Shear banding in monodisperse polymer melt.

We performed a series of molecular dynamics simulations on monodisperse polymer melts to investigate the formation of shear banding. Under high shear rates, shear banding occurs, which is intimately accompanied by the entanglement heterogeneity. Interestingly, the same linear relationship between the end-to-end distance Ree and entanglement density Z is observed at homogeneous flow before the onset of shear banding and at the shear banding state, where Ree ∼ ln(Wi0.87)-ξ0Z is proposed as the criterion to describe the dynamic force balance of the molecular chain in flow with a high rate. Deviating from this relation leads to a force imbalance and results in the emergence of shear banding. We establish a scaling relation between the disentanglement rate Vd and the Weissenberg number Wi as Vd∼Wi0.87 for stable flow in homogeneous shear and shear banding states. The formation of shear banding prevents chains from further stretching and disentanglement. The transition from homogeneous shear to shear banding partially dissipates the increased free energy from shear and reduces the free energy of the system.

Bond Orientation-Determined Enthalpic Stress in Polymer Glasses upon Deformation.

The mechanical properties of polymer glass are determined by both intermolecular local packing structures and aligned intrachain configurations. These configurations involve multiple space scales, and the underlying mechanism is not well understood yet. By applying mechanical stimulation to cold-drawn polymer glasses, the present simulation work shows a one-to-one correspondence between arising retractive stress and the segment orientation parameter on the length scale of the intrachain connecting bond. Such retractive stress is a newly produced enthalpic stress when segment orientation on the length scale of bonds and particle mobility coexist. This reveals a potential mechanism of how the intrachain orientation on the length scale of bonds influences the mechanical behaviors of polymer glasses.

Silencing circCAMSAP1 suppresses malignant behavior of endometrial cancer by targeting microRNA-370-3p/MAPK1.

The study was conducted to figure out the function and mechanism of circular RNA circCAMSAP1 in repressing malignant behavior of endometrial carcinoma (EC) by targeting microRNA (miR)-370-3p /MAPK1. Tumor tissues and normal adjacent tissues of EC patients were harvested, and circCAMSAP1 and MAPK1 were elevated but miR-370-3p was reduced in tissues and cells of EC patients. Functional test results clarified transfection of si-circCAMSAP1 or miR-370-3p-mimic refrained cancer cell proliferation, migration and invasion, but motivated cancer cell apoptosis. Meanwhile, the amount of E-cadherin elevated and the amount of N-cadherin elevated or reduced. After co-transfection with si-circCAMSAP1 and miR-370-3p-inhibitor, miR-370-3p-inhibitor blocked si-circCAMSAP1's therapeutic impact. Furthermore, after co-transfection of pcDNA-circCAMSAP1 and si-MAPK1, si-MAPK1 turned around the malignant effect of pcDNA-circCAMSAP1. It was testified that miR-370-3p was circCAMSAP1's target, and inversely controlled via circCAMSAP1. Meanwhile, enhancing miR-370-3p led to repressive MAPK1, which was recognized as miR-370-3p's downstream target. All in all, the results of this study convey silencing circCAMSAP1 refrains the malignant behavior of EC by controlling miR-370-3p /MAPK1 axis.

Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.

The efficacy and safety of silver needle in the treatment of rheumatoid arthritis: A protocol of randomized controlled trial.

BACKGROUND: Rheumatoid arthritis is a kind of chronic crippling disease, the condition is complex, the course of the disease is repeated, seriously affecting the quality of life of patients. Adverse reactions and drug resistance associated with conventional treatment can no longer meet the clinical need. Therefore, complementary and alternative therapies need to be explored. The evidence shows that silver needle therapy has advantages in the treatment of rheumatoid arthritis, but there is a lack of standard clinical studies to verify this conclusion. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of silver needles in the treatment of rheumatoid arthritis. Approved by the Clinical Research Ethics Committee of our hospital. The patients are randomly divided into a treatment group (silver needle treatment group) or control group (routine western medicine treatment group). The patients are followed up for 2 months after 4 weeks of treatment. Observation indicators include: TCM symptom score, HAQDI score, DAS-28 score, laboratory indicators, adverse reactions and so on. Data will be analyzed using the statistical software package SPSS version 18.0 (Chicago, IL). DISCUSSION: This study will evaluate the clinical efficacy of a silver needle in the treatment of rheumatoid arthritis. The results of this study will provide a reliable reference for the clinical use of a silver needle in the treatment of rheumatoid arthritis. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/4X5QB.

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes.

The pillar[5]arene mono- and di(oxyalkoxy)benzoic acids were successfully prepared in high yields by sequential alkylation of ω-bromoalkoxy-substituted pillar[5]arenes with methyl or ethyl p-hydroxybenzoate followed by a hydrolytic reaction under basic conditions. Under catalysis of HOBt/EDCl, the amidation reaction of pillar[5]arene mono(oxybutoxy)benzoic acid with monoamido-functionalized pillar[5]arenes afforded diamido-bridged bis-pillar[5]arenes. 1H NMR and 2D NOESY spectra clearly indicated that [1]rotaxanes were formed by insertion of longer diaminoalkylene unit into the cavity of one pillar[5]arene with another pillar[5]arene acting as a stopper. The similar catalysed amidation reaction of pillar[5]arene di(oxybutoxy)benzoic acid with monoamido-functionalized pillar[5]arenes resulted in the diamido-bridged tris-pillar[5]arenes, which successfully form the unique bis-[1]rotaxanes bearing longer than diaminopropylene diamido bridges.

ARID5B gene rs10821936 polymorphism is associated with childhood acute lymphoblastic leukemia: a meta-analysis based on 39,116 subjects.

Childhood acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related deaths among children. Two recent genome-wide association studies and several replicated studies have provided convincing evidence that inherited genetic variation in ARID5B contributes to childhood ALL predisposition. In the present study, we performed a meta-analysis to systematically summarize the association between ARID5B genetic polymorphism and the risk for ALL. We conducted a search of case-control studies on the association of ARID5B genetic polymorphisms with susceptibility to ALL in PubMed, EMBASE, Wanfang database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. ALL risk associated with ARID5B genetic polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Nine articles including 13 case-control studies were included in the present meta-analysis. We found that rs10821936 polymorphism in ARID5B gene was associated with increased risk for ALL (P < 0.0001; OR = 1.27; 95%CI, 1.17-1.37). This meta-analysis suggests that ARID5B genetic polymorphism was associated with the increased risk of ALL.

Bis(4-{2-[4-(diethyl-amino)-phen-yl]ethen-yl}pyridine-κN)diiodidozinc.

In the title compound, [ZnI2(C17H20N2)2], the Zn(II) atom is four-coordinated by two I atoms and the N atoms of two pyridine rings belonging to different ligands in a distorted tetra-hedral geometry. The coordinating pyridine rings are oriented in an almost perpendicular fashion, making a dihedral angle of 83.7 (5)°.