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SUMMARY: Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA‐mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase‐mediated H2O2. Exogenous SA and H2O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport‐related genes, thus reducing the Na+/K+ ratio in the salt‐treated K. obovata roots. In addition, exogenous SA‐enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA‐GSH cycle as well, then alleviated oxidative damages in the salt‐treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA‐induced salt tolerance of K. obovata depends on NADPH oxidase‐generated H2O2 that affects Na+/K+ and redox homeostasis in response to high salinity. [ABSTRACT FROM AUTHOR]

Graphite carbon nitride (g‐C3N4) has garnered considerable attention due to its excellent photocatalytic properties for the degradation of organic matter in wastewater treatment. Herein, sulfur‐doped g‐C3N4 nanosheets (CN−S‐X) were successfully synthesized via physical steam activation using thiourea and urea as precursors. Comprehensive characterizations demonstrate that the enhanced photocatalysis is attributed to the ultrathin structure, highly active site, vacancy defects, and high specific surface area due to the synergy of S doping and steam activation. The as‐prepared CN−S‐25 photocatalyst exhibits a desirable degradation efficiency of 95.4 % for methylene blue dye with a high degradation rate of 2.65×10−2 min−1 under visible‐light irradiation, which are 2.1 and 5.52 times those for bulk g‐C3N4, respectively as well as good reusability and stability. This study provides a simple and promising strategy to regulate the nanostructure of g‐C3N4 for highly efficient photocatalytic degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

Bile acids are synthesised in the liver and are essential amphiphilic steroids for maintaining the balance of cholesterol and energy metabolism in livestock and poultry. They can be used as novel feed additives to promote fat utilisation in the diet and the absorption of fat‐soluble substances in the feed to improve livestock performance and enhance carcass quality. With the development of understanding of intestinal health, the balance of bile acid metabolism is closely related to the composition and growth of livestock intestinal microbiota, inflammatory response, and metabolic diseases. This paper systematically reviews the effects of bile acid metabolism on gut health and gut microbiology in livestock. In addition, our paper summarised the role of bile acid metabolism in performance and disease control. [ABSTRACT FROM AUTHOR]

Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S‐nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine‐turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR‐regulated Na+/K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR‐biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt‐induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR‐mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+/K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+/K+ homeostasis. Summary Statement: Salinity increases brassinosteroid (BR)‐biosynthesis genes expression and endogenous BR in mangrove Kandelia obovata. BR enhances the activity and gene expression of S‐nitrosoglutathione reductase that negatively regulates nitric oxide signaling and reactive oxygen species level, while, BR regulates antioxidant enzymes and Na+/K+ homeostasis. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) is a natural triterpenoid with therapeutic potential for a multitude of diseases. However, the precise mechanism by which OA influences stress‐induced apoptosis of intestinal epithelial cells remains elusive. Therefore, the effect of OA on intestinal diseases under stressful conditions and its possible mechanisms have been investigated. In a hydrogen peroxide (H2O2)‐induced oxidative stress model, OA attenuated H2O2‐induced apoptosis in a concentration‐dependent manner. To investigate the underlying mechanisms, the gene expression profile of OA on IPEC‐J2 cells was analyzed using an RNA sequencing system. Results from gene ontology and Kyoto encyclopedia of genes and genomes analysis confirmed that OA may mitigate the cytotoxic effects of H2O2 by downregulating gene expression through the MAPK signaling pathway. Furthermore, Quantitative real‐time polymerase chain reaction results validated the differentially expressed genes data. Western blot analysis further demonstrated that OA effectively suppressed the expression level of c‐Jun protein induced by H2O2 in IPEC‐J2 cells. Collectively, our results indicate that OA pretreatment significantly attenuated H2O2‐induced apoptosis in intestinal epithelial cells through suppressing c‐Jun and MAPK pathway. [ABSTRACT FROM AUTHOR]

Bird's nest defect is an important cause of transmission line faults. To achieve accurate detection of bird nest defects in complex scenarios, a bird nest defect detection model for transmission lines was proposed that combines domain knowledge and occlusion reasoning networks. On the one hand, the model utilized the domain knowledge of the location of the bird's nest, using edge detection to obtain tower area information to constrain the location of candidate frames. This helps to reduce the false detection caused by complex backgrounds. On the other hand, on the basis of analyzing the occlusion characteristics of bird nests, the model employed occlusion reasoning networks that randomly erase features at the feature level to simulate the occlusion of bird nests in real scenes and improve the model's detection capability for occluded targets. Additionally, a multi‐scale feature fusion algorithm was designed in this paper to adapt the model to the scale variations of bird nests in aerial images. Experimental results demonstrate that the model outperforms advanced target detection models and other bird nest defect detection methods, with an AP50 of 78.8% and an AR10 of 72.4% for defect detection. [ABSTRACT FROM AUTHOR]

Objective: The drug‐refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy. Methods: This single‐center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non‐responders with VPA polytherapy (NR group) were collected. Non‐targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value >1, fold change >1.2 or <0.8, and p‐value <0.05 were regarded as statistically different substances. Results: A total of 204 small metabolites and 433 lipids comprising 16 different lipid subclasses were identified. The well‐established partial least squares‐discriminant analysis (PLS‐DA) revealed a good separation of the RE from the NR group. The FAs and glycerophospholipids status were significantly decreased in the NR group, but their triglycerides (TG) levels were significantly increased. The trend of TG levels in routine laboratory tests was in line with the lipidomics analysis. Meanwhile, cases from the NR group were characterized by a decreased level of citric acid and L‐thyroxine, but with an increased level of glucose and 2‐oxoglutarate. The top two enriched metabolic pathways involved in the DRE condition were biosynthesis of unsaturated FAs and linoleic acid metabolism. Significance: The results of this study suggested an association between metabolism of FAs and the medically intractable epilepsy. Such novel findings might propose a potential mechanism linked to the energy metabolism. Ketogenic acid and FAs supplementation might therefore be high‐priority strategies for DRE management. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ulcerative colitis is a gastrointestinal disease closely related to intestinal epithelial barrier damage and intestinal microbiome imbalance; however, effective treatment methods are currently limited. Rehmannia glutinosa polysaccharide (RGP) is an important active ingredient with a wide range of pharmacological activities, although its protective effect on colitis remains to be explored. In the present study, we verified the in vitro anti‐inflammatory effect of RGP, and observed the ameliorating effect of RGP on dextran sulfate sodium‐induced colitis in mice. RESULTS: The results showed that (i) RGP attenuates lipopolysaccharide‐induced overexpression of inflammatory factors in RAW264.7 cells; (ii) RGP improves the pathological damage caused by DSS, including weight loss, increased disease activity index and intestinal tissue ulcers; (iii) RGP improves tight junction proteins to protects the tightness of the intestinal epithelium; (iv) RGP inhibits the expression of inflammatory factors through the nuclear factor‐kappa B pathway, and improved the of intestinal tissues inflammation; and (v) RGP can maintain the species diversity of intestinal microbes, increase the content of short‐chain fatty acids and then restore the imbalance of intestinal microecology. CONCLUSION: RGP can improve the intestinal microbiota to strengthen the intestinal epithelial barrier and protect against DSS‐induced colitis. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Increased antibiotic resistance poses a major limitation in tackling inflammatory bowel disease and presents a large challenge for global health care. Antimicrobial peptides (AMPs) are a potential class of antimicrobial agents. Here, we have designed the potential oral route for antimicrobial peptide R7I with anti‐proteolytic properties to deal with bacterial enteritis in mice. The results revealed that R7I protected the liver and gut from damage caused by inflammation. RNA‐Seq analysis indicated that R7I promoted digestion and absorption in the small intestine by upregulating transmembrane transporter activity, lipid and small molecule metabolic processes and other pathways, in addition to upregulating hepatic steroid biosynthesis and fatty acid degradation. For the gut microbiota, Clostridia were significantly reduced in the R7I‐treated group, and Odoribacteraceae, an efficient isoalloLCA‐synthesizing strain, was the main dominant strain, protecting the gut from potential pathogens. In addition, we further discovered that R7I reduced the accumulation of negative organic acid metabolites. Overall, R7I exerted better therapeutic and immunomodulatory potential in the bacterial enteritis model, greatly reduced the risk of disease onset, and provided a reference for the in vivo application of antimicrobial peptides. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration. Methods: Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration‐to‐dose ratio (C0/Dose ratio) of PER was compared among patients on various potential influencing factors. Results: A 3‐month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C0 was 325.5 ng/mL. Under maintenance dosages, approximately 75% of the C0 values were 180.0‐610.0 ng/mL. The C0/Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P = 0.001). Enzyme‐inducing ASMs (EIASMs) decreased the C0/Dose ratio of PER by 25.9% (P = 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C0 value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P = 0.288). No significant difference was found in PER C0 values between patients with and without AEs (P = 0.082). Significance: In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C0/Dose ratios were identified, and complex PER‐ASMs interactions were observed. Notably, the reference range, that is, 180.0‐610.0 ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER. [ABSTRACT FROM AUTHOR]

This article presents a decentralized neuro‐control scheme for a class of continuous‐time nonlinear systems with mismatched interconnections through an optimal control method. The decentralized control problem of the studied nonlinear‐interconnected systems is transformed into a group of optimal control problems of auxiliary subsystems. First, the value functions of auxiliary subsystems are designed, which are related to the boundaries of interconnected terms. It is proved that, under certain conditions, the decentralized control consisting of optimal control policies of auxiliary subsystems can stabilize the entire interconnected system. Then, an adaptive dynamic programming algorithm is presented to solve the Hamilton–Jacobi–Bellman equations. Critic neural networks (NNs) are employed to approximate the value functions of auxiliary subsystems in order to acquire the optimal control policies. Moreover, the auxiliary subsystems' states and the critic NNs' weight estimation errors are proved to be uniformly ultimately bounded. Finally, a numerical example and an interconnected power system are provided to validate the proposed decentralized neuro‐control strategy. [ABSTRACT FROM AUTHOR]

Significance Statement: Interspecific introgression from Gossypium hirsutum has reorganized the genomic architecture of Gossypium barbadense. In this study, the genetic basis of population differentiation and the genetic diversity were deciphered and the introgression events and haplotype selection affecting associated fiber quality and environmental adaptation traits were illuminated in Gossypium barbadense. This study provides new insights into the breeding history of Gossypium barbadense and will guard the breeding programs of modern cultivated Gossypium barbadense. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti‐inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity. RESULTS: Illumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA‐seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity. CONCLUSION: Intake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aquaporins (AQP) are a class of water channel membrane proteins that are widely expressed in the gut. The biological functions of aquaporins, which regulate the absorption and secretion of water molecules and small solutes, maintain the stable state of the intestine, regulate cell proliferation and migration, participate in the process of intestinal inflammation, and mediate tumorigenesis, demonstrate the physiological significance of these channels in intestinal health. The pathology of many intestinal diseases is associated with changes in the location and expression of aquaporins, such as intestinal infection, which can change the expression and distribution of AQPs in intestinal tissues/cells by affecting cytokines and chemokines. This can lead to various intestinal diseases such as diarrhoea, which also suggests the importance of aquaporins in the prevention and treatment of intestinal diseases. This review summarizes the relationship between aquaporins and intestinal physiology and diseases and focuses on drugs (such as plant extracts) or diets that can regulate intestinal health by regulating aquaporins. It provides a basis for establishing aquaporins as biomarkers and therapeutic targets for intestinal health. [ABSTRACT FROM AUTHOR]

Treatment of microbial‐associated infections continues to be hampered by impaired antibacterial efficiency and the variability in nanomedicines. Herein, an octapeptide library with a double‐layered zipper, constructed via a systematic arrangement, simplifying the sequence and optimizing the structure (diverse motifs including surfactant‐like, central‐bola, and end‐bola), is assessed in terms of biological efficiency and self‐assembly properties. The results indicate that peptides with double‐layered Trp zipper exhibit significant antimicrobial activity. Extracellularly, affinity interactions between micelles and bacteria induce the lateral flow of the membrane and electric potential perturbation. Intracellularly, lead molecules cause apoptosis‐like death, as indicated by excessive accumulation of reactive oxygen species, generation of a DNA ladder, and upregulation of mazEF expression. Among them, RW‐1 performs the best in vivo and in vitro. The intersecting combination of Trp zipper and surfactants possesses overwhelming superiority with respect to bacterial sweepers (therapeutic index [TI] = 52.89), nanostructures (micelles), and bacterial damage compared to RW‐2 (central‐bola) and RW‐3 (end‐bola). These findings confirm that the combination of double‐layered Trp zipper and surfactants has potential for application as a combined motif for combating microbial infection and connects the vast gap between antimicrobial peptides and self‐assembly, such as Jacob's ladder. [ABSTRACT FROM AUTHOR]

Rationale: Dichotomitin is one of the bioactive constituents isolated from Belamcanda chinensis. The goal of this study was to identify the metabolites of dichotomitin produced by liver microsomes and hepatocytes. Methods: Using ultra‐high‐performance liquid chromatography and high‐resolution mass spectrometry (UPLC/HRMS), the metabolites were profiled and identified. The exact masses, elemental compositions and product ions of the metabolites were used to characterize their structures. Results: A total of ten metabolites were found and identified. The main metabolites identified in the incubation samples were M6 (3′,5,6,7‐tetrahydroxy‐4′,5′‐dimethoxyisoflavone) and M8 (8‐hydroxydichotomitin). Opening of 1,3‐benzodioxole, demethylation, hydroxylation, glucuronidation and sulfation were among the metabolic modifications for dichotomitin. A human recombinant cytochrome P450 enzyme study revealed that CYP 1A2, 2C19, and 2D6 facilitated the formation of M6, whereas CYP 1A2 catalyzed the formation of M8 exclusively. Conclusions: For the first time, data on the in vitro metabolic fates of dichotomitin were revealed in this work which would be helpful for us to understand the disposition of this bioactive constituent. [ABSTRACT FROM AUTHOR]

Ziritaxestat is a first‐in‐class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC–MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated using acetonitrile and then separated on an Acquity BEH C18 column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 ml/min. Ziritaxestat and the internal standard (crizotinib) were quantitatively monitored with precursor‐to‐product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range 0.5–2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter‐ and intra‐day precisions (RSD) were <11.20% and accuracies were in the range of −8.50–7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC–MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed a short half‐life (~3 h) and low bioavailability (20.52%). [ABSTRACT FROM AUTHOR]

Early weaning usually causes intestinal disorders, enteritis, and diarrhea in young animals and human infants. Astragalus polysaccharides (APS) possesses anti‐inflammatory activity. To study the anti‐inflammatory mechanisms of APS and its potential effects on intestinal health, we performed an RNA sequencing (RNA‐seq) study in lipopolysaccharide (LPS)‐stimulated porcine intestinal epithelial cells (IPEC‐J2) in vitro. In addition, LPS‐stimulated BALB/c mice were used to study the effects of APS on intestinal inflammation in vivo. The results from the RNA‐seq analysis show that there were 107, 756, and 5 differentially expressed genes in the control versus LPS, LPS versus LPS+APS, and control versus LPS+APS comparison groups, respectively. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB) signaling pathways play significant roles in the regulation of inflammatory factors and chemokine expression by APS. Further verification of the above two pathways by using western blot and immunofluorescence analysis revealed that the gene expression levels of the phosphorylated p38 MAPK, ERK1/2, and NF‐κB p65 were inhibited by APS, while the expression of IκB‐α protein was significantly increased (p <.05), indicating that APS inhibits the production of inflammatory factors and chemokines by the inhibition of activation of the MAPK and NF‐κB inflammatory pathways induced by LPS stimulation. Animal experiments further demonstrated that prefeeding APS in BALB/c mice can alleviate the expression of the jejunal inflammatory factors interleukin 6 (IL‐6), IL‐Iβ, and tumor necrosis factor‐α induced by LPS stimulation and improve jejunal villus morphology. [ABSTRACT FROM AUTHOR]

It is traditionally believed that the distribution of tryptophan (Trp) residues is critical for the novo design of antimicrobial peptides (AMPs). However, there is scarce knowledge regarding Trp residues arrangement at the head group level. Thus, a set of α‐helical AMPs containing different Trp residue arrangements at the N‐/C‐terminal of sequence were designed to increase the strategy database and analyze their biological activities. The arrangement of the N‐terminal Trp residue significantly improved the bacteriostatic activity of the peptides, but the C‐terminal Trp residue arrangement reduced the biocompatibility of them. WL and LW were effective against Gram‐negative microbes and had high selectivity for bacteria as compared to human erythrocytes and mammalian cells. They both maintained a relatively desirable activity in the presence of physiological salts and serum. It is observed through electron microscope, flow cytometry and fluorescence spectroscopy that target peptides can penetrate bacterial cell membrane and kill it by damaging cell membrane integrity. Collectively, we determined the structure–activity relationship of Trp residue distributions in a symmetric sequence structure and filled the gap in knowledge related to Trp arrangements at the head group level. The obtained results will be helpful in designing of artificial peptide‐based antimicrobials. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection always leads to chronic hepatitis via dysregulation of host immunity. Notch signaling also modulates the response of monocytes/macrophages. Thus, we aimed to investigate the regulatory role of Notch signaling to CD14+ monocytes. Forty patients with chronic hepatitis C and twenty normal controls (NC) were enrolled. CD14+ monocytes and CD4+ T cells were purified from peripheral bloods. Notch receptors' mRNA expression in CD14+ monocytes was semi‐quantified by real‐time PCR. Cytokine production by CD14+ monocytes in response to γ‐secretase inhibitor (GSI) was investigated by ELISA. GSI‐induced CD14+ monocytes activity to HCV clearance in Huh7.5 cells and to CD4+ T cell differentiation was also assessed in direct and indirect contact co‐culture system. Notch1 mRNA relative level was approximately 10‐fold elevated in CD14+ monocytes from chronic hepatitis C patients when compared with NC. GSI stimulation resulted in enhanced cytokines production by CD14+ monocytes from chronic hepatitis C patients. GSI‐stimulated CD14+ monocytes from chronic hepatitis C patients induced suppression of HCV RNA replication in both direct and indirect contact co‐culture system of CD14+ monocytes and HCVcc‐infected Huh7.5 cells, and this process was accompanied by elevation of interferon‐γ production but not increased target cell death. Moreover, GSI stimulation also enhanced CD14+ monocytes‐induced Th1 and Th17 cells activation, and this process required direct cell‐to‐cell contact. Effective antiviral therapy down‐regulated Notch1 mRNA expression and promoted cytokine production by CD14+ monocytes from chronic hepatitis C. Current data revealed an important immunoregulatory property of Notch signaling to CD14+ monocytes in chronic HCV infection. [ABSTRACT FROM AUTHOR]

The land surface, which interacts with lower atmosphere, is subject to substantial amounts of human activities. It results in regional climate fluctuations and must be assessed with a combination of future socioeconomic and emission policies to improve regional resilience and responsive efficiency on global mitigation and adaptation. Spatial heterogeneity in regional climate induced by land use changes of future global socioeconomic and emission scenarios is explored. Comparisons are carried out among both historical and future land use‐induced regional meteorological changes to investigate various climatic roles of land use conversions in China. The underlying changes in the surface albedo, leaf area index, energy exchange, and water balances are also examined. It is found that the increase of the summer temperature and the diurnal temperature range are the largest under the fifth Shared Socioeconomic Pathway characterized by more intensive urbanization. While temperature increase from urbanization and deforestation can be offset by cooling from vegetation evaporation increase under the extreme Representative Concentration Pathway (RCP) 8.5, which has no climate mitigation policies and high greenhouse gas concentration. In addition, RCP4.5 scenario would cause an average temperature increase of 1.41°C by 2050 at an annual rate of 0.028°C in China. The global climatic forcing warms the entire region and enhances precipitation intensity, and these effects are more substantial than those by regional land use changes, showing a strong background influence. Our research reveals the future climatic responses to regional anthropogenic land use changes under various scenarios and policies and provides ways to downscale global mitigation impacts into regional insights. Key Points: Land use change‐induced warming from urbanization would be offset by cooling from increased vegetation evaporation under RCP8.5Total temperature changes under RCP4.5 scenario increase 1.41°C by 2050 at an annual ratio of 0.028°C due to land use changesRegional climatic intensity brought by the global climatic forcing is more than those by the regional land use change [ABSTRACT FROM AUTHOR]

High manufacturing costs and weak cell selectivity have limited the clinical application of naturally occurring peptides when faced with an outbreak of drug resistance. To overcome these limitations, a set of antimicrobial peptides was synthesized with the general sequence of (WL)n, where n = 1, 2, 3, and WL was truncated from the N‐terminus of Cecropin P1 without initial serine residues. The antimicrobial peptide WL3 exhibited stronger antimicrobial activity against both Gram‐negative and Gram‐positive microbes than the parental peptide CP‐1. WL3 showed no hemolysis even at the highest test concentrations compared to the parental peptide CP‐1. The condition sensitivity assays (salts, serum, and trypsin) demonstrated that WL3 had high stability in vitro. Fluorescence spectroscopy and electron microscopy indicated that WL3 killed microbes by means of penetrating the membrane and causing cell lysis. In a mouse model, WL3 was able to significantly reduce the bacteria load in major organs and cytokines (TNF‐α, IL‐6, and IL‐1β) levels in serum. In summary, these findings suggest that WL3, which was modified from a natural antimicrobial peptide, has enormous potential for application as a novel antibacterial agent. [ABSTRACT FROM AUTHOR]

When wireless sensor network (WSN) is running, it needs data acquisition, fusion, and transmission, which makes the attacker distribute the malware code to the network to destroy the normal operation of the network. In this study, an improved two‐dimensional (2D) cellular automata model and a multi‐player evolutionary game model are proposed to describe the propagation process of malware propagation, aiming at the shortcomings of research on malware propagation in WSN. First, the authors introduce the node diversity model according to the difference between the cluster‐head node and the terminal node in WSN. Then, based on the existing 2D cellular automata malware model, an improved mechanism of epidemiological transmission is improved. To make the model more complete, a multi‐player evolutionary game model is established according to the different attack methods and the different coping strategies adopted by the cluster‐head node and the terminal node in WSN. The replication dynamic equation of the strategy evolution is also given. Simulation results show that the proposed model can accurately describe the propagation behaviour of malware in WSN and provide a basis for security defence research of WSN. [ABSTRACT FROM AUTHOR]

To meet the demands of the modern power system for satisfactory operation and control, here, a novel data‐driven control strategy is proposed to solve the load frequency control (LFC) problems of power systems, with complete convergence analysis. This data‐based LFC approach is designed based on the simultaneous perturbation stochastic approximation (SPSA) method and neural network ensemble. The data‐based controller is constructed using a function approximator, which is fixed as a neural network. Being the control parameters, the connection weights of the neural network controller are updated at each iteration step. In order to improve the overall control accuracy and get more stable control performance, the idea of neural network ensemble is introduced for the data‐based controller structure design. The proposed data‐based controller takes past and current system information as input and generates a control signal that can affect future system performance as output, and during the whole process, it is not necessary to build mathematical model for the controlled plant. A one‐area LFC problem with system parametric uncertainties as well as a typical two‐area LFC problem have been introduced for simulation tests, and the feasibility and effectiveness of this newly proposed data‐based LFC strategy is well revealed through simulation results. [ABSTRACT FROM AUTHOR]

Association mapping is a promising tool to identify genes for quantitative traits. A total of 172 upland cotton ( Gossypium hirsutum L.) accessions were assessed. The panel was phenotyped for four major early-maturating traits across multiple environments and genotyped using 331 polymorphic simple sequence repeat ( SSR) markers. The gene diversity of the 331 markers averaged 0.40 (range: 0.04-0.78), and the polymorphism information content ( PIC) averaged 0.34 (range: 0.04-0.75). Thirty-nine significant markers related to early-maturating traits were simultaneously detected in at least two environments. Among the 39 markers, 11 for seed period ( SP), seven for bud period ( BP), six for flower and boll period ( FBP), and 15 for growth period ( GP). These markers were stable and could be used for marker-assisted selection ( MAS). Favourable alleles for SP, BP, FBP and GP were explored. These alleles can be directly used in MAS to improve cotton early maturity. This study lays the foundation for analysing the genetic mechanisms underlying early maturity, as well as the use of MAS to target traits in cotton. [ABSTRACT FROM AUTHOR]

This study presents a non‐linear ensemble of partially connected neural networks for short‐term load forecasting. Partially connected neural networks are chosen as individual predictors due to their good generalisation capability. A group‐based chaos genetic algorithm is developed to generate diverse and effective neural networks. A novel pruning method is employed to develop partially connected neural networks. To further enhance prediction accuracy, an artificial neural network‐based non‐linear ensemble of partially connected neural network predictors is developed. The proposed non‐linear ensemble neural network is evaluated on a PJM market dataset and an ISO New England dataset with promising results of 1.76 and 1.29% error, respectively, demonstrating its capability as a promising predictor. [ABSTRACT FROM AUTHOR]

Two-factor user authentication scheme allows a user to use a smart card and a password to achieve mutual authentication and establish a session key between a server and a user. In 2012, Chen et al. showed that the scheme of Sood et al. does not achieve mutual authentication and is vulnerable to off-line password guessing and smart card stolen attacks. They also found that another scheme proposed by Song is vulnerable to similar off-line password guessing and smart card stolen attacks. They further proposed an improved scheme. In this paper, we first show that the improved scheme of Chen et al. still suffers from off-line password guessing and smart card stolen attacks, does not support perfect forward secrecy, and lacks the fairness of session key establishment. We then propose a new security-enhanced scheme and show its security and authentication using the formal verification tool ProVerif, which is based on applied pi calculus. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study proposes one novel data‐driven control strategy based upon the simultaneous perturbation stochastic approximation method with adaptive weighted gradient estimation for general discrete non‐linear systems. A function approximator is used to construct the controller, and here, it is fixed as a neural network (NN), whose structure is fixed previously, while allowing its connecting weights to be updated. The control parameters are then the connecting weights of the NN controller. The biggest advantage of this data‐driven control approach is that it can generate a control signal to affect system's future performance without establishing the plant's mathematical model first. In this novel approach, to improve the control ability and accuracy, an adaptive weighted gradient estimation method is designed to do the parametric estimation with convergence analysis. Non‐linear tracking problems for typical discrete‐time non‐linear plants are introduced for simulation comparison tests, and the convergence and feasibility of this newly proposed data‐driven control strategy are well demonstrated through the simulation results. Finally, empirical study on a simulated wastewater treatment system is carried out to further illustrate the effectiveness of this newly proposed approach. [ABSTRACT FROM AUTHOR]

Our previous study reported Val/Arg-rich peptides, and the relationship was linear between hydrophobicity and antimicrobial potency within a certain range. Here, we further develop a new series of analogs to investigate the effect of net charge and Pro residue on activity. Replacement of Gly with Ala or Pro led to the decrease in antimicrobial activity. The substitution of Gly with Ala retained its hemolytic activity, while the substitution with Pro significantly decreased the toxicity, suggesting positive effect of Pro on hemolytic activity. The increase in net charge from +4 to +6 significantly improved antimicrobial activity and decreased the hemolysis. However, antibacterial and hemolytic activities were not affected by increasing the net charge from +6 to +8, indicating a moderate net positive charge. The peptides produced larger blue shifts in PE/ PG than in PC/cholesterol, suggesting a stronger affinity with negatively charged membrane over zwitterionic membrane. Lowering the net charge or insert of Pro led to the lack of α-helical structure in SDS micelles, which may be correlated with weakened antimicrobial potency. This study indicated that Val/Arg-rich peptides should have moderate net charge and Pro may play a role in reducing the toxicity against red blood cells. [ABSTRACT FROM AUTHOR]

ABSTRACT Polytetrafluoroethylene (PTFE) is a semi-crystalline polymer whose fibrils can be easily formed by stretching because of its low tensile activation energy. We prepared two series of PTFE samples with different elongations and degrees of crystallinity, respectively. The morphology analysis of the first series determined that cavities were formed in the PTFE matrix under stretching, and this was a prerequisite for forming fibrils. The barrier between cavities became long and slim under tension, and grew into fibrils finally. It could be found that higher crystallinity is more suitable for forming fibrils. The main part of the fibrils' structure was semi-crystalline, and the degree of crystallinity could grow under stretching. Besides, the thickness of the lamellae decreased, while the crystalline grain refined at the same time. In the measurement of X-ray diffraction, it could be found that the lattice plane (108) was more sensitive to stretching, which could rotate to other positions. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3710-3717, 2013 [ABSTRACT FROM AUTHOR]

Hainan, an island linking mainland East Asia and Southeast Asia, lay in one of the routes of early migration to East Asia. The largest indigenous group of Hainan is called Hlai, possibly direct descendants of the earliest migrants. However, there are no sufficient genetic data to assess the population history of Hainan Island. Here, we have analyzed mitochondrial DNA control-region and coding-region sequence variations in 566 Hlai individuals from all five subgroups, Ha, Gei, Zwn, Moifau, and Jiamao. Our results suggest three phases for the peopling of Hainan. The first phase represents the initial settlement of the island as part of the African dispersal approximately 50 000 years ago. The second phase reflects colonization events from mainland Asia before the Last Glacial Maximum, which was recorded by wide distributed lineages, such as F*, B4a, and D4a.The third phase reflects population expansions under lineages F1b, M7b, and R9b after the Last Glacial Maximum and Neolithic migrations in and out of Hainan Island. Selection also started to play a role during the last phase. We also detected different distributions between paternal Y chromosome and maternal mitochondrial DNA among isolated Hlai populations, which might be caused by sex-biased cultural practices. [ABSTRACT FROM AUTHOR]

The Utsat people do not belong to one of the recognized ethnic groups in Hainan, China. Some historical literature and linguistic classification confirm a close cultural relationship between the Utsat and Cham people; however, the genetic relationship between these two populations is not known. In the present study, we typed paternal Y chromosome and maternal mitochondrial (mt) DNA markers in 102 Utsat people to gain a better understanding of the genetic history of this population. High frequencies of the Y chromosome haplogroup O1a*-M119 and mtDNA lineages D4, F2a, F1b, F1a1, B5a, M8a, M*, D5, and B4a exhibit a pattern similar to that seen in neighboring indigenous populations. Cluster analyses (principal component analyses and networks) of the Utsat, Cham, and other ethnic groups in East Asia indicate that the Utsat are much closer to the Hainan indigenous ethnic groups than to the Cham and other mainland southeast Asian populations. These findings suggest that the origins of the Utsat likely involved massive assimilation of indigenous ethnic groups. During the assimilation process, the language of Utsat has been structurally changed to a tonal language; however, their Islamic beliefs may have helped to keep their culture and self-identification. [ABSTRACT FROM AUTHOR]

Aim: To compare the surgical treatment outcomes between patients with colorectal liver metastases (CLM) and non-colorectal liver metastases (NCLM). Methods: The study population consisted of 132 patients undergoing hepatectomy at Tianjin Medical University Cancer Hospital between January 1996 and December 2008. Survival analyses were used to assess the differences in prognosis and survival between groups. Results: The primary tumor site was colorectal in 60 (45.5%), breast in 16 (12.1%), lung in 14 (10.6%), non-colorectal gastrointestinal in 12 (9.1%), genitourinary in 10 (7.6%), pancreatobiliary tumor ( n = 8, 6.1%) and others in 12 (9.1%). A curative liver resection was performed in all patients by pathological findings. After a median follow-up of 32 months, the overall 3- and 5-year survival rate was 44.7 and 29.5% in all patients, respectively. The 3- and 5-year survival rates were 53.3 and 36.7% for liver metastases from colorectal tumors, 62.5 and 43.8% from breast, 60.0 and 40.0% from genitourinary neoplasm, 41.7 and 25.0% from non-colorectal gastrointestinal cancer, 28.5 and 15.0% from lung, 12.5 and 0% from pancreatobiliary malignancies, and 41.7 and 8.3% from other sites, respectively. Conclusions: Hepatic resection is an effective and safe treatment for liver metastases mainly depending on primary tumor sites. Hepatic metastases from non-colorectal gastrointestinal cancer, pulmonary and pancreatobiliary malignancies have the worst prognosis; those from breast and genitourinary neoplasm show the best prognosis. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are major components of the innate self-defence system and a large number of peptides have been designed to study the mechanism of action. In the present study, a small combinatorial library was designed to study whether the biological activity of Val/Arg-rich peptides is associated with targeted cell membranes. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram-negative and Gram-positive bacteria, but weak haemolysis even at a concentration of 256 µM. CD spectra showed that the peptides formed α-helical-rich structure in the presence of negatively charged membranes. The tryptophan fluorescence and quenching experiments indicated that the peptides bound preferentially to negatively charged phospholipids over zwitterionic phospholipids, which corresponds well with the biological activity data. In the in vivo experiment, the peptide G6 decreased the bacterial counts in the mouse peritoneum and increased survival after 7 days. Overall, a high binding affinity with negatively charged phospholipids correlated closely with the cell selectivity of the peptides and some peptides in this study may be likely candidates for the development of antibacterial agents. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram-negative and Gram-positive bacteria, but weak haemolysis. The peptides bound preferentially to negatively charged phospholipids over zwitterionic phospholipids, which correspond well with the biological activity data. [ABSTRACT FROM AUTHOR]

Bacterial pathogens often harbour a type III secretion system (TTSS) that injects effector proteins into eukaryotic cells to manipulate host processes and cause diseases. Identification of host targets of bacterial effectors and revealing their mechanism of actions are crucial for understating bacterial virulence. We show that EspH, a type III effector conserved in enteric bacterial pathogens including enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli and Citrobacter rodentium, markedly disrupts actin cytoskeleton structure and induces cell rounding up when ectopically expressed or delivered into HeLa cells by the bacterial TTSS. EspH inactivates host Rho GTPase signalling pathway at the level of RhoGEF. EspH directly binds the DH-PH domain in multiple RhoGEFs, which prevents their binding to Rho and thereby inhibits nucleotide exchange-mediated Rho activation. Consistently, infection of mouse macrophages with EPEC harbouring EspH attenuates phagocytosis of the bacteria as well as FcγR-mediated phagocytosis. EspH represents the first example of targeting RhoGEFs by bacterial effectors, and our results also reveal an unprecedented mechanism used by enteric pathogens to counteract the host defence system. [ABSTRACT FROM AUTHOR]

Abstract: JNK pathway is an important pro-apoptotic kinase cascade mediating cell death in response to a variety of extracellular stimuli including excitotoxicity, which results in selective and delayed neuronal death in the hippocampal CA1. On the contrary, activation of the protein kinase Akt, which is controlled by the opposing actions of PI3K and PTEN, contributes to enhanced resistance to apoptosis through multiple mechanisms. We here demonstrate that the temporal pattern of Akt activation reversely correlates with JNK1/2 activation following various time points of ischemic reperfusion. However, the activation of JNK1/2 could be decreased by the elevation of Akt activation via increasing the tyrosine phosphorylation of PTEN by bpv(pic), a potent PTPases inhibitor for PTEN, or by intracerebroventricular infusion of PTEN antisense oligodeoxynucleotides (AS-ODNs). In contrast, JNK1/2 activation was significantly increased by preventing PTEN degradation after pretreatment with proteasome inhibitor. The neuroprotective effects of bpv(pic) and PTEN AS-ODNs were significant in the CA1 subfield after transient global ischemia. In conclusion, the present results clearly show that PTEN plays a key regulatory role in the cross-talk between cell survival PI3K/Akt pathway and pro-death JNK pathway, and raise a new possibility that agents targeting phosphatase PTEN may offer a great promise to expand the therapeutic options in protecting neurons form ischemic brain damage. [Copyright &y& Elsevier]

SUMMARY Mangroves grow in tropical/subtropical intertidal habitats with extremely high salt tolerance. Trehalose and trehalose‐6‐phosphate (T6P) have an alleviating function against abiotic stress. However, the roles of trehalose in the salt tolerance of salt‐secreting mangrove Avicennia marina is not documented. Here, we found that trehalose was significantly accumulated in A. marina under salt treatment. Furthermore, exogenous trehalose can enhance salt tolerance by promoting the Na+ efflux from leaf salt gland and root to reduce the Na+ content in root and leaf. Subsequently, eighteen trehalose‐6‐phosphate synthase (AmTPS) and 11 trehalose‐6‐phosphate phosphatase (AmTPP) genes were identified from A. marina genome. Abscisic acid (ABA) responsive elements were predicted in AmTPS and AmTPP promoters by cis‐acting elements analysis. We further identified AmTPS9A, as an important positive regulator, that increased the salt tolerance of AmTPS9A‐overexpressing Arabidopsis thaliana by altering the expressions of ion transport genes and mediating Na+ efflux from the roots of transgenic A. thaliana under NaCl treatments. In addition, we also found that ABA could promote the accumulation of trehalose, and the application of exogenous trehalose significantly promoted the biosynthesis of ABA in both roots and leaves of A. marina. Ultimately, we confirmed that AmABF2 directly binds to the AmTPS9A promoter in vitro and in vivo. Taken together, we speculated that there was a positive feedback loop between trehalose and ABA in regulating the salt tolerance of A. marina. These findings provide new understanding to the salt tolerance of A. marina in adapting to high saline environment at trehalose and ABA aspects. [ABSTRACT FROM AUTHOR]

Anthrax lethal toxin (LT) is known to induce NLRP1B inflammasome activation and pyroptotic cell death in macrophages from certain mouse strains in its metalloprotease activity‐dependent manner, but the underlying mechanism is unknown. Here, we establish a simple but robust cell system bearing dual‐fluorescence reporters for LT‐induced ASC specks formation and pyroptotic lysis. A genome‐wide siRNA screen and a CRISPR‐Cas9 knockout screen were applied to this system for identifying genes involved in LT‐induced inflammasome activation. UBR2, an E3 ubiquitin ligase of the N‐end rule degradation pathway, was found to be required for LT‐induced NLRP1B inflammasome activation. LT is known to cleave NLRP1B after Lys44. The cleaved NLRP1B, bearing an N‐terminal leucine, was targeted by UBR2‐mediated ubiquitination and degradation. UBR2 partnered with an E2 ubiquitin‐conjugating enzyme UBE2O in this process. NLRP1B underwent constitutive autocleavage before the C‐terminal CARD domain. UBR2‐mediated degradation of LT‐cleaved NLRP1B thus triggered release of the noncovalent‐bound CARD domain for subsequent caspase‐1 activation. Our study illustrates a unique mode of inflammasome activation in cytosolic defense against bacterial insults. Synopsis: Anthrax lethal toxin cleaves its host sensor NLRP1B and causes inflammasome activation. Genetic screens identify the N‐end rule ubiquitin ligase UBR2 that mediates proteasomal degradation of the cleaved NLRP1B, causing the release of its CARD domain for caspase‐1 activation. siRNA and CRISPR‐Cas9 screens identify an N‐end rule ubiquitin ligase UBR2 that mediates anthrax lethal toxin‐induced NLRP1B inflammasome activation.UBR2 partners with UBE2O to induce proteasomal degradation of lethal toxin‐cleaved NLRP1B.UBR2‐mediated degradation releases NLRP1B CARD domain for caspase‐1 activation. [ABSTRACT FROM AUTHOR]

Implantable photonic probes are of increasing interest to the field of biophotonics and in particular, optogenetic neural stimulation. Active probes with onboard light emissive elements allow for electronic multiplexing and can be manufactured through existing microelectronics methods. However, as the optogenetics field moves towards clinical practice, an important question arises as to whether such probes will cause excessive thermal heating of the surrounding tissue. Light emitting diodes typically produce more heat than light. The resultant temperature rise of the probe surface therefore needs to be maintained under the regulatory limit of 2°C. This work combines optical and thermal modelling, which have been experimental verified. Analysis has been performed on the effect of probe/emitter geometries, emitter, and radiance requirements. Finally, the effective illumination volume has been calculated within thermal limits for different probe emitter types and required thresholds. Implantable photonic probes are of increasing interest to the field of biophotonics and in particular, optogenetic neural stimulation. Active probes with onboard light emissive elements allow for electronic multiplexing and can be manufactured through existing microelectronics methods. However, as the optogenetics field moves towards clinical practice, an important question arises as to whether such probes will cause excessive thermal heating of the surrounding tissue. Light emitting diodes typically produce more heat than light. The resultant temperature rise of the probe surface therefore needs to be maintained under the regulatory limit of 2°C. This work combines optical and thermal modelling which have been experimental verified. Analysis has been performed on the effect of probe/emitter geometries, emitter, and radiance requirements. Finally, the effective illumination volume has been calculated within thermal limits for different probe emitter types and required thresholds. [ABSTRACT FROM AUTHOR]

The title compound, C(20)H(30)ClNO(3), was obtained via a tandem asymmetric Michael addition-elimination reaction of (5S)-3,4-dichloro-5-(l-menth-yloxy)-2(5H)-furan-one and diallyl-amine in the presence of potassium fluoride. The mol-ecular structure contains an approximately planar five-membered furan-one ring [maximum atomic deviation = 0.0221 (3) Å] and a six-membered ring adopting a chair conformation.