Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery.

Selection, Design and Immunogenicity Studies of ASFV Antigens for Subunit mRNA Cocktail Vaccines with Specific Immune Response Profiles.

Development of safe and effective subunit vaccines for controlling African Swine Fever Virus (ASFV) infection has been hampered by a lack of protective viral antigens, complex virion structures, and multiple mechanisms of infection. Here, we selected ASFV antigens based on their localization on the virion, known functions, and homologies to the subunits of the protective vaccinia virus vaccine. We also engineered viral capsid proteins for inducing optimal antibody responses and designed T cell-directed antigen for inducing broad and robust cellular immunity.

Accurate prediction of protein function using statistics-informed graph networks.

Understanding protein function is pivotal in comprehending the intricate mechanisms that underlie many crucial biological activities, with far-reaching implications in the fields of medicine, biotechnology, and drug development. However, more than 200 million proteins remain uncharacterized, and computational efforts heavily rely on protein structural information to predict annotations of varying quality. Here, we present a method that utilizes statistics-informed graph networks to predict protein functions solely from its sequence.

Structure-based design of non-hypertrophic apelin receptor modulator.

Apelin is a key hormone in cardiovascular homeostasis that activates the apelin receptor (APLNR), which is regarded as a promising therapeutic target for cardiovascular disease. However, adverse effects through the β-arrestin pathway limit its pharmacological use. Here, we report cryoelectron microscopy (cryo-EM) structures of APLNR-G complexes bound to three agonists with divergent signaling profiles.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

Background: Intracellular Ca cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca-ATPase 2a) is responsible for the sequestration of cytosolic Ca into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear.

SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis.

Background: Angiogenesis, which plays a critical role in embryonic development and tissue repair, is controlled by a set of angiogenic signaling pathways. As a TF (transcription factor) belonging to the basic helix-loop-helix family, HEY (hairy/enhancer of split related with YRPW motif)-1 (YRPW motif, abbreviation of 4 highly conserved amino acids in the motif) has been identified as a key player in developmental angiogenesis. However, the precise mechanisms underlying HEY1's actions in angiogenesis remain largely unknown.

Refractive Associations With Whole Eye Movement Distance and Time Among Chinese University Students: A Corvis ST Study.

Purpose: Eye movement has been frequently studied in clinical conditions, but the association with myopia has been less explored, especially in population-based samples. The purpose of this study was to assess the associations of eye movement measured by the Corvis ST with refractive status in healthy university students.

Methods: A total of 1640 healthy students were included in the study (19.

Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.

Background: Hypoxia is a major cause and promoter of pulmonary hypertension (PH), a representative vascular remodeling disease with poor prognosis and high mortality. However, the mechanism underlying how pulmonary arterial system responds to hypoxic stress during PH remains unclear. Endothelial mitochondria are considered signaling organelles on oxygen tension.

Identification and characterization of a novel cell binding and cross-reactive region on spike protein of SARS-CoV-2.

Given that COVID-19 continues to wreak havoc around the world, it is imperative to search for a conserved region involved in viral infection so that effective vaccines can be developed to prevent the virus from rapid mutations. We have established a twelve-fragment library of recombinant proteins covering the entire region of spike protein of both SARS-CoV-2 and SARS-CoV from Escherichia coli. IgGs from murine antisera specifically against 6 spike protein fragments of SARS-CoV-2 were produced, purified, and characterized.

Association of Lifestyle With Incidence of Heart Failure According to Metabolic and Genetic Risk Status: A Population-Based Prospective Study.

Background: Whether lifestyle factors are similarly associated with risk of heart failure (HF) for individuals with different metabolic or genetic risk status remains unclear.

Methods: We included 464 483 participants from UK Biobank who were free of major cardiovascular disease or HF during baseline recruitment. Healthy lifestyle factors included avoidance of smoking, no obesity, regular physical activity, and healthy diet.

LECT2 Ameliorates Blood-Retinal Barrier Impairment Secondary to Diabetes Via Activation of the Tie2/Akt/mTOR Signaling Pathway.

Purpose: Current treatments for diabetic retinopathy (DR) have considerable limitations, emphasizing the need for new therapeutic options. The effect of leukocyte cell-derived chemotaxin 2 (LECT2) on diabetes-induced blood-retinal barrier impairment and the possible underlying mechanism were investigated both in vivo and in vitro.

Methods: Twenty diabetic and 22 nondiabetic eyes were included in this study.

Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants.

Omicron (B.1.1.

Metabolism of a Selective Serotonin and Norepinephrine Reuptake Inhibitor Duloxetine in Liver Microsomes and Mice.

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor, widely used for the treatment of major depressive disorder. Although DLX has shown good efficacy and safety, serious adverse effects (e.g.

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.

First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811.

Treatment options for patients with HER2-positive advanced gastric cancer are limited, and the prognosis for these patients is poor. Pembrolizumab has demonstrated promising antitumor activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma as monotherapy, in combination with chemotherapy and in combination with trastuzumab. Combining pembrolizumab with trastuzumab and chemotherapy may therefore provide a benefit for patients with advanced HER2-positive gastric cancer.

Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency.

Objective: To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients.

Methods: A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis.

A Thermostable mRNA Vaccine against COVID-19.

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV).

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation.

A salt-resistant Janus evaporator assembled from ultralong hydroxyapatite nanowires and nickel oxide for efficient and recyclable solar desalination.

Solar energy-driven interfacial water evaporation is a promising energy utilization technology in the field of seawater desalination and water purification. However, the accumulation of salt on the heating surface severely impairs the water evaporation performance and long-time stability. Herein, we demonstrate a new kind of photothermal paper comprising a high-temperature-resistant paper made from ultralong hydroxyapatite nanowires and glass fibers and black nickel oxide (NiO) nanoparticles for solar energy-driven desalination.

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples.