Bavachin Rejuvenates Sensitivity of Colistin against Colistin-Resistant Gram-Negative Bacteria.

The emergence of plasmid-mediated colistin resistance threatens the efficacy of colistin as a last-resort antibiotic used to treat infection caused by Gram-negative bacteria (GNB). Given the shortage of new antibiotics, the discovery of adjuvants to existing antibiotics is a promising strategy to combat infections caused by multidrug-resistant (MDR) GNB. This study was designed to investigate the potential synergistic antibacterial activity of bavachin, a bioactive compound extracted from the Psoralea Fructus, combined with colistin against MDR GNB. Herein, the synergistic efficacy in vitro and the therapeutic efficacy of colistin combined with bavachin in vivo were evaluated. The synergistic mechanism was detected by fluorescent probe and the transcript levels of mcr-1. Bavachin combined with colistin showed an excellent synergistic activity against GNB, as the FICI ≤ 0.5. In contrast to colistin alone, combination therapy dramatically increased the survival rate of Galleria mellonella and mice in vivo. Moreover, the combination of bavachin and colistin significantly reduced the amount of bacterial biofilm formation, improved the membrane disruption of colistin and inhibited mcr-1 transcription. These findings show that bavachin is a potential adjuvant of colistin, which may provide a new strategy to combat colistin-resistant bacteria infection with lower doses of colistin.

The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

Numerical Simulation on Solidification during Vertical Centrifugal Casting Process for TC4 Alloy Wheel Hub with Enhanced Mechanical Properties.

The Ti-6Al-4V (TC4) alloy wheel hub has exhibited some defects that affect the properties during the vertical centrifugal casting process. Therefore, the analysis of the solidification process would contribute to solving the above-mentioned problems. In this study, an orthogonal experimental design was employed to optimize the process parameters (rotational speed, mold preheating temperature, and pouring temperature) of the vertical centrifugal casting method. The effects of process parameters on the velocity field, temperature field, and total shrinkage porosity during the solidification process were explored, and the microstructure and mechanical properties of the wheel hub prepared by the vertical centrifugal casting method were also investigated. The results showed that the rotational speed mainly induced the change of the velocity field. The pouring temperature and mold preheating temperature affected the temperature field and solidification time. Based on the analysis of the orthogonal experiment, the optimal parameters were confirmed as a rotational speed of 225 rpm, mold preheating temperature of 400 °C, and pouring temperature of 1750 °C, respectively. The simulation results of total shrinkage porosity were in agreement with the experiment results. The wheel hub was composed of nonuniform α and ß phases. The lath α phase precipitated from larger ß grains with different orientations. Compared with the other samples at different locations, the α phase in the PM sample (middle of the TC4 wheel hub) displayed high peak intensity and uniformly distributed ß phase along the radial direction of the wheel hub. Moreover, the PM sample revealed a higher tensile strength of 820 MPa and similar Vickers hardness of 318 HV compared with the other samples at different locations, which were higher than those of rolling and extrusion molding. This experiment design would provide a good reference for the vertical centrifugal casting of the TC4 alloy.

Microstructure evolution, mechanical properties, and enhanced bioactivity of Ti-13Nb-13Zr based calcium pyrophosphate composites for biomedical applications.

The present study reports the results of the microstructure, mechanical properties and in vitro bioactivity of the Ti-13Nb-13Zr based composite with 10 wt% CPP (calcium pyrophosphate), densified using spark plasma sintering process (SPS) at different sintering temperatures (900-1200 °C). The results show that the sintered composites mainly consist of ß-Ti, α-Ti, and ceramic interphases (Ti2O, CaTiO3, CaZrO3, CaO, TixPy). With the sintering temperature increasing, α-Ti and ceramic interphases gradually increase, and relative density, elastic modulus, compressive strength and yield strength of the composites also reveal an increasing tendency. However, Ti-13Nb-13Zr-10CPP composite sintered at 1000 °C exhibits high matching elastic modulus (46 GPa) and compressive strength (1617 MPa) due to uniform structure and high density. In addition, in vitro mineralization assays demonstrate the apatite-forming ability of the composite (1000 °C) and its higher surface bioactivity as compared to the Ti-13Nb-13Zr alloy. Furthermore, ROS1728 osteoblast culture evidences that the composite (1000 °C) stimulates cell adhesion and growth due to the pore characteristics and ceramic interphases. Therefore, the prepared Ti-13Nb-13Zr-10CPP composite at 1000 °C exhibits immense potential as a biomedical material.