SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding.

Validation of evidence-based questionnaire for TCM syndrome differentiation of heart failure and evaluation of expert consensus.

Background: Traditional Chinese Medicine (TCM) is widely used to treat heart failure (HF). Syndrome differentiation is a unique and crucial component in TCM practice for guiding disease diagnosis and treatment strategies as well as clinical research. The major bottlenecks in TCM syndrome differentiation are the diversity of the syndrome differentiation criteria and the broad spectrum of syndrome patterns, hindering evidence-based studies for clinical research.

Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity.

Background: Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive.

Methods: We investigated a total of 137 APs infected with SARS-CoV-2.

Lockd promotes myoblast proliferation and muscle regeneration via binding with DHX36 to facilitate 5' UTR rG4 unwinding and Anp32e translation.

Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process.

A prebiotically plausible scenario of an RNA-peptide world.

The RNA world concept is one of the most fundamental pillars of the origin of life theory. It predicts that life evolved from increasingly complex self-replicating RNA molecules. The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution.

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models.

Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal.

Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2.

Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens.

Be Still and You Will Know: A Mixed-Method Study on Solitude and Consideration of Future Consequences Among Youth in Rehabilitation.

Although solitude is found to be undesirable to many, systematic practice of it can yield positive psychological outcomes. This mixed-method study explored the process and influence of solitude as a behavioral intervention among youths in a therapeutic community in Hong Kong. Qualitative interviews with 43 youths (67.

Tandem bispecific antibody prevents pathogenic SHIV infection and disease progression.

Although progress has been made on constructing potent bi-specific broadly neutralizing antibody (bi-bNAb), few bi-bNAbs have been evaluated against HIV-1/AIDS in non-human primates (NHPs). Here, we report the efficacy of a tandem bi-bNAb, namely BiIA-SG, in Chinese-origin rhesus macaques (CRM) against the CRM-adapted R5-tropic pathogenic SHIV challenge. Pre-exposure BiIA-SG injection prevents productive viral infection in 6 of 6 CRMs with unmeasurable proviral load, T cell responses, and seroconversion.

HLA-B*58:01 screening to prevent allopurinol-induced severe cutaneous adverse reactions in Chinese patients with chronic kidney disease.

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness.

Proteomic and Transcriptome Profiling of G-Quadruplex Aptamers Developed for Cell Internalization.

Nucleic acid medicine is expected to be among the most promising next-generation therapies. Applications of nucleic acid are still challenging as a result of the difficulties in direct cell penetration without external assistance. To facilitate the cellular delivery of therapeutic nucleic acid, we developed cell-penetrating aptamers using cell-internalization Systematic Evolution of Ligands by EXponential enrichment (SELEX).

Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC range, 0.0007-0.

Amino Acid Modified RNA Bases as Building Blocks of an Early Earth RNA-Peptide World.

Fossils of extinct species allow us to reconstruct the process of Darwinian evolution that led to the species diversity we see on Earth today. The origin of the first functional molecules able to undergo molecular evolution and thus eventually able to create life, are largely unknown. The most prominent idea in the field posits that biology was preceded by an era of molecular evolution, in which RNA molecules encoded information and catalysed their own replication.

Structural analysis and cellular visualization of APP RNA G-quadruplex.

RNA G-quadruplexes (rG4s) are emerging structural motifs that are of pivotal importance in chemistry and biology; however, the current structural information of rG4s is limited, with their folding status and functions in cells remaining elusive. Here, we develop and employ a multi-disciplinary approach to characterize the structure, formation and function of an individual rG4 of interest and in cells. We apply this strategy to a biologically important rG4 in amyloid precursor protein (APP) transcript and reveal distinct structural features of rG4.

Specific Binding of a d-RNA G-Quadruplex Structure with an l-RNA Aptamer.

G-quadruplex (G4) structures are of general importance in chemistry and biology, such as in biosensing, gene regulation, and cancers. Although a large repertoire of G4-binding tools has been developed, no aptamer has been developed to interact with G4. Moreover, the G4 selectivity of current toolkits is very limited.

G-Quadruplex-Based Fluorescent Turn-On Ligands and Aptamers: From Development to Applications.

Guanine (G)-quadruplexes (G4s) are unique nucleic acid structures that are formed by stacked G-tetrads in G-rich DNA or RNA sequences. G4s have been reported to play significant roles in various cellular events in both macro- and micro-organisms. The identification and characterization of G4s can help to understand their different biological roles and potential applications in diagnosis and therapy.

Spectroscopic analysis reveals the effect of a single nucleotide bulge on G-quadruplex structures.

Here we investigate and reveal the effect of bulge position and bulge identity on G-quadruplexes using label-free spectroscopic techniques. Notably, we report significant differences in the spectroscopic features of bulged DNA and RNA G-quadruplexes, and demonstrate that intrinsic fluorescence can be generally used to detect the formation of canonical and non-canonical G-quadruplexes.

Structural analysis reveals the formation and role of RNA G-quadruplex structures in human mature microRNAs.

Here we identify hundreds of RNA G-quadruplex (rG4) candidates in microRNAs (miRNAs), characterize the miRNA structure and miRNA-mRNA interactions on several mammalian-conserved miRNAs, and reveal the formation of rG4s in miRNAs. Notably, we study the effect of these rG4s in cells and uncover the role of rG4s in miRNA-mediated post-transcriptional regulation.

A Cancer Cell-Selective and Low-Toxic Bifunctional Heterodinuclear Pt(IV)-Ru(II) Anticancer Prodrug.

Although different types of metal-based anticancer complexes have been synthesized, novel complexes to reduce the serious side effect of cisplatin and conquer cancer metastasis are still highly desired. Here, we report the synthesis, characterization, and biological activity of a novel heterodinuclear Pt(IV)-Ru(II) anticancer prodrug. The Pt(IV)-Ru(II) complex exhibits good stability in both water and PBS solution.