Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.In our previous work, we discussed the emergence of the dual fluorescence phenomenon in selected compounds from the group of 1,3,4-thiadiazoles. The results obtained in a number of experimental studies, supported by [TD]DFT calculations, clearly indicated that the phenomenon of dual fluorescence stemmed from an overlap of several factors, including the correct conformation of the analyzed molecule and, very significantly in this context, aggregation effects. Where those two conditions were met, we could observe the phenomenon of intermolecular charge transfer (CT) and the emergence of electronic states responsible for long wave emissions. However, in light of the new studies presented in this paper, we were able, for the first time, to provide a specific theory for the effect of dual fluorescence observed in the analyzed group of 1,3,4-thiadiazoles. We present the results of spectroscopic measurements conducted for two selected analogues from the 1,3,4-thiadiazole group, both in polar and non-polar solvents, which clearly evidence (as we have already suspected in the past, albeit have not shown in publications to date) the possibility of processes related to emission from the tautomer formed in the process of excited state intramolecular proton transfer, which is responsible for the long-wavelength emissions observed in the selected analogues. The presented results obtained with the use of UV-Vis, fluorescence (stationary and time-resolved), FTIR, and Raman spectroscopy, as well as from calculations of dipole moment changes between the ground and excited state with the use of two derivatives with different structures of the resorcylic system, corroborated our standing hypothesis. At the same time, they excluded the presence of ground state keto forms of the analyzed analogues unless necessitated by the structure of the molecule itself. In this case, aggregation factors enhance the observed effects related to the dual fluorescence of the analyzed compounds (by way of AIE-aggregated induced emissions).Understanding of the pathogenesis of the coronavirus disease-2019 (COVID-19) remains incomplete, particularly in respect to the multi-organ dysfunction it may cause. We were the first to report the analogous biological and physiological features of COVID-19 pathogenesis and the harmful amplification loop between inflammation and tissue damage induced by the dysregulation of neutrophil extracellular traps (NETs) formation. Given the rapid evolution of this disease, the nature of its symptoms, and its potential lethality, we hypothesize that COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. Here, we describe in-depth the correlations of COVID-19 symptoms and biological features with those where uncontrolled NET formation is implicated in various sterile or infectious diseases. General clinical conditions, as well as numerous pathological and biological features, are analogous with NETs deleterious effects. Among NETs by-products implicated in COVID-1 with DNase-1, with the anti-diabetic Metformin, or with drugs targeting elastase (i.e., Silvelestat). With a longer perspective, we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type lectin-like receptors (CLEC) inhibitors, NET-inhibitory peptides, and on anti-IL-26 therapies.Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.Objective The developmental maturation of forward and backward digit spans-indices of working memory-in boys with nonsense (nm) Duchenne muscular dystrophy (DMD) (nmDMD) was assessed using prospective, longitudinal data. Methods Fifty-five boys of the 57 subjects with genetically confirmed nmDMD-who were from the placebo arm of a 48-week-long phase 2b clinical trial-were evaluated. Forward and backward digit spans were obtained every 12 weeks for a total of five assessments in all study subjects. Changes in forward and backward digit spans were evaluated based on age, corticosteroid treatment, and DMD mutation location. Results Boys with nmDMD had lower mean scores on normalized forward digit span. Normalized forward digit spans were comparable between subjects stratified by age and between corticosteroid-naïve and corticosteroid-treated subjects. When stratified by DMD mutation location, normalized forward digit spans were lower in nmDMD subjects with mutations downstream of DMD exon 30, exon 45, and exon 63, both at baseline evaluation and at follow-up evaluation at 48 weeks. On average, normalized backward digit span scores were stable over 48 weeks in these subjects. Developmental growth modeling showed that subjects with nmDMD mutations upstream of DMD exon 30, upstream of DMD exon 45, and upstream of DMD exon 63 appeared to make better gains in working memory than subjects with mutations downstream of DMD exon 30, downstream of DMD exon 45, and downstream of DMD exon 63. Conclusion Performance in working memory shows deficits in nmDMD and differed based on nmDMD location. Maturation in cognition was seen over a 48-week period. The developmental trajectory of working memory in this cohort was influenced by DMD mutation location.Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG).Advanced fibrosis/cirrhosis and related biomarkers have been recognized as useful predictors of the development of hepatocellular carcinoma (HCC) by patients with chronic hepatitis C (CHC) following hepatitis C virus (HCV) cure by direct-acting antivirals (DAAs). However, it remains unclear if DAAs themselves have an influence on or facilitate the development of HCC. This multicenter cohort study included CHC patients without a history of HCC who achieved HCV elimination by DAAs. Cohorts of 835 patients treated with a sofosbuvir (SOF)-based regimen and 835 treated with a SOF-free regimen were matched 11 by propensity scoring with nine variables to evaluate differences in HCC incidence. The median observation period was 3.5 years. Sixty-nine cases of HCC were found during 5483.9 person-years (PY) over the entire follow-up period. The annual incidence was similar for both groups (SOF-based 1.25 and SOF-free 1.27 per 100 PY, respectively adjusted hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.75-2.12, p = 0.39). However, the annual incidence within the first two years was higher for patients treated with SOF than for those without, but did not reach significance (1.50 and 0.97 per 100 PY incidence rates, respectively adjusted HR 2.05, 95% CI 0.98-4.25, p = 0.06). In summary, DAA treatment with SOF was not associated with an increase in the development of de novo HCC.Rodent models have been widely used as analogs for estimating spaceflight-relevant molecular mechanisms in human tissues. NASA GeneLab provides access to numerous spaceflight omics datasets that can potentially generate novel insights and hypotheses about fundamental space biology when analyzed in new and integrated fashions. Here, we performed a pilot study to elucidate space biological mechanisms across tissues by reanalyzing mouse RNA-sequencing spaceflight data archived on NASA GeneLab. Our results showed that clock gene expressions in spaceflight mice were altered compared with those in ground control mice. Furthermore, the results suggested that spaceflight promotes asynchrony of clock gene expressions between peripheral tissues. Abnormal circadian rhythms are associated not only with jet lag and sleep disorders but also with cancer, lifestyle-related diseases, and mental disorders. Overall, our findings highlight the importance of elucidating the causes of circadian rhythm disruptions using the unique approach of space biology research to one day potentially develop countermeasures that benefit humans on Earth and in space.Bone loss and bone fractures are common complications after organ transplantation. Many factors contribute to the pathogenesis of transplant osteoporosis, such as bone disease preceding transplantation, immunosuppressive medications, and nutritional and lifestyle factors. This study aimed to assess the incidence of vertebral fractures before and after lung and heart transplantation. This longitudinal study analyzed 213 electronic medical records of patients who underwent lung transplantation (n = 128) and heart transplantation (n = 85) at Siena University Medical Center between January 2000 and December 2018. In lung and heart transplant recipients, the bone mineral density in the femoral sub-regions show a significant decrease at post-transplantation and at follow up visits. In both lung and heart recipients, we found an increase in the fracture incidence in the first period after transplantation (19.5% vs. 50.4% in lung recipients; 9.6% vs. 25.7% in heart recipients). Moreover, in lung recipients, vertebral fractures were predicted primarily by age, BMD at the femur, and any history of fracture.