Tysondawson9013

The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years. Owing to their anti-inflammatory effects and regenerative property, adipose-derived mesenchymal stem cells (AD-MSCs) have been adapted for clinical application in fat grafting, although the mechanism underlying their action remains unclear. Recently, exosomes derived from MSCs were suggested as a better alternative, and these exosomes have also been applied in diverse clinical therapies. Accumulating evidence suggests that MSCs modulate macrophage differentiation via exosome secretion, and the connection between macrophage regulation and the rate of fat graft survival has been established. Here, we identified that let-7c, the key factor in the regulatory process, is shuttled by AD-MSC-derived exosomes to downregulate the transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ. The downregulation of C/EBP-δ resulted in the attenuation of pro-inflammatory M1 macrophages and elevation of anti-inflammatory M2 macrophages. These results suggest that AD-MSC-derived exosomes promote the survival of fat grafts by regulating macrophage polarization via let-7c. Filanesib order This is the first study to elucidate the mechanism underlying the promotion of the fat graft survival rate by AD-MSCs and to evaluate the immunotherapeutic potential of AD-MSC-derived exosomes in fat grafting.Asthenoteratospermia is an important cause of male infertility. Here, we report two infertile patients with severe asthenoteratospermia accompanied by new genetic abnormality. Whole-exome sequencing and bioinformatics analysis suggested that compound heterozygous mutations in DNAH8 (MIM603337) may be responsible for multiple morphological abnormalities of the sperm flagella (MMAF). Immunofluorescence assay showed that DNAH8 protein expression was significantly decreased in the sperm tail of the patients, and electron microscopy exhibited an abnormal flagellum ultrastructure, while clinical pregnancy could be achieved by intracytoplasmic sperm injection. Therefore, the compound heterozygous mutations in the DNAH8 gene may be responsible for MMAF.

Using the multiphase optimization strategy (MOST), we previously developed and optimized an online behavioral intervention, itMatters, aimed at reducing the risk of sexually transmitted infections (STI) among first-year college students by targeting the intersection of alcohol use and sexual behaviors.

We had two goals (a) to evaluate the optimized itMatters intervention and (b) to determine whether the candidate sexual violence prevention (SVP) component (included at the request of participating universities) had a detectable effect and therefore should be added to create a new version of itMatters. We also describe the hybrid evaluation-optimization trial we conducted to accomplish these two goals in a single experiment.

First year college students (N = 3,098) at four universities in the USA were individually randomized in a hybrid evaluation-optimization 2 × 2 factorial trial. Data were analyzed using regression models, with pre-test outcome variables included as covariates in the models. Analyses were conducted separately with (a) immediate post-test scores and (b) 60-day follow-up scores as outcome variables.

Experimental results indicated a significant effect of itMatters on targeted proximal outcomes (norms) and on one distal behavioral outcome (binge drinking). There were no significant effects on other behavioral outcomes, including the intersection of alcohol and sexual behaviors. In addition, there were mixed results (positive short-term effect; no effect at 60-day follow-up) of the SVP component on targeted proximal outcomes (students' self-efficacy to reduce/prevent sexual violence and perceived effectiveness of protective behavioral strategies).

The hybrid evaluation-optimization trial enabled us to evaluate the individual and combined effectiveness of the optimized itMatters intervention and the SVP component in a single experiment, conserving resources and providing greatly improved efficiency.

NCT04095065.

NCT04095065.

The recent discovery of numerous non-coding RNAs (long non-coding RNAs, in particular) has transformed our perception about the roles of RNAs in living organisms. Our ability to understand them, however, is hampered by our inability to solve their secondary and tertiary structures in high resolution efficiently by existing experimental techniques. Computational prediction of RNA secondary structure, on the other hand, has received much-needed improvement, recently, through deep learning of a large approximate data, followed by transfer learning with gold-standard base-pairing structures from high-resolution 3-D structures. Here, we expand this single-sequence-based learning to the use of evolutionary profiles and mutational coupling.

The new method allows large improvement not only in canonical base-pairs (RNA secondary structures) but more so in base-pairing associated with tertiary interactions such as pseudoknots, noncanonical and lone base-pairs. In particular, it is highly accurate for those RNAs of ned above.

Standalone-version of SPOT-RNA2 is available at https//github.com/jaswindersingh2/SPOT-RNA2. Direct prediction can also be made at https//sparks-lab.org/server/spot-rna2/. The datasets used in this research can also be downloaded from the GITHUB and the webserver mentioned above.

Re-cellularization of the trabecular meshwork (TM) using stem cells is a potential novel treatment for ocular hypertension associated with glaucoma. To assess the therapeutic efficacy of this approach, improved in vivo and ex vivo models of TM pathophysiology are needed. Here, we investigate whether oxidative stress, induced by hydrogen peroxide (H2O2), can model glaucomatous ocular hypertension in the readily available porcine anterior segment organ culture model.

The impact of H2O2 on TM cell viability and function was first evaluated in vitro using primary porcine TM cells. Oxidative stress was then induced by H2O2 infusion into perfused porcine anterior segments. Trabecular meshwork function was assessed by tracking matrix metalloproteinase (MMP) activity and the ability of the preparation to maintain intraocular pressure (IOP) homeostasis after a flow challenge (doubled fluid infusion rate). Finally, the TM was evaluated histologically.

H2O2 treatment resulted in a titratable reduction in cellularity across multiple primary TM cell donor strains.