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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.

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.