Capture of RNA-binding proteins across mouse tissues using HARD-AP.

RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs.

Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.

The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented.

The construction and optimization of engineered yeast chassis for efficient biosynthesis of 8-hydroxygeraniol.

Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.

Biphasic Scaffold Loaded With Autologous Cartilage Yields Better Clinical Outcome and Magnetic Resonance Imaging Filling Compared With Marrow Stimulation for Focal Osteochondral Lesions in the Knee.

Purpose: To evaluate the effectiveness of marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (scaffold) in treating focal osteochondral lesions of the knee.

Methods: In total, 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the scaffold group or the MS group. International Knee Documentation Committee subjective score, the Knee Injury Osteoarthritis Outcome Score, and magnetic resonance imaging (MRI) were assessed preoperatively and at 1 and 2 years after operation to compare treatment outcomes.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up).

Intermittent Theta-Burst Stimulation for Stroke: Primary Motor Cortex Versus Cerebellar Stimulation: A Randomized Sham-Controlled Trial.

Background: Stroke survivors with impaired balance and motor function tend to have relatively poor functional outcomes. The cerebellum and primary motor cortex (M1) have been suggested as targets for neuromodulation of balance and motor recovery after stroke. This study aimed to compare the efficacy and safety of intermittent theta-burst stimulation (iTBS) to the cerebellum or M1 on balance and motor recovery in patients with stroke.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

Purpose: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients.

Design: Cross-sectional, matched case-control comparison study.

Methods: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.

Different Impacts of Heat-Killed and Viable TWK10 on Exercise Performance, Fatigue, Body Composition, and Gut Microbiota in Humans.

TWK10, a probiotic strain, has been demonstrated to improve exercise performance, regulate body composition, and ameliorate age-related declines. Here, we performed a comparative analysis of viable and heat-killed TWK10 in the regulation of exercise performance, body composition, and gut microbiota in humans. Healthy adults ( = 53) were randomly divided into three groups: Control, TWK10 (viable TWK10, 3 × 10 colony forming units/day), and TWK10-hk (heat-killed TWK10, 3 × 10 cells/day) groups.

FGF21-Sirtuin 3 Axis Confers the Protective Effects of Exercise Against Diabetic Cardiomyopathy by Governing Mitochondrial Integrity.

Background: Exercise is an effective nonpharmacological strategy to alleviate diabetic cardiomyopathy (DCM) through poorly defined mechanisms. FGF21 (fibroblast growth factor 21), a peptide hormone with pleiotropic benefits on cardiometabolic homeostasis, has been identified as an exercise responsive factor. This study aims to investigate whether FGF21 signaling mediates the benefits of exercise on DCM, and if so, to elucidate the underlying mechanisms.

Safety and Efficacy of Nonoperative Treatment in Esophageal Perforation Caused by Foreign Bodies.

Introduction: Esophageal foreign bodies are often treated by endoscopy, but the treatment of esophageal perforation caused by foreign bodies remains controversial. The purpose of this study was to investigate the safety and efficacy of nonoperative treatment of esophageal perforation caused by foreign bodies.

Methods: We retrospectively analyzed 270 patients admitted to our hospital for esophageal perforation caused by foreign bodies from January 2012 to December 2020, all of whom received nonoperative treatment.

Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening.

Introduction: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation.

Methods: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial.

Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome: SADS-TW BrS Registry.

Background: Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events.

Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure.

On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium, Cardiovascular Bioengineering Symposium, was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance the understanding and treatment of heart failure was the theme of the meeting. Over 150 attendees were present, and >40 scientists presented their latest work on engineering human functional myocardium for disease modeling, drug development, and heart failure research.

Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA.

Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer.

Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer.

Subclonal architecture and genomic evolution of small-cell lung cancer (SCLC) under treatment has not been well studied primarily due to lack of tumor specimens, particularly longitudinal samples acquired during treatment. SCLC is characterized by early hematogenous spread, which makes circulating cell-free tumor DNA (ctDNA) sequencing a promising modality for genomic profiling. Here, we perform targeted deep sequencing of 430 cancer genes on pre-treatment tumor biopsies, as well as on plasma samples collected prior to and during treatment from 22 SCLC patients.

Ruminal and abomasal starch hydrolysate infusions selectively decrease the expression of cationic amino acid transporter mRNA by small intestinal epithelia of forage-fed beef steers.

Although cationic amino acids (CAA) are considered essential to maximize optimal growth of cattle, transporters responsible for CAA absorption by bovine small intestinal epithelia have not been described. This study was conducted to test 2 hypotheses: 1) the duodenal, jejunal, and ileal epithelia of beef cattle differentially express 7 mRNA associated with 4 mammalian amino acid (AA) transport activities: y(+) (CAT1), B(0,+) (ATB(0,+)), b(0,+) (b(0,+)AT and rBAT), and y(+)L (y(+)LAT1, y(+)LAT2, and 4F2hc), and 2) the expression of these mRNA is responsive to small intestinal luminal supply of AA substrates (derived from ruminal microbes) or glucose-derived energy (from starch hydrolysate, SH), or both. Eighteen ruminally and abomasally catheterized Angus steers (body weight = 260 +/- 17 kg) fed an alfalfa cube-based diet at 1.

Purification, characterization, and the complete amino acid sequence of porcine pancreatic deoxyribonuclease.

Porcine pancreatic DNase has been purified to homogeneity. The polypeptide exhibits a single band of Mr = 34,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is a glycoprotein containing glucosamine.