A Cascade of Conformational Switches in SARS-CoV-2 Frameshifting: Coregulation by Upstream and Downstream Elements.

Targeting ribosomal frameshifting has emerged as a potential therapeutic intervention strategy against COVID-19. In this process, a -1 shift in the ribosomal reading frame encodes alternative viral proteins. Any interference with this process profoundly affects viral replication and propagation.

Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.

Frameshifting is an essential mechanism employed by many viruses including coronaviruses to produce viral proteins from a compact RNA genome. It is facilitated by specific RNA folds in the frameshift element (FSE), which has emerged as an important therapeutic target. For SARS-CoV-2, a specific 3-stem pseudoknot has been identified to stimulate frameshifting.

Perceptions of improvements and mental health outcomes of micro-renewal in old Danwei community: a survey of residents in Hengyang, China.

Introduction: Danwei communities are a testament to China's socialist urban development, characterized by the self-sufficiency, strong social networks, and institutional management. In the historical context of urban development in China, many old communities have evolved from former housing areas of Danwei. After more than 40 years of use, the buildings, and environments in the old Danwei communities remain in disrepair, dirty, disorderly and poor condition.

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses.

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge.

An intricate balancing act: Upstream and downstream frameshift co-regulatory elements.

Targeting ribosomal frameshifting has emerged as a potential therapeutic intervention strategy against Covid-19. During ribosomal translation, a fraction of elongating ribosomes slips by one base in the 5' direction and enters a new reading frame for viral protein synthesis. Any interference with this process profoundly affects viral replication and propagation.

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses.

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge.

Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability.

The frameshifting RNA element (FSE) in coronaviruses (CoVs) regulates the programmed -1 ribosomal frameshift (-1 PRF) mechanism common to many viruses. The FSE is of particular interest as a promising drug candidate. Its associated pseudoknot or stem loop structure is thought to play a large role in frameshifting and thus viral protein production.

Which Specific Exercise Models Are Most Effective on Global Cognition in Patients with Cognitive Impairment? A Network Meta-Analysis.

(1) Introduction: Physical exercise interventions can impart significant cognitive benefits to older adults suffering from cognitive impairment (CI). However, the efficacy of these interventions can vary widely, depending on the type, intensity, duration and frequency of exercise. (2) Aim: To systematically review the efficacy of exercise therapy on global cognition in patients with CI using a network meta-analysis (NMA).

Evolutionarily distinct and sperm-specific supersized chromatin loops are marked by Helitron transposons in Xenopus tropicalis.

Transposable elements (TEs) are abundant in metazoan genomes and have multifaceted effects on host fitness. However, the mechanisms underlying the functions of TEs are still not fully understood. Here, we combine Hi-C, ATAC-seq, and ChIP-seq assays to report the existence of multimegabase supersized loop (SSL) clusters in the Xenopus tropicalis sperm.

Computational Modeling of RNA Aptamers: Structure Prediction of the Apo State.

RNA aptamers are single-stranded oligonucleotides that bind to specific molecular targets with high affinity and specificity. To design aptamers for new applications, it is critical to understand the ligand binding mechanism in terms of the structure and dynamics of the ligand-bound and apo states. The problem is that most of the NMR or X-ray crystal structures available for RNA aptamers are for ligand-bound states.

Influence of the Urban Built Environment on Physical and Mental Health of the Elderly under the Background of Big Data.

With the advent of the information technology revolution and the Internet era, information technology is gradually occupying an important position and becoming an important strategic factor in economic development. As an emerging technology that has been developing continuously in recent years, big data is becoming an important industry to improve the innovation and development of the urban economy. Like AI technology, cloud computing, and the Internet, big data has become an important application technology for economic growth and economic efficiency improvement in today's world.

Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression.

The SARS-CoV-2 frameshifting element (FSE), a highly conserved mRNA region required for correct translation of viral polyproteins, defines an excellent therapeutic target against Covid-19. As discovered by our prior graph-theory analysis with SHAPE experiments, the FSE adopts a heterogeneous, length-dependent conformational landscape consisting of an assumed 3-stem H-type pseudoknot (graph motif 3_6), and two alternative motifs (3_3 and 3_5). Here, for the first time, we build and simulate, by microsecond molecular dynamics, 30 models for all three motifs plus motif-stabilizing mutants at different lengths.

Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression.

Conserved SARS-CoV-2 RNA regions of critical biological functions define excellent targets for anti-viral therapeutics against Covid-19 variants. One such region is the frameshifting element (FSE), responsible for correct translation of viral polyproteins. Here, we analyze molecular-dynamics motions of three FSE conformations, discovered by graph-theory analysis, and associated mutants designed by graph-based inverse folding: two distinct 3-stem H-type pseudoknots and a 3-way junction.

Adjusting COVID-19 Seroprevalence Survey Results to Account for Test Sensitivity and Specificity.

Population-based seroprevalence surveys can provide useful estimates of the number of individuals previously infected with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still susceptible, as well as contribute to better estimates of the case-fatality rate and other measures of coronavirus disease 2019 (COVID-19) severity. No serological test is 100% accurate, however, and the standard correction that epidemiologists use to adjust estimates relies on estimates of the test sensitivity and specificity often based on small validation studies. We have developed a fully Bayesian approach to adjust observed prevalence estimates for sensitivity and specificity.

To Knot or Not to Knot: Multiple Conformations of the SARS-CoV-2 Frameshifting RNA Element.

The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has a profound effect on viral replication and propagation.

Meta-Analysis of Clinical Efficacy and Safety of Polyglycosides Tablets in the Treatment of Chronic Kidney Disease.

Objective: polyglycosides tablet (TGt) is an oral preparation extracted from plant . It has the effects of anti-inflammation and inhibition of cellular and humoral immunity. However, many reports of adverse reactions caused by TGt have limited its application.

To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element.

The SARS-CoV-2 frameshifting RNA element (FSE) is an excellent target for therapeutic intervention against Covid-19. This small gene element employs a shifting mechanism to pause and backtrack the ribosome during translation between Open Reading Frames 1a and 1b, which code for viral polyproteins. Any interference with this process has profound effect on viral replication and propagation.

Meta-Analysis of Randomized Controlled Trials of Xueshuantong Injection in Prevention of Deep Venous Thrombosis of Lower Extremity after Orthopedic Surgery.

Objective: To systematically evaluate the clinical efficacy of Xueshuantong injection ( saponins) in preventing deep venous thrombosis (DVT) of lower extremity after orthopedic surgery.

Methods: The randomized controlled trials (RCTs) of Xueshuantong injection in prevention of lower extremity DVT after orthopedic surgery were retrieved from CNKI, Wanfang database, VIP, PubMed, and Cochrane Library by August 2020. Revman5.

Structure-altering mutations of the SARS-CoV-2 frameshifting RNA element.

With the rapid rate of COVID-19 infections and deaths, treatments and cures besides hand washing, social distancing, masks, isolation, and quarantines are urgently needed. The treatments and vaccines rely on the basic biophysics of the complex viral apparatus. Although proteins are serving as main drug and vaccine targets, therapeutic approaches targeting the 30,000 nucleotide RNA viral genome form important complementary approaches.

Sampling Performance of Multiple Independent Molecular Dynamics Simulations of an RNA Aptamer.

Using multiple independent simulations instead of one long simulation has been shown to improve the sampling performance attained with the molecular dynamics (MD) simulation method. However, it is generally not known how long each independent simulation should be, how many independent simulations should be used, or to what extent either of these factors affects the overall sampling performance achieved for a given system. The goal of the present study was to assess the sampling performance of multiple independent MD simulations, where each independent simulation begins from a different initial molecular conformation.

Computed tomography (CT) imaging evaluation of integrated traditional Chinese medicine cooperative therapy in treating acute cerebral infarction: A randomized controlled trial.

Introduction: Acute cerebral infarction is a clinically common cerebrovascular disease. Acute cerebral infarction is characterized by sudden onset, dangerous illness, high risk of death, and disability. Computed tomography perfusion imaging can detect abnormal brain tissue perfusion 30 minutes after the onset of cerebral ischemia, providing the earliest and most valuable information for clinical diagnosis and treatment.

Effects of Different Processed Products of on the Liver.

Objective: Based on in vitro and in vivo experimental studies, the changes of the main components of and different processed products and their effects on hepatotoxicity were investigated.

Methods: The components of different processed products of and different processed products and their effects on hepatotoxicity were investigated.

Results: With the extension of processing time, the contents of various chemical components in and different processed products and their effects on hepatotoxicity were investigated.

Common Secondary and Tertiary Structural Features of Aptamer-Ligand Interaction Shared by RNA Aptamers with Different Primary Sequences.

Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target molecule. Here, we have combined computational and experimental approaches to understand if aptamers with different sequences but the same molecular target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding.

Structural stability and elastic and electronic properties of rhenium borides: first principle investigations.

The structural stability and elastic and electronic properties of rhenium borides with different boron concentration are calculated systemically by means of first principle total energy calculations. The total energy calculations reveal that the WC-type structure is more energetically favorable for ReB and that the Re(2)P-type structure is more preferred for Re(2)B. The formation enthalpy of these borides have been studied by the solid synthesis routes.