Tmc gene therapy(Harvard Medical School)

Infections associated with medical implants due to bacterial adhesion and biofilm formation are a serious problem, leading to acute health risks to patients by compromising their immune system. Therefore, suppressing biofilm formation on biomedical implants is a challenging task, especially for overcoming the drug resistance of bacterial biofilms. Herein, a synergistic efficient surface coating method was developed to inhibit biofilm formation on a model medical implant by combining the antimicrobial property of trimethyl chitosan (TMC) with either 2D material graphene oxide (GO) or black phosphorus (BP) sheets using layer-by-layer (LbL) self-assembly. The multilayer coatings of TMC/GO and TMC/BP were optimized on the glass surface (a model implant) and characterized by using spectroscopic and microscopy techniques. Next, we investigated the antibiofilm formation properties of the TMC/GO and TMC/BP coatings on glass surfaces against both Gram-negative, Escherichia coli (E. coli), and Gram-positive, Bacillus subtilis (B. subtilis), bacteria. The antibiofilm formation was studied using crystal violet (CV) and live/dead assays. Both the live/dead and the CV assays confirmed that the TMC/2D material (2DM)-coated surfaces prevented biofilm formation much more effectively compared to the uncoated surfaces. Scanning electron microscopy analyses revealed that the bacteria were affected physically by incubating with TMC/2DM-coated surfaces due to membrane perturbation, thereby preventing cell attachment and biofilm formation. Further, BP composite coatings (TMC/BP) showed a much better ability to thwart biofilm formation than GO composite coatings (TMC/GO). Also, multilayer coatings showed superior cytocompatibility with human foreskin fibroblast (HFF). Our results demonstrate that the developed coatings TMC/2DMs could be potential candidates for thwarting biofilm formation on medical implants.

This study focuses on the association between seminal concentration of prosaposin and ambient air pollutants and whether the association affects the normal fertilization rate in vitro fertilization (IVF) treatment.

The cohort of 323 couple participants aged 22-46 was recruited from Jan. 2013 to Jun. 2018. At enrollment, resident address information was obtained and semen parameters of male counterparts were evaluated according to WHO criteria. We used inverse distance weighting interpolation to estimate the levels of ambient pollutants (SO₂, O₃, CO, NO₂, PM_2.5, and PM₁₀) in the surrounding area. The exposure of each participant was estimated based on the data gathered from air quality monitoring stations and their home address over various periods (0-9, 10-14, and 0-90 days) before semen sampling. The generalized linear regression model (GLM) and the Bayesian kernel machine regression (BKMR) were used to analyze the associations between pollutants, semen parameters, prosaposin, and normal fertilization. Additionally, the mediating effect of prosaposin and semen parameters on the link between pollutants and normal fertilization was investigated.

GLM and BKMR showed exposure to ambient air pollutants was all associated with the concentration of seminal prosaposin, among them, O₃ and CO were also associated with normal fertilization (-0.10, 95 %CI: -0.13, -0.06; -26.43, 95 %CI: -33.79, -19.07). Among the semen parameters, only the concentration of prosaposin and total motile sperm count (TMC) was associated with normal fertilization (0.059, 95 %CI: 0.047, 0.071; 0.016, 95 %CI: 0.012, 0.020). Mediation analysis showed that prosaposin played a stronger mediating role than TMC in the relationship between short-term exposure to O₃ and fertilization (66.83 %, P<0.001 versus 3.05 %, P>0.05).

Seminal plasma prosaposin showed a stronger meditating effect reflect the correlation between ambient air pollutants and normal fertilization rate than conventional semen parameters, which may be used as one of the indicators between pollution and fertilization in IVF.