Sickle-cell disease (SCD) is a debilitating hematological disorder with very few approved treatment options. Therapeutic reactivation of fetal hemoglobin (HbF) is one of the most pursued methods for ameliorating the systemic manifestations of SCD. Despite this, very few pharmacological agents have advanced to clinical trials or marketing for use. In this study, we report the development of an HbF in situ intracellular immunoblot assay coupled to a high-throughput drug screen to identify Food and Drug Administration (FDA) approved drugs that can be repurposed clinically for treatment of SCD. Using this assay we evaluated the National Institute of Health (NIH) Clinical Collection (NCC), a publicly available library of 725 small molecules, and found nine candidates that can significantly re-express HbF in erythroid cell lines as well as primary erythroblasts derived from SCD patients. Furthermore, we show the strong effects on HbF expression of these candidates to occur with minimal cytotoxicity in 7 of the 9 drugs. Given these data and their proven history of use for other indications, we hypothesize that several of these candidate drugs warrant further investigation for use in SCD.The world is currently shadowed by the pandemic of COVID-19. Confirmed cases and the death toll has reached more than 12 million and more than 550,000 respectively as of 10 July 2020. In the unsettling pandemic of COVID-19, the whole Earth has been on an unprecedented lockdown.  https://www.selleckchem.com/products/bms-927711.html  Social distancing among people, interrupted international and domestic air traffic and suspended industrial productions and economic activities have various far-reaching and undetermined implications on air quality and the climate system. Improvement in air quality has been reported in many cities during lockdown, while the death rate of COVID-19 has been found to be higher in more polluted cities. The relationship between the spread of the SARS-CoV-2 virus and air quality is under investigation. In addition, the battle against COVID-19 could bring short-lived and long-lasting and positive and negative impacts to the warming climate. The impacts on the climate system and the role of the climate in modulating the COVID-19 pandemic are the foci of scientific inquiry. The intertwined relationship among environment, climate change and public health is exemplified in the pandemic of COVID-19. Further investigation of the relationship is imperative in the Anthropocene, in particular, in enhancing disaster preparedness. This short article intends to give an up-to-date glimpse of the pandemic from air quality and climate perspectives and calls for a follow-up discussion.The Thoroughbred (TB) horse has hugely impacted the development of horse breeding around the world. This breed has unique genetic qualities due to having had a closed studbook for approximately 300 years. In Russia, TBs have been bred since the second half of the 18th century. Here, we analyzed the genetic diversity and the inbreeding level in TB horses (n = 9680) for the period from 1990 to 2018 using polymorphisms of 17 microsatellite loci. We found that the genetic structure of the TB breed in Russia is represented by 100 alleles of panel STR (short tandem repeat) loci and has been stable for the past three decades. The conducted monitoring revealed a slight increase in the Wright's inbreeding coefficient in all age and sex groups of TB horses (stallions, broodmares, and foals) from 0.68% to 0.90%, which was followed by a decrease in the degree of heterozygosity, Ho, from 68.5% to 67.6%. The Spearman's rank correlation coefficient between the level of inbreeding and the degree of homozygosity was estimated (r = 0.022; p > 0.05). The obtained data on the DNA genotypes of horses of different breeds provide a unique base for the evaluation of genetic variability and the control of genetic variability of horses in selection programs.Coir fiber (CF), an eco-friendly and renewable natural fiber, was introduced into magnesium phosphate cement (MPC) mortar to improve its crack resistance. A total of 21 specimens were employed to investigate the failure pattern, compressive strength, stress-strain curve, and energy absorption of MPC with varying CF lengths (0, 5, 10, 15, 20, 25, and 30 mm) after a curing period of 28 days through a static compressive test. The results demonstrated that compressive strength, elastic modulus, and secant modulus decreased with the increase in CF length. However, energy absorption presented a convex curve, which increased to the maximum value (77.0% relative to the value of the specimen without CF) with a CF length of 20 mm and then declined. A series of modern micro-tests were then carried out to analyze the microstructure and composition of specimens to explain the properties microscopically.The dichotomy index (I less then O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I less then O deterioration below 97.5%-(I less then O)low-were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I less then O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption-(I less then O)low-was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I less then O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I less then O exceeding 97.5%-(I less then O)high-(p less then 0.012). Six (I less then O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I less then O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.