Ectopic 'humanized ossicles' (hOss) are miniaturized, engineered human bone organs in mice displaying a similar structure and function to native mouse bones. However, they are composed of human mesenchymal derived cells forming a humanized bone marrow niche. This in vivo reconstitution of human skeletal and hematopoietic compartments provides an opportunity to investigate the cellular and molecular processes involved in their establishment and functions in a human setting. However, current hOs strategies vary in their engineering methods and their downstream applications, undermining comprehensive exploitation of their potential. This review describes the specificities of the hOs models and highlights their potential and limits. Ultimately, we propose directions for the development of hOss as a technological platform for human hematopoietic studies.Stroke is a leading cause of death and disability in developed countries. N-methyl-D-aspartate glutamate receptors (NMDARs) have important roles in stroke pathology and recovery. Depending on their subtypes and locations, these NMDARs may promote either neuronal survival or death. Recently, the functions of previously overlooked NMDAR subtypes during stroke were characterized, and NMDARs expressed at different subcellular locations were found to have synergistic rather than opposing functions. Moreover, the complexity of the neuronal survival and death signaling pathways following NMDAR activation was further elucidated. In this review, we summarize the recent developments in these areas and discuss how delineating the dual roles of NMDARs in stroke has directed the development of novel neuroprotective therapeutics for stroke.The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists.Aim To investigate the association between mean fasting glucose (FG) and variability in visit-to-visit FG and risk of mortality in people with type 2 diabetes (T2D). Methods This retrospective cohort study included 48,077 Chinese men and women with T2D. The yearly mean and coefficient of variation for fasting glucose (mean-FG and FG-CV, respectively) were based on at least two measurements taken each year over a mean duration of 4.5 years. Deaths and their causes were identified using the Shanghai Vital Statistics registry. Mean-FG and FG-CV served as time-dependent variables in Cox models to estimate their associations with risk of mortality; hazard ratios (HRs) were adjusted for baseline risk factors. Potential non-linear associations were examined by restricted cubic splines. Results During an average 4.5 years of follow-up, 2095 men and 1923 women died. Men with low mean-FG and women with low or high FG were at greater risk of death. Mean-FG was not associated with either cardiovascular disease (CVD) or cancer-specific mortality, whereas higher yearly FG-CV was associated with all-cause and CVD-/cancer-specific mortality in both genders. Compared with a yearly FG-CV of 1.76 (5th percentile), men and women with an FG-CV of 14.14 (75th percentile) had HRs (95% CI) of 1.41 (1.24-1.61) and 1.44 (1.26-1.65), respectively, for all-cause mortality. Conclusion Variability of visit-to-visit FG may be a more sensitive predictor of risk of death than mean-FG in people with T2D.The development of cancer is not just the growth and proliferation of a single transformed cell, but its surrounding environment also coevolves with it. Indeed, successful cancer progression depends on the ability of the tumor cells to develop a supportive tumor microenvironment consisting of various types of stromal cells. The interactions between the tumor and stromal cells are bidirectional and mediated through a variety of growth factors, cytokines, metabolites, and other biomolecules secreted by these cells. Tumor-stromal crosstalk creates optimal conditions for the tumor growth, metastasis, evasion of immune surveillance, and therapy resistance, and its targeting is being explored for clinical management of cancer. Natural agents from plants and marine life have been at the forefront of traditional medicine. Numerous epidemiological studies have reported the health benefits imparted on the consumption of certain fruits, vegetables, and their derived products. Indeed, a significant majority of anti-cancer drugs in clinical use are either naturally occurring compounds or their derivatives. In this review, we describe fundamental cellular and non-cellular components of the tumor microenvironment and discuss the significance of natural compounds in their targeting. Existing literature provides hope that novel prevention and therapeutic approaches will emerge from ongoing scientific efforts leading to the reduced tumor burden and improve clinical outcomes in cancer patients.Background The incidence of hemodialysis (HD)-dependent renal failure after total artificial heart (TAH) implantation is high. We sought to determine the preoperative predictors of HD after TAH implantation. Methods and results We studied 87 patients after TAH implantation at our institution between April 2006 and March 2017. Baseline clinical data were obtained from the medical records, and patients were followed until death or heart transplantation. We performed logistic regression analysis to identify predictors of HD after TAH implantation. Of the patients, 24 (28%) required postimplantation HD. Those requiring HD were more likely to have histories of coronary artery disease (58% vs 29%; P = 0.01), required preoperative membrane oxygenation (33% vs 4.8%; P = 0.001) and had lower baseline estimated glomerular filtration rates (54 ± 29 vs 67 ± 24 mL/min/1.73m2; P = 0.04). Patients requiring HD were at a higher risk of death on device at 1 year (33% vs 5%, P = 0.001; log rank test P =0.001, hazard ratio 6.6 [95% CI1.8-23], P = 0.003).  https://www.selleckchem.com/Caspase.html  Conclusions The incidence of postimplantation HD is high and is associated with increased likelihood of mortality. Lower baseline estimated glomerular filtration rates, histories of coronary artery disease and preoperative membrane oxygenation support are predictors of postimplantation requirement of HD. These data may help to identify patients at risk for adverse outcomes after TAH implantation.