Causal association between gut microbiota and hyperemesis gravidarum: a two-sample Mendelian randomization study.

Background: Observational studies have reported an association between the gut microbiota (GM) and hyperemesis gravidarum (HG). However, the causal relationship is unclear. In this study, Mendelian randomization (MR) was used to infer causal relationships between GM and HG. Methods: Inverse-variance weighted MR was performed using summary statistics for genetic variants from genome-wide association studies (GWAS). Sensitivity analyses were performed to validate the MR results and assess the robustness of the causal inference. Reverse MR analysis was performed for bacterial taxa that were causally linked to the HG risk in the forward MR analysis to evaluate reverse causality. Results: MR analysis revealed that the genera Defluviitaleaceae UCG011, Ruminococcus1, Ruminococcus2, Turicibacter, and unknowngenus and phylum Verrucomicrobiota are positively associated with the risk of HG. Additionally, the genus Coprococcus2 was related to a decreased risk of HG. Sensitivity studies validated the strength and reliability of the link between the composition of the GM and HG. No evidence for reverse causality from HG to identified bacterial taxa was found. Conclusion: Our MR analysis provided novel insight into the association between GM and HG. In particular, our results indicated that targeting the GM could serve as an effective therapeutic strategy for HG.

Network Pharmacology Analysis of the Mechanisms Underlying the Therapeutic Effects of Yangjing Zhongyu Tang on Thin Endometrium.

Purpose: Yangjing Zhongyu Tang (YJZYT) is a classic Chinese prescription for infertility treatment and exerts therapeutic effects via activity on the thin endometrium (TE). However, the major components and underlying mechanisms of YJZYT actions remain to be established. The main objectives of this study were to clarify the effects of YJZYT on the TE and provide insights into the related mechanisms based on network pharmacology and molecular docking analyses. Methods: Network pharmacology was employed to explore the main bioactive components and targets of YJZYT. TE-related genes were obtained from the Genecards database and screened for intersections with YJZYT. The Cytoscape 3.8.2 was used to build a "compounds-disease-targets" network and molecular docking analysis performed on key targets. The mechanism of action of YJZYT was further validated in vivo using a rat model. Results: A total of 98 YJZYT active ingredients, 2409 thin endometrium-associated genes, and 186 common targets were obtained. Through topological analysis, 10 core objectives were screened. Data from the PPI network suggest that AKT1, TNF, VEGFA, IL-6, TP53, INS, ESR1, MMP9, ALB, and ACTB serve as key targets in the action of YJZYT on TE. PI3K-Akt, TNF, apoptosis, IL-17 and MAPK were established as the main functional pathways. Molecular docking analysis revealed high affinity of the active ingredients of YJZYT, specifically, ursolic acid, palbinone, stigmasterol, and beta-sitosterol, for TNF, VEGFA, IL-6, AKT, and MMP9. YJZYT improved endometrial recovery, promoted endometrial angiogenesis, and upregulated protein expression of VEGF, PI3K, AKT, and p-AKT in the TE rat model. Conclusion: Network pharmacological and animal studies facilitated the prediction and validation of the active components and key targets of YJZYT potentially contributing to TE. Preliminary evidence from in vivo experiments showed that YJZYT promotes angiogenesis and thin endometrial repair via regulation of the PI3K/AKT pathway, providing a reference for further research.

Impact of program/erase operation on the performances of oxide-based resistive switching memory.

Further performance improvement is necessary for resistive random access memory (RRAM) to realize its commercialization. In this work, a novel pulse operation method is proposed to improve the performance of RRAM based on Ti/HfO2/Pt structure. In the DC voltage sweep of the RRAM device, the SET transition is abrupt under positive bias. If current sweep with positive bias is utilized in SET process, the SET switching will become gradual, so SET is current controlled. In the negative voltage sweep for RESET process, the change of current with applied voltage is gradual, so RESET is voltage controlled. Current sweep SET and voltage sweep RESET shows better controllability on the parameter variation. Considering the SET/RESET characteristics in DC sweep, in the corresponding pulse operation, the width and height of the pulse series can be adjusted to control the SET and RESET process, respectively. Our new method is different from the traditional pulse operation in which both the width and height of program/erase pulse are simply kept constant which would lead to unnecessary damage to the device. In our new method, in each program or erase operation, a series of pulses with the width/height gradually increased are made use of to fully finish the SET/RESET switching but no excessive stress is generated at the same time, so width/height-controlled accurate SET/RESET can be achieved. Through the operation, the uniformity and endurance of the RRAM device has been significantly improved.