The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear.
View Article and Find Full Text PDFHypoxia-inducible factor prolyl hydroxylase (PHD) inhibitors have been approved for treating renal anemia yet have failed clinical testing for inflammatory bowel disease because of a lack of efficacy. Here we used a multimodel multimodal generative artificial intelligence platform to design an orally gut-restricted selective PHD1 and PHD2 inhibitor that exhibits favorable safety and pharmacokinetic profiles in preclinical studies. ISM012-042 restores intestinal barrier function and alleviates gut inflammation in multiple experimental colitis models.
View Article and Find Full Text PDFVast shotgun metagenomics data remain an underutilized resource for novel enzymes. Artificial intelligence (AI) has increasingly been applied to protein mining, but its conventional performance evaluation is interpolative in nature, and these trained models often struggle to extrapolate effectively when challenged with unknown data. In this study, we present a framework (DeepMineLys [deep mining of phage lysins from human microbiome]) based on the convolutional neural network (CNN) to identify phage lysins from three human microbiome datasets.
View Article and Find Full Text PDFBackground: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this.
Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM.
Aims: Cardiovascular disease (CVD) is a leading cause of mortality, especially in developing countries. This study aimed to develop and validate a CVD risk prediction model, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), for recurrent cardiovascular events using machine learning technique.
Methods And Results: Three cohorts of Chinese patients with established CVD were included if they had used any of the public healthcare services provided by the Hong Kong Hospital Authority (HA) since 2004 and categorized by their geographical locations.
Microbes employ effectors to disrupt immune responses and promote host colonization. Conserved motifs including RXLR, LFLAK-HVLVxxP (CRN), Y/F/WxC, CFEM, LysM, Chitin-bind, DPBB_1 (PNPi), and Cutinase have been discovered to play crucial roles in the functioning of effectors in filamentous fungi. Nevertheless, little is known about effectors with conserved motifs in endophytes.
View Article and Find Full Text PDFRationale And Objectives: To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients.
Materials And Methods: In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC.
Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells.
View Article and Find Full Text PDFPurpose: To generate a single-cell RNA-sequencing (scRNA-seq) map and construct cell-cell communication networks of mouse corneas.
Methods: C57BL/6 mouse corneas were dissociated to single cells and subjected to scRNA-seq. Cell populations were clustered and annotated for bioinformatic analysis using the R package "Seurat.
High-fidelity three-dimensional (3D) models of tooth-bone structures are valuable for virtual dental treatment planning; however, they require integrating data from cone-beam computed tomography (CBCT) and intraoral scans (IOS) using methods that are either error-prone or time-consuming. Hence, this study presents Deep Dental Multimodal Fusion (DDMF), an automatic multimodal framework that reconstructs 3D tooth-bone structures using CBCT and IOS. Specifically, the DDMF framework comprises CBCT and IOS segmentation modules as well as a multimodal reconstruction module with novel pixel representation learning architectures, prior knowledge-guided losses, and geometry-based 3D fusion techniques.
View Article and Find Full Text PDFRationale And Objectives: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC.
Materials And Methods: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression.
Background And Objectives: The objective of this study was to examine whether the regional methylation levels at the most distal D4Z4 repeat units (RU) in the 4qA-permissive haplotype were associated with disease severity and progression in facioscapulohumeral muscular dystrophy type 1 (FSHD1).
Methods: This 21-year, retrospective, observational cohort study was conducted at the Fujian Neuromedical Center (FNMC) in China. Methylation levels of the most distal D4Z4 RU, including 10 CpGs, were assessed in all participants by bisulfite sequencing.
Background: Mechanical thrombectomy (MT) has been proved to be a highly effective therapy to treat acute ischemic stroke due to large vessel occlusion. Often, the ischemic core extent on baseline imaging is an important determinant for endovascular treatment eligibility. However, computed tomography (CT) perfusion (CTP) or diffusion-weighted imaging may overestimate the infarct core on admission and, consequently, smaller infarct lesions called "ghost infarct cores.
View Article and Find Full Text PDFJ Occup Environ Med
July 2023
Objectives: This study aimed to explore the association between multiple metals' exposure and children's height.
Methods: We collected urine samples and physical measurement data of 1477 preschoolers in China. Children's actual height was measured, and whether reached target height was also assessed.
Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain.
View Article and Find Full Text PDF