Search

The Papain-Like proteases (PLpro) of SARS-CoV-2 play a crucial role in viral replication and the formation of nonstructural proteins. To find available inhibitors, the 3D structure of PLpro of SARS2 was obtained by homologous modelling, and we used this structure as a target to search for inhibitors through molecular docking and MM/GBSA binding free energy rescoring. A novel hydrogen bonding penalty was applied to the screening process, which meanwhile took desolvation into account. Finally, 61 compounds were acquired and 4 of them with IC

A printing technology was developed to construct 75 kbit IO/IGZO heterojunction photoelectric synaptic transistor arrays for an artificial visual memory system.

Anlotinib is a multi-target tyrosine kinase inhibitor, approved in China for treating several cancer types. Dose individualization based on therapeutic drug monitoring (TDM) is a useful tool to reduce toxicity. However, it is not convenient for patients to go to hospital for routine TDM via venous blood sampling at a certain time.An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determination of anlotinib in human plasma and dried blood spot (DBS), characterized by simple sample preparation, high sensitivity, and short analysis time. The assay was validated in the concentration range of 0.2-200 ng/mL in plasma and 5-1000 ng/mL in DBS. This method was applied to monitor anlotinib exposure levels in patients with advanced biliary tract cancer (BTC) and non-small cell lung cancer (NSCLC).The trough plasma concentration (CAnlotinib exhibits a high inter-individual variability in plasma exposure, and DBS sampling could be a promising tool for TDM of anlotinib.

A monostatic/bistatic ground-based synthetic aperture radar (GB-SAR) system using an optical electric field sensor (OEFS) as the bistatic receiving unit has been designed for target imaging and 2-D displacement estimation purposes. The designed system has the capability of acquiring the monostatic and bistatic SAR images simultaneously from different looking angles, enabling the displacement vector estimation of the illuminated area. The spatial baseline between the monostatic and bistatic receivers is selected according to the estimation precision analysis. Experimental results are presented to evaluate the performance of the designed system and the proposed method. The displacement estimation accuracies in x- and y- directions can reach up to millimeter level.

Graphical abstract, Excessive inflammation and the pyroptosis of vascular endothelial cells caused by estrogen deficiency is one cause of atherosclerosis in post-menopausal women. Because autophagy is highly regulated by estrogen, we hypothesized that estrogen can reduce vascular endothelial cell pyroptosis through estrogen receptor alpha (ERα)-mediated activation of autophagy to improve atherosclerosis in post-menopausal stage. Aortic samples from pro-menopausal and post-menopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female ApoE-/- mice and homocysteine (Hcy)-treated HUVECs were used to analyze the effect of estrogen supplementation therapy. The aortic endothelium showed a decrease in ERα expression and autophagy, but presented an increase in inflammation and pyroptosis in female post-menopausal patients. Estrogen treatment accelerated autophagy and ameliorated cell pyroptosis in the cardiac aortas of OVX ApoE-/- mice and Hcy-treated HUVECs. Estrogen had therapeutic effect on atherosclerosis and improved the symptoms associated with lipid metabolism disorders in OVX ApoE-/- mice. Inhibition and silencing of ERα led to a reduction in the autophagy promoting ability of estrogen and aggravated pyroptosis. Moreover, the inhibition of autophagy promoted pyroptosis and abolished the protective effect of estrogen, but had no influence on ERα expression. Thus, the results of the present study demonstrated that post-menopausal women present decreased autophagy and ERα expression and excessive damage to the ascending aorta. In addition, in vitro and in vivo assay results demonstrated that estrogen prevents atherosclerosis by upregulating ERα expression and subsequently induces autophagy to reduce inflammation and pyroptosis.

Mastery of gibbsite (α-Al(OH)3) nucleation and crystal growth is significant in fundamental aluminum chemistry and also beneficial for industrial applications and the remediation of nuclear waste. Herein, we developed an additive-free two-step route to size and morphology controlled synthesis of gibbsite nanoplates. Independent temperature manipulation of nucleation and crystal growth regimes was used to control the efficacy and yield of the process, producing gibbsite nanoplates with tunable morphologies and sizes. We achieve morphologies ranging from hexagon, pseudo hexagon, truncated triangle to rhombic, and average basal plane diameters from 120 to 850 nm, with thicknesses between 8 and 45 nm. Analysis of gibbsite structure, size and morphology with techniques including powder X-ray diffraction (p-XRD), 27Al magic angle spinning nuclear magnetic resonance spectroscopy (MAS NMR), scanning electron microscopy (SEM), and atomic force microscopy (AFM) provided key details on the nucleation and crystal growth mechanisms. The results indicate the temperature of the nucleation aging step is the most important factor controlling the final particle size. Particularly small nanoplates were obtained with a low nucleation aging temperature followed by high crystal growth temperature, suggesting that gibbsite growth can be approximated via a LaMer-type burst nucleation and crystal growth mechanism. Scalability was demonstrated by triplicate of 2 L experiments which prepared gibbsite nanoplates of ∼200 nm size and with an average yield of ∼55% after 84 h. Compared to existing techniques, this improved two-step route is cheaper, more efficient and environmentally friendly.

International audience; Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABAB receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1 and GABAB2 subunits. The oncogenic role of the isoform GABAB1e (GB1e) containing only the extracellular domain of GABAB1 remains unclear. We revealed that GB1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1e promoted the malignancy of BrCa cells both in vitro and in vivo. We propose that GB1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB1e isoform might play an important oncogenic role in BrCa and that GB1e is of interest for the treatment of some cancers.

Summary Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABAB receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1 and GABAB2 subunits. The oncogenic role of the isoform GABAB1e (GB1e) containing only the extracellular domain of GABAB1 remains unclear. We revealed that GB1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1e promoted the malignancy of BrCa cells both in vitro and in vivo. We propose that GB1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB1e isoform might play an important oncogenic role in BrCa and that GB1e is of interest for the treatment of some cancers., Graphical abstract, Highlights • GABAB1e promotes the malignancy of breast cancer cells both in vitro and in vivo • Specific phosphorylation of GABAB1e is critical for its association with PTPN12 • GABAB1e disrupts EGFR interacting with PTPN12 and induces EGFR-PI3K/Akt signaling, Biological sciences; Molecular biology; Neuroscience

Gibbsite, bayerite, and boehmite are important aluminum (oxy)hydroxide minerals in nature and have been widely deployed in various industrial applications. They are also major components in caustic nuclear wastes stored at various U.S. locations. Knowledge of their crystallization and phase transformation processes contributes to understanding their occurrence and could help optimize waste treatment processes. While it has been reported that partial conversion of bayerite and gibbsite to boehmite occurs in basic solutions at elevated temperatures, systematic studies of factors affecting the phase transformation as well as the underlying reaction mechanisms are nonexistent, particularly in highly alkaline solutions. We explored the effects of sodium hydroxide concentrations (0.1-3 M), reaction temperatures (60-100 °C), and aluminum concentrations (0.1-1 M) on the crystallization and transformation of these aluminum (oxy)hydroxides. Detailed structural and morphological characterization by X-ray diffraction (XRD), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) spectrometry revealed that these processes depend largely on the reaction temperature and the Al/OH- ratio. When 1 ≤ Al/OH- ≤ 2.5, the reactions favor formation of high-crystallinity precipitates, whereas at an Al/OH- ratio of ≥2.5 precipitation ceases unless the Al concentration is higher than 1 M. We identified pseudoboehmite, bayerite, and gibbsite as intermediate phases to bayerite, gibbsite and boehmite, respectively, all of which transform via dissolution-reprecipitation. Gibbsite transforms to boehmite in both acidic and weak caustic environments at temperatures above 80 °C. However, a "bar-shaped" gibbsite morphology dominates in highly caustic environments (3 M NaOH). The findings enable a robust basis for the selection of various solid phases by tuning the reaction conditions.

Several bacteria have been defined as extracellular pathogens; however, in recent years, it has been confirmed that they have the ability to survive and escape the attack of host phagocytes, thus causing further infection. Previous studies have shown that Aeromonas hydrophila could survive in fish macrophages; however, the mechanism remains unknown. In this study, sodA and sodB of the strain A. hydrophila B11 were stable silenced by shRNA. The survival rates of intracellular sodA-RNAi and sodB-RNAi decreased by 91.8% and 74.9% and the immune escape rates decreased by about 32% and 92% respectively. At the same time, reactive oxygen species (ROS) in fish macrophages that phagocytosed sodA-RNAi and sodB-RNAi increased by 40% and 32.6%, respectively, compared to those of macrophages that phagocytosed the wild-type strain. Compared to sodA, the expression of sodB predominates in A. hydrophila without oxidative stress; however, when exposed to oxidative stress, the magnitude of up-regulation of sodA expression is significantly higher than that of sodB. With increased of methyl viologen concentration, the survival rates of sodA-RNAi and sodB-RNAi were significantly decreased. The expressions of sodA and sodB did not affect the growth of A. hydrophila without oxidative stress, but the inhibition of sodA and sodB expression led to a slight decrease in bacterial growth under oxidative stress. These results indicated that (1) sodA and sodB play an important role in the process of bacterial resistance to ROS damage in host phagocytic cells, allowing them to survive or even escape fish macrophages; (2) the sodB expression was dominant in A. hydrophila without oxidative stress, the sodA expression was up-regulated more significantly under oxidative stress, and sodA and sodB contributed equally to the process of bacterial resistance to ROS; (3) sodA and sodB complement each other and cooperate in the process of intracellular survival of bacteria to protect against ROS damage.

Survival in host macrophages is an effective strategy for pathogenic bacteria to spread. Aeromonas hydrophila has been found to survive in fish macrophages, but the mechanisms remain unknown. In this paper, the roles and possible mechanisms of IcmF in bacterial survival in fish macrophages were investigated. First, a stable silencing strain icmF-RNAi was constructed by shRNA and RT-qPCR confirmed the expression of icmF was down-regulated by 94.42%. The expression of Hcp, DotU and VgrG was also decreased in icmF-RNAi. The intracellular survival rate of the wild-type strain was 92.3%, while the survival rate of icmF-RNAi was only 20.58%. The escape rate of the wild-type strain was 20%, while that of the icmF-RNAi was only 7.5%. Further studies indicated that the expression of icmF can significantly affect the adhesion, biofilm formation, motility and acid resistance of A. hydrophila, but has no significant effect on the growth of A. hydrophila even under the stress of H2 O2 . The results indicated that IcmF of A. hydrophila not only acts as a structural protein which participates in virulence-related characteristics such as bacterial motility, adhesion and biofilm formation, but also acts as a key functional protein which participates in the interaction between bacteria and host macrophages.

Background: To investigate the expression levels of microRNA-146b (miR-146b) and cardiac troponin I (anticTnI) in serum of children with viral myocarditis and their clinical significance. Methods: Forty-eight children with viral myocarditis (patient group) and 40 healthy physical examinees (healthy group), who were diagnosed in Jinan City People’s Hospital Affiliated to Shandong First Medical University, China from Feb 2018 to May 2019, were enrolled as study subjects. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the level of miR-146b in serum of children. ELISA was used to detect the expression of anti-cTnI in serum of children. Pearson was used to analyze the correlation between the level of miR-146b and the level of anti-cTnI, and the factors affecting the prognosis. Results: The levels of miR-146b and anti-cTnI in serum of children in patient group were statistically significantly higher than those of healthy group (P

By adopting an ultra-wide bandwidth and exploiting a wide-angle synthetic aperture, SAR can achieve high spatial resolutions in the range and azimuth directions, respectively. Incorporate with polarimetry diversity, which allows to explore the polarimetric scattering mechanism of the illuminated targets. Integrated these characteristics aforementioned, wide-angle ultra-wideband polarimetric synthetic aperture radar with canonical targets have been investigated numerically and experimentally. To further validate the simulated results, the corresponding experiment with a dihedral was conducted by a GB-SAR system in the field, which exhibit good agreement with the simulated results.

Under the background of economic globalization, China and the world economy are increasingly connected. BRI upholds the spirit of open-style and synergetic regional cooperation, follows the principle of “Wide Consultation, Joint Contribution and Shared Benefits,” and calls for all-inclusive globalization. Construction of “The Belt and Road” is centered on policy coordination, facility connectivity, unimpeded trade, financial integration and people-to-people bonds, and will redefine economic and trade contacts among participant nations while boosting “inclusive globalization” and “globalization benefiting all.” BRI opens new horizons and provides new cooperation arenas for SMEs to plunge in globalization. Open-style participation, as proposed by BRI, implies that not only various countries along “The Belt and Road,” but also other countries and international and regional organizations are greeted to participate in and achieve all-win cooperation.

The aim of the present study was to explore the risk factors of diabetes peripheral neuropathy (DPN) in type 2 diabetes mellitus, and to propose corresponding nursing intervention measures to provide the basis for early diagnosis, treatment and prevention of DPN. A retrospective analysis was performed on 130 patients with type 2 diabetes mellitus (T2DM) in the communities surrounding our hospital from January 2017 to June 2018. They were divided into a DPN group (62 cases) and non-DPN group (control group, 68 cases). First, a univariate analysis was performed. DPN or non-DPN were used as dependent variables, and statistically significant parameters in univariate analysis were used as independent variables. Multivariate logistic regression analysis was included to analyze the peripheral nerves in type 2 diabetes mellitus. At the same time, the patients with DPN were given individualized comprehensive nursing intervention. Univariate analysis showed that body mass index (BMI), diabetes duration, smoking history, drinking history, family history of diabetes, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure, 24-h urine microalbumin excretion (24hmALB), glomerular filtration rate (GFR), serum creatinine in DPN group were significantly different from those in the control group (P

Aeromonas hydrophila B11 strain was isolated from diseased Anguilla japonica, which had caused severe gill ulcers in farmed eel, causing huge economic losses. EnvZ‐OmpR is a model two‐component system in the bacteria and is widely used in the research of signal transduction and gene transcription regulation. In this study, the ompR of A. hydrophila B11 strain was first silenced by RNAi technology. The role of ompR in the pathogenicity of A. hydrophila B11 was investigated by analyzing both the bacterial comparative transcriptome and phenotype. The qRT‐PCR results showed that the expression of ompR in the ompR‐RNAi strain decreased by 97% compared with the wild‐type strain. The virulence test showed that after inhibition of the ompR expression, the LD50 of A. hydrophila B11 decreased by an order of magnitude, suggesting that ompR is involved in the regulation of bacterial virulence. Comparative transcriptome analysis showed that the expression of ompR can directly regulate the expression of several important virulence‐related genes, such as the bacterial type II secretion system; moreover, ompR expression also regulates the expression of multiple genes related to bacterial chemotaxis, motility, adhesion, and biofilm formation. Further studies on the phenotype of A. hydrophila B11 and ompR‐RNAi also confirmed that the downregulation of ompR expression can decrease bacterial chemotaxis, adhesion, and biofilm formation., After the expression of ompR was inhibited, the virulence of Aeromonas hydrophila B11 decreased, which suggested that ompR is involved in the bacterial virulence regulation. Comparative transcriptome analysis revealed that the expression of ompR can directly regulate the expression of some important virulence‐related genes, especially the bacterial type II secretion system, as well as regulate the expression of multiple genes related to bacterial chemotaxis, motility, adhesion, and biofilm formation.

The Ngari area in Tibet is in the forefront of land-continent collisions. The area is accompanied by the polymerization of plates, forming complex structures such as the Tethys Himalayan pleat belt, the Yarlung Zangbo suture belt, and the Gangdese continental margin magma arc from the south to the north. The multi-period dive collision-inland convergence process, the geological structure is complex and the seismicity is very high. Based on the Chinese historical earthquake catalogue, the China Modern Earthquake Catalogue and the seismic data from the International Seismological Center (ISC), we analyzed the seismic activity, focal mechanism and modern tectonic stress field in the Ngari area, and then analyzed the seismicity and its source of geodynamics. The main conclusions are as follows:(1) The seismic activities in the Ngari area are mainly distributed in the Himalayan tectonic belt, the Bangong-Nujiang tectonic belt, the Alkin-East Kunlun tectonic belt, and some near north-south trending tectonic belts; (2) Earthquakes near the Himalayan tectonic belt is dominated by reverse faulting events. The seismic activity near the Bangong-Nujiang tectonic belt and the Alkin-East Kunlun tectonic belt is dominated by strike-slip earthquakes. Near the north-south extensional tectonic belt, the earthquakes show as the normal faulting events. (3) The main direction of the modern tectonic stress field in the study area is near north-south direction; (4) Seismic activity, focal mechanism and modern tectonic stress field show that the geodynamic source in the Ngari region is from Collision and squeezing the between the Eurasian plate and the Indian Ocean plate.

In recent years, the discovery of ‘magic angle’ graphene has given new inspiration to the formation of heterojunctions. Similarly, the use of hexagonal boron nitride, known as white graphene, as a substrate for graphene devices has more aroused great interest in the graphene/hexagonal boron nitride heterostructure system. Based on the first principles method of density functional theory, the band structure, density of states, Mulliken population, and differential charge density of a tightly packed model of twisted graphene/hexagonal boron nitride/graphene sandwich structure have been studied. Through the establishment of heterostructure models twisted bilayer-graphene inserting hBN with different twisted angles, it was found that the band gap, Mulliken population, and charge density, exhibited specific evolution regulars with the rotation angle of the upper graphene, showing novel electronic properties and realizing metal–insulator phase transition. We find that the particular value of the twist angle at which the metal–insulator phase transition occurs and propose a rotational regulation mechanism with angular periodicity. Our results have guiding significance for the practical application of heterojunction electronic devices.

International audience; A passive bistatic radar (PBR) system, which exploits the digital terrestrial television broadcasting (DTTB) emitter as the illumination source without using a dedicated transmitter, has been developed for subsurface target detection. Its main features are low system cost, high system flexibility, and no need for frequency allocation. In this paper, at first, the fundamental concept, system components, and basic signal processing methods are introduced. The characteristics of the adopted DTTB signal with the Japan ISDB-T standard are evaluated. Then, one of the key techniques for ISDB-T DTTB signal based PBR, i.e., reference signal refinement (reconstruction and modification), is presented to suppress the strong sidelobes in the range-Doppler domain caused by the waveform properties and multipath echoes. Preliminary experimental results are shown to demonstrate the basic functions of the developed radar system. It has been found that the reference signal refinement method can work well in practice and a metallic plate buried in the sand can be effectively detected by the developed PBR system. At last, potential improvement directions of the PBR system for subsurface target detection, e.g., combing multiple bands, working with cooperative targets, and using super-resolution algorithms, are provided.