The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
Activation of Pannexin 1 (PANX1) ion channels causes release of intercellular signaling molecules in a variety of (patho)physiological contexts. PANX1 can be activated by G protein-coupled receptors ...(GPCRs), including α1-adrenergic receptors (α1-ARs), but how receptor engagement leads to channel opening remains unclear. Here, we show that GPCR-mediated PANX1 activation can occur via channel deacetylation. We find that α1-AR-mediated activation of PANX1 channels requires Gαq but is independent of phospholipase C or intracellular calcium. Instead, α1-AR-mediated PANX1 activation involves RhoA, mammalian diaphanous (mDia)-related formin, and a cytosolic lysine deacetylase activated by mDia - histone deacetylase 6. HDAC6 associates with PANX1 and activates PANX1 channels, even in excised membrane patches, suggesting direct deacetylation of PANX1. Substitution of basally-acetylated intracellular lysine residues identified on PANX1 by mass spectrometry either prevents HDAC6-mediated activation (K140/409Q) or renders the channels constitutively active (K140R). These data define a non-canonical RhoA-mDia-HDAC6 signaling pathway for GαqPCR activation of PANX1 channels and uncover lysine acetylation-deacetylation as an ion channel silencing-activation mechanism.
Flow slide is a flow-type landslide, which has high mobility and is destructive to the downstream infrastructures and buildings. In this study, a numerical method is presented to simulate the runout ...process of flow slide, and the interactions between flow slide and buildings on three-dimensional terrain considering the destruction process. In this proposed method, the flow slide is simulated by smoothed particle hydrodynamics (SPH) and the buildings are simulated by the finite element method (FEM). A node-to-surface contact algorithm is adopted to transfer displacements and contact forces between the flow slide and the buildings. An element erosion algorithm is adopted to simulate the destruction process. The method is validated using an analytical solution to dam break problem and the experimental results in two flume tests. A catastrophic flow slide involving building destruction is then simulated to further test the model performance. The flow depth, flow velocity, deposition area, and building damage degree are all reasonably simulated. The typical destruction process of buildings and patterns of the flow slide are also identified. The method will contribute to a better understanding of flow-structure interactions and is a promising tool for hazard analysis and mitigation.
Actinomycetes have being regarded as a treasure reservoir of various bioactive secondary metabolites and devoted many antibiotics in clinicals. Amycolatopsis sp. YNNP 00208 was isolated from a soil ...sample collected in Gaoligong Mountain area, Yunnan Province, China. Chemical investigation of its fermentation broth led to a new amide, baoshanmycin (1), and a new furanone derivative, 3‐(1,3‐dihydroxybutyl)‐4‐methylfuran‐2(H)‐one (2), together with eight known compounds, including two amides (3–4), four cyclic dipeptides (5–8), and two deoxyribonucleosides (9–10). Their structures were established on basis of the 1D‐ and 2D‐NMR spectroscopic data, along with the HR‐ESI‐MS experiments. Baoshanmycin (1) showed moderate antimicrobial activities against Candida albicans, and weak activities against Staphylococcus aureus, multi‐drug resistant Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, fluconazole‐resistant Candida albicans. Baoshanmycin (1) presented strong antioxidant activity and moderate anti‐acetylcholinesterase activity. The other compound 3‐(1,3‐dihydroxybutyl)‐4‐methylfuran‐2(H)‐one (2) and the known compounds (3–10) showed moderate antioxidant activity.
Drivers who lack sufficient experience would be unable to achieve handling stability due to the variation and dynamics of the combined vehicles (CVs). Drivers face hurdles in the stabilization ...attempt once these vehicles are rendered unstable. In this investigation, the use of the behavior of real vehicles to track the desired properties of the developed combined vehicles can help maintain good handling stability despite the present varying dynamics. This paper provides an appropriate design method for CVs to gain suitable handling property for such vehicles. The developed adaptive steering controller (ASC) allows the tracking of the desired vehicle by the real vehicle, despite the variation of parameter and lack of information of the real vehicle. Simulation results are obtained to validate that the handling stability was improved by using one design parameter, which minimizes frequency oscillation caused in the wheel steering angles. The introduction of a driver model that can simulate the real vehicle demonstrated that the adoption of the ASC is useful in the driver-tractor-semitrailer system.
Background and objectives
MicroRNA‐9 is frequently dysregulated in many human carcinoma types, including gastric cancer (GC). Previous studies demonstrated that the expression of TNFAIP8 in GC is ...correlated with tumour occurrence, development, invasion, metastasis and prognosis. However, till now, the relationship between MicroRNA‐9 and TNFAIP8 in GC has not been reported.
Materials and methods
Levels of miR‐9 and TNFAIP8 expression in GC tissues and in human GC cell lines were studied using qualitative real‐time PCR (qRT‐PCR) and Western blotting. Cell viability was detected using the CCK‐8 and clone formation assays. A dual‐luciferase reporter system was used to confirm the target gene of miR‐9.
Results
We found that the expression level of MicroRNA‐9 in GC tissues and cell lines was significantly lower than that in adjacent non‐cancerous tissues and human immortalized gastric epithelial cell (GES) line, respectively. In addition, overexpression of MicroRNA‐9 markedly inhibited GC cell proliferation in vitro and tumour growth in vivo. Further experiments revealed that TNFAIP8 was a direct and functional target of MicroRNA‐9 in GC and overexpression of MicroRNA‐9 obviously down‐regulated the expression of TNFAIP8, which was involved in the gastric carcinogenesis and cancer progression.
Conclusion
Our results suggested that MicroRNA‐9‐TNFAIP8 might represent a promising diagnostic biomarker for GC patients and could be a potential therapeutic target in the prevention and treatment of GC.
Background:
Sleep deprivation can markedly influence vigilant attention that is essential to complex cognitive processes. The hypothalamus plays a critical role in arousal and attention regulation. ...However, the functional involvement of the hypothalamus in attentional impairments after total sleep deprivation (TSD) remains unclear. The purpose of this study is to investigate the alterations in hypothalamic functional connectivity and its association with the attentional performance following TSD.
Methods:
Thirty healthy adult males were recruited in the study. Participants underwent two resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI for the left and right hypothalamus. Vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered hypothalamic functional connectivity and PVT performance after TSD.
Results:
After TSD, enhanced functional connectivity was observed between the left hypothalamus and bilateral thalamus, bilateral anterior cingulate cortex, right amygdala, and right insula, while reduced functional connectivity was observed between the left hypothalamus and bilateral middle frontal gyrus (AlphaSim corrected,
P
< 0.01). However, significant correlation between altered hypothalamic functional connectivity and PVT performance was not observed after Bonferroni correction (
P
> 0.05).
Conclusion:
Our results suggest that TSD can lead to disrupted hypothalamic circuits, which may provide new insight into neural mechanisms of attention impairments following sleep deprivation.
The aim of this study was to investigate the influence of Se deficiency on the transcription of inflammatory factors and selenoprotein genes in the kidneys of broiler chicks. One hundred fifty ...1-day-old broiler chicks were randomly assigned to two groups fed with either a low-Se diet (L group, 0.033Â mg/kg Se) or an adequate Se diet (C group, 0.2Â mg/kg Se). The levels of uric acid (UA) and creatinine (Cr) in the serum and the mRNA levels of 6 inflammatory factors and 25 selenoprotein genes in the kidneys were measured as the clinical signs of Se deficiency occurred at 20Â days old. The results indicated that the contents of UA and Cr in the serum increased in L group (pÂ
The species Citrus hongheensis is an endangered species and the most primitive Citrus species with the most developed winged leaves. It is endemic to south Yunnan Province, southwest China, and only ...distributed in a very narrow area along the south bank of the Honghe river (the Yuanjiang river). By combining ISSR and morphological data from 11 populations, it shows that the species has rich genetic diversity among and within populations although the population is declining gradually. According to field and market surveys, the local Hani people have traditionally used C. hongheensis for a long time, such as the dried young fruits of the species as Chinese traditional medicine, leaves as food spice, as well as other organs. By collecting all existing knowledge of traditional and present uses, as well as further potential uses, we demonstrate that the species has good development prospects. Based on rich diversity, ethnobotanical uses, and a positive cultural environment, it was decided to choose four populations (YJNNDM, LCDX, HHDYJ, and YJYJYJ) of C. hongheensis for in situ conservation and artificial sexual reproduction. This will allow to develop new uses of the species, while providing indications for the conservation of other endangered species.
The thalamus is a key node for sleep-wake pathway gate switching during acute sleep deprivation (ASD), and studies have shown that it plays a certain role in emotion changes. However, there are no ...studies on the association between the thalamus and emotion changes in ASD. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore whether changes in the functional connections between the thalamus and other brain regions are related to emotion changes and further explored the function of the thalamus under total ASD conditions.
Thirty healthy, right-handed adult men underwent emotional assessment according to the Profile of Mood States Scale and R-fMRI scans before and after ASD. The correlations between changes in functional connectivity between the thalamus and other brain regions and emotion changes were then studied.
Positive emotions and psychomotor performance were reduced, and negative emotions were increased following ASD. The functional connections between the left thalamus and left middle temporal gyrus, left inferior frontal gyrus, right thalamus, right inferior temporal gyrus, left middle temporal pole gyrus, right calcarine, left cuneus, left rectus and left medial superior frontal gyrus were significantly altered. Decreased functional connectivity between left thalamus and left inferior frontal gyrus related to emotion changes following ASD.
This study finds that functional changes in the thalamus are associated with emotion changes during ASD, suggesting that the left thalamus probably plays an essential role in emotion changes under ASD conditions.
PDF
