A portable device was designed and constructed for studying the properties of biomaterials in physiologically relevant fluids under controllable flow conditions that closely simulate fluid flow inside the body. The device can fit entirely inside a cell incubator; and, thus, it can be used directly under standard cell culture conditions. An impedance-driven pump was built in the sterile flow loop to control the flow rates of fluids, which made the device small and portable for easy deployment in the incubator. To demonstrate the device functions, magnesium (Mg) as a representative biodegradable material was tested in the flow device for immersion degradation under flow versus static conditions, while the flow module was placed inside a standard cell incubator. The flow rate was controlled at 0.17 ± 0.06 ml/s for this study; and, the flow rate is adjustable through the controller module outside of incubators for simulating the flow rates in the ranges of blood flow in human artery (0.05 ∼0.43 ml/s) and vein (0.02 ∼0.08 ml/s). Degradation of Mg under flow versus static conditions was characterized by measuring the changes of sample mass and thickness, and Mg2+ ion concentrations in the immersion media. Surface chemistry and morphology of Mg after immersion under flow versus static conditions were compared. The portable impedance-driven flow device is easy to fit inside an incubator and much smaller than a peristaltic pump, providing a valuable solution for studying biomaterials and implants (e.g. vascular or ureteral stents) in body fluids under flow versus static conditions with or without cells.

Watershed integrity, the capacity of a watershed to support and maintain ecological processes essential to the sustainability of services provided to society, can be influenced by a range of landscape and in-stream factors. Ecological response data from four intensively monitored case study watersheds exhibiting a range of environmental conditions and landscape characteristics across the United States were used to evaluate the performance of a national level Index of Watershed Integrity (IWI) at regional and local watershed scales. Using Pearson's correlation coefficient (r), and Spearman's rank correlation coefficient (rs ), response variables displayed highly significant relationships and were significantly correlated with IWI and ICI (Index of Catchment Integrity) values at all watersheds. Nitrogen concentration and flux-related watershed response metrics exhibited significantly strong negative correlations across case study watersheds, with absolute correlations (|r|) ranging from 0.48 to 0.97 for IWI values, and 0.31 to 0.96 for ICI values. Nitrogen-stable isotope ratios measured in chironomids and periphyton from streams and benthic organic matter from lake sediments also demonstrated strong negative correlations with IWI values, with |r| ranging from 0.47 to 0.92, and 0.35 to 0.89 for correlations with ICI values. This evaluation of the performance of national watershed and catchment integrity metrics and their strong relationship with site level responses provides weight-of-evidence support for their use in state, local and regionally focused applications.

Magnesium (Mg) and its alloys have shown attractive biocompatibility and mechanical strength for medical applications, but low corrosion resistance of Mg in physiological environment limits its broad clinical translation. Hydroxyapatite (HA) nanoparticles (nHA) are promising coating materials for decreasing degradation rates and prolonging mechanical strength of Mg-based implants while enhancing bone healing due to their osteoconductivity and osteoinductivity. Conformal HA coatings with nano-to-submicron structures, namely nHA and mHA coatings, were deposited successfully on Mg plates and rods using a transonic particle acceleration (TPA) process under two different conditions, characterized, and investigated for their effects on Mg degradation in vitro. The nHA and mHA coatings enhanced corrosion resistance of Mg and retained 86-90% of ultimate compressive strength after in vitro immersion in rSBF for 6 weeks, much greater than non-coated Mg that only retained 66% of strength. Mg-based rods with or without coatings showed slower degradation than the respective Mg-based plates in rSBF after 6 weeks, likely because of the greater surface-to-volume ratio of Mg plates than Mg rods. This indicates that Mg-based plate and screw devices may undergo different degradation even when they have the same coatings and are implanted at the same or similar anatomical locations. Therefore, in addition to locations of implantation, the geometry, dimension, surface area, volume, and mass of Mg-based implants and devices should be carefully considered in their design and processing to ensure that they not only provide adequate structural and mechanical stability for bone fixation, but also support the functions of bone cells, as clinically required for craniomaxillofacial (CMF) and orthopedic implants. When the nHA and mHA coated Mg and non-coated Mg plates were cultured with bone marrow derived mesenchymal stem cells (BMSCs) using the in vitro direct culture method, greater cell adhesion densities were observed under indirect contact conditions than that under direct contact conditions for the nHA and mHA coated Mg. In comparison with non-coated Mg, the nHA and mHA coated Mg reduced BMSC adhesion densities directly on the surface, but increased the average BMSC adhesion densities under indirect contact. Further long-term studies in vitro and in vivo are necessary to elucidate the effects of nHA and mHA coatings on cell functions and tissue healing.

Precocious puberty is frequently associated with obesity, which will lead to long-term effects, especially on growth and reproduction. However, the effect of precocious puberty on children's neurodevelopment is still unknown.

Becker muscular dystrophy (BMD) is an X-linked recessive muscular disorder caused by mutations in the dystrophin. We generated a human iPSC line from peripheral blood mononuclear cells (PBMCs) of a patient with duplications of exons 2-19 in the dystrophin. The PBMCs were reprogrammed using the episomal reprogramming plasmids contained a combination of expressions of human OCT4, SOX2, NANOG, LIN28, C-MYC, KLF4 and SV40LT. We conducted the tests on the iPSCs including Karyotype analysis, expressed pluripotency markers and teratoma forming three germ layers. The iPSC line is a useful cell model to further research on genetic treatment or new therapeutic drugs.

To examine the role of high-fat and high-sugar (HFHS) diet-induced oxidative stress, which is a risk factor for various diseases, in premature ovarian failure (POF).

Polysyndactyly (PSD) is an autosomal dominant genetic limb malformation caused by mutations.

Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs. These results implicate Ub signaling in coordinating RNA processing by TLR pathways during an immune response and in premalignant hematologic diseases, such as MDS.

Tripterygium glycosides (TGs) are chemotherapeutic drugs and immunosuppressant agents for the treatment of cancer and autoimmune diseases. We have previously reported that TGs induces premature ovarian failure (POF) by inducing cytotoxicity in ovarian granulosa cells (OGCs). Hence, we report that TGs suppress the expression of the Hippo-YAP/TAZ pathway in murine OGCs in vitro and in vivo. We found that the expressions of miR-181b, miR-15a, and miR-30d, were elevated significantly in the POF. Luciferase reporter assays confirmed that miR-15a targets Lats1 through a miR-15a binding site in the Lats1 3'UTR. Overexpression of miR-15a in mOGCs not only inhibited proliferation and growth of mOGCs, but also induced aging of mOGCs. Western blot and qPCR analysis indicated that miR-15a suppresses the expression of the Hippo-YAP/TAZ pathway in mOGCs. When the exogenous miR-15a was expressed on mouse OGCs, it could elevate the cytotoxicity effect of TG on mOGCs. We conclude that tripterygium glycosides promote cytotoxicity, senescence, and apoptosis in ovarian granulosa cells by inducing endogenous miR-15a expression and inhibiting the Hippo-YAP/TAZ pathway.

Solid nanogenerators often have limited charge transfer due to their low contact area. Liquid-liquid nanogenerators can transfer a charge better than the solid-solid and solid-liquid counterparts. However, the precise manipulation of the liquid morphology remains a challenge because of the fluidity limits of the liquid. In this work, using the surface tension of a droplet to fix its shape, a liquid-liquid triboelectric nanogenerator in Contact-Separation mode is designed using an immiscible aqueous-aqueous interface, achieving a contact surface charge transfer of 129 nC for a single droplet. The configuration is proven to be applicable in humid environments, and the two-phase materials have good biocompatibility and can be used as an effective drug carrier. Therefore, this nanogenerator is useful for designing future implantable devices. Meanwhile, this design also establishes the foundation of aqueous electronics, and additional applications can be achieved using this route.

Gene knock-in (KI) in animal cells via homology-directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency.