On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30–50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31–2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23–2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.

Photocatalytic hydrogen evolution from water splitting is a promising approach in energy conversion and storage. Here, the 0D/1D CdS quantum dots (QDs)/CeO2 nanorods heterojunction was designed and fabricated by a facile two-step method. The optimum photocatalytic H2 evolution activity for CeO2-based composites with 3 at. % CdS QDs (101.12 μ mol h–1 g–1) was 45 times as high as that of pure CeO2 nanorods (2.25 μ mol h–1 g–1) under light irradiation. Meanwhile, the photocurrent response intensity increased 17.75 times higher than pure CeO2 nanorods. Furthermore, the 0D/1D CdS QDs/CeO2 heterojunctions exhibited enhanced photocatalytic stability for long lifetime (60 h). The reasons that dramatically enhanced photocatalytic performance could be the improved light harvesting, enhanced photoresponse and stronger electronic conductivity while the CdS QDs was loaded in CeO2 nanorods to form the 0D/1D heterojunctions CdS QDs/CeO2 nanocomposites. What’s more, the remarkably increased photocatalytic performance of CdS QDs/CeO2 composites was mainly attributed to the Z-scheme between CdS QDs and CeO2 nanorods, which was confirmed by the PL (photoluminescence) method. Therefore, the proposed system is highly promising for large scale photocatalytic hydrogen evolution.

Sugar transport, including the symplasmic pathway in plasmodesmata and apoplasmic pathway mediated by sugar transporters, accelerated sugar accumulation in cultivated jujube, while sugar metabolism-related genes played weak roles in jujube domestication. The fruit of Chinese jujube (Ziziphus jujuba Mill.) is high in sugar concentration. By contrast, wild type-sour jujube (Z. jujuba Mill. var. spinosa Hu) contains markedly less sugar. It is unknown whether sugar transport or sugar metabolism drove sugar accumulation during jujube domestication. Using a combination of ultrastructural observations, phylogenetic analysis, testing for soluble sugars, and transcriptional analysis, the sugar accumulation mechanism was studied in the developmental stages of cultivated jujube and sour jujube. Our results indicate that the symplasmic transport pathway in plasmodesmata is present in cultivated jujube, but not in sour jujube. Sugar transporter genes have higher frequencies of duplication than sugar metabolism-related genes. Gene expression patterns indicate that sugar transporter genes, especially ZjSUT2, ZjSWEET1, ZjSWEET7, ZjSWEET11, ZjSTP3, and ZjSTP13a, rather than sugar metabolism-related genes showed higher expression levels in cultivated jujube versus sour jujube during fruit sugar accumulation. These findings suggest that sugar transport, including apoplasmic and symplasmic transport, rather than sugar biosynthesis, is associated with the difference in sugar accumulation between jujube and sour jujube, and that it may drive jujube domestication. This study provides valuable genetic information for jujube improvement, and offers new insights into fruit tree domestication related to sugar accumulation.

Children tend to produce words earlier when they are connected to a variety of other words along the phonological and semantic dimensions. Though these semantic and phonological connectivity effects have been extensively documented, little is known about their underlying developmental mechanism. One possibility is that learning is driven by lexical network growth where highly connected words in the child's early lexicon enable learning of similar words. Another possibility is that learning is driven by highly connected words in the external learning environment, instead of highly connected words in the early internal lexicon. The present study tests both scenarios systematically in both the phonological and semantic domains across 10 languages. We show that phonological and semantic connectivity in the learning environment drives growth in both production-and comprehension-based vocabularies, even controlling for word frequency and length. This pattern of findings suggests a word learning process where children harness their statistical learning abilities to detect and learn highly connected words in the learning environment.

The prevalence of type II diabetes mellitus (T2DM) in coronary artery disease (CAD) patients has been steadily increasing, especially in East Asian countries. Although many studies have suggested that certain genetic variants may predispose to the development of T2DM, very few studies investigated the genetic link with T2DM in CAD patients of East Asia. In this study, we investigated the relationship between Glu504Lys polymorphism in the acetaldehyde dehydrogenase 2 (ALDH2) gene, a key enzyme of alcohol metabolism, and the risk of having T2DM in Chinese Han CAD patients. We enrolled 542 CAD patients (180 women and 362 men) and 309 CADÀ/DMÀ subjects (152 women and 157 men). T2DM was confirmed in 47.4% of CAD patients. Logistic and linear regression analyses showed that ALDH2 mutant genotypes (*1/*2 and *2/*2) were an independent risk factor for both T2DM in female CAD patients, even after controlling for alcohol consumption (OR¼1.95, P¼0.043), and fasting plasma glucose (FPG) in CADÀ/DMÀ women (P¼0.015), whereas the association with FPG disappeared after controlling for high-sensitivity C-reactive protein, a classic inflammatory biomarker. However, there was no relationship between the ALDH2 genetic polymorphism and T2DM or FPG in men. These findings suggest that the ALDH2 polymorphism is associated with an increased risk of T2DM in female CAD patients, and this association could be causal on the basis of the association between the polymorphism and FPG, which is partly explained by an increased inflammatory status. These findings will benefit the screening and treatment of a high-risk population in East Asians.

Edited by Stuart Ferguson Keywords:Aldehyde dehydrogenase 2 Acetylation Endothelial nitric-oxide synthase Ethanol Reactive oxygen species SIRT3 a b s t r a c tModerate alcohol consumption has beneficial effects on endothelial nitric-oxide synthase (eNOS) activation, which can engender an array of anti-atherogenic actions. Here we show that in human aortic endothelial cells (HAECs), rapid activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) mediates ethanol-induced eNOS activation by preventing reactive oxygen species (ROS) accumulation. Furthermore, activation of ALDH2 by ethanol is due to its hyperacetylation by SIRT3 inactivation. These data suggest that ethanol-induced eNOS activation in HAECs may be dependent on ALDH2 hyperacetylation by SIRT3 inactivation.

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesized that the anti-VEGF drug bevacizumab might be beneficial for treating Covid-19 patients. We recruited 26 patients from 2-centers (China and Italy) with confirmed severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest radiological imaging. This trial was conducted from Feb 15 to April 5, 2020, and followed up for 28 days. Relative to comparable control patients with severe Covid-19 admitted in the same centers, bevacizumab showed clinical efficacy by improving oxygenation and shortening oxygen-support duration. Among 26 hospitalized patients with severe Covid-19 (median age, 62 years, 20 [77%] males), bevacizumab plus standard care markedly improved the PaO2/FiO2 ratios at days 1 and 7 (elevated values, day 1, 50.5 [4.0,119.0], p<0.001; day 7, 111.0 [85.0,165.0], p<0.001). By day 28, 24 (92%) patients showed improvement in oxygen-support status, 17 (65%) patients were discharged, and none showed worsen oxygen-support status nor died. Significant reduction of lesion areas and ratios were shown in chest CT or X-ray analysis within 7 days. Of 14 patients with fever, body temperature normalized within 72 hours in 13 (93%) patients. Lymphocyte counts in peripheral blood were significantly increased and CRP levels were markedly decreased as shown in available data. Our findings suggested bevacizumab plus standard care was highly beneficial for treating patients with severe Covid-19. Clinical efficacy of bevacizumab warrants double blind, randomized, placebo-controlled trials.