Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.

Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.

Abnormal Exercise Electrocardiography With Normal Stress Echocardiography Is Associated With Subclinical Coronary Atherosclerosis.

Background: Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/-Echo), have an increased risk of adverse cardiovascular events compared with patients with a normal (negative) ECG and a normal stress Echo (-ECG/-Echo). However, it is unclear if +ECG/-Echo discordance is associated with a greater burden of subclinical coronary atherosclerosis.

Methods: Project Baseline Health Study participants who underwent a stress Echo and coronary artery calcium (CAC) scan were stratified by stress Echo result: -ECG/-Echo or +ECG/-Echo.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.

Objectives: Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.

The Effects of Thunb. on the Alleviation of Joint Pain: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Arthritis is mainly a geriatric disease that causes joint pain and lowers the quality of life. This clinical trial was performed to evaluate the efficacy of Thunb. (HY-LL) in alleviating joint pain.

Herbicide-resistant plants produced by precision adenine base editing in plastid DNA.

CRISPR-free, protein-only cytosine base editors (CBEs) or adenine base editors, composed of DNA-binding proteins such as zinc finger proteins or transcription activator-like effectors (TALEs) and nucleobase cytosine or adenine deaminases, respectively, enable organellar DNA editing in cultured cells, animals and plants. TALE-linked double-stranded DNA deaminase toxin A (DddA)-derived CBEs (DdCBEs) and TALE-linked adenine deaminases (TALEDs) install C-to-T and A-to-G single-nucleotide conversions, respectively, in mitochondria and chloroplasts. Interestingly, whereas TALEDs exclusively induce A-to-G conversions without C-to-T conversions in mammalian mitochondrial DNA, they often install unwanted C-to-T edits in addition to intended A-to-G edits in plastid DNA.

Healing wounds with plasma-activated hydrogel therapy.

Chronic wound infections are a silent pandemic in danger of becoming a global healthcare crisis. Innovations to control infections and improve healing are required. In the context of this challenge, researchers are exploiting plasma-activated hydrogel therapy (PAHT) for use either alone or in combination with other antimicrobial strategies.

Five-day Wearable Respiratory Support With a Novel Ambulatory Pulmonary Assist System in an Awake Ovine Model.

Background: The pulmonary assist system (PAS) is a wearable respiratory support system that is currently under development for patients with chronic lung disease as a bridge to lung transplantation or as destination therapy. This study evaluates the long-term performance and biocompatibility of the PAS in a 5-d awake, ovine model.

Methods: The PAS was attached to normal sheep in venovenous configuration.

Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future.

Background: At present, there is a dearth of comprehensive data at the global, national, and regional levels regarding the adult non-alcoholic fatty liver disease (NAFLD) prevalence. This cross-sectional study aims at ascertaining the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH), utilizing body mass index (BMI) as a determining factor.

Methods: Based on the NHANES database, sigmoidal fitting curves were generated to establish the relationship between BMI and the risk of NAFLD/NASH.

Ethanol extract from Astilbe chinensis inflorescence suppresses inflammation in macrophages and growth of oral pathogenic bacteria.

Chronic oral inflammation and biofilm-mediated infections drive diseases such as dental caries and periodontitis. This study investigated the anti-inflammatory and antibacterial potential of an ethanol extract from Astilbe chinensis inflorescence (GA-13-6) as a prominent candidate for natural complex substances (NCS) with therapeutic potential. In LPS-stimulated RAW 264.

Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

Background: The Murray law-based quantitative flow ratio (μFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesions with μFR >0.

Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump.

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS's axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each).

Clinical and Genomic Landscape of RAS Mutations in Gynecologic Cancers.

Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.

Experimental Design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model.

Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations.

Nonsense mutations - the underlying cause of approximately 11% of all genetic diseases - prematurely terminate protein synthesis by mutating a sense codon to a premature stop or termination codon (PTC). An emerging therapeutic strategy to suppress nonsense defects is to engineer sense-codon decoding tRNAs to readthrough and restore translation at PTCs. However, the readthrough efficiency of the engineered suppressor tRNAs (sup-tRNAs) largely varies in a tissue- and sequence context-dependent manner and has not yet yielded optimal clinical efficacy for many nonsense mutations.

Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants.