Chronic Sleep Deprivation Impairs Visual Functions via Oxidative Damage in Mice.

Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages.

Models for Meibomian gland dysfunction: In vivo and in vitro.

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.

MAP4Ks inhibition promotes retinal neuron regeneration from Müller glia in adult mice.

Mammalian Müller glia (MG) possess limited regenerative capacities. However, the intrinsic capacity of mammalian MG to transdifferentiate to generate mature neurons without transgenic manipulations remains speculative. Here we show that MAP4K4, MAP4K6 and MAP4K7, which are conserved Misshapen subfamily of ste20 kinases homologs, repress YAP activity in mammalian MG and therefore restrict their ability to be reprogrammed. However, by treating with a small molecule inhibitor of MAP4K4/6/7, mouse MG regain their ability to proliferate and enter into a retinal progenitor cell (RPC)-like state after NMDA-induced retinal damage; such plasticity was lost in YAP knockout MG. Moreover, spontaneous trans-differentiation of MG into retinal neurons expressing both amacrine and retinal ganglion cell (RGC) markers occurs after inhibitor withdrawal. Taken together, these findings suggest that MAP4Ks block the reprogramming capacity of MG in a YAP-dependent manner in adult mammals, which provides a novel avenue for the pharmaceutical induction of retinal regeneration in vivo.

A high-performance porous flexible composite film sensor for tension monitoring.

Flexible, lightweight sensors with a wide strain-sensing range are showing increasing significance in structural health monitoring compared with conventional hard sensors, which typically have a small strain range, are heavyweight, and have a large volume. In this work, salt particle precipitation and mechanical coating methods are used to fabricate porous graphene nanoplatelet (GNP)/polydimethylsiloxane (PDMS) flexible sensors for tension monitoring in structural health applications. The signal transformation through the Back Propagation (BP) algorithm is integrated to provide monitoring data that are comparable with other sensors. The results reveal that the flexible sensors with a low content of GNPs (0.1-0.25 wt%) possess better flexibility, allowing tensile strains over 200% to be measured. In addition, due to the enhanced deformation capacity of the pore structures, they can achieve high sensitivity (1-1000) under 65% strain, and a fast response time (70 ms) under 10% strain at 60 mm min-1. They also show high performance in the fatigue test (20 000 cycles) under 5% strain, and can effectively respond to bending and torsion. In addition, the sensors show an obvious response to temperature. Overall, the prepared flexible composite sensors in this work have the advantages of a wide strain-sensing range, a full-coverage conductive network, and being lightweight, and show potential for structural health monitoring in the near future.

Wogonin affects proliferation and the energy metabolism of SGC-7901 and A549 cells.

Many studies have focused on the identification of therapeutic targets for the treatment of certain types of cancer. Wogonin is a natural flavonoid compound that exhibits a potent anti-cancer effect. The underlying mechanism of wogonin may therefore reveal an effective way to identify novel therapeutic targets. In the current study, growth curves and MTT assays were performed to determine the effects of wogonin in human gastric cancer cells (SGC-7901) and human lung adenocarcinoma cells (A549), respectively. Changes in morphology were observed using hematoxylin and eosin (H&E) staining. The activities of key enzymes in the glycolysis and tricarboxylic acid cycle were measured using spectrophotometry. Western blot analysis was performed to determine the expression levels of hypoxia inducible factor-1α (HIF-1α) and monocarboxylate transporter-4 (MCT-4). Wogonin inhibited cell proliferation in a time- and dose-dependent manner in SGC-7901 and A549 cells. H&E staining suggested that wogonin induced cell morphology changes. In SGC-7901 cells, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities and adenosine triphosphate (ATP) generation were decreased significantly by wogonin treatment compared with the untreated control. In A549 cells, wogonin significantly reduced LDH activity, but exhibited no significant effects on kinase activities or ATP generation. Furthermore, wogonin significantly decreased HIF-1α and MCT-4 protein expression in SGC-7901 cells, but not in A549 cells. The results demonstrated that wogonin inhibited the energy metabolism, cell proliferation and angiogenesis in SGC-7901 and A549 cells by negatively regulating HIF-1α and MCT-4 expression. The differential regulatory roles of wogonin in metabolism-associated enzymes in human gastric cancer and lung adenocarcinoma cells indicated its various antitumor mechanisms. The different metabolic regulatory mechanisms exhibited by wogonin in different tumor tissues should therefore be considered for antitumor therapy.