Abstract Activating transcription factor 3 (ATF3) is an adaptive-response protein induced by various environmental stresses and is implicated in the pathogenesis of many disease states. However, the ...role of ATF3 SUMOylation in hypertension-induced vascular injury remains poorly understood. Here we investigated the function of ATF3 SUMOylation in vascular endothelial cells (ECs). The expression of ATF3 and small ubiquitin-like modifier 1 (SUMO1) was increased in angiotensin II (Ang II)-induced human umbilical vein endothelial cells (HUVECs). Microscopic analyses further revealed that the expression of ATF3 and SUMO1 is upregulated and colocalized in the endothelium of thoracic aortas from Ang II-induced hypertensive mice. However, Ang II-induced upregulation of ATF3 and SUMO1 in vitro and in vivo was blocked by Ang II type I receptor antagonist olmesartan. Moreover, Ang II induced ATF3 SUMOylation at lysine 42, which is SUMO1 dependent. ATF3 SUMOylation attenuated ATF3 ubiquitination and in turn promoted ATF3 protein stability. ATF3 or SUMO1 knockdown inhibited Ang II-induced expression of inflammatory molecules such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8. Wild type ATF3 but not ATF3-K42R (SUMOylation defective mutant) reduced the production of nitric oxide (NO), a key indicator of EC function. Consistently, ginkgolic acid, an inhibitor of SUMOylation, increased NO production in HUVECs and significantly improved vasodilatation of aorta from Ang II-induced hypertensive mice. Our findings demonstrated that ATF3 SUMOylation is involved in Ang II-induced EC inflammation and dysfunction in vitro and in vivo through inhibiting ATF3 ubiquitination and increasing ATF3 protein stability.
This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID‐19). A cohort of patients with ...COVID‐19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all‐cause in‐hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID‐19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range IQR: 25.71‐69.70) was higher than that of survival group (median: 4.11; IQR: 2.44‐8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all‐cause in‐hospital mortality (odds ratio = 44.351; 95% confidence interval = 4.627‐425.088). These results suggest that the NLR at hospital admission is associated with in‐hospital mortality among patients with COVID‐19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID‐19. However, further investigation is needed to validate this relationship with data collected prospectively.
Highlights
NLR is a significant prognostic biomarker of outcomes in critically ill patients with COVID‐19.
COVID‐19 is more likely to infected those elder men with chronic comorbidities.
NLR may also help in the early identification of older patients at higher risk of COVID‐19.
Close monitoring and timely intervention are needed for elderly patients with COVID‐19.
In the Internet plus era, the environment of the world’s economy is changing towards globalization and information. The development of Chinese enterprises is facing hitherto unknown opportunities. ...Meanwhile, the financial risks facing enterprises are increasing day by day, because the constraints of environmental factors, economic and market factors, laws and regulations, social and cultural factors, policy environmental factors, and other unpredictable environmental factors have brought uncertainty to the financial situation of enterprises. The way a company handles its own financial risk has a big impact on its overall success. Many enterprises fall into economic crisis early because they do not pay enough attention to financial problems in the early stages and do not take effective measures to deal with the crisis situation in a timely manner, resulting in internal management confusion, deterioration of the external environment, capital chain problems, and serious asset losses. It is difficult to recover, and individuals who are experiencing a more significant financial crisis are at risk of becoming bankrupt. As a result, the success or failure of an enterprise’s early development is determined by the success or failure of its subsequent development. As a result, in order to devote more resources to the study of enterprise financial risk, this paper develops a variety of dynamic early warning models of financial crises in publicly traded companies by analyzing relevant theories of financial risk and combining the particle swarm optimization algorithm. This model has great efficiency and scientific early warning capabilities, and it can better forecast business financial crises.
The Mei (Prunus mume Sieb. et Zucc.) is one of the most widely used landscape plants and important germplasm resources in China. The study of pollen cryopreservation and the construction of a pollen ...cryo-bank have great importance in Mei research. From 2003 to 2007 we cryopreserved
pollen from 51 Mei cultivars. In vitro germination of cryopreserved pollen was not significantly different from that of fresh pollen, even after four years of storage in liquid nitrogen. Cryopreserved pollen of 19 cultivars was used successfully for intraspecific hybridizations at Wuhan
and Beijing in 2005 and 2006.
•The solar-activated peroxydisulfate was adopted as a pretreatment prior to ultrafiltration.•Solar light and heating effects played different roles in degrading NOMs at different ...temperatures.•Terrestrially derived humic-like matters were the main cause of total membrane fouling.•Irreversible membrane fouling was mainly attributed to protein-like substances.•UV254 can be used for elevating membrane fouling control strategies to avoid excessive treatment.
Solar energy is considered one of the most promising energy sources for the degradation of pollutants in the water treatments. An innovative solar photo-thermochemical system involving peroxydisulfate (PDS) as an oxidant and xenon lamp as a solar irradiation light source was applied with hopes to degrade organic matters and alleviate the ultrafiltration (UF) membrane fouling when treating the real surface water. Moreover, heat-activated PDS pretreatment was used as a comparison to explore the respective proportions of solar light and heating effects, finding that solar light effect dominated the activation of PDS to degrade natural organic matters (NOMs) when the reaction temperature was below 50 °C and they both contributed to the production of free radicals at the temperature of >50 °C. The results indicated that solar-activated PDS pretreatment significantly alleviated membrane fouling caused by Songhua River water with the highest transmembrane pressure (TMP) reduction of approximately 69.6% at 70 °C. Organic substances (characterized by DOC, UV254 and the maximum florescent intensity) and micropollutant (atrazine) in the feed water were better degraded in the presence of solar light. Both total fouling index (TFI) and hydraulic irreversible fouling index (HIFI) were moderate correlated with the UV254 and DOC, whereas remarkably correlated with the Fmax of component 2 (C2) and component 3 (C3). In addition, no significant correlation was observed between fouling indexes (TFI and HIFI) and the Fmax of component 1 (C1). The membrane irreversible fouling was attributed to the accumulation of cake layers mainly composed of protein-like substances on the membrane surface. Solar-activated PDS pretreatment would efficiently degrade the protein-like substances and terrestrially derived humic-like matters to control UF membrane fouling. The findings are beneficial to develop new strategies for membrane fouling alleviation based on the solar irradiation and PDS oxidation.
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Organic ammonium salts have been widely used for defect passivation to suppress nonradiative charge recombination in perovskite solar cells (PSCs). However, they are prone to form undesirable ...in‐plane favored 2D perovskites with poor charge transport capability that hamper device performance. Herein, the defects passivation role of alkyldiammonium including 1.6‐hexamethylenediamine dihydriodide (HDAI2), 1,3‐propanediamine dihydriodide (PDAI2), and 1.4‐butanediamine dihydriodide (BDAI2) for formamidinium‐cesium perovskite is systematically investigated. With help of density functional theory (DFT) calculations, BDA with suitable size can synergistically passivate two defect sites on perovskite surfaces, showing the best defect passivation effect among the above three alkyldiammonium salts. Perovskite films based on BDAI2 modification are found to keep the 3D perovskite phase with considerably reduced trap‐state density, and enhanced carrier extraction. As a result, the BDAI2‐modified devices deliver impressive efficiencies of 23.1% and 20.9% for inverted PSCs on the rigid and flexible substrates, respectively. Moreover, the corresponding encapsulated rigid devices maintain 92% of the initial efficiency after operating under continuous 1‐sun illumination with the maximum power point tracking for 1000 h. Furthermore, the mechanical flexibility of the BDAI2‐modified flexible device is also improved due to the release of residual stress.
BDA can make full use of the two ammonium cations for passivation and strengthen the absorption of BDA onto the VFA defect as well as enhance the formation energy of VFA, and thereby anchor the perovskite surfaces, so as to improve the photovoltaic performance of rigid and flexible devices.
Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that ...they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.
The mu opioid agonist morphine has distinct effects on spinal dorsal horn neurons in the superficial and deep laminae. However, it is not clear if the inhibitory effect of morphine on dorsal horn ...projection neurons is secondary to its potentiating effect on inhibitory interneurons. In this study, we tested the hypothesis that removal of GABAergic and glycinergic inhibitory inputs attenuates the effect of morphine on dorsal horn projection neurons and the reduced spinal GABAergic tone contributes to attenuated morphine effect in neuropathic pain. Single-unit activity of deep dorsal horn projection neurons was recorded in anesthetized normal/sham controls and L(5) and L(6) spinal nerve-ligated rats. Spinal application of 10 microM morphine significantly inhibited the evoked responses of dorsal horn neurons in both normal/sham controls, and this effect was abolished by the specific mu opioid antagonist. However, the effect of morphine on dorsal horn projection neurons was significantly reduced in nerve-injured rats. Furthermore, topical application of the GABA(A) receptor antagonist bicuculline (20 microM) almost abolished the effect of morphine in normal/sham control rats but did not significantly attenuate the morphine effect in nerve-injured rats. On the other hand, the glycine receptor antagonist strychnine (4 microM) significantly decreased the effect of morphine in both nerve-injured and control animals. These data suggest that the inhibitory effect of opioids on dorsal horn projection neurons depends on GABAergic and glycinergic inputs. Furthermore, reduced GABAergic tone probably contributes to diminished analgesic effect of opioids in neuropathic pain.
Lasing signals with easily distinguishable readout and cavity-geometry-dependent output are emerging as novel cryptographic primitives for two-dimensional (2D) optical encryption, while their ...practical application is restricted by the challenge of integrating different lasing elements onto an identical 2D pattern. Herein, a lithographic template-confined crystallization approach was proposed to prepare large-scale perovskite microstructures with any desired geometries and locations, which enabled them to serve as 2D lasing patterns for reliable encryption and authentication. These prepatterned perovskite microstructures realized whispering-gallery-mode lasing and also demonstrated outstanding reproducibility of lasing actions. Benefiting from the feature of their cavity-geometry-dependent lasing thresholds, we achieved controllable laser output from different shaped elements, which was further utilized for the proof-of-concept demonstration of a cryptographic implementation. The remarkable lasing performance and feasible preparation of 2D microlaser patterns with customized geometries and locations provide us deep insights into the concepts and fabrication technologies for 2D optical encryption.