ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Incidence, causes and risk factors of vision loss in rural Southern China: 6-year follow-up of the Yangxi Eye Study.

PURPOSE: To report the 6-year incidence, causes and risk factors for vision loss (visual impairment (VI) and blindness), among elderly adults in rural southern China. METHODS: Population-based, cohort study. Initiated in 2014, the study recruited participants aged 50 and older using random cluster sampling from Yangxi County. All eligible participants were invited to attend interviews and comprehensive eye examinations at the 6-year follow-up between November 2020 and March 2021. The WHO categories of vision loss were used to define incident cases of VI (3/60≤VA <6/12), moderate-to-severe VI (MSVI) (3/60≤VA<6/18) and blindness (VA <3/60) in the better-seeing eye. RESULTS: Among the 5825 baseline participants, 3187 (64.4%) of 4946 surviving subjects participated in the 6-year follow-up. Based on presenting and best-corrected VA, respectively, the crude incidence rate of blindness was 0.8% (95% CI 0.5% to 1.1%) vs 0.3% (95% CI 0.1% to 0.5%), for MSVI 6.7% (95% CI 5.7% to 7.6%) vs 4.6% (95% CI 3.8% to 5.4%) and for any VI 16.1% (95% CI 14.5% to 17.6%) vs 12.9% (95% CI 11.6% to 14.1%). Cataract (48.3%) and refractive errors (44.4%) were the most common causes of vision loss. Factors significantly associated with greater incident vision loss were older age, female sex, less education, living alone and longer axial length (all p<0.05). CONCLUSIONS: Substantial work is still required to reduce avoidable vision loss in rural China. Screening outreach and efforts to improve awareness which target the poorer and less educated are urgently needed to reduce the growing unmet need for eye care due to ageing.

The Multi-Modal Risk Analysis and Medical Prevention of Lumbar Degeneration, Fatigue, and Injury Based on FEM/BMD for Elderly Chinese Women Who Act as Stay-Home Grandchildren Sitters.

Background: An increasing number of Chinese elderly women stay at home and act as grandchildren sitters. In consequence of the frequent load-bearing, chronic lumbar fatigue probably caused a higher risk of lumbar degeneration, fatigue, and injury which has become one of the most important aging and health problems in China. In this study, a multi-mode lumbar finite element model (FEM) with specific bone mineral density (BMD) were developed and validated for further spine injury prevention and control. Methods: The material properties of lumbar vertebra were modified according to degenerated bone mineral density, and geometry was adjusted based on intervertebral disc height. The motion of lifting children was simulated by a 76 year-old Chinese women's FEM, and the stress distribution was calculated and predicted. Results: The pressure of L5-S intervertebral disc in the bending 3-year-old dummy lifting posture was significantly higher than the same posture without lifting, the maximum effective stress of endplate cartilage in the upright child lifting posture was 1.6 times that of the bending without lifting posture. And the fatigue risk limitation frequency of the upright with dummy posture was predicted with the functional equation of fatigue and stress which was deduced by genetic algorithm, which combined with the effective stress of lumbar vertebrae spongy bone calculated from FEM. Conclusions: The child-lifting motion could increase the risk of lumbar degeneration, fatigue, and injury in elderly women, and they should keep below the frequency limit of the motion of lifting children in their daily life. This study could put forward scientific injury prevention guidance to Chinese elderly women who lift children in daily life frequently.