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Loft Estrada posted an update 6 months ago
We investigated the impact of HDAC8 in MCL cell lines. Inhibition or genetic loss of HDAC8 caused MCL cells to undergo apoptosis. In contrast, exposure of primary human NK cells to an HDAC8 inhibitor does not alter viability, receptor expression, or antibody dependent cellular cytotoxicity (ADCC). However, an increase in effector cytokine interferon-gamma (IFNγ) producing NK cells was observed in response to HDAC8 inhibition. Taken together these data suggest that selective HDAC8 inhibitors may simultaneously preserve NK functional activity, while impairing MCL tumor growth, establishing a rationale for future clinical evaluation.Osteoporosis is a common skeletal complication of diabetes mellitus (DM). The mechanisms underlying the pathophysiology of diabetic osteoporosis are complex. Glycogen synthase kinase-3β (GSK-3β) is a widely expressed serine/threonine kinase and associated with both DM and bone metabolism, which arouse our concern. In this study, we established the diabetic mouse model by high-fat diet combined with streptozotocin injection. Decreased bone mass and reduced osteogenesis were observed in femurs of the mice. Besides, we identified that there is an activated expression of GSK3β in the bone marrow mesenchymal stem cells (BMSCs) of diabetic mice. see more To explore the link between GSK3β and diabetic osteoporosis, we exposed BMSCs to a high glucose microenvironment in vitro and discovered that the glucose-induced GSK3β activation has negative osteogenic effects on BMSCs by suppressing β-catenin/Tcf7/Ccn4 signaling axis. Inhibition of GSK3β by specific concentrations of LiCl could reverse the impaired osteogenesis of BMSCs and increase expression of β-catenin, Tcf7 and Ccn4. Our research indicated that abnormal activation of GSK3β plays a role in diabetic osteoporosis and might be a potential target to treat diabetic osteoporosis.SARS-CoV-2 first emerged in the human population in late 2019 in Wuhan, China, and in a matter of months, spread across the globe resulting in the Coronavirus Disease 19 (COVID-19) pandemic and substantial economic fallout. SARS-CoV-2 is transmitted between humans via respiratory particles, with infection presenting a spectrum of clinical manifestations ranging from asymptomatic to respiratory failure with multiorgan dysfunction and death in severe cases. Prior experiences with human pathogenic coronaviruses and respiratory virus diseases in general have revealed an important role for cellular immunity in limiting disease severity. Here, we review some of the key mechanisms underlying cell-mediated immunity to respiratory viruses and summarize our current understanding of the functional capacity and role of SARS-CoV-2-specific T cells following natural infection and vaccination.It is difficult to control systems with multi-uncertainties directly based on traditional active disturbance rejection control (ADRC) framework, due to the mismatched condition, non integral-chain form. Besides, the traditional Hurwitz bounded stability of the extended state observer (ESO) may not guarantee acceptable observation accuracy. To this end, this paper presents an improved generalized proportional integral observer (IGPIO) to estimate the multi-uncertainties and the derivatives, and an IGPIO based control (IGPIOBC) strategy is proposed to eliminate the multi-uncertainties actively and accurately. The proof of bounded stability for the IGPIO and the closed loop system are derived by the singular perturbation approach and Lyapunov theory. Meanwhile, the corresponding relationship between the gain parameters and the bandwidth of the IGPIO is deduced. The simulations of the numerical example, RLC circuit and DC motor system verify the effectiveness of the proposed method.A high-performance control system is essential to transfer maximum power from wind power generation system (WPGS) to the utility grid. In this paper, a fuzzy fractional-order terminal sliding mode control (Fuzzy-FOSMC) is presented based on the boundary layer approach. This boundary layer approach leads to the trade-off between chattering elimination and control performances. Initially a fractional order terminal sliding mode control (FOTSMC) is designed in this paper. Then, the reaching control part of the FOTSMC is replaced by a fuzzy system that eliminates the chattering even in the presence of lumped parametric uncertainties. The fuzzy control part is designed such that(a) it maintains the stability of the system by introducing a non-linear slope inside the thin boundary layer near the sliding surface, and (b) it eliminates the chattering by acting like a saturation function. A novel wind speed estimation technique is also proposed in this paper based on Gaussian process regression (GPR). The inputs to the GPR framework are selected as the wind turbine power and its rotational speed. The superior performance of the proposed wind speed estimation technique is verified using error comparison with pre-existing techniques. The stability of the proposed GPR-based Fuzzy-FOSMC control paradigm is ensured by using the Lyapunov stability theorem. The proposed paradigm is compared with benchmark sliding mode control (SMC) and FOTSMC strategies. The proposed Fuzzy-FOSMC performance in terms of chattering elimination and stability is validated under normal conditions and lumped parametric uncertainties using extensive simulations in Matlab/SIMULINK and processor in the loop based experimental workbench.Aminated poly(N-isopropylacrylamide) (PNIPAm-NH2) was grafted onto oxidized galactomannan polysaccharide extracted from Delonix regia (OXGM) via Schiff base reaction by a simple, rapid synthetic route, deprived of the use of organic solvents. Grafting was confirmed by FTIR and 1H NMR and the self-organizing ability of the obtained nanoparticle copolymers was investigated by dynamic light scattering (DLS). The minimum concentration required for self-organization (CAC) at 25 °C was higher than at 50 °C. Lower critical solution temperature (LCST) was in the range 34-40 °C, depending on both inserted PNIPAm-NH2 molar mass and on the presence of reduced imine bond. Synthesized copolymers are promising candidates for drug delivery as they show good cell viability, particle size around 250 nm and transition temperature closer to that of human body. Reaction success points out to the possibility of use free aldehyde groups of oxidized polysaccharide, not used in the copolymerization, to form a pro-drug with substances that possess NH2 groups in their structure, such as doxorubicin.