Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.

Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.

Sexual behavior shapes male genitourinary microbiome composition.

The origin, composition, and significance of the distal male urethral microbiome are unclear, but vaginal microbiome dysbiosis is linked to new sex partners and several urogynecological syndromes. We characterized 110 urethral specimens from men without urethral symptoms, infections, or inflammation using shotgun metagenomics. Most urethral specimens contain characteristic lactic acid bacteria and Corynebacterium spp.

Bi and Tb Co-doped CsAgInCl Lead-free double perovskite nanocrystals for detection of temperature and copper ions.

The content of Cu in lubricating oil and lubricant temperature are important indicators predicting mechanical failure. Therefore, developing a nontoxic fluorescence probe is necessary to detect Cu and temperature in lubricating oil. The lead-free inorganic double perovskite nanocrystals (NCs) CsAgInCl are potential candidates.

High-Resolution MRI for Evaluation of the Possibility of Successful Recanalization in Symptomatic Chronic ICA Occlusion: A Retrospective Study.

Background And Purpose: Accurate radiologic evaluation of the possibility of successful recanalization in symptomatic chronic ICA occlusion remains challenging. This study aimed to investigate the high-resolution MR imaging characteristics of symptomatic chronic ICA occlusion and their association with successful recanalization.

Materials And Methods: Consecutive patients with symptomatic chronic ICA occlusion who underwent balloon dilation plus stent implantation were identified retrospectively and divided into 2 groups: a successful recanalization group and an unsuccessful recanalization group.

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost.

Broad and ultra-potent cross-clade neutralization of HIV-1 by a vaccine-induced CD4 binding site bovine antibody.

Human immunodeficiency virus type 1 (HIV-1) vaccination of cows has elicited broadly neutralizing antibodies (bNAbs). In this study, monoclonal antibodies (mAbs) are isolated from a clade A (KNH1144 and BG505) vaccinated cow using a heterologous clade B antigen (AD8). CD4 binding site (CD4bs) bNAb (MEL-1872) is more potent than a majority of CD4bs bNAbs isolated so far.

Structure and luminescence investigation of Gd-sensitized perovskite CaLaTiO:Eu: A novel red-emitting phosphor for high-performance white light-emitting diodes and plants lighting.

A novel perovskite CaLaTiO:Eu red-emitting phosphor was synthesized via a sol-combustion method, and Gd was further co-doped into structure to improve the luminescence performance. The effects of Eu doping and Gd co-doping concentrations on the microstructure and luminescence properties were investigated. The red emission peaks of as-prepared phosphors originate from the D→F electron transitions of Eu ions.

Sirtuin 5-Mediated Lysine Desuccinylation Protects Mitochondrial Metabolism Following Subarachnoid Hemorrhage in Mice.

Background And Purpose: Sirt5 (Sirtuin 5) desuccinylates multiple metabolic enzymes and plays an important role in maintaining energy homeostasis. The goal of this study was to determine whether Sirt5-mediated desuccinylation restores the energy metabolism and protects brain against subarachnoid hemorrhage (SAH).

Methods: Male C57BL/6 or Sirt5 mice were used.

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.

Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.

Mutation Screening of mtDNA Combined Targeted Exon Sequencing in a Cohort With Suspected Hereditary Optic Neuropathy.

Purpose: Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the two commonest forms of hereditary optic neuropathy. The aim of this study was to comprehensively investigate the incidence and spectrum of mutations in patients with suspected hereditary optic neuropathy by combining mitochondrial DNA (mtDNA) genome-wide and targeted exon sequencing.

Methods: A cohort of 1101 subjects were recruited to participate in the study, comprising 177 families (177 probands and their family members, a total of 537 subjects, including 254 patients) and 164 sporadic cases with suspected hereditary optic neuropathy, and 400 unrelated control subjects for genetic analysis: all subjects (including control subjects) underwent a comprehensive ophthalmologic examination and were subjected to sequencing analysis of mtDNA genome-wide and targeted exon.

Impact of Bleeding and Myocardial Infarction on Mortality in All-Comer Patients Undergoing Percutaneous Coronary Intervention.

Background: Bleeding and myocardial infarction (MI) after percutaneous coronary intervention are independent risk factors for mortality. This study aimed to investigate the association of all-cause mortality after percutaneous coronary intervention with site-reported bleeding and MI, when considered as individual, repeated, or combined events.

Methods: We used the data from the GLOBAL LEADERS trial (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-Platelet Therapy After Stent Implantation), an all-comers trial of 15 968 patients undergoing percutaneous coronary intervention.

Alterations in leaf photosynthetic electron transport in Welsh onion (Allium fistulosum L.) under different light intensity and soil water conditions.

Welsh onions (Allium fistulosum L.) are often affected by stressful environments, such as high light and drought, during summer cultivation, which hinders their growth. We used CO assimilation, OJIP transient and MR curves to analyse the photosynthetic characteristics of Welsh onion.

Dexamethasone-Induced Liver Enlargement Is Related to PXR/YAP Activation and Lipid Accumulation but Not Hepatocyte Proliferation.

Dexamethasone (Dex), a widely prescribed anti-inflammatory drug, was reported to induce liver enlargement (hepatomegaly) in clinical practice and in animal models. However, the underlying mechanisms are not elucidated. Dex is a known activator of pregnane X receptor (PXR).

The self-reduction synthesis and luminescent properties of Eu /Eu activated BaZr Si O phosphors with white light emission for white light-emitting diodes.

The BaZr Si O :Eu /Eu (2%, molar ratio) phosphors were prepared with adding different amounts of zirconium dioxide (ZrO ) (x = 0, 0.2, 0.4, 0.

Structure-guided combination therapy to potently improve the function of mutant CFTRs.

Available corrector drugs are unable to effectively rescue the folding defects of CFTR-ΔF508 (or CFTR-F508del), the most common disease-causing mutation of the cystic fibrosis transmembrane conductance regulator, a plasma membrane (PM) anion channel, and thus to substantially ameliorate clinical phenotypes of cystic fibrosis (CF). To overcome the corrector efficacy ceiling, here we show that compounds targeting distinct structural defects of CFTR can synergistically rescue mutant expression and function at the PM. High-throughput cell-based screens and mechanistic analysis identified three small-molecule series that target defects at nucleotide-binding domain (NBD1), NBD2 and their membrane-spanning domain (MSD) interfaces.

Metabolic Profiling of the Novel Hypoxia-Inducible Factor 2 Inhibitor PT2385 In Vivo and In Vitro.

PT2385 is a first-in-class, selective small-molecule inhibitor of hypoxia-inducible factor-2 (HIF-2) developed for the treatment of advanced clear cell renal cell carcinoma. Preclinical results demonstrated that PT2385 has potent antitumor efficacy in mouse xenograft models of kidney cancer. It also has activity toward metabolic disease in a mouse model.