Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy

Dilated cardiomyopathy(DCM)is the leading cause of heart transplantation.By microRNA(miRNA)array,a Kaposi’s sarcoma-associated herpes virus(KSHV)-encoded miRNA,kshv-miR-K12-1-5p,was detected in patients with DCM.The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 patients with DCM were measured and these patients were followed-up.

A life support-based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis: a multiple center study

Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR(81 cases),which includes(i) mechanical life support(positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation),(ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and(iii) application of neuraminidase inhibitors, and those receiving conventional treatment(88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients(26.0%) died in hospitals. Inhospital mortality was 3.7%(3/81) for LSBCTR group and 46.6%(41/88) for traditional treatment(P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces inhospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed.This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.

;heoretical analysis for optomechanical all-optical transistor

In this paper, we propose an on-chip all optical transistor driven by optical gradient force. The transistor consists of a single micro-ring resonator, half of which is suspended from the substrate, and a bus waveguide. The free-standing arc is bent by optical gradient force generated when the control light is coupled into the ring. The output power of the probe light is tuned continuously as the transmission spectrum red-shift due to the displacement of the free-standing arc. The transistor shows three working regions known as cutoff region, amplified region and saturate region, and the characteristic curve is tunable by changing the wavelength of the control light. Potential applications of the all optical transistor include waveform regeneration and other optical computing.