Characterization of cis-regulatory elements and functional variants in colorectal cancer using epigenomics and CRISPRi screenings.

Genetic variants associated with colorectal cancer (CRC) are primarily noncoding and reside in cis-regulatory elements (CREs), yet their underlying mechanisms remain elusive. Here we established a dynamic epigenetic atlas using multiomics data from 533 colorectal tissues spanning normal to advanced adenoma to cancer, identifying 7,492 differential CREs linked to 5,490 target genes. High-throughput CRISPR interference screening revealed 265 functional CREs involved in CRC cell proliferation.

Genetic architecture of bone marrow fat fraction implies its involvement in osteoporosis risk.

Bone marrow adipose tissue, as a distinct adipose subtype, has been implicated in the pathophysiology of skeletal, metabolic, and hematopoietic disorders. To identify its underlying genetic factors, we utilized a deep learning algorithm capable of quantifying bone marrow fat fraction (BMFF) in the vertebrae and proximal femur using magnetic resonance imaging data of over 38,000 UK Biobank participants. Genome-wide association analyses uncovered 373 significant BMFF-associated variants (P-value < 5 × 10), with enrichment in bone remodeling, metabolism, and hematopoiesis pathway.

Genetic Control of tRNA-Derived Fragments Contributes to Cancer Risk.

Transfer RNA-derived fragments (tRFs) are a class of small non-coding RNAs that have exhibited several functions in cancer. Recent studies have shown that mutations in tRNA genes can lead to global changes in tRF expression levels and may affect tRF function, highlighting the need to further elucidate the regulation and functions of tRFs in cancer. Here, we conducted a pan-cancer analysis of tRF quantitative trait loci (tRFQTLs), encompassing 16,703 genetic variants associated with tRF expression across 31 cancer types.

Identification and validation of blood leukocyte DNA methylation biomarkers for early detection of colorectal neoplasm.

Background: Identifying high-risk populations for colorectal cancer (CRC) is critical for precise screening. This study aimed to develop a novel risk prediction model using blood DNA methylation biomarkers to identify individuals at high risk for colorectal neoplasms.

Methods: The biomarker discovery phase involved 106 samples (56 advanced adenomas and 50 healthy controls) collected from the TARGET-C screening cohort between May 2018 and May 2021, which were analyzed using the Illumina Infinium MethylationEPIC v2.

Chromosome-level assemblies of the White bream Parabramis pekinensis.

White bream Parabramis pekinensis is an omnivorous fish belong to Cyprinidae that is widespread in Asia. In this study, we presented chromosome-level genome assemblies of P. pekinensis by using PacBio HiFi long reads and Hi-C technology.

Effect of Dietary Protein and Lipid Level on Growth, Antioxidant, and Gene Expression of Juvenile .

Unreasonable ratio of protein to lipid in feeds could affect growth, antioxidant, and related pathway genes expression. This study aimed to investigate the suitable proportion of protein to lipid in feed with . The ratio protein-lipid (/ indicated by G1 (2.

Single-cell eQTL Mapping Reveals Cell Subtype-specific Genetic Control and Mechanism in Malignant Transformation of Colorectal Cancer.

Unlabelled: Colorectal cancer is a heterogeneous disease that develops through a stepwise accumulation, yet the underlying mechanisms at single-cell resolution remain unclear. In this study, we profiled 751,531 single-cell transcriptomes, spatial transcriptomics, and snMultiomes from 142 multistage samples, revealing the cellular and molecular alterations and dynamic intercellular cross-talk during colorectal cancer development. Additionally, we created a colorectal cancer single-cell expression quantitative trait locus (sc-eQTL) map identifying 16,833 significant pairs across 28 cell subtypes, with more than 76% of sc-eQTLs being cell type-specific and fewer than 15% detectable in bulk datasets.

Environmental Chemical-Induced Cardiometabolic Disorders: Combined Epidemiological and Experimental Evidence.

Screening environmental pollutants that are harmful to the cardiometabolic status and understanding their key toxic pathways are crucial for effective clinical intervention. Based on exposure data of 46 chemicals in a nationally representative 13,286 people, logistic regression and mixture modeling were used to preliminarily identify environmental pollutants with significant impacts on 12 indicators for cardiometabolic disorders. A total of 15 chemicals were found to be associated with the integrated latent class, among which four chemicals (perfluorononanoic acid [PFNA], perfluorooctanoic acid [PFOA], thiocyanate, and thallium) also contributed significantly to the mixture effect.

Comprehensive analysis of transplacental transfer of environmental pollutants detected in paired maternal and cord serums.

Prenatal exposure to hazardous environmental pollutants is a critical global concern due to their confirmed presence in umbilical cord blood, indicating the ability of pollutants to cross the placental barrier and expose the fetus to harmful compounds. However, the transplacental transfer efficiencies (TTEs) of many pollutants remain underexplored. Herein, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantitatively analyze 91 environmental pollutants, including 13 bisphenols (BPs), 18 organophosphorus flame retardants (OPFRs), 7 brominated and other flame retardants (BFRs), 34 phthalates (PAEs), and 19 per- and polyfluoroalkyl substances (PFASs), in paired maternal and cord serums.

Design, fabrication, and application of bioengineering vascular networks based on microfluidic strategies.

Vascularization is a critical component of tissue engineering research and is essential for enhancing the success rate of tissue construction and function. Over the past decade, researchers have explored various methods to construct vascular networks, including 3D printing, cell sphere technology, and microfluidics. Microfluidic technology has garnered significant attention due to its notable advantages in precision, controllability, flexibility, and applicability.

Integrative functional screen of genomic loci uncovers CCND2 and its genetic regulatory mechanism in colorectal cancer development.

Although genome-wide association studies have identified dozens of loci associated with colorectal cancer (CRC) susceptibility, the causal genes or risk variants within these loci and their biological functions often remain elusive. Recently, the genomic locus 12p13.32, with the tag single-nucleotide polymorphism rs10774214, was identified as a crucial CRC risk locus in Asian populations.

A enhancer transcriptionally regulates Wnt signaling dosage to balance homeostasis and tumorigenesis of intestinal epithelia.

The β-catenin-dependent canonical Wnt signaling is pivotal in organ development, tissue homeostasis, and cancer. Here, we identified an upstream enhancer of - the coding gene for β-catenin, named ieCtnnb1 (ntestinal nhancer of ), which is crucial for intestinal homeostasis. ieCtnnb1 is predominantly active in the base of small intestinal crypts and throughout the epithelia of large intestine.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition.

Integrated systematic functional screen and fine-mapping decipher the role and genetic regulation of RPS19 in colorectal cancer development.

Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations.

Healthy dietary patterns, genetic risk, and gastrointestinal cancer incident risk: a large-scale prospective cohort study.

Background: Dietary patterns have been associated with several cancers, especially gastrointestinal cancer (GIC). However, whether a healthy dietary pattern could modify the risk of GIC among people with different genetic backgrounds is not clear.

Objective: The objective of the study was to investigate how dietary patterns and genetic susceptibility contribute to the risk of GIC independently and jointly.