COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10−10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10−9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10−8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body’s natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients’ quality of life through functional vision.

Heat stress limits plant growth, development, and crop yield, but how plant cells precisely sense and transduce heat stress signals remains elusive. Here, we identified a conserved heat stress response mechanism to elucidate how heat stress signal is transmitted from the cytoplasm into the nucleus for epigenetic modifiers. We demonstrate that HISTONE DEACETYLASE 9 (HDA9) transduces heat signals from the cytoplasm to the nucleus to play a positive regulatory role in heat responses in Arabidopsis . Heat specifically induces HDA9 accumulation in the nucleus. Under heat stress, the phosphatase PP2AB′β directly interacts with and dephosphorylates HDA9 to protect HDA9 from 26S proteasome-mediated degradation, leading to the translocation of nonphosphorylated HDA9 to the nucleus. This heat-induced enrichment of HDA9 in the nucleus depends on the nucleoporin HOS1. In the nucleus, HDA9 binds and deacetylates the target genes related to signaling transduction and plant development to repress gene expression in a transcription factor YIN YANG 1–dependent and –independent manner, resulting in rebalance of plant development and heat response. Therefore, we uncover an HDA9-mediated positive regulatory module in the heat shock signal transduction pathway. More important, this cytoplasm-to-nucleus translocation of HDA9 in response to heat stress is conserved in wheat and rice, which confers the mechanism significant implication potential for crop breeding to cope with global climate warming.

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