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Activin A has been widely regarded as an important promoter of trophoblast invasion during the first trimester of pregnancy. However, whether integrin β3 is involved in activin A-upregulated trophoblast invasion and the underlying molecular mechanisms remain largely unknown.We utilized immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells, as well as first-trimester chorionic villous explants as study models to investigate the function and underlying molecular mechanisms of integrin β3 in activin A-promoted human trophoblast invasion.We found that activin A increased integrin β3 mRNA and protein levels in both HTR8/SVneo and primary EVT cells, and knockdown of integrin β3 significantly decreased basal and activin A-upregulated trophoblast invasion. Moreover, SB431542 (a specific inhibitor of TGF-β type Ι receptor kinase) abolished activin A-upregulated integrin β3 expression and SMAD2/3 phosphorylation. In addition, siRNA-mediated knockdown of ALK4 or SMAD4 both abolished activin A-upregulated integrin β3 expression in HTR8/SVneo cells, while knockdown of ALK4 or SMAD4 attenuated activin A-upregulated integrin β3 expression in primary EVTs.Our findings reveal the mediation role of integrin β3 in activin A-upregulated human trophoblast invasion and that activin An upregulates integrin β3 expression in an ALK4-SMAD4 signaling-dependent manner.

The epidermal growth factor receptor (EGFR) is a pleiotropic glycoprotein which plays a role in regulating cell proliferation, migration and differentiation. However, the genetic diversity of EGFR in crustaceans as well as its function, such as whether it is involved in immune regulation, remains obscure. In this study, two EGFR genes, including EGFR1 and EGFR2, and three transcripts were identified and characterized in Scylla Paramamosain for the first time. To our knowledge, this is the first time that more than one EGFR gene was identified in a single species. The complete open reading frames (ORFs) of SpEGFR1, SpEGFR2a and SpEGFR2b were 4377 bp, 4404 bp and 4341 bp encoding deduced proteins of 1458 amino acids (aa), 1467 aa and 1446 aa, respectively. All EGFR had a signal peptide region and two Recep_L_domain region, followed by a transmembrane region and a conserved tyrosine kinase domain (TyrKc), and phylogenetic analysis demonstrated three SpEGFRs clustered together with invertebrate EGFR branch. Tissue specific expression analysis depicted that all SpEGFRs presented similar transcription patterns. The expression levels of SpEGFR1 and SpEGFR2s in hepatopancreas and gills were significantly altered after the stimulation of bacterial and viral pathogens including Staphylococcus aureus, Vibrio alginolyticus, White spot syndromre virus and Polycytidylinic acid. The in vivo RNA interference assays demonstrated that expression levels of SpIKK, two members of NF-κB (SpRelish and SpDorsal) and six antimicrobial peptide (AMP) genes (SpCrustin and SpALF1-5) were significantly reduced when SpEGFR1 or SpEGFR2 was silenced, respectively. The transcription patterns of SpIKK, SpRelish, SpDorsal and AMPs exhibited similar down- or up-regulation trend when the primary cultured hemocytes were treated with EGFR antagonist or agonist for 24 h. These results suggested that SpEGFR might play an important role in innate immune responses to bacterial and viral infections by regulating the NF-κB pathway. It also provided a better understanding of the origin or evolution of EGFR in crustaceans and even invertebrates.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine.We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 10Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p0·0001).We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination.National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

Chinese rice wine (Huangjiu), a typical representative of traditional fermented foods in China, is distinguished for its unique flavor. Microorganisms play the most important role in the formation of the unique flavor of Huangjiu. The complex flavor components in Huangjiu are closely related to the metabolism of various microorganisms during the traditional brewing. Therefore, understanding the influence of microbiota on the formation of flavor components in Huangjiu is conducive to the production of Huangjiu with high-quality flavor. In recent years, many scholars have conducted a large number of studies on the microbial community and flavor metabolites during the traditional brewing process of Huangjiu, with the help of high-throughput sequencing (HTS) and mass spectrometry-based metabolomics. This review mainly summarized the current study progress of the microbial diversity of fermentation starters (Qu) and brewing process of Huangjiu, and explored the potential relationship between the microbial community and the characteristic flavor formation of Huangjiu. Through the comparative analysis of literatures, we found that Huangjiu has strong regional characteristics due to the differences in raw materials, Qu and traditional brewing techniques. Dynamics of microbial composition during the traditional brewing of Huangjiu in different regions of China are quite different, making Huangjiu in each region have their own flavor characteristics. Therefore, revealing the relationship between brewing microorganisms and flavor characteristics of Huangjiu is helpful to the directional regulation of flavor quality. According to the current research status, it is proposed that in the future, emerging technologies such as multi-omics, artificial intelligence, and machine learning should be applied to further improve the accuracy of the analysis of microbial flora and flavor components in Huangjiu, so as to accurately reveal the relationship between the microbial community and the formation of characteristic flavor of Huangjiu. Afterwards, high-throughput screening of excellent functional strains from the traditional brewing system should be applied to the industrial production of Huangjiu, so as to improve the overall flavor quality and commercial value.

Limosilactobacillus reuteri was encapsulated using Maillard-reaction-products (MRPs) of soy protein isolate (SPI) and α-lactose monohydrate by freeze-drying. The mixed solution of SPI and α-lactose monohydrate was placed in a water bath at 89°C for 160 min for Maillard reaction, and then freeze-dried to obtain MRPs. The effects of Maillard reaction on functional characteristics of MRPs and the properties of MRPs-microcapsules were studied. SDS-PAGE indicated that SPI subunit reacted with lactose to form a polymer, and the band of MRPs disappeared around the molecular weights of 33, 40, 63, and 100 kDa. Compared with SPI, the emulsion stability, emulsion activity, foaming capacity, foam stability, and gel strength of MRPs were increased by 259%, 55.71%, 82.32%, 58.53%, and 3266%, respectively. The results of Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and scanning electron micrographs confirmed that the protein structure also changed significantly. Then, MRPs were used as wall material to prepare L. reuteri microcapsules. Physical properties and viable counts of L. reuteri during the simulated gastrointestinal digestion and storage period were determined. The particle size of MRPs-microcapsules (68 μm) was smaller than that of SPI-microcapsules (91 μm). The viable counts of L. reuteri in simulated gastrointestinal digestion and after storage for 30 days were improved. The modifications with Maillard reaction can improve emulsification, foaming, and gel strength of SPI, and MRPs could be used as a new type of wall material in the production of L. reuteri microcapsules.

Background In China, OXA-48-producing Enterobacterales have been identified sporadically, causing only small-scale outbreaks in certain regions. This study aimed to investigate the molecular epidemiology, transmission and evolution of OXA-48-producing Enterobacterales and pOXA-48 from mainland of China.Enterobacterales METHODS: We conducted a multi-center bacterial resistance monitoring project from 2013 to 2018. The genome sequencing of OXA-48-produicng isolates was performed. Single-nucleotide polymorphism (SNP) was analysed. Eleven isolates were selected for subsequent single-molecule real-time (SMRT) sequencing. Genome sequences were annotated, and alignment of the complete sequences of the blaOXA-48-carrying plasmids from a subset of isolates that underwent long read sequencing was performed. Results A total of 41 OXA-48-producing Enterobacterales were involved in this study, including 34 K. pneumoniae, 3 E. coli, 3 E. cloacae and one K. oxytoca. OXA-48-produicng K. pneumoniae (OXAKp) ST383, ST147 and ST11 caused outbreaks of different scales in our hospital. In addition, OXA-48-producing E. coli ST156 and ST648, E. cloacae ST414 and ST418, and K. oxytoca ST34 were also identified. The blaOXA-48 gene was embedded in a Tn1999.2 structure, which was located in IncL plasmids with different sizes (63.58∼109.14 kb). Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has been identified in our hospital and it was possible that KPC-2-producing K. pneumoniae ST11 obtained the blaOXA-48-carrying plasmid during the spread. A novel blaOXA-48-carrying IncL plasmid with size of 109 kb has been identified from OXAKp ST11. It was possible that two plasmids in OXAKp ST383 were integrated to form this larger plasmid. Conclusions The OXA-48-produicng Enterobacterales were sporadic in China. Importantly, K. pneumoniae ST11 co-producing KPC-2 and OXA-48 has emerged and caused outbreak in China. This high-risk multidrug-resistant clone exhibited high compatibility and strong integration ability with foreign resistant plasmids.

The majority (~80%) of patients with cancer do not derive clinical benefit from current immunotherapy, largely due to attenuation of immune responses imposed by robust immunosuppression at tumor sites. Here, a cell-based tumor antigen delivery strategy was developed to boost tumor-specific immunity. Notably, the platform constructing ferric oxide nanoparticle-trained macrophages loading tumor antigens (MFe-N) acquired an immunostimulatory program and functioned as the tumoritropic "cytokine-microfactories" to sustainably produce high levels of multiple therapeutic cytokines (GM-CSF, TNFα, and MIP-1α), which are important in activation of immune cells with antitumor potential. Indeed, MFe-N markedly enhanced recruitment of the professional antigen-presenting cells, dendritic cells (DCs), to the tumor sites of an established B16F10 mouse melanoma model. Subsequently, MFe-N effectively delivered tumor antigens to DCs by gap junction-mediated cell-to-cell transmission. And this trafficking was critical for DC maturation to augment antitumor T-cell responses. Simultaneously, the "cytokine-microfactories" elicited high production of the tumoricidal effectors, and in turn blunted the pro-angiogenic activity of tumor-associated macrophages, resulting in conversion of the tumor-supporting milieu to a tumoricidal function that favored infiltration of antitumor T-cells. The findings provided a novel "cytokine-microfactories" harnessing effective delivery of tumor antigens and production of therapeutic cytokines to robustly promote antigen presentation and reshape the tumor immune milieu for priming antitumor immunity. This can enhance existing T-cell mediated immunotherapeutic potency and extend the curative potential immunotherapy to a broader range of patients.

Carbon dioxide electrochemical reduction (eCO2RR) has been regarded as an important solution for low-carbon economy. However, challenges remain for searching low-cost and high selectivity catalysts. Here, we investigated electrocatalytic activity of molecular catalysts containing transition metal single atom supported on corrole as the eCO2RR catalysts (TM/SACC) by DFT. Various C1 products can be produced on the 14 TM/SACC, including methane (CH4), formic acid (HCOOH) and CO. We found CO and formic acid are major products on TM/SACC (TM = Ni, Pd, Zn, Cu, Au, Ag) at higher overpotentials, while methane are major eCO2RR products on TM/SACC (TM = Mn, Cr, Nb, Mo, Zr, V, Ti, Cd) at lower overpotentials. Our studies indicate Mn/SACC gives high selectivity for methane formation. Due to the lowest overpotential value of 0.46 V, Mn/SACC can be a quite promising catalyst with excellent performance for reduction of CO2 to methane along the most favorable pathway: CO2 → COOH∗ → CO∗ → CHO∗ → CH2O∗ → CH2OH∗ → CH3OH∗→CH3∗→CH4∗→CH4(g), among which the hydrogenation of CHO∗ to CH2O∗ and CH3OH∗ to CH3∗ and H2O are the limiting-potential step and rate-determining step, respectively. The study shows corrole with different transition metal could adjust the catalytic performance of electrocatalysts, which offer a hopeful strategy for the design of molecular catalysts.

Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients.172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed.In this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898.This study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.

Designing low-cost, highly efficient, and durable electrocatalysts for carbon dioxide reduction reaction (eCO2RR) to value-added chemicals is an appealing approach to balance the global carbon emission. Heterogeneous molecular catalysts is emerging as an important area for CO2 utilization. Herein, a series of atomically isolated transition metal-N4 sites anchored on porphyrin framework (TM/PRF) molecular catalysts are employed as electrocatalysts for eCO2RR because of their well-defined structure, the versatility and relatively low cost, and remarkable activity, which allow the establishment of precise structural model for a better understanding of the CO2 reduction mechanism. Based on density functional theory calculations and the computational hydrogen electrode model on 27 candidates, we propose a number of TM/PRF (TMs = Ni, Co, Mn, Cu, Ag, Au, Zn, Pd, Ti, V, Cr, Ta, W), which show promise of highly active and selective catalysts for carbon monoxide, formic acid, methane and methanol production, while simultaneously suppress competing hydrogen evolution reaction. Studies have shown that the TM center plays a crucial role in determining the catalytic performance of the material. And the TM/PRF molecule tends to stabilize different radical intermediates at the TM site. Thus, when reacted with a greater number of electrons, highly reduced products are formed. Among the different TM/PRF materials, Ta/PRF and W/PRF have been shown to produce CH3OH selectively at low overpotentials (0.39 and 0.58 V), whereas Ti/PRF has been found as highly selective toward CH4 production with low overpotential of 0.58 V, outperforming most known electrodes. The calulation of activation energy and the d-band center reveal that Cr/PRF shows higher catalystic activity in comparison with other TM/PRF. The advantages of the outstanding selectivity of products, the reduced overpotentials and the higher activity of catalyst allow these new systems TM/PRF (TMs = Ta, W, Ti, Cr) to be promising catalysts, which will motivate more fundamental mechanism studies and technological applications for eCO2RR.

Oxide-supported copper-containing materials have attracted considerable research attention as promising candidates for acrolein formation. Nevertheless, the elucidation of the structure-performance relationships for these systems remains a scientific challenge. In this work, copper oxide clusters deposited on a high-surface-area silica support were synthesized via a deposition-precipitation approach and exhibited remarkable catalytic reactivity (up to 25.5% conversion and 66.8% selectivity) in the propylene-selective oxidation of acrolein at 300 °C. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy combined with X-ray absorption fine structure measurements of the catalyst before and after the reaction confirmed the transformation of the small-sized copper oxide (CuO) clusters into cuprous oxide (Cu2O) clusters. With the aid of in situ X-ray diffraction and in situ dual beam Fourier transform infrared spectroscopy (DB-FTIR), the allyl intermediate (CH2=CHCH2*) was clearly observed, along with the as-formed Cu2O species. The intermediate can react with oxygen atoms from neighboring Cu2O species to form acrolein during the catalytic process, and the small-sized Cu2O clusters play a crucial role in the generation of acrolein via the selective oxidation of propylene.

Bonding to fluorotic dentin is weaker than to sound dentin, but methods to improve bonding have not been well addressed.The purpose of this in vitro study was to investigate the effects of dimethyl sulfoxide (DMSO) pretreatment on the bond strength and resin-dentin surface of fluorotic dentin of different severity.Phosphoric acid-etched dentin specimens exhibiting mild fluorosis (ML-F), moderate fluorosis (MD-F), and severe fluorosis (SE-F) were randomly bonded with Single Bond 2 (SB2) pretreated with 50% DMSO (experimental groups) or deionized water (control groups). The bonded teeth were sectioned for microshear bond strength (μSBS) testing immediately or after aging, for micromorphology observation of the bonding interface under a scanning electron microscope, and for resin tags and microleakage evaluation under a confocal laser scanning microscope. The degree of conversion of the adhesive resin was calculated by Fourier transform infrared spectroscopy. According to varying bonding steps, the mineralized dentin powders of ML-F, MD-F, and SE-F were randomly divided into 4 subgroups (blank, PA, PA+SB2, and PA+DMSO+SB2) and incubated in artificial saliva to examine the level of enzymatic degradation product of type I collagen. Data were analyzed by using ANOVA and the Tukey test (α=.05).Dental fluorosis and thermocycling had negative effects on μSBS (P.001), while DMSO pretreatment preserved or even improved μSBS (P.001). DMSO had no influence on the degree of conversion (P=.618). Significant effects were found for bonding steps (P.001), but not that of dental fluorosis (P=.131) on the enzymatic degradation product of type I collagen. Images showed sparser and more expanded collagen fibril meshwork, deeper resin penetration, and less microleakage in the experimental groups.DMSO pretreatment provided increased and durable dentin bonding to fluorotic dentin probably by dispersing collagen fibrils into a sparser network and inhibiting the degradation of type I collagen.

The present study investigated the composition of water extract of Grifola frondosa (GFWE) and its regulatory effects on glycolipid metabolism and gut microbiota in rats. Structural characteristics of GFWE were detected by high performance liquid chromatography and ultra-high-performance liquid chromatography with mass spectrometry. The hypoglycemic and hypolipidemic activities of GFWE were obtained by inhibition of weight gain, recovery of serum glucose and lipid, and reverse of liver tissue damage. GFWE has up-regulated the relative mRNA and protein expression levels of adenine monophosphate activated protein kinase-α, peroxisome proliferator-activated receptors-α, and glucokinase, while down-regulated sterol regulatory element-binding transcription factor-1c and acetyl CoA carboxylase. Moreover, GFWE increased the abundances of caecal bacteria Oscillibacter and Barnesiella, which showed a significant negative correlation with serum glucose and lipid parameters. And GFWE enhanced the levels of total bile acids and short-chain fatty acids in the cecum. These results indicated that GFWE could be provided as a potential candidate to regulate glycolipid metabolism and gut microbiota.

The non-alcoholic fatty liver disease (NAFLD), as a critical liver disease, is still lack of effective treatments because the molecular mechanism revealing the NAFLD pathogenesis remains unclear. Dual specific phosphatase 6 (DUSP7) shows effects on inflammatory response and is a negative feedback mechanism of the mitogen-activated protein kinase (MAPK) superfamily, which are critical factors in regulating NAFLD progression. However, the effects of DUSP7 on hepatic steatosis are still not fully understood. Here, we found that DUSP7 functioned as a negative regulator of NAFLD and in various metabolic disorders. DUSP7 expression was markedly reduced in liver samples from patients with simple hepatic steatosis or non-alcoholic steatohepatitis (NASH), as well as in liver tissues from high fat diet (HFD)-challenged mice or genetically obese (ob/ob) mice. DUSP7 knockout markedly accelerated insulin resistance, glucose intolerance, liver dysfunction, fibrosis and hepatic steatosis in HFD-fed mice. In addition, inflammatory response was significantly exacerbated in HFD-challenged mice with DUSP7 deletion, which was associated with the elevated activation of nuclear factor-κB (NF-κB) and MAPKs signaling pathways. Moreover, oxidative stress was detected in liver of HFD-induced mice, and this phenomenon was aggravated in mice with DUSP7 knockout. Importantly, we demonstrated that DUSP7 physically interacted with transforming growth factor β (TGF-β)-activated kinase (TAK1). DUSP7 deletion considerably promoted the activation of TAK1 in mice after HFD feeding, contributing to the lipid deposition, inflammatory response and reactive oxygen species (ROS) production. Taken together, DUSP7 might function as a protective factor against NAFLD development and metabolic disorder through alleviating dyslipidemia, inflammation and oxidative stress by directly interacting with TAK1 in hepatocytes, which was involved in the suppression of fibrosis. Thus, we may provide an effective strategy for the treatment of hepatic steatosis via targeting DUSP7.

Background The present study analyzed the synergistic protective effect of β-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. Results Combined treatment with β-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of β-alanine and taurine. β-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 μM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 μM. Conclusion Taken together, these results suggest that the combined supplementation of β-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion. How to cite: Hou X, Sun G, Gou L. Cardioprotective effect of taurine and β-alanine against cardiac disease in myocardial ischemia and reperfuson induced rats. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.04.003

We present a combined density functional theory (DFT) and microkinetic modeling study of synthesis gas conversion on Cu and Ca modified Mo6S8 catalysts to value-added products. Our results show that CO∗ + H∗ → HCO∗ + (H) → H2CO∗ + (H) → H3CO∗ + (H) → CH3OH∗ → CH3OH (g) is an optimal pathway on the Ca–Mo6S8 surface. With the combination of Energetic span model (ESM) and binding energy analysis, we conclude that Ca–Mo6S8 is a promising catalyst for formaldehyde and methanol from synthesis gas conversion. Meanwhile, the most energetically favorable outcome on the Cu–Mo6S8 surface is the production of ethanol. Microkinetics simulations are carried out on the basis of the first-principles data, which predict the synthesis gas conversion rate and the product distribution. This study demonstrates that introducing metal Cu or Ca into Mo6S8 will design high-performance catalysts with synergistic interactions for tuning selectivity.

Background & Aims Although CD8+T cell exhaustion hampers viral control during chronic HBV infection, the pool of CD8+T cells is phenotypically and functionally heterogeneous. Therefore, a specific subpopulation of CD8+T cells should be further investigated. This study aims to dissect a subset of CD8+T cells expressing C-X-C motif chemokine receptor 5 (CXCR5) in chronic HBV infection. Methods The frequency of CXCR5+CD8+T cells and the levels of C-X-C motif chemokine ligand 13 (CXCL13), a chemokine of CXCR5, were measured in patients with chronic HBV infection. C57BL/6, interleukin (IL)-21 receptor- or B cell-deficient mice were hydrodynamically injected with pAAV-HBV1.2 plasmids. Phenotype and functions of peripheral and intrahepatic CXCR5+ and CXCR5−CD8+T cells were assessed. Results CXCR5+CD8+T cells were partially exhausted but possessed a stronger antiviral ability than the CXCR5− subset in patients with chronic HBV infection; moreover, CXCR5+CD8+T cells were associated with a favorable treatment response in patients with chronic hepatitis B (CHB). High levels of CXCL13 from patients with CHB facilitated the recruitment of intrahepatic CXCR5+CD8+T cells, and this subpopulation produced high levels of HBV-specific interferon (IFN)-γ and IL-21. Notably, PD1 (programmed death 1) blockade and exogenous IL-21 enhanced the production of IFN-γ. More strikingly, mice injected with CXCR5+CD8+T cells showed remarkably decreased expression of HBsAg. Additionally, an impaired production of HBV-specific IFN-γ from intrahepatic CXCR5+CD8+T cells was observed in IL-21 receptor- or B cell-deficient mice. Conclusion CXCL13 promotes the recruitment of CXCR5+CD8+T cells to the liver, and this subpopulation improves viral control in chronic HBV infection. The identification of this unique subpopulation may contribute to a better understanding of CD8+T cell functions and provide a potential immunotherapeutic target in chronic HBV infection. Lay summary Exhaustion of CD8+ T cells is an important factor in the development of chronic hepatitis B virus (HBV) infection. CD8+ T cells expressing the receptor CXCR5 are partially exhausted, but have potent antiviral activity, as they produce high levels of HBV-specific cytokines in chronic HBV infection. Increased expression of CXCL13 within the liver facilitates the recruitment of CXCR5+CD8+T cells and establishes effective immune control of HBV infection.

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.