A powdery mildew (Pm) resistance locus PmRc1 was identified and transferred from Roegneria ciliaris into wheat. Two compensative translocation lines carrying PmRc1 were developed. Powdery mildew (Pm), caused by the biotrophic fungal pathogen Blumeria graminis f.
View Article and Find Full Text PDFCyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.
View Article and Find Full Text PDFAccurately 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.
View Article and Find Full Text PDFPurpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals.
Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models.
Introduction: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas.
Methods: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet.
Iron-mediated induction of bone morphogenetic protein (BMP)6 expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for the metal-ion transporter ZIP8 in regulating BMP6 expression under high-iron conditions.
View Article and Find Full Text PDFChemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis.
View Article and Find Full Text PDFHepcidin is the master hormone governing systemic iron homeostasis. Iron regulates hepcidin by activating bone morphogenetic protein (BMP)6 expression in liver endothelial cells (LECs), but the mechanisms are incompletely understood. To address this, we performed proteomics and RNA-sequencing on LECs from iron-adequate and iron-loaded mice.
View Article and Find Full Text PDFThe beneficial effects of butyric acid in poultry production are well documented, while the relationship between sodium butyrate (SB) and microcapsule sustained-release sodium butyrate (MSSB), especially in yellow broilers, remains poorly investigated. This study was designed to elucidate the function as well as the potential mechanisms of SB and MSSB in enhancing health in yellow broilers. In total, 360 one-day-old yellow broilers were allocated to three treatment groups.
View Article and Find Full Text PDFOncogenic KRAS mutations are a key driver for initiation and progression in non-small cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity remain largely unclear. Here, we show that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysines 182 and 184.
View Article and Find Full Text PDFA new FHB resistance locus FhbRc1 was identified from the R. ciliaris chromosome 7S and transferred into common wheat by developing alien translocation lines. Fusarium head blight (FHB) caused by multiple Fusarium species is a globally destructive disease of common wheat.
View Article and Find Full Text PDFBackground: Collateral formation from the extracranial carotid artery to ischemic brain tissue determines the clinical success of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adult patients with moyamoya disease, but postoperative collateral formation (PCF) after STA-MCA bypass surgery is unpredictable. Accurate preoperative prediction of acceptable PCF could improve patient selection. This study aims to develop a prediction nomogram model for PCF in this patient population.
View Article and Find Full Text PDFBackground: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied.
Methods: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability).
Background: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited.
Methods: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control).
Introduction: Biliary atresia (BA) is a devastating obstructive bile duct disease found in newborns. This study aims to investigate the roles and involved mechanisms of beta-amyloid (Aβ) in the pathogenesis of BA.
Methods: We examined the distribution of Aβ protein and its precursor in the livers of patients with BA.
Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort.
View Article and Find Full Text PDFNVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08.
View Article and Find Full Text PDFBackground: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO).
Methods: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT.
Mol Ther Nucleic Acids
June 2022
Impressive achievements in clinical trials to treat hemophilia establish a milestone in the development of gene therapy. It highlights the significance of AAV-mediated gene delivery to liver. AAV5 is a unique serotype featured by low neutralizing antibody prevalence.
View Article and Find Full Text PDFBackground And Purpose: There is also a risk of stroke in the asymptomatic hemispheres of moyamoya disease (MMD), but it does not draw enough attention. The study investigated the differences between the three types of asymptomatic hemispheres in MMD and their associations with the two types of symptomatic hemispheres, respectively.
Methods: Retrospectively reviewed clinical and imaging characteristics of asymptomatic and symptomatic hemispheres in consecutive cases of single-center MMD patients, with an emphasis on imaging characterization regarding vascular morphology and cerebral perfusion.
We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.
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