MARS and RNAcmap3: The Master Database of All Possible RNA Sequences Integrated with RNAcmap for RNA Homology Search.

Recent success of AlphaFold2 in protein structure prediction relied heavily on co-evolutionary information derived from homologous protein sequences found in the huge, integrated database of protein sequences (Big Fantastic Database). In contrast, the existing nucleotide databases were not consolidated to facilitate wider and deeper homology search. Here, we built a comprehensive database by incorporating the non-coding RNA (ncRNA) sequences from RNAcentral, the transcriptome assembly and metagenome assembly from metagenomics RAST (MG-RAST), the genomic sequences from Genome Warehouse (GWH), and the genomic sequences from MGnify, in addition to the nucleotide (nt) database and its subsets in National Center of Biotechnology Information (NCBI).

Design and synthesis of large Stokes shift DNA dyes with reduced genotoxicity.

Despite intensive search over the past decades, only a few small-molecule DNA fluorescent dyes were found with large Stokes shifts. These molecules, however, are often too toxic for widespread usage. Here, we designed DNA-specific fluorescent dyes rooted in benzimidazole architectures with a hitherto unexplored molecular framework based on thiazole-benzimidazole scaffolding.

Examining the correlates of cigarette smoking, e-cigarette use and dual use among Canadian post-secondary students.

Many Canadians use nicotine products such as cigarettes and e-cigarettes. A particular subpopulation of concern is post-secondary students given they have a higher prevalence of use. Many correlates of cigarette smoking and e-cigarette use have been identified.

IDR-targeting compounds suppress HPV genome replication via disruption of phospho-BRD4 association with DNA damage response factors.

Compounds binding to the bromodomains of bromodomain and extra-terminal (BET) family proteins, particularly BRD4, are promising anticancer agents. Nevertheless, side effects and drug resistance pose significant obstacles in BET-based therapeutics development. Using high-throughput screening of a 200,000-compound library, we identified small molecules targeting a phosphorylated intrinsically disordered region (IDR) of BRD4 that inhibit phospho-BRD4 (pBRD4)-dependent human papillomavirus (HPV) genome replication in HPV-containing keratinocytes.

Multiple sequence alignment-based RNA language model and its application to structural inference.

Compared with proteins, DNA and RNA are more difficult languages to interpret because four-letter coded DNA/RNA sequences have less information content than 20-letter coded protein sequences. While BERT (Bidirectional Encoder Representations from Transformers)-like language models have been developed for RNA, they are ineffective at capturing the evolutionary information from homologous sequences because unlike proteins, RNA sequences are less conserved. Here, we have developed an unsupervised multiple sequence alignment-based RNA language model (RNA-MSM) by utilizing homologous sequences from an automatic pipeline, RNAcmap, as it can provide significantly more homologous sequences than manually annotated Rfam.

Glycosylated, Lipid-Binding, CDR-Like Domains of SARS-CoV-2 ORF8 Indicate Unique Sites of Immune Regulation.

The outbreak of the novel coronavirus SARS-CoV-2 has posed a significant threat to human health and the global economy since the end of 2019. Unfortunately, due to the virus's rapid evolution, preventingand controlling the epidemic remains challenging. The ORF8 protein is a unique accessory protein in SARS-CoV-2 that plays a crucial role in immune regulation, but its molecular details are still largely unknown.

Consistency of the anesthesia consciousness index versus the bispectral index during laparoscopic gastrointestinal surgery with sevoflurane anesthesia: A prospective multi-center randomized controlled clinical study.

Background: This study aimed to compare the consistency of anesthesia consciousness index (Ai) with that of bispectral index (BIS) in monitoring the depth of anesthesia (DOA) during sevoflurane anesthesia, to reveal the optimal cutoff values in different states of consciousness, and explore the stability of DOA monitoring during intraoperative injurious stimulation.

Methods: We enrolled 145 patients (97 men and 48 women) from 10 medical centers. General anesthesia was induced using intravenous anesthetics and maintained with sevoflurane.

Inhibiting the transcription and replication of Ebola viruses by disrupting the nucleoprotein and VP30 protein interaction with small molecules.

Ebola virus (EBOV) causes hemorrhagic fever in humans with high morbidity and fatality. Although over 45 years have passed since the first EBOV outbreak, small molecule drugs are not yet available. Ebola viral protein VP30 is a unique RNA synthesis cofactor, and the VP30/NP interaction plays a critical role in initiating the transcription and propagation of EBOV.

HNF4G stimulates the development of pancreatic cancer by promoting IGF2BP2 transcription.

Objective: Pancreatic cancer is a devastating and lethal malignancy. Our study investigated the effective mechanism of HNF4G on pancreatic cancer cell functions through the IGF2BP2 transcription.

Methods: HNF4G and IGF2BP2 expressions in pancreatic cancer were examined.

Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease.

SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro.

High-throughput mapping of RNA solvent accessibility at the single-nucleotide resolution by RtcB ligation between a fixed 5'-OH-end linker and unique 3'-P-end fragments from hydroxyl radical cleavage.

Given the challenges for the experimental determination of RNA tertiary structures, probing solvent accessibility has become increasingly important to gain functional insights. Among various chemical probes developed, backbone-cleaving hydroxyl radical is the only one that can provide unbiased detection of all accessible nucleotides. However, the readouts have been based on reverse transcription (RT) stop at the cleaving sites, which are prone to false positives due to PCR amplification bias, early drop-off of reverse transcriptase, and the use of random primers in RT reaction.

Identification of the Immune Status of Hypertrophic Cardiomyopathy by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

Objectives: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy and immune infiltration is considered an indispensable factor involved in its pathogenesis. In this study, we attempted to combine bulk sequencing and single-cell sequencing to map the immune infiltration-related genes in hypertrophic cardiomyopathy.

Methods: The GSE36961, GSE160997, and GSE122930 datasets were obtained from the Gene Expression Omnibus database.

Probing RNA structures and functions by solvent accessibility: an overview from experimental and computational perspectives.

Characterizing RNA structures and functions have mostly been focused on 2D, secondary and 3D, tertiary structures. Recent advances in experimental and computational techniques for probing or predicting RNA solvent accessibility make this 1D representation of tertiary structures an increasingly attractive feature to explore. Here, we provide a survey of these recent developments, which indicate the emergence of solvent accessibility as a simple 1D property, adding to secondary and tertiary structures for investigating complex structure-function relations of RNAs.

High-throughput split-protein profiling by combining transposon mutagenesis and regulated protein-protein interactions with deep sequencing.

Splitting a protein at a position may lead to self- or assisted-complementary fragments depending on whether two resulting fragments can reconstitute to maintain the native function spontaneously or require assistance from two interacting molecules. Assisted complementary fragments with high contrast are an important tool for probing biological interactions. However, only a small number of assisted-complementary split-variants have been identified due to manual, labour-intensive optimization of a candidate gene.

Nitrogen and phosphorus removal efficiency and algae viability in an immobilized algae and bacteria symbiosis system with pink luminescent filler.

In this study, an immobilized algae and bacteria symbiotic biofilm reactor (ABSBR) with pink luminescent filler (PLF) was constructed. The effects of PLF addition in the construction of an algae and bacteria symbiotic biofilm system on the nitrogen and phosphorus removal efficiencies and algae viability were evaluated. Our results showed that for influent TN and TP concentrations of 40 ± 5 and 5 ± 0.

Nutrient leaching in extensive green roof substrate layers with different configurations.

Due to substrate layers with different substrate configurations, extensive green roofs (EGRs) exhibit different rainfall runoff retention and pollution interception effects. In the rainfall runoff scouring process, nutrient leaching often occurs in the substrate layer, which becomes a pollution source for rainwater runoff. In this study, six EGR devices with different substrate layer configurations were fabricated.

Design and Evaluation of a Novel Peptide-Drug Conjugate Covalently Targeting SARS-CoV-2 Papain-like Protease.

Coronavirus disease 2019 (COVID-19) pandemic, a global health threat, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 papain-like cysteine protease (PLpro) was recognized as a promising drug target because of multiple functions in virus maturation and antiviral immune responses. Inhibitor GRL0617 occupied the interferon-stimulated gene 15 (ISG15) C-terminus-binding pocket and showed an effective antiviral inhibition.