose, rhamnose, and fructose. Deletion of the Mst1 gene impaired germination and mycelial growth in medium containing the sugars that it can transport. Homologs of MST1 were widely found in many fungi, including plant symbionts such as Trichoderma spp. and mycorrhizal fungi and plant pathogens such as Fusarium spp. This work significantly advances insights into the development of symbiotic relationships between plants and fungi. IMPORTANCE Over 90% of all vascular plant species develop an intimate symbiosis with fungi, which has an enormous impact on terrestrial ecosystems. It is widely recognized that plant-symbiotic fungi are supported by photosynthates, but little is known about the mechanisms for fungi to utilize plant-derived carbon sources. In the fungus Metarhizium robertsii, we identified a novel monosaccharide transporter (MST1) that is an H+ symporter and can transport a broad spectrum of monosaccharides, including glucose, sorbose, mannose, rhamnose, and fructose. MST1 is involved in the colonization of the rhizoplane and acts additively with the previously characterized oligosaccharide transporter MRT to colonize the rhizosphere. Homologs of MST1 were found in many fungi, including plant symbionts and plant pathogens, suggesting that the utilization of plant-derived sugars by MST1 homologs could also be important for other fungi to develop a symbiotic or parasitic relationship with their respective plant hosts.

In this study, an innovative method was used to assess the spatial and temporal patterns of the hydrological connectivity in soil profiles in the Yellow River Delta wetland. In this method, field dye-tracing experiments conducted in the study area (i.e., large [LWa] and small communities [LWb] of Phragmites australis and Suaeda glauca [JP]) were considered, and the root-soil interface in the region and the status of the wetland degradation were analyzed. The results revealed that the index of hydrological connectivity (IHC) significantly changed both spatially and temporally. The high IHC values reaching a 0.392 ± 0.209 gradient were concentrated in the middle and western parts of the study areas. The spatial distribution of the high hydrological connectivity has been extremely fragmented since 2010. The LWb (severely degraded wetland) and JP (extremely degraded wetland) were found to be more seriously degraded than the LWa (moderately degraded wetland) in the study area. The changes in the IHC were positively correlated with the principal component (PC) values of the wetland degradation. The IHC is a novel indicator of the status of wetland degradation. Furthermore, the soil holding capacity, soil non-capacity porosity, and soil ventilation were relatively important for the changes in the IHC. Compared with the soil properties, the hydrological responses of the roots systems can be neglected at the root-soil interface. Based on our results, we propose an alternative wetland restoration solution for the Yellow River Delta wetland: 1) a seepage layer in the surface soils (0–10 cm), shallow ploughing treatment, and litter or straw return to the soil surface should be conducted to increase the hydrological connectivity of the soil surface; 2) reeds should not be reaped every year to remove the nutrients from this area; and 3) appropriate freshwater inputs should be strengthened.

Legume plants are pioneer species in desert ecosystem that can be used to reestablish degraded ecosystem functions and soil properties, and reshape underground microbial communities. However, the distribution in soil nutrients and bacterial communities after introducing leguminous shrubs have not been well described. Here, we quantified the variations in soil nutrients and bacterial communities in soil profiles (0–100 cm) across stand ages (5-year, 8-year, 15-year) and severe desertification (SD), and further investigated the bacterial contributions to soil nutrients during stand development. The total phosphorus (TP), total nitrogen (TN) and organic carbon (OC) contents significantly increased, whereas the available nitrogen (AN) and available phosphorus (AP) contents showed a downward trend across stand ages. Bacterial diversity increased after introducing leguminous shrubs. Vertical spatial variation of bacterial communities attenuated during stand development. Bacterial beta-diversity, specific microbial phyla (i.e., Proteobacteria and Firmicutes) and nitrification process were strongly associated with vertical spatial variation in soil nutrients. Combined analyses revealed that leguminous shrubs can ameliorate soil OC, TN and TP with increasing legumes growth time, but could still exhibit no facilitating effect on the improvement of soil available N and P even for legumes aged 15 years. Improving the bioavailability of nutrient elements and microbial function diversity could be targeted for further studies in arid barren sandy.

Management intensity was considered an important factor in evaluating and regulating the anthropogenic restoration measures for a degraded ecosystem. By comparing selected conventional soil physicochemical, microbial and incorporating aggregate-associated indices between wetland plot with high-intensity freshwater replenishment (HI wetlands) and wetland plot with low-intensity freshwater replenishment (LI wetlands), edaphic responses of degraded estuarine wetlands to freshwater replenishment at different intensity were assessed in the present study. The results showed that high-intensity freshwater replenishment exerted better soil salinization and alkalization alleviation effects on degraded estuarine wetlands, which caused lower EC and pH values in HI wetlands than those in LI wetlands. And soil microbial biomass was promoted, with freshwater replenishment intensity increased, as indicated by MBC and total PLFAs. Minor alternation of soil microbial community composition was observed with an elevated abundance of arbuscular mycorrhizal fungi (AMF) in HI wetlands. On the other hand, freshwater replenishment at low intensity was found to contribute to organic matter accumulation, as indicated by both higher SOC concentrations and carbon stocks in LI wetlands than those in HI wetlands. And soil aggregate-associated indicators provided more scientific clues that freshwater replenishment at low intensity favored the formation of large macroaggregates, and thus supported higher soil aggregate stability. Moreover, a transfer of allocations of aggregate-associated carbon and nitrogen stocks from microaggregates to large macroaggregates was induced as the freshwater replenishment intensity decreased, and the principle governing factors were the proportion of large macroaggregates in soils, soil salinity and microbial decomposition rates based on multivariate statistical analysis. The findings of this study could provide basic data regarding soil physicochemical properties, microbial characteristics and soil structure stability in restored wetlands of the Yellow River Delta with freshwater replenishment at different intensity and guiding adaptive management strategies of freshwater replenishment to enhance the ecological functions of estuarine wetlands.

Ascomycete fungi usually produce small hydrophobic asexual conidia that are easily dispersed and essential for long-term survival under a variety of environmental conditions. Several upstream signaling regulators have been documented to control conidiation via regulation of the central regulatory pathway that contains the transcription factors BrlA, AbaA and WetA. Here, we showed that the Slt2-MAPK signaling pathway and the transcription factor RNS1 constitute a novel upstream signaling cascade that activates the central regulatory pathway for conidiation in the Ascomycetes fungus M. robertsii. The BrlA gene has two overlapping transcripts BrlAα and BrlAβ; they have the same major ORF, but the 5’ UTR of BrlAβ is 835 bp longer than the one of BrlAα. During conidiation, Slt2 phosphorylates the serine residue at the position 306 in RNS1, which self-induces. RNS1 binds to the BM2 motif in the promoter of the BrlA gene and induces the expression of the transcript BlrAα, which in turn activates the expression of the genes AbaA and WetA. In conclusion, the Slt2/RNS1 cascade represents a novel upstream signaling pathway that initiates conidiation via direct activation of the central regulatory pathway. This work provides significant mechanistic insights into the production of asexual conidia in an Ascomycete fungus.

Abstract Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC = 0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.

With the rapid development of industry, studies on lead pollution in total suspended particulate matter (TSP) have received extensive attention. This paper analyzed the concentration and pollution sources of lead in the Cuihu Wetland in Beijing during the period of 2016–2017. The results show that the lead contents in TSP in the Cuihu Wetland were approximately equal in summer and spring, greater in winter, and greatest in autumn. The corresponding lead concentrations were 0.052, 0.053, 0.101, and 0.115 ng/m3, respectively. We compared the 206Pb/207Pb data with other materials to further understand the potential sources of atmospheric lead. The mean values of 206Pb/207Pb from spring to winter were 1.082, 1.098, 1.092, and 1.078, respectively. We found that the lead sources may be associated with coal burning, brake and tire wear, and vehicle exhaust emissions. We also calculated the enrichment factor values for the four seasons, and the values were all much greater than 10, indicating that the lead pollution is closely related to human activities.

Human infrastructure development drives habitat loss and fragmentation worldwide. In China, over the last 20 years, rapid infrastructure development impacted the habitats of endangered species. To facilitate conservation efforts, studies of how human infrastructure affects the distribution of Reeves’s pheasant (Syrmaticus reevesii), an endangered species by the International Union for Conservation of Nature (IUCN) and a nationally protected species in China, are critically needed. We assessed how the distribution of Reeves’s pheasant was impacted by human infrastructure development over the past 20 years in the Dabie Mountains, the main distribution range of the species. We surveyed Reeves’s pheasants by direct sightings and indirect evidence through line transects which were randomly distributed in the Dabie Mountains from 2001 to 2002 and 2018 to 2019. We evaluated the variation of the roads and buildings in these areas in the last 20 years, and then modeled the relationship of the distribution of this pheasant with the road and building data from 2000 and 2017. Human infrastructure became more extensively distributed throughout the Dabie Mountains during the period, with all lands within 10 km of a road or a building. The distribution of Reeves’s pheasants became closer to the buildings and roads and there was a significantly positive relationship between the occurrence of Reeves’s pheasants and the distance to the nearest buildings and roads in 2018–2019. These results suggest that the increased density of buildings and roads in the Dabie Mountains may have caused negative effects on Reeves’s pheasants.

It is well known that arginase II leads to decreased synthesis of nitric oxide (NO) by competing with endothelial nitric oxide synthase (eNOS) for their same substrate L-arginine. However, the regulatory mechanisms of arginase II production remain unclear. In this study, we hypothesized that poly- (ADP-ribose) transferase/polymerase-1 (PARP-1) may be a critical factor responsible for ox-LDL (oxidized Low Density Lipoprotein)-enhanced arginase II activity. We used serial deletions within plasmid constructs and found that a core promoter region of arginase II was located at the element of -774 to -738 bp and PARP-1 was identified specifically binding to this region. Inhibition of PARP-1 markedly reduced the endogenous arginase II expression and enhanced eNOS and NO production. Similarly, ox-LDL-induced increase in arginase II production and eNOS and NO reduction was substantially abolished by PARP-1 inhibition both in vitro and in vivo. Significant decrease in arginase II expression and increase in eNOS expression and NO levels, as well as improved endothelial function were observed in PARP-1-/- mice. The underlying mechanisms of ox-LDL-induced changes of PARP-1 expression involved migration of phosphorylated ERK2 into nuclei and direct interaction with PARP-1 which dramatically enhanced PARP-1 production, followed by histone acetylation to activate arginase II transcription process. Our studies demonstrated for the first time that PARP-1 regulates basal transcription process and ox-LDL-induced up-regulation of arginase II. These results demonstrated that PARP-1 offers a promising therapeutic target for endothelial dysfunction and atherosclerosis.

Objectives: We investigated the role of miR-205 in the osteogenic differentiation of vascular smooth muscle cells (VSMCs). Methods: Osteogenic differentiation of human aortic smooth muscle cells (HASMCs) was induced by 10 mM β-glycerophosphate (β-GP). Alizarin Red S staining, alkaline phosphatase (ALP) activity and osteocalcin secretion were used to determine osteogenic differentiation of HASMCs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expression of miR-205 in HASMCs. Results: The expression of endogenous miR-205 was decreased in HASMCs during β-glycerophosphate-induced calcification. Overexpression of miR-205 inhibited the differentiation of HASMCs into osteoblast-like cells, as evidenced by a decrease in ALP activity, osteocalcin secretion, and Runx2 expression, whereas miR-205 depletion enhanced osteoblastic differentiation of HASMCs. Runx2 and Smad1 were identified as direct targets of miR-205 by computational analysis and experimental assays. Conclusion: The present study shows that miR-205 may negatively regulate the β-glycerophosphate-induced calcification of HASMCs, at least partially by targeting Runx2 and Smad1.

Background Irisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis. Methods and Results We used a carotid partial ligation model of apolipoprotein E–deficient mice fed on a high‐cholesterol diet to test the anti‐atherosclerosis effect of irisin. Irisin treatment significantly suppressed carotid neointima formation. It was associated with increased endothelial cell proliferation. In addition, irisin promoted human umbilical vein endothelial cell survival via upregulating microRNA126‐5p expression through the ERK signaling pathway. Inhibition of microRNA126‐5p using the microRNA126‐5p inhibitor abolished the prosurvival effect. The same results were demonstrated in vivo as the expression of microRNA126‐5p noticeably increased in ligated carotid artery after irisin treatment. Furthermore, in vivo blockade of microRNA126‐5p expression using the antagomir abolished the inhibitory effects of irisin on neointima formation, lesional lipid deposition, macrophage area, and the pro‐proliferation effects on endothelial cells. Conclusions Taken together, our study demonstrates that irisin significantly reduces atherosclerosis in apolipoprotein E–deficient mice via promoting endothelial cell proliferation through microRNA126‐5p, which may have a direct therapeutic effect on atherosclerotic diseases.

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

LIM homeobox 8 (Lhx8) is a germ cell-specific transcription factor essential for the development of oocytes during early oogenesis. In mice, Lhx8 deficiency causes postnatal oocyte loss and affects the expression of many oocyte-specific genes. The aims of this study were to characterize the bovine Lhx8 gene, determine its mRNA expression during oocyte development and early embryogenesis, and evaluate its interactions with other oocyte-specific transcription factors. The bovine Lhx8 gene encodes a protein of 377 amino acids. A splice variant of Lhx8 (Lhx8_v1) was also identified. The predicted bovine Lhx8 protein contains two LIM domains and one homeobox domain. However, one of the LIM domains in Lhx8_v1 is incomplete due to deletion of 83 amino acids near the N terminus. Both Lhx8 and Lhx8_v1 transcripts were only detected in the gonads but none of the somatic tissues examined. The expression of Lhx8 and Lhx8_v1 appears to be restricted to oocytes as none of the transcripts was detectable in granulosa or theca cells. The maternal Lhx8 transcript is abundant in GV and MII stage oocytes as well as in early embryos but disappear by morula stage. A nuclear localization signal that is required for the import of Lhx8 into nucleus was identified, and Lhx8 is predominantly localized in the nucleus when ectopically expressed in mammalian cells. Finally, a novel interaction between Lhx8 and Figla, another transcription factor essential for oogenesis, was detected. The results provide new information for studying the mechanisms of action for Lhx8 in oocyte development and early embryogenesis.

Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

As a link between exercise and metabolism, irisin is assumed to be involved in increased total body energy expenditure, reduced body weight, and increased insulin sensitivity. Although our recent evidence supported the contribution of irisin to vascular endothelial cell (ECs) proliferation and apoptosis, further research of irisin involvement in the angiogenesis of ECs was not conclusive. In the current study, it was found that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) angiogenesis via increasing migration and tube formation, and attenuated chemically-induced intersegmental vessel (ISV) angiogenic impairment in transgenic TG (fli1: GFP) zebrafish. It was further demonstrated that expression of matrix metalloproteinase (MMP) 2 and 9 were also up-regulated in endothelial cells. We also found that irisin activated extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling by using U0126 decreased the pro-migration and pro-angiogenic effect of irisin on HUVEC. Also, U0126 inhibited the elevated expression of MMP-2 and MMP-9 when they were treated with irisin. In summary, these findings provided direct evidence that irisin may play a pivotal role in maintaining endothelium homeostasis by promoting endothelial cell angiogenesis via the ERK signaling pathway.

Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is associated with metabolic disorder and cell death, which are important triggers in diabetic cardiomyopathy (DCM). We aimed to explore whether NLRP3 inflammasome activation contributes to DCM and the mechanism involved.Type 2 diabetic rat model was induced by high fat diet and low dose streptozotocin. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Gene silencing therapy was used to investigate the role of NLRP3 in the pathogenesis of DCM. High glucose treated H9c2 cardiomyocytes were used to determine the mechanism by which NLRP3 modulated the DCM. The cell death in vitro was detected by TUNEL and EthD-III staining. TXNIP-siRNA and pharmacological inhibitors of ROS and NF-kB were used to explore the mechanism of NLRP3 inflammasome activation.Diabetic rats showed severe metabolic disorder, cardiac inflammation, cell death, disorganized ultrastructure, fibrosis and excessive activation of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1, activated caspase-1 and mature interleukin-1β (IL-1β). Evidence for pyroptosis was found in vivo, and the caspase-1 dependent pyroptosis was found in vitro. Silencing of NLRP3 in vivo did not attenuate systemic metabolic disturbances. However, NLRP3 gene silencing therapy ameliorated cardiac inflammation, pyroptosis, fibrosis and cardiac function. Silencing of NLRP3 in H9c2 cardiomyocytes suppressed pyroptosis under high glucose. ROS inhibition markedly decreased nuclear factor-kB (NF-kB) phosphorylation, thioredoxin interacting/inhibiting protein (TXNIP), NLRP3 inflammasome, and mature IL-1β in high glucose treated H9c2 cells. Inhibition of NF-kB reduced the activation of NLRP3 inflammasome. TXNIP-siRNA decreased the activation of caspase-1 and IL-1β.NLRP3 inflammasome contributed to the development of DCM. NF-κB and TXNIP mediated the ROS-induced caspase-1 and IL-1β activation, which are the effectors of NLRP3 inflammasome. NLRP3 gene silencing may exert a protective effect on DCM.

Irisin is a newly discovered myokine that links exercise with metabolic homeostasis. It is involved in modest weight loss and improves glucose intolerance. However, the direct effects and mechanisms of irisin on vascular endothelial cells (ECs) are not fully understood. In the current study, we demonstrated that irisin promoted Human Umbilical Vein Endothelial Cell (HUVEC) proliferation. It was further demonstrated that this pro-proliferation effect was mediated by irisin-induced activation of extracellular signal-related kinase (ERK) signaling pathways. Inhibition of ERK signaling with U0126 decreased the pro-proliferation effect of irisin on HUVECs. It was also demonstrated that irisin reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax, Caspase-9 and Caspase-3 expression. In summary, these results suggested that irisin plays a novel role in sustaining endothelial homeostasis by promoting HUVEC proliferation via the ERK signaling pathway and protects the cell from high glucose-induced apoptosis by regulating Bcl-2,Bax and Caspase expression.

BACKGROUND: Glucocorticoids (GCs) are a first-line treatment for asthma for their anti-inflammatory effects, but they also hinder the repair of airway epithelial injury. The anti-inflammatory protein GC-induced leucine zipper (GILZ) is reported to inhibit the activation of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway, which promotes the repair of airway epithelial cells around the damaged areas. We investigated whether the inhibition of airway epithelial repair imposed by the GC dexamethasone (DEX) is mediated by GILZ. METHODS: We tested the effect of DEX on the expressions of GILZ mRNA and GILZ protein and the MAPK-ERK signaling pathway in human airway epithelial cells, via RT-PCR and Western blot. We further evaluated the role of GILZ in mediating the effect of DEX on the MAPK-ERK signaling pathway and in airway epithelium repair by utilizing small-interfering RNAs, MTT, CFSE labeling, wound-healing and cell migration assays. RESULTS: DEX increased GILZ mRNA and GILZ protein levels in a human airway epithelial cell line. Furthermore, DEX inhibited the phosphorylation of Raf-1, Mek1/2, Erk1/2 (components of the MAPK-ERK signaling pathway), proliferation and migration. However, the inhibitory effect of DEX was mitigated in cells when the GILZ gene was silenced. CONCLUSIONS: The inhibition of epithelial injury repair by DEX is mediated in part by activation of GILZ, which suppressed activation of the MAPK-ERK signaling pathway, proliferation and migration. Our study implicates the involvement of DEX in this process, and furthers our understanding of the dual role of GCs.

Wetlands play important ecological, economic, and cultural roles in societies around the world. However, wetland degradation has become a serious ecological issue, raising the global sustainability concern. An accurate wetland map is essential for wetland management. Here we used a fuzzy method to create a hybrid wetland map for China through the combination of five existing wetlands datasets, including four spatially explicit wetland distribution data and one wetland census. Our results show the total wetland area is 384,864 km(2), 4.08% of China's national surface area. The hybrid wetland map also shows spatial distribution of wetlands with a spatial resolution of 1 km. The reliability of the map is demonstrated by comparing it with spatially explicit datasets on lakes and reservoirs. The hybrid wetland map is by far the first wetland mapping that is consistent with the statistical data at the national and provincial levels in China. It provides a benchmark map for research on wetland protection and management. The method presented here is applicable for not only wetland mapping but also for other thematic mapping in China and beyond.