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The development of therapeutic approaches based on direct cardiac reprogramming of fibroblasts into induced-cardiomyocytes (iCM) has emerged as an attractive strategy to repair the injured myocardium. The identification of the mechanisms driving lineage conversion represents a crucial step toward the development of new and more efficient regenerative strategies. To this aim, here we show that pre-treatment with the Bmi1 inhibitor PTC-209 is sufficient to increase the efficiency of Chemical-induced Direct Cardiac Reprogramming both in mouse embryonic fibroblasts and adult cardiac fibroblasts. PTC-209 induces an overall increase of spontaneously beating iCM at end-stage of reprogramming, expressing high levels of late cardiac markers Troponin T and myosin muscle light chain-2v. The inhibition of Bmi1 expression occurring upon PTC-209 pre-treatment was maintained throughout the reprogramming protocol, contributing to a significant gene expression de-regulation. RNA profiling revealed that, upon Bmi1 inhibition a significant down-regulation of genes associated with immune and inflammatory signalling pathways occurred, with repression of different genes involved in interleukin, cytokine and chemokine pathways. Accordingly, we observed the down-regulation of both JAK/STAT3 and MAPK/ERK1-2 pathway activation, highlighting the crucial role of these pathways as a barrier for cardiac reprogramming. These findings have significant implications for the development of new cardiac regenerative therapies.Cell cycle proteins that are often dysregulated in malignant cells, such as cyclin-dependent kinase 4 (CDK4) and CDK6, have attracted considerable interest as potential targets for cancer therapy. In this context, multiple inhibitors of CDK4 and CDK6 have been developed, including three small molecules (palbociclib, abemaciclib and ribociclib) that are currently approved for the treatment of patients with breast cancer and are being extensively tested in individuals with other solid and haematological malignancies. Accumulating preclinical and clinical evidence indicates that the anticancer activity of CDK4/CDK6 inhibitors results not only from their ability to block the cell cycle in malignant cells but also from a range of immunostimulatory effects. In this Review, we discuss the ability of anticancer cell cycle inhibitors to modulate various immune functions in support of effective antitumour immunity.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract – severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.To find a therapeutic alternative for the treatment of skin and soft tissue infections, we evaluated the effects of combinations of retapamulin with macrolide, lincosamide, and streptogramin (MLS) antibiotics against Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecium, and Enterococcus faecalis. Using both the disk diffusion test and checkerboard assay, we initially examined the effects of combinations of retapamulin with MLS antibiotics against standard strains of these species. Combinations of retapamulin with erythromycin, quinupristin/dalfopristin and quinupristin showed synergistic activity against E. faecalis only. Synergy of retapamulin with clindamycin and dalfopristin was not observed. Then, a checkerboard assay was performed to evaluate the effects of the combinations against 15 clinical strains of E. faecalis. Retapamulin and quinupristin, the most synergistic combination, showed activity against all erythromycin-susceptible, -intermediate, and -resistant strains tested. Among the eight strains with high-level erythromycin resistance, five strains were synergistically inhibited in the presence of only 1 μg of retapamulin per ml. Time-kill assay revealed that combinations of retapamulin with erythromycin and quinupristin were bacteriostatic. These results suggest that combinations of retapamulin with erythromycin and quinupristin have in vitro synergistic activity against E. faecalis, including strains with high-level erythromycin resistance.In this paper, we present platinum/ruthenium nanoparticles supported on Vulcan carbon (PtRu@VC) as a nanocatalyst for the dehydrogenation of dimethylamine-borane (DMAB) in aqueous solution under mild conditions. PtRu@VC nanocatalyst was fabricated using the alcohol-reduction techniques which is a facile and effective method. The prepared PtRu@VC nanocatalyst exhibited a good stabilization and an effective catalytic activity for hydrogen evolution from the DMAB dehydrogenation in water at room temperature. The composition of PtRu@VC nanocatalyst was investigated using different analytical techniques inductively coupled plasma optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (P-XRD) and X-ray photoelectron spectroscopy (XPS). A monodispersedPt/Ru metals distributions on VC (as supporting material) were revealed by TEM and HR-TEM analyses. The mean particle size of PtRu@VC nanocatalyst was found to be 3.15 ± 0.76 nm. XPS analysis for PtRu@VC nanocatalyst showed that almost Pt-Ru metals were found to be the metallic state. Catalytic experimental results showed that PtRu@VC nanocatalyst has a high catalytic activity with an excellent turn-over frequency (TOFinitial) value of 14926.2 h-1 (248.77 min-1) in the dehydrogenation of DMAB in water at room temperature. Additionally, in the paper, we report some different kinetic data obtained from different experimental parameters of temperature, catalyst and substrate concentrations conducted for DMAB dehydrogenation in water catalyzed with PtRu@VC nanocatalyst.Electroluminescence polarization measurements have been performed on a series of semi-polar InGaN light emitting diodes (LEDs) grown on semi-polar (11-22) templates with a high crystal quality. The emission wavelengths of these LEDs cover a wide spectral region from 443 to 555 nm. A systematic study has been carried out in order to investigate the influence of both indium content and injection current on polarization properties, where a clear polarization switching at approximately 470 nm has been observed. The shortest wavelength LED (443 nm) exhibits a positive 0.15 polarization degree, while the longest wavelength LED (555 nm) shows a negative -0.33 polarization degree. All the longer wavelength LEDs with an emission wavelength above 470 nm exhibit negative polarization degrees, and they further demonstrate that the dependence of polarization degree on injection current enhances with increasing emission wavelength. Moreover, the absolute value of the polarization degree decreases with increasing injection current. In contrast, the polarization degree of the 443 nm blue LED remains constant with changing injection current. This discrepancy can be attributed to a significant difference in the density of states (DOS) of the valence subbands.In vestibular schwannoma patients with functional hearing status, surgical resection while preserving the hearing is feasible. Hearing levels, tumor size, and location of the tumor have been known to be candidates of predictors. We used a machine learning approach to predict hearing outcomes in vestibular schwannoma patients who underwent hearing preservation surgery middle cranial fossa, or retrosigmoid approach. After reviewing the medical records of 52 patients with a pathologically confirmed vestibular schwannoma, we included 50 patient’s records in the study. Hearing preservation was regarded as positive if the postoperative hearing was within serviceable hearing (50/50 rule). The categorical variable included the surgical approach, and the continuous variable covered audiometric and vestibular function tests, and the largest diameter of the tumor. Four different algorithms were lined up for comparison of accuracy support vector machine(SVM), gradient boosting machine(GBM), deep neural network(DNN), and diffuse random forest(DRF). The average accuracy of predicting hearing preservation ranged from 62% (SVM) to 90% (DNN). The current study is the first to incorporate machine learning methodology into a prediction of successful hearing preservation surgery. Although a larger population may be needed for better generalization, this study could aid the surgeon’s decision to perform a hearing preservation approach for vestibular schwannoma surgery.Small regulatory RNAs and antisense RNAs play important roles in the regulation of gene expression in bacteria but are underexplored, especially in natural populations. While environmentally relevant microbes often are not amenable to genetic manipulation or cannot be cultivated in the laboratory, extensive metagenomic and metatranscriptomic datasets for these organisms might be available. Hence, dedicated workflows for specific analyses are needed to fully benefit from this information. Here, we identified abundant sRNAs from oceanic environmental populations of the ecologically important primary producer Prochlorococcus starting from a metatranscriptomic differential RNA-Seq (mdRNA-Seq) dataset. We tracked their homologs in laboratory isolates, and we provide a framework for their further detailed characterization. Several of the experimentally validated sRNAs responded to ecologically relevant changes in cultivation conditions. The expression of the here newly discovered sRNA Yfr28 was highly stimulated in low-nitrogen conditions. Its predicted top targets include mRNAs encoding cell division proteins, a sigma factor, and several enzymes and transporters, suggesting a pivotal role of Yfr28 in the coordination of primary metabolism and cell division. A cis-encoded antisense RNA was identified as a possible positive regulator of atpF encoding subunit b’ of the ATP synthase complex. The presented workflow will also be useful for other environmentally relevant microorganisms for which experimental validation abilities are frequently limiting although there is wealth of sequence information available.The lack of tools to reliably detect RanBP9 in vivo has significantly hampered progress in understanding the biological functions of this scaffold protein. We report here the generation of a novel mouse strain, RanBP9-TT, in which the endogenous protein is fused with a double (V5-HA) epitope tag at the C-terminus. We show that the double tag does not interfere with the essential functions of RanBP9. In contrast to RanBP9 constitutive knock-out animals, RanBP9-TT mice are viable, fertile and do not show any obvious phenotype. The V5-HA tag allows unequivocal detection of RanBP9 both by IHC and WB. Importantly, immunoprecipitation and mass spectrometry analyses reveal that the tagged protein pulls down known interactors of wild type RanBP9. Thanks to the increased detection power, we are also unveiling a previously unknown interaction with Nucleolin, a protein proposed as an ideal target for cancer treatment. buy Etomoxir In summary, we report the generation of a new mouse line in which RanBP9 expression and interactions can be reliably studied by the use of commercially available αtag antibodies.