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Water electrolysis is a promising technology to produce hydrogen but it was severely restricted by the slow oxygen evolution reaction (OER). Herein, we firstly reported an advanced electrocatalyst of MOF-derived hollow Zn–Co–Ni sulfides (ZnS@Co9S8@Ni3S2-1/2, abbreviated as ZCNS-1/2) nanosword arrays (NSAs) with remarkable hydrogen evolution reaction (HER), OER and corresponding water electrolysis performance. To reach a current density of 10 mA cm−2, the cell voltage of assembled ZCNS-1/2//ZCNS-1/2 for urea electrolysis (1.314 V) is 208 mV lower than that for water electrolysis (1.522 V) and stably catalyzed for over 15 h, substantially outperforming the most reported water and urea electrolysis electrocatalysts. Density functional theory calculations and experimental result clearly reveal that the properties of large electrochemical active surface area (ECSA) caused by hollow NSAs and fast charge transfer resulted from the Co9S8@Ni3S2 heterostructure endow the ZCNS-1/2 electrode with an enhanced electrocatalytic performance.

The large yellow croaker (Larimichthys crocea) is an economically important marine species with the highest annual production among the farmed marine fishes in China. However, the aquaculture industry of this species is suffering from severe problems that include weakened disease resistance, decreased growth rate, and reduced meat quality due to frequent inbreeding. Genome editing, which has a huge potential for solving those problems by introducing favorable genetic changes, is not yet available for the large yellow croaker. Here, we pioneered the techniques of embryo microinjection and genome editing using the CRISPR/Cas9 system in this species. Recombinant plasmids encoding green fluorescent protein (GFP) were introduced into the fertilized eggs of L. crocea by microinjection before the chorion had hardened. A high survival rate (40%) and GFP-positive larvae rate (81.8%) were achieved, indicating that the microinjection technique in L. crocea was successfully established. On this basis, Cas9 mRNA and sgRNA targeting the tyrosinase a gene in L. crocea (Lc-tyra) were co-injected into fertilized eggs of L. crocea. Mutant individuals with insertion and deletion mutations of Lc-tyra were detected. These results indicated that the CRISPR/Cas9-based genome editing technology established herein could efficiently introduce mutations at a specific site in the L. crocea genome. This method provides the potential for genetic improvement and functional genomic study in this species. This is the first report on effective CRISPR/Cas9-based genome editing in L. crocea.

Intracellular cyclic GMP (cGMP) inhibits platelet function. Platelet cGMP levels are controlled by phosphodiesterase 5A (PDE5A)-mediated degradation. However, the exact role of PDE5A in platelet function and thrombus formation remains poorly understood. In this study, we characterized the role of PDE5A in platelet activation and function. Platelets were isolated from wild type or PDE5A−/− mice to measure platelet aggregation, activation, phosphatidylserine exposure (annexin-V binding), reactive oxygen species (ROS) generation, platelet spreading as well as clot retraction. Cytosolic calcium mobilization was measured using Fluo-4 AM by a microplate reader. Western blot was used to measure the phosphorylation of VASP, ERK1/2, p38, JNK, and AKT. FeCl3-induced arterial thrombosis and venous thrombosis were assessed to evaluate the in vivo hemostatic function and thrombus formation. Additionally, in vitro thrombus formation was assessed in a microfluidic whole-blood perfusion assay. PDE5A-deficient mice presented significantly prolonged tail bleeding time and delayed arterial and venous thrombus formation. PDE5A deficiency significantly inhibited platelet aggregation, ATP release, P-selectin expression, and integrin aIIbb3 activation. In addition, an impaired spreading on collagen or fibrinogen and clot retraction was observed in PDE5A-deficient platelets. Moreover, PDE5A deficiency reduced phosphatidylserine exposure, calcium mobilization, ROS production, and increased intracellular cGMP level along with elevated VASP phosphorylation and reduced phosphorylation of ERK1/2, p38, JNK, and AKT. In conclusion, PDE5A modulates platelet activation and function and thrombus formation, indicating that therapeutically targeting it might be beneficial for the treatment of thrombotic diseases.

Hypoxia-inducible factor-1α (HIF-1α) involves in redox reactions. Considering the role of reactive oxygen species (ROS) in platelet function, whether it regulates platelet function remains unclear. Using an inhibitor of HIF prolyl–hydroxylase, IOX-2, we intend to investigate its effect on platelet function. Human platelets were treated with IOX-2 (0, 10, 25, and 50 μM) followed by analysis of platelet aggregation, granule secretion, receptor expression, platelet spreading, or clot retraction. Additionally, IOX-2 (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time and arterial thrombosis. IOX-2 significantly inhibited collagen-related peptide (CRP; 0.25 μg/mL) or thrombin (0.03 U/mL)-induced platelet aggregation and ATP release dose dependently without affecting P-selectin expression and the surface levels of glycoprotein (GP)Ibα, GPVI, or αIIbβ3. In addition, IOX-2-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction. Moreover, IOX-2 administration into mice significantly impaired the in vivo hemostatic function of platelets and arterial thrombus formation without affecting the number of circulating platelets and coagulation factors (FVIII and FIX). Further, IOX-2 significantly upregulated HIF-1α in platelets, decreased ROS generation, and downregulated NOX1 expression. Finally, IOX-2 increased the phosphorylation level of VASP (Ser157/239), and inhibited the phosphorylation of p38 (Thr180/Tyr182), ERK1/2 (Thr202/Tyr204), AKT (Thr308/Ser473), and PKCδ (Thr505) in CRP- or thrombin-stimulated platelets. In conclusion, inhibition of HIF prolyl-hydroxylase modulates platelet function and arterial thrombus formation, possibly through upregulation of HIF-1α expression and subsequent inhibition of ROS generation, indicating that HIF-1α might be a novel target for the treatment of thrombotic disorders.

Abrasive particles have a crucial influence on the material removal rate and surface quality of the workpiece in tribochemical mechanical polishing. Therefore, this article selects a self-made catalytic abrasive cluster to polish the 6H-SiC and explore the removal mechanism of polishin silicon carbide in the new catalytic abrasive cluster. The tribochemical mechanical polishing test and friction and wear test of 6H-SiC were carried out with three different abrasives, and the evaluation parameters such as material removal rate, surface roughness and friction coefficient were obtained. Quanta 200 scanning electron microscope(SEM) and oxfobrdinca 250 energy dispersive spectrometer (EDS) and x-ray diffraction(XRD)diffractometer were used to observe the surface, analyze the elements and determine the composition of silicon carbide workpiece after tribochemical mechanical polishing. The experimental result shows that oxygen is produced in the tribochemical mechanical polishing of silicon carbide by catalytic abrasive cluster, which makes the silicon carbide surface generate SiO2 shear film that is easy to be removed. Comparing with iron-based white corundum mixed abrasive and Al2O3 abrasive, the catalytic abrasive cluster has better processability for 6H-SiC, and the material removal rate can reach to 42.928nm/min.

Clarifying the influence of the dress process parameters of the abrasive water jet on the dressing effect of fixed-abrasive pads (FAPs) is a prerequisite for online controllable dressing of abrasive water jets. This paper uses three factors and three horizontal response surface methods to explore the influence of jet pressure, abrasive concentration, and nozzle angle on FAP dressing quality. The prediction model of the material removal rate of a FAP machined using three process parameters is established. The influence of pairwise interactions of the three process parameter variables on the dressing effect and the optimal process parameters under each target is analyzed. Finally, the optimal process parameters predicted by the model are verified by experiments. The results show that the best dressing parameters with the MRR of the workpiece as the response value are as follows: jet pressure 3.8 MPa, abrasive concentration 3%, and nozzle angle 73°. The predicted value of the optimal process performance is 464.574 nm/min, and the experimental verification result is 469.136 nm/min; the error between the experimental value and the predicted value is within a reasonable range.

Electrocatalytic water splitting is identified as one of the most promising solutions to energy crisis. The CoSe2@NiSe2 materials were first prepared and in situ grown on nickel foam by typical hydrothermal and selenification process at 120 °C. The results show that the CoSe2@NiSe2 material used as the 3D substrates electrode can maximize the synergy between the CoSe2 and NiSe2, and also exhibits high efficiency of water splitting reaction. The lower overpotential of only 235 mV is presented to attain 20 mA cm−2 compared to the benchmark of RuO2 electrodes (270 mV @ 20 mA cm−2). Besides, the CoSe2@NiSe2 material also shows a remarkable improved hydrogen evolution reaction activity compared to NiSe2 (192 mV@10 mA cm−2) and Co precursor catalysts (208 mV@10 mA cm−2) individually, which a low overpotential of only 162 mV is achieved at 10 mA cm−2. The CoSe2@NiSe2 catalysts exhibit excellent water splitting performance (cell voltage of 1.50 V@ 10 mA cm−2) under alkaline conditions. It was proved that the high water splitting performance of the catalyst is attributed to high electrochemical activity area and synergistic effect. The work offers new ideas for the exploitation of synergistic catalysis of composite catalysts and adds new examples for the exploitation of efficient, better and relatively non-toxic electrocatalysts.

Through a structure-based molecular hybridization strategy, a series of new N-acylhydrazone derivatives containing the benzothiazole and indole based moiety were designed, synthesized and screened for in vitro antiproliferative activity against Hep G2 cancer cell line. One compound (7a) exhibited excellent antiproliferative activity with IC50 values of 0.78 μM against Hep G2. In addition, C-5 substitutions of the indole ring of target compounds might be crucial for their cytotoxic activities. Additionally, the relative configuration of target compounds was confirmed as the E isomer. Further chemical manipulation of derivative 7a can make it possible to obtain new potential antitumor agents.

Salidroside is the main bioactive component in Rhodiola rosea and possesses multiple biological and pharmacological properties. However, whether salidroside affects platelet function remains unclear. Our study aims to investigate salidroside’s effect on platelet function. Human or mouse platelets were treated with salidroside (0-20 μM) for 1 hour at 37°C. Platelet aggregation, granule secretion, and receptors expression were measured together with detection of platelet spreading and clot retraction. In addition, salidroside (20 mg/kg) was intraperitoneally injected into mice followed by measuring tail bleeding time, arterial and venous thrombosis. Salidroside inhibited thrombin- or CRP-induced platelet aggregation and ATP release and did not affect the expression of P-selectin, glycoprotein (GP) Ibα, GPVI and αIIbβ3. Salidroside-treated platelets presented decreased spreading on fibrinogen or collagen and reduced clot retraction with decreased phosphorylation of c-Src, Syk and PLCγ2. Additionally, salidroside significantly impaired hemostasis, arterial and venous thrombus formation in mice. Moreover, in thrombin-stimulated platelets, salidroside inhibited phosphorylation of AKT (T308/S473) and GSK3β (Ser9). Further, addition of GSK3β inhibitor reversed the inhibitory effect of salidroside on platelet aggregation and clot retraction. In conclusion, salidroside inhibits platelet function and thrombosis via AKT/GSK3β signaling, suggesting that salidroside may be a novel therapeutic drug for treating thrombotic or cardiovascular diseases.

In the present study, the neurotoxicity and mechanisms of di-(2-ethylhexyl) phthalate (DEHP) exposure on pubertal normal (P-normal) and pubertal type 2 diabetes mellitus (P-T2DM) mice were investigated by typical neurobehavioral methods and transcriptome analysis. Pubertal male ICR mice were orally exposed to DEHP (0.18, 1.8, 18 and 180 mg/kg/d) for 3 weeks. In Open field test, DEHP significantly increased the time in central area staying and decreased the total distance and clockwise (CW) rotation of P-normal and P-T2DM mice. Morris water maze showed that DEHP significantly increased the latency in locating platform and decreased the original platform quadrant and residence time in target quadrant of P-normal and P-T2DM mice. Transcriptome analysis results revealed the effects of DEHP exposure on neural signaling pathway including biogenic amines neurotransmitters, nerve receptors, neurobiological processes, etc. Enzyme-linked immunosorbent assay (ELISA) and western blotting results showed that DEHP significantly decreased the contents of 5-HT, cAMP, GABA and Ca2+, the levels of CREB, phosphorylation of PKA, ERK1/2 and CREB, increased the levels of CaM and phosphorylation of CaMKII in P-normal and P-T2DM mice. Factorial analysis results showed that P-T2DM mice were more sensitive than those of P-normal mice. The potential neurotoxicity mechanism of DEHP may be synergistically mediated by the cAMP-PKA-ERK1/2-CREB signaling and the Ca2+ signaling pathway.

Cancer, as one of the most life-threatening diseases, has attracted the attention of researchers to develop drugs with minimal side effects. The bioactive macromolecules, such as the polysaccharides, are considered the potential candidates against cancer due to their anti-tumor activities and non-toxic characteristics. The present review provides an overview on polysaccharides' extraction, isolation, purification, mechanisms for their anti-tumor activities, structure-activity relationships, absorption and metabolism of polysaccharides, and the applications of polysaccharides in anti-tumor therapy. Numerous research showed extraction methods of polysaccharides had a significant influence on their activities. Additionally, the anti-tumor activities of the polysaccharides are closely related to their structure, while molecular modification and high bioavailability may enhance the anti-tumor activity. Moreover, most of the polysaccharides exerted an anti-tumor activity mainly through the cell cycle arrest, anti-angiogenesis, apoptosis, and immunomodulation mechanisms. Also, recommendations were made to utilize the polysaccharides against cancer.

TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of the main derivatives of TBBPA, has been widely detected in environmental samples and been discovered to be potential neurotoxic. In this study, the juvenile zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure, and to reveal the neurotoxicity susceptibility in different sexes. Behavioral studies revealed that TBBPA-DHEE could significantly reduce the swimming velocity, maximum acceleration and cumulative duration of high-speed mobility, significantly increasing the cumulative duration of low-speed mobility and average social distance. It significantly reduced the contents of ATP, glutamate and Ca

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a protein tyrosine phosphatase that negatively regulates T-cell signaling. However, whether it is expressed and functions in platelets remains unknown. Here we investigated the expression and role of PTPN22 in platelet function. We reported PTPN22 expression in both human and mouse platelets. Using PTPN22−/− mice, we showed that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation without affecting venous thrombosis and the coagulation factors VIII and IX. Consistently, PTPN22-deficient platelets exhibited enhanced platelet aggregation, granule secretion, calcium mobilization, lamellipodia formation, spreading, and clot retraction. Quantitative phosphoproteomic analysis revealed the significant difference of phosphodiesterase 5A (PDE5A) phosphorylation in PTPN22-deficient platelets compared with wild-type platelets after collagen-related peptide stimulation, which was confirmed by increased PDE5A phosphorylation (Ser92) in collagen-related peptide–treated PTPN22-deficient platelets, concomitant with reduced level and vasodilator-stimulated phosphoprotein phosphorylation (Ser157/239). In addition, PTPN22 interacted with phosphorylated PDE5A (Ser92) and dephosphorylated it in activated platelets. Moreover, purified PTPN22 but not the mutant form (C227S) possesses intrinsic serine phosphatase activity. Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction, and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

Zhongwei goat is a unique Chinese native goat breed for excellent lamb fur. The pattern of flower spikes of the lamb fur was significantly reduced due to the reduction of the bending of the hair strands with growth. In order to explore the molecular mechanism underlying hair bending with growth, we performed the comprehensive analysis of transcriptome and proteome of skins from 45-days, 108-days and 365-days goat based on TMT-based quantitative proteomics and RNA-seq methods. In the three comparison groups, 356, 592 and 282 differentially expressed proteins (DEPs) were screened, respectively. KEGG pathway analysis indicated that DEPs were significantly enriched in a set of signaling pathways related to wool growth and bending, such as ECM-receptor interaction, PI3K-Akt signaling pathway, PPAR signaling pathway, protein digestion and absorption, and metabolic pathways. In addition, 20 DEPs abundance of goat skin at three development stages were examined by PRM method, which validated the reliability of proteomic data. Among them, KRT and collagen alpha family may play an important role in the development of goat hair follicle and wool bending. COL6A1, COL6A2, CRNN, TNC and LOC102178129 were identified as candidate genes based on combined analysis of transcriptome and proteome data and PRM quantification. Our results identify the differential expressed proteins as well as pathways related to the wool bending of Zhongwei goats and provide a theoretical basis for further revealing the molecular mechanism underlying wool bending of goats.

Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.

The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.

In this study, the immature mice were taken to assess the potential neurological toxicity of lead (Pb) and di (n-butyl) phthalates (DBP) combination exposure. Mouse administration with DBP combination with Pb exhibited longer escape latency and lower average number of crossing of the platform. Pb content in the tissues was increased, especially in the brain, after Pb exposure as compared to those without Pb exposure. The alterations of oxidative damages in tissues (MDA and SOD) and biochemical indicators in the brain (AChE, TNOS, and iNOS) were observed, as well as the synergistic effect of joint exposure. Expressions of apoptosis-related protein (bax/bcl-2 ratio and caspase-3) were significantly increased in the hippocampus, while the bcl-2 was remarkably decreased and no significant differences were observed on the bax. The results suggested that the possible mechanisms for the learning and memory ability impairments were as follows: Firstly, the combination exposure induced the occurrence of lipid peroxidation in the brain, leading to damage to the brain cells. Secondly, it destroyed the normal metabolic balance of ACh, causing nerve damage in mice. Thirdly, it induced apoptosis in mouse hippocampal cells. The overall findings revealed that Pb and DBP co-exposure greatly influenced the developmental nervous system and accompanied with synergistic toxic effect.

Exploiting environmentally friendly and relatively low toxic oxygen evolution reaction (OER) electrocatalysts to improve water oxidation is still one of the biggest difficulties at the moment for overall water splitting. In this work, molybdenum-doped cobalt iron layered double hydroxide (CoFeMo LDH) nanorods are in situ grown on nickel foam (NF) for the first time using a typical and feasible hydrothermal approach. When the CoFeMo LDH/NF sample acts as an electrocatalyst, it presents superior OER performance, requiring small overpotentials of only 240 and 350 mV at 100 and 500 mA cm-2 with a low Tafel slope of 82.8 mV dec-1 in an alkaline medium. Additionally, the combination of Mo doping and CoFe LDH results in the enhanced conductivity of the material. The density functional theory calculation and experimental results prove that the electronic structure tailoring, abundant active sites and the existence of crystalline-amorphous phase boundaries can result in the high catalytic activity of the material. This work presents a novel and feasible approach to design highly efficient and robust catalysts based on advanced LDH-based materials for OER electrocatalysis.

To observe the antibacterial effect of Ag2, 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric method was used to detect minimal inhibitory concertation (MIC) of Ag-TiOAg-TiOBoth Ag-TiO

Matrine is a naturally occurring alkaloid and possesses a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, anti-inflammatory effects. However, whether it affects platelet function and thrombosis remains unclear. This study aims to evaluate the effect of matrine on platelet function and thrombus formation. Human platelets were treated with matrine (0–1 mg/ml) for 1 h at 37°C followed by measuring platelet aggregation, granule secretion, receptor expression by flow cytometry, spreading and clot retraction. In addition, matrine (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time, arterial and venous thrombus formation. Matrine dose-dependently inhibited platelet aggregation and ATP release in response to either collagen-related peptide (Collagen-related peptide, 0.1 μg/ml) or thrombin (0.04 U/mL) stimulation without altering the expression of P-selectin, glycoprotein Ibα, GPVI, or αIIbβ3. In addition, matrine-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction along with reduced phosphorylation of c-Src. Moreover, matrine administration significantly impaired the in vivo hemostatic function of platelets, arterial and venous thrombus formation. Furthermore, in platelets stimulated with CRP or thrombin, matrine significantly reduced Reactive oxygen species generation, inhibited the phosphorylation level of ERK1/2 (Thr202/Tyr204), p38 (Thr180/Tyr182) and AKT (Thr308/Ser473) as well as increased VASP phosphorylation (Ser239) and intracellular cGMP level. In conclusion, matrine inhibits platelet function, arterial and venous thrombosis, possibly involving inhibition of ROS generation, suggesting that matrine might be used as an antiplatelet agent for treating thrombotic or cardiovascular diseases.

Environmental friendly sodium alginate (SA) cannot be used as a binder in aqueous batteries due to its high solubility in water. A water-insoluble polyvinylidene difluoride (PVDF) binder has been widely applied for an aqueous battery, in which the toxic and expensive organic solvent of N-methy-2-pyrrolidone (NMP) is required during the coating process. Herein, we report that the water-soluble SA can be utilized as a binder in aqueous Zn batteries because SA could cross-link with the Zn2+ ion to form a water-insoluble and mechanically super strong binder for electrodes. Aqueous Zn||LiFePO4 cells are assembled to demonstrate the performance of the SA binder for LiFePO4 cathodes. Due to the high adhesion strength of cross-linked Zn-SA, LiFePO4 with the SA binder displays a high capacity retention of 93.7% with a high Coulombic efficiency of nearly 100% after 100 cycles at a 0.2 C rate, while the capacity of LiFePO4 with the PVDF binder quickly decays to 84.7% after 100 cycles at 0.2 C. In addition, the LiFePO4 cathode with the SA binder also has smaller redox polarization, faster ion diffusion rate, and more favorable electrochemical kinetics than that with the PVDF binder.

As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) is associated with various health risks, especially on immune system, which is sensitive to environmental pollutants. In addition, there is a problem of multi-index estimation and lack of comprehensive evaluation in immune toxicity study. In this study, the immunotoxicity of BDE-209 was systematically estimated from the aspects of immunopathology, humoral immunity, cellular immunity and non-specific immunity, etc., and integrated biomarker responses (IBR) combined with principal component analysis was applied to comprehensively evaluate the immunotoxicity of BDE-209 and its self-recovery after discontinuation. Results showed that BDE-209 exposure could cause immunotoxicity. This response seems to depend on (1) atrophying immune organs (thymus and spleen), hepatomegaly accompanied by increasing aspartate aminotransferase and oxidative stress;(2) changing humoral (immunoglobulins) and cellular (lymphocyte proliferation and cytokine secretion) immunity indices; (3) altering related expressions of genes, and further leading to imbalance of Th1/Th2 (Th, helper T cell). Integrated biomarker responses (IBR) companied with principal component analysis selected five biomarkers (mRNA expression of GATA-3, malondialdehyde level in thymus, count of white blood cell, serum IgG and lipopolysaccharide-induced splenic lymphocyte proliferation) to clarify the immunotoxicity induced by BDE-209. Furthermore, IBR combined with factorial analysis revealed that the effect of BDE-209 could be dose-dependently reduced after withdrawal of BDE-209. Overall results suggested that BDE-209 has immunotoxicity on adult Balb/c mice, whereas this immunotoxicity could be reduced by the self-regulation of organisms to some extent.

To explore the comprehensive utilization of agricultural wastes, solid-state fermentation was applied to residues of Flammulina velutipes (F. velutipes) and vinegar for use in culturing earthworms. Fermentation technology and earthworm culture technology were optimized by response surface methodology in this study. The optimal fermentation product for earthworm culture was obtained under an inoculum amount of 7.5%, fermentation temperature of 25.6 °C, pH 7.7 and protein content of 18.23%. The optimum culture conditions were a culture density of 18.4 individuals/dm3, an initial pH of 7.2 and a fermentation temperature of 26.8 °C. The daily weight gain multiplier of earthworms was 0.0387 units, and it increased significantly compared with that of the unfermented and cow dung groups. The fermented product of F. velutipes and vinegar residues could be used to culture earthworms and improve the metabolism and antioxidant capacities of earthworms. This provides a new way to comprehensively utilize agricultural waste resources.

Aerogel nanocomposites from biomass are one of the attractive emerging materials in the field of material chemistry and catalyst industry, but their lower catalytic efficiency and mechanical performance have limited their wide range applications. In this work, alginate-based aerogels with perfect catalytic performance and great mechanical strength were prepared through incorporating graphene oxide (GO) and SiO2 via a simple one-pot reaction. GO played as the second catalytic activity sites and endowed the aerogels the perfect catalytic performance (conversion of phenol reached 90.1 % in phenol hydroxylation reaction). Meanwhile, SiO2 and GO could improve the particle compressive strength of the aerogel to 36.0 kg/cm2. This alginate-based aerogel provides a novel and environmentally friendly catalyst for next generation catalytic industry.

In this study, a Se-deficient mice model was successfully developed by feeding a Se-deficient diet (0.02 mg Se/kg diet) for 4 weeks, and Se supplementation by Se-polysaccharides (Se-GFP-22) was lasted for 4 weeks. The immunomodulatory activity and Se supplementation of Se-GFP-22 from Se-enriched G. frondosa was investigated. Results showed that Se-GFP-22 remarkably enhanced glutathione peroxidase (GSH-Px) and thioredoxin reductase (TrxR) activities in liver, kidney and plasma, and serum, liver, spleen and kidney Se levels of Se-deficient mice. Se-GFP-22 increased the thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes and DTH reaction. Se-GFP-22 caused significant increments in cytokine (IL-1β, TNF-α and IFN-γ) levels and Ig G, Ig A, Ig M and Ig E levels. Se-GFP-22 exhibited superior immunomodulatory effects than GFP-22. These findings indicated that Se-GFP-22 promote the protective effects against Se deficiency-induced immunosuppression and could be a potential immunomodulatory agent and a dietary Se-supplement.

To assess the immunomodulatory and antioxidant activities of a Se-polysaccharide from Se-enriched G. frondosa (Se-GFP-22), immunosuppressed mice models were generated by cyclophosphamide (CTX) administration and then treated with Se-GFP-22. Results showed that Se-GFP-22 could increase thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes, DTH reaction, serum hemolysin formation and immunoglobulin (Ig G, Ig A and Ig M) levels in CTX-treated mice. Se-GFP-22 significantly enhanced the antioxidant activity in CTX-treated mice, as shown by the evaluation of GSH-Px, SOD and CAT activities, as well as MDA levels in serum, liver and kidney. Se-GFP-22 strongly stimulated inflammatory cytokines (IL-2 and IFN-γ) and NO productions by up-regulating mRNA expressions of IL-2, IFN-γ and iNOS. Se-GFP-22 possessed the immunomodulatory activity by up-regulating various transcription factors (JNK, ERK, and p38) in MAPKs signaling pathways. This study suggested that Se-GFP-22 may provide an alternative strategy in lessening chemotherapy-induced immunosuppression.

Antibiotics have become common pollutants in the environment. In most cases, the antibiotics in the environment exist as mixtures, posing joint effects on the organisms. Therefore, the mixture toxicity of the antibiotics can better reflect their environmental risks. In this paper, three types of commonly used antibiotics, i.e., sulfonamides (SAs), SA potentiators (SAPs) and tetracyclines (TCs) were investigated for their binary and tertiary mixture toxicity on three bacteria, Escherichia coli (E. coli), Vibrio fischeri (V. fischeri) and Bacillus subtilis (B.subtilis). It was found that SA-SAP mixtures and SA-SAP-TC mixtures presented synergetic effects on the three bacteria, while SA-TC and SAP-TC mixtures showed antagonistic effects. QSAR investigation suggested that the actual concentration ratio of the components in a mixture could vary a lot from the designed concentration ratio; moreover, the TCs in the ternary mixtures altered the toxic ratio of SAs and SAPs, which lead to the varying joint effects of the ternary mixtures on different bacteria. The present research proposes a novel idea for the mechanistic study of the mixture toxicity, both theoretically and methodologically; and the QSAR studies provide a reference for the prediction of the mixture toxicity, which could be helpful to the risk assessment on joint exposure to antibiotic mixtures.

Mortality prediction for patients in intensive care unit (ICU) is necessary to prioritize resources as well as to help the medical staff to make decisions, and hence more accurate methods for identifying high risk patients are very important for improving clinical care. However, many existing approaches including some scoring systems now being used in the hospital are not good enough since they try to establish a global/average offline model, which may be unsuitable for a specific patient. Thus, a more robust and effective monitoring model adaptable to individual patients is needed. To establish a more personalized model, this study proposes a two-step framework, in which the first step is for clustering and while the second one is for mortality predication. A novel method combining just-in-time learning (JITL) and extreme learning machine (ELM), referred to JITL-ELM, is proposed for mortality prediction, which applies global optimization of variables and neighborhood of appropriate samples to build an accurate patient-specific model. In addition, a simplified JITL-ELM with less key physiological variables is developed. In the experiment, 4000 real clinical records of ICU patients are collected to validate the proposed algorithm, of which the AUC index is 0.8568, which is much better than the existing traditional global/average models, and furthermore the simplified JITL-ELM still performs well.

Transition metal oxides are well-known for their excellent activity and stability during oxygen evolution reaction process, while their hydrogen evolution reaction performance still is unsatisfactory. Herein, we firstly introduced the selectively Se-doped Co3O4@CeO2 nanoparticle-dotted nanoneedle arrays through three continuous operations of mild hydrothermal, air calcination and selective selenation. The remarkable HER and OER performance of SCCN-1 resulted from abundant oxygen vacancy as well the heterostructure and was testified by the overpotentials at a certain current density: 48 mV@10 mA cm−2 and 175 mV@50 mA cm−2 for HER; 188 mV@20 mA cm−2 and 293 mV@50 mA cm−2 for OER. In addition, the SCCN-1//SCCN-1 electrode couple only required a small cell voltage of 1.49 V to deliver a current density of 10 mA cm−2, which outperformed most recently reported bifunctional catalyst and exhibited outstanding stability in 1.0 M KOH over 12 h for overall water splitting process. Density functional theory calculations show that Se-doped Co3O4 exhibits stronger water adsorption energy compared to CeO2, which proves that Se-doped Co3O4 is a true reactive center. It's worth noting that this selective Se doping strategy is versatile to improve the HER activity of transition metal oxides and further use for catalyzing water splitting process.

Long non-coding RNAs (lncRNAs) have been demonstrated that they not only play important roles in tumorgenicity but also associate with cancer prognosis. Recently, highly up-regulated in liver cancer (HULC) is abnormally expressed in liver cancer and other cancers, and participated in cancers progression; however, it is unclear whether its expression is associated with prognosis. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value and metastasis of HULC in various cancer patients. The meta-analysis was performed using a systematic search of PubMed, Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to assess its prognosis and metastasis in human cancer. A total of 1134 patients from 11 studies were included. The results indicated that overexpression of HULC was associated with poor overall survival (OS) (HR = 1.89, 95% CI: 1.32-2.47). Furthermore, subgroup analysis showed that cancer type (digestive system cancer or non-digestive system cancers) and sample size (more or less than 100) significantly associated between HULC and OS. In addition, overexpression of HULC expression was significantly associated with metastasis in cancers (HR = 2.67, 95% CI: 0.94-4.39). The meta-analysis indicated that lncRNA HULC could serve as a new molecular marker for cancer prognosis and metastasis.

The differential expression of soluble programmed death ligand 1 (sPD-L1) has been found in some cancers; however, the correlation between sPD-L1 expression and prognosis value in tumour is still unclear. Here, we conducted a meta-analysis and systematic review to assess the prognostic value of sPD-L1 in patients with cancer. Eligible studies were searched for in the databases including PubMed, Web of Science, ScienceDirect and Wiley Online Library database. The pooled hazard ratios (HRs) with a 95% confidence interval (95%CI) were calculated to assess the prognostic significance of sPD-L1 in human cancer. Eight studies and 1102 patients with cancer were included in the final analysis, and the combined analysis indicated that a higher level of sPD-L1 was associated with worse overall survival (OS) (HR = 1.60, 95%CI: 1.21-1.99). Furthermore, statistical significance was also observed in subgroup analysis stratified by the cancer type (haematological neoplasms or non-haematological neoplasms), sample size (more or less than 100), cut-off value of sPD-L1 (more or less than 6.51 ng/ml) and ethnicity (Asian or European). The meta-analysis indicates that circulating sPD-L1 changes may serve as a useful biomarker for cancer prognosis, and higher level of sPD-L1 may also be associated with poor outcomes in patients with cancer.

The identification of genome-wide selection signatures can provide insights on the mechanisms of natural and/or artificial selection and uncover genes related to biological functions and/or phenotypes. Tibetan sheep are an important livestock in Tibet, providing meat and wool for Tibetans who are renown for breeding livestock that adapt well to high altitudes. Using whole-genome sequences with an effective sequencing depth of 5×, we investigated the genomic diversity and structure and, identified selection signatures of White Tibetan, Oula and Poll Dorset sheep. We obtained 30,163,679 Single Nucleotide Polymorphisms (SNPs) and 5,388,372 indels benchmarked against the ovine Oar_v4.0 genome assembly. Next, using FST, ZHp and XP-EHH approaches, we identified selection signatures spanning a set of candidate genes, including HIF1A, CAPN3, PRKAA1, RXFP2, TRHR and HOXA10 that are associated with pathways and GO categories putatively related to hypoxia responses, meat traits and disease resistance. Candidate genes and GO terms associated with coat color were also identified. Finally, quantification of blood physiological parameters, revealed higher levels of mean corpuscular hemoglobin measurement and mean corpuscular hemoglobin concentration in Tibetan sheep compared with Poll Dorset, suggesting a greater oxygen-carrying capacity in the Tibetan sheep and thus better adaptation to high-altitude hypoxia. In conclusion, this study provides a greater understanding of genome diversity and variations associated with adaptive and production traits in sheep.

BackgroundElevated red blood cell distribution width (RDW) and decreased platelet count (PLT) can be clinically relevant to the prognosis in cancer patients. However, their prognostic values in patients with diffuse large B-cell lymphoma (DLBCL) need to be further explored.MethodsHealthy donors (n = 130) and patients with DLBCL (n = 349) were included and evaluated retrospectively in this study. The prognostic influence of clinical and pathological factors including RDW and PLT on overall survival (OS) and progression-free survival (PFS) were studied by Kaplan-Meier curves. To evaluate the independent prognostic relevance of RDW and PLT, univariate and multivariate Cox proportional hazards regression models were applied. The adjusted IPI model was established based on the results of multivariate analysis, and verified by Harrell’s C statistical analysis.ResultsKaplan-Meier curves indicated that an elevated RDW value and thrombocytopenia are poor factors for OS (P P = 0.006) and PFS (P = 0.003,P P = 0.003) and decreased PLT count (HR =1.749, 95%CI = 1.010–3.028,P = 0.046) were both independent prognostic factors. The c-index of IPI and NCCN-IPI were increased when RDW level and PLT were supplemented in our cohort.ConclusionsOur study shows that elevated RDW level and decreased PLT are independent poor prognostic factors in newly diagnosed DLBCL patients. Adding RDW and PLT to the IPI score may improve its predictive ability, and the adjusted IPI may be more powerful in predicting the survival of DLBCL patients in the rituximab era.

Anthocyanins (ANCs) are phytochemicals with several health effects and undergo significant degradation and subsequent biotransformation during complex metabolic processes. The aim of the present study was to determine the bioaccessibility and biotransformation of cyanidin-3-glucoside (C3G) during the simulated gastric-intestinal digestion in vitro and the metabolism in rats in vivo. Characterization of C3G and its metabolites was conducted by HPLC-ESI-MS/MS. After gastric-intestinal digestion, C3G was detected with a recovery of 88.31% in the gastric-digestive system, and a small amount of methylated-C3G occurred. In the intestinal-digestive system, C3G occurred with a recovery of 6.05%, and mainly decomposed into protocatechuic acid (PCA) and 2,4,6-trihydroxybenzaldehyde. The pharmacokinetic trial of C3G in rats showed rapid elimination in plasma. In tissues, C3G underwent rapid absorption and metabolism into phenolic acids or their derivatives. C3G and methylated-C3G passed through the blood–brain barrier and caused rapid distribution of C3G in the brain. Understanding the conversion of C3G and its metabolites helps in the future design of dietary interventions and the exploration of biological activities of ACNs.

The prevalence of adolescent type 2 diabetes mellitus (A-T2DM) is increasing year by year. Di-(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer, could exacerbate type 2 diabetes mellitus (T2DM). The study aimed to investigate the metabolic toxicity, susceptibility and mechanism of DEHP exposure to A-T2DM. DEHP was administered orally (0, 0.18, 1.8, 18, and 180 mg/kg/day) for 3 weeks to adolescent normal mice (A-normal mice) and established A-T2DM mice. The results of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels showed that the susceptibility of A-T2DM mice to DEHP exposure was more significant than that of A-normal mice. DEHP, interfering with glucose and lipid metabolism of A-normal and A-T2DM mice, caused the body weight increase of A-normal mice and decrease of A-T2DM mice. Besides, DEHP could cause more injury of cardiovascular, hepatic and renal function to A-T2DM mice than A-normal mice. Hepatic transcriptome analysis revealed that DEHP exposure interfered with the biological feedback adjustment of endocrine and metabolic system in A-T2DM mice and then led to the development of T2DM. According to the transcriptome results, insulin signaling transduction pathway was applied and researched by immunoassay. It was discovered that DEHP reduced insulin sensitivity and disturbed insulin signaling transduction, glucose utilization, lipid synthesis and protein synthesis. Collectively, DEHP could disturb the endocrine and metabolic functions and increase the insulin resistance in adolescent mice. Moreover, the adolescent T2DM mice are more sensitive to DEHP-induced endocrine and metabolic toxicity than the healthy adolescent mice.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cells-mediated platelet clearance. Tacrolimus is an immunosuppressive agent which selectively inhibits T cell activation. Whether tacrolimus plays a role in ITP remains unclear. This study aimed to investigate the effect of tacrolimus on ITP in mice. An ITP mouse model was established by injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin and treated with tacrolimus followed by isolation of peripheral blood mononuclear cells and plasma. The mRNA expression of T-bet, GATA3, and Foxp3 was measured by RT-PCR, and level of IFN-γ, IL-12p70, IL-4, IL-13, and TGF-β in plasma was measured by ELISA. Tacrolimus inhibited antiplatelet antibody-mediated platelet clearance in ITP mouse model. Meanwhile, tacrolimus-treated ITP mice displayed a significant decrease in the mRNA expression of T-bet and plasma level of IFN-γ and IL-12p70 compared with ITP mice but without differences when compared with normal mice. Furthermore, the expression of GATA3, Foxp3, and plasma level of IL-4 and TGF-β were upregulated in tacrolimus-treated ITP mice without significant differences to normal mice (except TGF-β). Tacrolimus prevents antiplatelet antibody-mediated thrombocytopenia in ITP mice possibly through regulating T cell differentiations, suggesting it might be a novel approach for preventing ITP.

Exploring and designing multicomponent transition-metal sulfides, phosphides and selenides has been identified as an fascinating approach to promote the water splitting performance of single-component transition-metal sulfides, phosphides and selenides. However, this is rarely reported about water splitting applications of quaternary sulfides, phosphides and selenides. In this work, the Zn–Ni–Co–M (M = O, S, P and Se) nanoneedle arrays was in situ grown on nickel foam (Zn–Ni–Co–M/NF) for the first time by typical hydrothermal, sulfurization, phosphorization, and selenylation methods. In a typical three-electrode device, a small overpotential of 190 mV is obtained at 50 mA cm−2 for water oxidation reaction utilizing the new Zn–Ni–Co–S/NF as anodic material. Moreover, a small overpotential of 94 mV was required at 10 mA cm−2 for water reduction reaction when the new Zn–Ni–Co–P/NF sample is utilized as cathode material. The assembled electrolytic cell with Zn–Ni–Co–S/NF as the positive electrode and Zn–Ni–Co–P/NF as the negative material displays a superior electrocatalytic activity (1.52 V@10 mA cm−2) and a relatively surprising durability. The accessible and novel strategy for Zn–Ni–Co–M (M = O, S, P and Se) preparation provide a new view to develop new overall water splitting electrocatalyst with a superior activity and durability.