Publications by authors named "W-J Wu"

Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half-life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo-controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults.

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Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional.

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Purpose: To investigate whether lateral femoral condyle ratio (LFCR) and lateral femoral condyle index (LFCI) were associated with a greater risk of anterior cruciate ligament (ACL) injury and concomitant injuries.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered on PROSPERO. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to April 1, 2024.

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Article Synopsis
  • The study focuses on a dual-layer polycaprolactone (PCL) scaffold designed to enhance soft tissue repair in oral mucosal defects.
  • The scaffolds feature different fiber patterns (parallel, rhombic, square) and showed improved properties like surface wettability and tensile strength compared to disordered scaffolds.
  • Notably, the square-patterned scaffold promoted cell differentiation and accelerated wound healing, suggesting strong potential for clinical applications in a bacteria-prone oral environment.
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Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

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Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation.

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  • Small interfering RNAs (siRNAs) have the potential to target and silence difficult disease-related genes, providing new ways to treat diseases.* -
  • While delivering siRNAs to the liver via N-acetylgalactosamine (GalNAc) has proven effective, delivering siRNAs to other cell types remains a challenge.* -
  • Research shows that certain cellular mechanisms, including retrograde transport and lipid droplets, can enhance the effectiveness of siRNA delivery and gene silencing in both liver and non-liver cell types.*
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  • The study focused on R544C variant carriers in Taiwan who have CADASIL, investigating if white matter hyperintensities (WMHs) appear before symptoms and how these WMHs relate to cognitive function.
  • It included 63 asymptomatic R544C carriers and 37 controls, revealing that the carriers had significantly higher WMH volumes and cognitive scores were lower, especially after age 48.
  • Factors linked to increased WMH volumes were identified as age, hypercholesterolemia, and a vascular risk factor index, with a notable association between WMHs and cognitive performance.
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  • Biallelic loss of CDK12 is linked to a specific subtype of metastatic castration-resistant prostate cancer (mCRPC), raising questions about its role in cancer development versus exposing drug targets.
  • Research shows that loss of CDK12 leads to early cancer-like changes and enhances cancer cell growth when combined with mutations in other genes like Trp53, while it inhibits tumor growth in the absence of another tumor suppressor gene, Pten.
  • CDK12 loss causes genomic instability and makes tumors sensitive to treatments targeting another protein, CDK13, highlighting CDK12 as a crucial tumor suppressor and suggesting new therapeutic approaches for CDK12-mutant mCRPC.
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Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

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Accurately predicting ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties early in drug development is essential for selecting compounds with optimal pharmacokinetics and minimal toxicity. Existing ADMET-related benchmark sets are limited in utility due to their small dataset sizes and the lack of representation of compounds used in drug discovery projects. These shortcomings hinder their application in model building for drug discovery.

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Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD.

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Background: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions.

Methods: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China.

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Background And Objective: China has the highest number of hepatitis C virus (HCV) infections in the world. However, it is unclear what levels of screening and treatment are needed to achieve the WHO 2030 hepatitis C elimination targets. We aimed to evaluate the impact of scaling up interventions on the hepatitis C epidemic and determine how and at what cost these elimination targets could be achieved for the whole population in China.

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This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment.

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Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake.

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Article Synopsis
  • The evolution of SARS-CoV-2 variants highlights the need for multivalent vaccines, leading to the development of SCTV01E, a tetravalent COVID-19 vaccine targeting variants Alpha, Beta, Delta, and Omicron BA.1.
  • A double-blind placebo-controlled trial showed SCTV01E had a vaccine efficacy of 69.4% against COVID-19 seven days post-vaccination, with higher efficacy rates in preventing symptomatic and all infections at 14 days.
  • The vaccine demonstrated a significant neutralizing antibody response against Omicron BA.5 and had mild reactogenicity, indicating its potential effectiveness against emerging SARS-CoV-2 variants.
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Background: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed.

Methods: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.

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This paper investigates the effects of steel fiber and PVA fiber hybrid blending on the compressive strength (fcc), splitting tensile strength (fts), compression energy (W1.0), and shrinkage properties of concrete. It also establishes a multi-factor crack resistance index evaluation model based on the Analytic Hierarchy Process (AHP) to comprehensively evaluate the crack resistance of concrete.

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This paper explores the impact of steel-PVA hybrid fibers (S-PVA HF) on the flexural performance of panel concrete via three-point bending tests. Crack development in the concrete is analyzed through Digital Image Correlation (DIC) and Scanning Electron Microscope (SEM) experiments, unveiling the underlying mechanisms. The evolution of cracks in concrete is quantitatively analyzed based on fractal theory, and a predictive model for flexural strength (PMFS) is established.

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Introduction: An association between female sex hormones and inflammatory bowel disease (IBD) has been reported in epidemiological studies. However, a solid causal relationship has not been established. Therefore, we performed a 2-sample Mendelian randomization (MR) study to explore the causal association between genetically predicted female sex hormone exposure, especially estrogen, and IBD.

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Article Synopsis
  • The gene IDH1 often changes in many cancers, leading to a harmful substance that messes with the body's natural defenses.
  • Tumors with this change often keep immune cells out, but blocking the mutant IDH1 can help the body's immune system attack the cancer.
  • The study shows that the mutant IDH1 silences certain genes that would usually help the immune system work, but stopping this mutation can help reactivate those genes and boost immunity against tumors.
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Introduction: This study builds on previous research and its limitations, which indicate the need for further investigation in prospective cohorts. Our aim was to explore the association between estimated 24-hour urinary sodium excretion (indicative of daily sodium consumption) and the occurrence of pancreatic cancer in the UK Biobank's large prospective cohort.

Methods: Using the INTERSALT equation, the study computed estimated 24-hour urinary sodium excretion by analyzing the baseline spot urine sodium measurements of 434,372 individuals enrolled in the UK Biobank.

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