Folds from fold: Exploring topological isoforms of a single-domain protein.

Expanding the protein fold space beyond linear chains is of fundamental significance, yet remains largely unexplored. Herein, we report the creation of seven topological isoforms (i.e.

The Toxoplasma Effector GRA4 Hijacks Host TBK1 to Oppositely Regulate Anti-T. Gondii Immunity and Tumor Immunotherapy.

Toxoplasma gondii (T. gondii)-associated polymorphic effector proteins are crucial in parasite development and regulating host anti-T. gondii immune responses.

Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination.

Background: Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well tolerated and immunogenic in a phase 1/2 study.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background And Objectives: Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date.

Learning Representations from Heart Sound: A Comparative Study on Shallow and Deep Models.

Leveraging the power of artificial intelligence to facilitate an automatic analysis and monitoring of heart sounds has increasingly attracted tremendous efforts in the past decade. Nevertheless, lacking on standard open-access database made it difficult to maintain a sustainable and comparable research before the first release of the PhysioNet CinC Challenge Dataset. However, inconsistent standards on data collection, annotation, and partition are still restraining a fair and efficient comparison between different works.

Neutralization of SARS-CoV-2 BA.2.86 and JN.1 by CF501 adjuvant-enhanced immune responses targeting the conserved epitopes in ancestral RBD.

The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.

Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade.

Backgrounds: Immune checkpoint blockade (ICB) is widely considered to exert long-term treatment benefits by activating antitumor immunity. However, many cancer patients show poor clinical responses to ICB due in part to the lack of an immunogenic niche. Focal adhesion kinase (FAK) is frequently amplified and acts as an immune modulator across cancer types.

Alkaline-based aqueous sodium-ion batteries for large-scale energy storage.

Aqueous sodium-ion batteries are practically promising for large-scale energy storage, however energy density and lifespan are limited by water decomposition. Current methods to boost water stability include, expensive fluorine-containing salts to create a solid electrolyte interface and addition of potentially-flammable co-solvents to the electrolyte to reduce water activity. However, these methods significantly increase costs and safety risks.

A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity.

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913).

Postnatal Dynamics and Clinical Associations of Fecal Calprotectin in Very Preterm Infants: Implications for Necrotizing Enterocolitis and Feeding Intolerance.

Introduction: To elucidate the postnatal dynamics and clinical associations of fecal calprotectin (FC) in very preterm infants, with a focus on necrotizing enterocolitis (NEC) and feeding intolerance (FI).

Methods: We performed a prospective observational cohort study in infants with a gestational age of <32 weeks or birth weight <1,500 g with weekly feces collection. The relationships between FC, NEC, and FI were investigated, adjusting for demographic and clinical factors.

A phosphoglycerate mutase 1 allosteric inhibitor overcomes drug resistance to EGFR-targeted therapy via disrupting IL-6/JAK2/STAT3 signaling pathway in lung adenocarcinoma.

Resistance to epidermal growth factor receptor (EGFR) inhibitors, from the first-generation erlotinib to the third generation osimertinib, is a clinical challenge in the treatment of patients with EGFR-mutant lung adenocarcinoma. Our previous work found that a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1), HKB99, restrains erlotinib resistance in lung adenocarcinoma cells. However, the role of HKB99 in osimertinib resistance and its underlying molecular mechanism remains to be elucidated.

A pan-sarbecovirus vaccine based on RBD of SARS-CoV-2 original strain elicits potent neutralizing antibodies against XBB in non-human primates.

The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma.

Synovial Oxygenation at Photoacoustic Imaging to Assess Rheumatoid Arthritis Disease Activity.

Background Synovial hypoxia is a hallmark of rheumatoid arthritis (RA). Photoacoustic (PA) imaging, based on the use of laser-generated US, can detect the oxygenation status of tissue in individuals with RA. However, large studies are lacking, with few investigating the correlation between oxygenation status and disease activity.

Adherence to Stroke Care Performance Measures in Different Regions in China, 2015-2019: Evidence From the Chinese Stroke Center Alliance.

Background And Objectives: To explore the regional discrepancy of the adherence to guideline-recommended stroke interventions for the stroke belt division (north vs south), the economic development division (east vs middle vs west), and potential interaction.

Methods: We conducted a retrospective observational study using data from the Chinese Stroke Center Alliance from August 2015 to August 2019. The primary outcome was hospital personnel adherence to 11 individual guideline-recommended treatments.

RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants.

With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling.

A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs.

The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs.

Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays.

Introduction: Previous studies have demonstrated that autoantibodies against tumor-associated antigens (TAAs) in patients with cancer can be used as sensitive immunodiagnostic biomarkers for the detection of cancer. Most of these TAAs are involved in the tumorigenesis pathway. Cancer driver genes with intragenic mutations can promote tumorigenesis.

Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation.

Objective: Angiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. This study aims to investigate the role of endothelial cell-derived FSTL1 (follistatin-like protein 1) in vascular homeostasis. Approach and Results: Using conditional knockout mouse models, we show that loss of FSTL1 in endothelial cells () led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves.

Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis.

Recent interest in the control of bone metabolism has focused on a specialized subset of CD31endomucin vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31endomucin endothelium in human and mouse bone.

Neutral Au-Doped Cluster Catalysts AuTiO for CO Oxidation by O.

Oxide supported gold catalysts (e.g., Au/TiO) are of great significance in heterogeneous catalysis owing to their extraordinary catalytic activity.

Ablation of the Ligament of Marshall and Left Stellate Ganglion Similarly Reduces Ventricular Arrhythmias During Acute Myocardial Infarction.

Background: Sympathetic denervation exerts protective effects against ventricular arrhythmias (VAs) induced by acute myocardial infarction. The results of a previous study indicated that the distal part of the ligament of Marshall (LOM) might be a sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study was designed to compare the effects between LSG and LOM ablation on ischemia-induced VAs.

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.

Oncogenic c-ros oncogene1 (ROS1) fusion kinases have been identified in a variety of human cancers and are attractive targets for cancer therapy. The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer. However, emerging clinical evidence has shown that patients can develop resistance by acquiring secondary point mutations in ROS1 kinase.