Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

Background: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19.

Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination.

Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models.

Development and Validation of an Automatic Image-Recognition Endoscopic Report Generation System: A Multicenter Study.

Introduction: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance.

Methods: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation.

Comparison of the two up-to-date sequencing technologies for genome assembly: HiFi reads of Pacific Biosciences Sequel II system and ultralong reads of Oxford Nanopore.

Background: The availability of reference genomes has revolutionized the study of biology. Multiple competing technologies have been developed to improve the quality and robustness of genome assemblies during the past decade. The 2 widely used long-read sequencing providers-Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT)-have recently updated their platforms: PacBio enables high-throughput HiFi reads with base-level resolution of >99%, and ONT generated reads as long as 2 Mb.

Genetic Ablation of TASK-1 (Tandem of P Domains in a Weak Inward Rectifying K Channel-Related Acid-Sensitive K Channel-1) (K3.1) K Channels Suppresses Atrial Fibrillation and Prevents Electrical Remodeling.

Background: Despite an increasing understanding of atrial fibrillation (AF) pathophysiology, translation into mechanism-based treatment options is lacking. In atrial cardiomyocytes of patients with chronic AF, expression, and function of tandem of P domains in a weak inward rectifying TASK-1 (K channel-related acid-sensitive K channel-1) (K3.1) atrial-specific 2-pore domain potassium channels is enhanced, resulting in action potential duration shortening.

Ion Channel Dysfunctions in Dilated Cardiomyopathy in Limb-Girdle Muscular Dystrophy.

Background: Limb-Girdle muscular dystrophies (LGMD) are a heritable group of genetically determined disorders with a primary involvement of the pelvic or shoulder girdle musculature with partially cardiac manifestation, such as dilated cardiomyopathy (DCM) and life-threatening tachyarrhythmia. We report here that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from a patient with LGMD2I and DCM associated with recurrent ventricular tachycardia displayed ion channel dysfunction and abnormality of calcium homeostasis.

Methods: Dermal fibroblasts obtained from a patient with LGMD2I harboring a fukutin-related protein gene mutation (826C>A; Leu276Ile) and 3 healthy donors were reprogrammed to hiPSCs.

[Research of the Stormwater Runoff and Pollution Characteristics in Rural Area of Yuhang District, Hangzhou].

In order to investigate the pollution characteristics of stormwater runoff in the southern developed rural region, the runoff samples were collected from four different underlying surfaces during three storm events in Caoqiao and Pujia Tou, which are two typical villages and are located in Yuhang District of Hangzhou. The content of nutrition (nitrogen and phosphorus) and heavy metals (Mn, Cu, Zn, Ni, Cr, Cd, As, Pb) in the simples were analyzed, and the difference of EMC ( event mean concentration) and pollution load of the contaminants in the runoff on different underlying surfaces were compared. The results showed that the EMC of TSS, COD, NH4(+)-N, TP and TN were 16.

Methyl-CpG-binding domain protein MBD7 is required for active DNA demethylation in Arabidopsis.

Although researchers have established that DNA methylation and active demethylation are dynamically regulated in plant cells, the molecular mechanism for the regulation of active DNA demethylation is not well understood. By using an Arabidopsis (Arabidopsis thaliana) line expressing the Promoter RESPONSIVE TO DEHYDRATION 29A:LUCIFERASE (ProRD29A:LUC) and Promoter cauliflower mosaic virus 35S:NEOMYCIN PHOSPHOTRANSFERASE II (Pro35S:NPTII) transgenes, we isolated an mbd7 (for methyl-CpG-binding domain protein7) mutant. The mbd7 mutation causes an inactivation of the Pro35S:NPTII transgene but does not affect the expression of the ProRD29A:LUC transgene.

Dynamics of a semiflexible polymer or polymer ring in shear flow.

Polymers exposed to shear flow exhibit a remarkably rich tumbling dynamics. While rigid rods rotate on Jeffery orbits, a flexible polymer stretches and coils up during tumbling. Theoretical results show that in both of these asymptotic regimes the corresponding tumbling frequency f(c) in a linear shear flow of strength γ scales as a power law Wi(2/3) in the Weissenberg number Wi = γτ, where τ is a characteristic time of the polymer's relaxational dynamics.

[A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth].

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor.

Circulating sclerostin associated with vertebral bone marrow fat in older men but not women.

Context: Osteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF.

Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis.

BH3-only proteins integrate apoptosis and autophagy pathways, yet regulation and functional consequences of pathway cross-talk are not fully resolved. The BH3-only protein Bnip3 is an autophagy receptor that signals autophagic degradation of mitochondria (mitophagy) via interaction of its LC3-interacting region (LIR) with Atg8 proteins. Here we report that phosphorylation of serine residues 17 and 24 flanking the Bnip3 LIR promotes binding to specific Atg8 members LC3B and GATE-16.

[Identification of two small molecule inhibitors of hypoxia-inducible factor 1 with different cell-based screening model].

Objective: To investigate the inhibitory activity of HIF-1 by triptolide and manasaantin A, two cell-based models with luciferase report gene assay were established.

Method: Two cell-based models of HIF-1 were used to evaluate HIF-1 inhibition activity of triptolide and manasaantin A. Secreted VEGF expression induced by hypoxia was detected by ELISA with two compounds.

Hyperglycemia and insulin therapy in the critically ill child.

Objective: To canvass the current opinion of pediatric intensivists in the United Kingdom regarding the importance of hyperglycemia,their approach to management, and their views in relation to a potential intervention trial of tight glycemic control.

Design: Electronic survey comprising a 17-point questionnaire,along with six clinical scenarios describing cases of bronchiolitis, septic shock, major trauma, postcardiac surgery, necrotizing enterocolitis,and acute respiratory distress syndrome.

Setting: All pediatric intensive care units in the United Kingdom(n = 21).

[Oxidative damages of long-term exposure to low level fullerenes (C60) in Carassius auratus].

To determine the potential effects of fullerenes (C60) on aquatic organism, larval Carassius auratus was exposed to low level C60 (0.04-1.0 mg x L(-1)) for 32 days.

[Acoustic rhinometry measurement from the patients with deviation of nasal septum].

Objective: Investigating the acoustic rhinometry parameter values from the patients with deviation of nasal septum.

Method: Testing 60 cases with deviation of nasal septum by means of Eccovision acoustic rhinometry, recording and statistics analysing nasal minimal cross sectional area (NMCA), nasal cavity value (NCV), distance of minimal cross section area from the nostril (DCAN) and nasal resistance (NR).

Result: NMCA: (0.

Induction of apoptosis by enediyne antibiotic calicheamicin thetaII proceeds through a caspase-mediated mitochondrial amplification loop in an entirely Bax-dependent manner.

Calicheamicin thetaII is a member of the enediyne class of antitumor antibiotics that bind to DNA and induce apoptosis. These compounds differ, however, from conventional anticancer drugs as they bind in a sequence-specific manner noncovalently to DNA and cause sequence-selective oxidation of deoxyriboses and bending of the DNA helix. Calicheamicin is clinically employed as immunoconjugate to antibodies directed against, for example, CD33 in the case of gemtuzumab ozogamicin.

Role of calcium in the rate-dependent depression of atrioventricular nodal conduction in the dog heart under vagal influence.

Increase in heart rate may be detrimental to atrioventricular conduction. The effects of such an increase were investigated in the paced intact dog heart, by measuring the conduction time in the atrioventricular node (obtained from the His bundle potential recording) and the effective refractory period in this node as determined by the extrastimulus method. Investigations on atrioventricular nodal conduction were performed with and without vagal influence.