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Background: Premature rupture of membranes is an important cause of preterm birth and its associated high infant mortality and morbidity, and is an important public health problem worldwide, but the mechanism is unknown, and clinical treatment is currently mainly conservative, with a lack of effective interventions. We compared the differential metabolites in vaginal secretions between patients with preterm premature rupture of membranes and those with normal pregnancies and screened for the protective substance N-acetyl-d-galactosamine (GalNAc), an important ligand for galectin, which has several biological activities such as anti-inflammatory, antioxidant and in vitro wound healing properties. Methods: We evaluated the inflammatory response, oxidative stress, proliferation migration, EMT and ECM remodelling of human amniotic epithelial cells (WISH) by ELISA, ROS, transwell, scratch and CCK-8 assays, and examined the expression of PCNA and AKT by Western Blot. Results: The results showed that GalNAc enhanced galectin production and inhibited cellular inflammation and oxidative stress, promoted cellular EMT and migration, and altered ECM composition. In addition, GalNAc reduced the total and phosphorylated protein levels of AKT enhancing the pro-cell migration ability of GalNAc to stimulate wound healing. Conclusions: The results showed that GalNAc enhanced galectin production and inhibited cellular inflammation and oxidative stress, promoted cellular EMT and migration, synthesized GAG and altered ECM composition. The GalNAc-galectin pathway may provide a theoretical basis and a new target for the prevention and treatment of premature rupture of membranes. This study provides a theoretical basis and a new target for the prevention and treatment of premature rupture of membranes.

Members of the genus Bacillus are known to play an important role in promoting plant growth and protecting plants against phytopathogenic microorganisms. In this study, 21 isolates of Bacillus spp. were obtained from the root micro-ecosystem of Suaeda glauca. Analysis of the 16S rRNA genes indicated that the isolates belong to the species Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus subtilis, Bacillus pumilus, Bacillus aryabhattai and Brevibacterium frigoritolerans. One of the interesting findings of this study is that the four strains B1, B5, B16 and B21 are dominant in rhizosphere soil. Based on gyrA, gyrB, and rpoB gene analyses, B1, B5, and B21 were identified as B. amyloliquefaciens and B16 was identified as B. velezensis. Estimation of antifungal activity showed that the isolate B1 had a significant inhibitory effect on Fusarium verticillioides, B5 and B16 on Colletotrichum capsici (syd.) Butl, and B21 on Rhizoctonia cerealis van der Hoeven. The four strains grew well in medium with 1-10% NaCl, a pH value of 5-8, and promoted the growth of Arabidopsis thaliana. Our results indicate that these strains may be promising agents for the biocontrol and promotion of plant growth and further study of the relevant bacteria will provide a useful reference for the development of microbial resources.

A facile and effective tandem reaction of ynones and methyl salicylates was developed to obtain a broad range of 3-acyl chromones in moderate-to-excellent yields. This protocol underwent a Michael addition and cyclization process, which exhibited easily accessible substrates, broad substrate scope, and high regioselectivity under mild and transition-metal-free conditions. Moreover, gram-scale reaction and further chemical transformation of the products were also further studied.

BackgroundBiological agents have been used with extreme caution in children because of their possible adverse effects.ObjectivesThis study used high-quality randomized controlled trials (RCTs) to provide high-level evidence to assess the effectiveness and safety of biological agents for treating children with psoriasis.MethodsWe searched PubMed, Embase, Cochrane, and Web of Science databases through October 31, 2021. We included trials reporting at least one adverse event after treatment with biological agents of patients less than 18-year-old diagnosed with psoriasis. RevMan 5.3 and Stata 15.0 software were used for meta and Bayesian analyses.ResultsSix trials with 864 participants were included in the analysis. The results showed a 2.37-fold higher response rate in all biologics groups than in the control group for psoriasis area and severity index 75 (PASI75) (RR= 2.37, P-value < 0.01, 95% confidence interval [CI] [1.22, 4.62]). Compared with placebo, the PASI75 response rates of etanercept (RR= 2.82, 95% [CI] [1.10, 7.21]), ustekinumab low dose (RR= 7.45, 95%[CI] [1.25, 44.58]), and ustekinumab high dose (RR= 7.25, 95%[CI] [1.21, 43.41]) were superior. Additionally, the incidence of total adverse reactions was 1.05 times higher for biologics than for controls, indicating a good safety profile (RR= 1.05, P-value = 0.53, 95%[CI] [0.92, 1.19]). Overall, these six high-quality randomized controlled trials suggest that biologics are effective and safe for pediatric patients with psoriasis.LimitationsInclusion of few relevant, high-quality RCTs.ConclusionThe results of this study indicate that biologics can be used to treat children with moderate-to-severe psoriasis without the risk of adverse effects. Ustekinumab showed the best efficacy and the fewest adverse effects.

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl-d-galactosamine and sucrose were downregulated (P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide (P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid (P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4′-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline (P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721

Backgound: Type 2 diabetes mellitus remains a major public health challenge in the worldwide. The control of blood glucose is essential in the metabolic management of diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are new hypoglycemic agents with good hypoglycemic effect. However, the difference of efficacy and tolerability among different kinds of DPP-4 inhibitors remains unclear and no network meta-analysis(NMA) has been performed yet to compare different kinds of DPP-4 inhibitors comprehensively. Our research aims to investigate and rank different kinds of DPP-4 inhibitors on efficacy and tolerability.Methods/design: English language studies will be searched in the electronic databases(PubMed, the Cochrane Library and EMBASE), without time restriction. Parallel-group randomized controlled trials (RCTs) meeting the following criteria will be included, regardless of the blinding design: (1) T2DM patients aged over 18, pregnant or breastfeeding female patients and patients with T2DM on Maintenance Hemodialysis will be excluded, (2) interventions with DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, lindagliptin, alogliptin, omarigliptin and trelagliptin), traditional antidiabetic agents includes α-glucosidase inhibitors, sulphonylureas, non-sulfonylureas and thiazolidinediones, or placebo and (3) change in HbA1c concentration, weight and FPG from baseline to the end of treatment and proportions of patients in achieving HbA1c < 7.0%, patients with treatment-emergent adverse events leading to treatment discontinuation and patients with hypoglycaemia. Random effects pairwise and Bayesian NMA will be performed for these outcomes. Subgroup analyses are carried out for race and dosing frequency.Discussion: Our NMA will be the first to systematically summarize, compare and rank the efficacy and tolerability of different kinds of DPP-4 inhibitors in T2DM patients. We are confident that our research project will significantly contribute to optimizing hypoglycemic therapy.Systematic review registration:PROSPERO:CRD42021253822

BACKGROUND: Premature rupture of membranes (PROM) is a major pregnancy complication in China and usually leads to adverse pregnancy outcomes. The major aim of this study was to search for microorganisms and their related metabolites that have direct relationship with PROM. METHODS: For vaginal discharge samples, metagenomics sequencing was applied to identify microorganisms that were enriched in PROM subjects, and untargeted metabolomics was applied to characterize the metabolites changes in PROM subjects compared to healthy controls (HC). Correlation analysis was then used to explore the relationship between these microorganisms and metabolites changes. RESULTS: Two upstream metabolites of glycolysis, N-acetyl-D-galactosamine (GalNAc) and sucrose, were found downregulated in the PROM group (P=0.04 and P=0.041, respectively). Higher percentages of conditional pathogens, such as of Streptococcus (8.4% vs. 6.1% in HC group, P=0.15) and Chlamydia (4.3% vs. 2.3% in HC group, P=0.07) were found in PROM group. Other common conditional pathogens including Prevotella, Staphylococcus, Mycobacterium and Enterobacter, were also higher in PROM group, although their absolute percentages were low and the differences did not reach statistical significance due to relative small sample size. Correlation analysis further demonstrated a positive correlation of downregulation of glycolysis metabolites with higher percentage of conditional pathogens. CONCLUSIONS: Integrated metagenomics and metabolomics analysis can be used to track the subtle changes in the vaginal microenvironment. Downregulation of glycolysis substrates (GalNAc and sucrose) and increase of related pathogenic microorganisms (Streptococcus and Chlamydia) could serve as early warning biomarkers of PROM.

AgNPs are nanomaterials with many potential biomedical applications. In this study, the two novel yeast strains HX-YS and LPP-12Y capable of producing biological silver nanoparticles were isolated. Sequencing of ribosomal DNA-ITS fragments, as well as partial D1/D2 regions of 26S rDNA indicated that the strains are related to species from the genus Metschnikowia. The BioAgNPs produced by HX-YS and LPP-12Y at pH 5.0–6.0 and 26 °C ranged in size from 50 to 500 nm. The antibacterial activities of yeast BioAgNPs against five pathogenic bacteria were determined. The highest antibacterial effect was observed on P. aeruginosa, with additional obvious effects on E. coli ATCC8099 and S. aureus ATCC10231. Additionally, the BioAgNPs showed antiproliferative effects on lung cancer cell lines H1975 and A579, with low toxicity in Beas 2B normal lung cells. Therefore, the AgNPs biosynthesized by HX-YS and LPP-12Y may have potential applications in the treatment of bacterial infections and cancer.

Members of the genus

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human cytochrome P450 (CYP) 3A4 (CYP3A4) and liver microsomes. Eighteen Sprague–Dawley rats were randomly divided into three groups: group A (control group), group B (50 mg/kg resveratrol), and group C (150 mg/kg resveratrol). After 30 min administration of resveratrol, a single dose of ticagrelor (18 mg/kg) was administered orally. The in vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated ultra high-performance liquid chromatography – tandem mass spectrometer methods. For the in vivo study, the area under the concentration–time curve and mean peak plasma concentrations of ticagrelor in group B and C appeared to be significantly higher than the control group, while volume of distribution in terminal phase and apparent clearance of ticagrelor in group B and C were significantly decreased. For the in vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The half-maximal inhibitory concentration values of resveratrol were 56.75 μM, 69.07 μM, and 14.22 μM, respectively. Our results indicated that resveratrol had an inhibitory effect on the metabolism of ticagrelor in vitro and in vivo. Further research should focus on the clinical combination of resveratrol with ticagrelor, and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Chitinase can degrade chitin and play an essential role in animal immunity and plant defense. The immune functions of Chitinase in Procambarus clarkii (P. clarkii) remain to elucidate. Here, we identified PcChitinase 2 gene sequence from P. clarkii and studied its spatial and temporal expression profiles. The PcChitinase 2 transcribed unequally in different tissues; however, its expression was highest in those of stomach, gut, and hepatopancreas. The challenge with lipolysaccharide or peptidoglycan significantly up-regulated the expression of PcChitinase 2 in hepatopancreas. The knockdown of the PcChitinase 2 gene by double-stranded RNA suppressed most of the Toll-pathway-related immune genes (phospholipase, lectin, sptazle Cactus, serine proteikinase, anti-lipopolysaccharide factor, and Toll) production were significantly increased. Our results suggest PcChitinase 2 may be involved in the innate immune responses of P. clarkii by modulating the toll pathway.

Barium zirconate titanate (BZT) (Ba(ZrxTi1–x)O3) ceramics with Zr4+ contents of x = 5, 10, 15, 20, 25, and 30 mol % were prepared using a solid-state reaction approach. The microstructures, morphologies, and electric properties were characterized using X-ray diffraction, scanning electron microscopy, and impedance analysis methods, respectively. The dielectric analyses indicate that the BZT bulk ceramics show characteristics of phase transition from a normal ferroelectric to a relaxor ferroelectric with the increasing Zr4+ ionic content. The electrocaloric effect adiabatic temperature change decreases with the increasing Zr4+ content. The highest adiabatic temperature change obtained is 2.4 K for BZT ceramics with a 5 mol % of Zr4+ ionic content.

Vertical van der Waals heterostructures (vdWH) composed of two monolayer (ML) materials can provide new opportunities for layered electronic devices. Here we present a detailed theoretical investigation about the electronic properties of BP/SnS vdWH by applying in-plane uniaxial and biaxial strains. Our first principles calculations suggest that the direct bandgap of BP/SnS vdWH can be maintained within a large range of uniaxial and biaxial strains. We also find that the bandgap, band alignment and contact type of BP/SnS vdWH can be tuned by uniaxial and biaxial strains. In addition, the Poisson’s ratio exhibits an intense anisotropy with respect to the uniaxial strain along zigzag (ZZ) and armchair directions. The easily tunable electronic properties and highly anisotropic character of BP/SnS vdWH make it to be a promising material in the field of photovoltaic cells, photodetectors, and other functional nano devices.

Type-I heterostructure, in which electrons and holes are confined in same region, is widely used in light emitting diodes and semiconductor lasers. Type-II heterostructure is widely used in photovoltaic devices because of its excellent spatial separation property of electrons and holes. Can we integrate photovoltaic, photoelectric properties with luminescent property in one device? Here we report a van der Waals heterostructure formed by black phosphorus (BP) and SnS monolayers. It is expected to realize these functions in one device. By first-principles methods, the structural stability, electronic properties and optical properties are investigated. It was found that the BP/SnS bilayer is type-II heterostructure with an indirect bandgap of 0.56 eV. The p-like character of the band edge in BP/SnS vdW heterostructure makes it to be an excellent optoelectronic material. The type-II stability of the system can be improved by applying a negative electric field. However, when the positive electric field is bigger than 0.1 V Å−1, the system begins to transform from type-II to type I. Therefore, by adding a gate voltage the bandgap and band alignment of this system can be controlled. The photovoltaic and photoelectric properties can be integrated in one device based on this heterostructure.

To improve the apoptosis/necrosisTheThe acinar cells in the improved ascites model were mainly characterized by necrosis; compared with the other 3 groups, the apoptosis rate and necrosis rate were both up-regulated, RIP1 and BAX protein expression levels were up-regulated, and Bcl-2 protein was down-regulated. TEM results showed the organelle structure of acinar cells was destroyed, and the cell membrane was degraded in the improved ascites model. Compared with the control group, apoptosis rate of acinar cells in the cerulein and cerulein+LPS models were increased and necrosis rate were not changed. The expression of pro-apoptotic protein Bax was increased, while the expression level of RIP1 was not significantly increased. TEM results showed that in cerulein group and cerulein+LPS group, the chromatin of the cells was condensed into a mass, the cytoplasm was degraded and the cell membrane was intact, showing typical apoptosis characteristics.Compared with cerulein and cerulein +LPS models, which mainly focus on apoptosis of acinar cells and applied to mild acute pancreatitis study, the improved ascites model mainly focuses on the necrosis of acinar cells and is a good model for studying acinar cell necrosis and severe acute pancreatitis.

Cathepsin D belongs to aspartic protease family, produced in the rough endoplasmic reticulum, and then transported to lysosomes, where it participates in various physiological processes. Despite its importance, only a few reports available on the functional role of cathepsin D in crustaceans. Herein, we cloned a cDNA fragment of cathepsin D from the hepatopancreas of the red swamp crayfish, Procambarus clarkii (Pc-cathepsin D) for the first time. It included 1158 base pairs open reading frame, encoding a protein of 385 amino acids. Multiple alignment analysis confirmed the presence of aspartic proteinase active sites and N glycosylation sites. Pc-cathepsin D mRNA expression was high in the gills followed by gut, heart, hepatopancreas of P. clarkii. At different time points post-infection with lipopolysaccharides, peptidoglycan, or polyinosinic polycytidylic acid, Pc-cathepsin D mRNA expression significantly enhanced compared with the control group. Knockdown of the Pc-cathepsin D by double-stranded RNA, strikingly, changed the expression of all the tested P. clarkii immune-associated genes, including Pc-Toll, Pc-lectin, Pc-cactus, Pc-anti-lipopolysaccharide factor, Pc-phospholipase, and Pc-sptzale. Altogether, these results suggest that Pc-cathepsin D is needed to confer innate immunity against microbial pathogens by modulating the expression of crucial transcripts that encode immune-associated genes.

Barium zirconate titanate (BZT) (Ba(Zr