Single-cell RNA sequencing reveals the CRTAC1 population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1 macrophage.

Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration.

Atypical chemokine receptor 1-positive endothelial cells mediate leucocyte infiltration and synergize with secreted frizzled-related protein 2/asporin-positive fibroblasts to promote skin fibrosis in systemic sclerosis.

Background: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis.

Objectives: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem.

Quantitative Assessment of Ultraviolet-Induced Erythema and Tanning Responses in the Han Chinese Population.

Unlabelled: Ultraviolet radiation (UVR) can induce erythema and tanning responses with strong diversity within and between populations, but there were no precise method for evaluating the variation in these responses. In this study, we assessed the time course of ultraviolet (UV)-induced responses based on the erythema index (EI) and melanin index (MI) over 14 consecutive days in a pilot cohort study (N = 31). From safety evaluations, we found that no skin blisters occurred at a UV dosage of 45 mJ/cm, but there were significant skin reactions.

Blue light protection factor: a method to assess the protective efficacy of cosmetics against blue light-induced skin damage in the Chinese population.

Background: Previous studies have shown that visible light (VL), especially blue light (BL), could cause significant skin damage. With the emergence of VL protection products, a harmonization of light protection methods has been proposed, but it has not been widely applied in the Chinese population.

Objective: Based on this framework, we propose an accurate and simplified method to evaluate the efficacy of BL photoprotection for the Chinese population.

Harnessing HetHydrogel: A Universal Platform to Dropletize Single-Cell Multiomics.

A universal platform is developed for dropletizing single cell plate-based multiomic assays, consisting of three main pillars: a miniaturized open Heterogeneous Hydrogel reactor (abbreviated HetHydrogel) for multi-step biochemistry, its tunable permeability that allows Tn5 tagmentation, and single cell droplet barcoding. Through optimizing the HetHydrogel manufacturing procedure, the chemical composition, and cell permeation conditions, simultaneous high-throughput mitochondrial DNA genotyping and chromatin profiling at the single-cell level are demonstrated using a mixed-species experiment. This platform offers a powerful way to investigate the genotype-phenotype relationships of various mtDNA mutations in biological processes.

Comprehensive Identification of Mitochondrial Pseudogenes (NUMTs) in the Human Telomere-to-Telomere Reference Genome.

Practices related to mitochondrial research have long been hindered by the presence of mitochondrial pseudogenes within the nuclear genome (NUMTs). Even though partially assembled human reference genomes like hg38 have included NUMTs compilation, the exhaustive NUMTs within the only complete reference genome (T2T-CHR13) remain unknown. Here, we comprehensively identified the fixed NUMTs within the reference genome using human pan-mitogenome (HPMT) from GeneBank.

TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis.

Objectives: Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear.

GRB2 serves as a viable target against skin fibrosis in systemic sclerosis by regulating endothelial cell apoptosis.

Background: Systemic Sclerosis (SSc) is an autoimmune disease characterized by vascular and immune system dysfunction, along with tissue fibrosis. Our previous study found GRB2 was downregulated by salvianolic acid B, a small molecule drug that attenuated skin fibrosis of SSc.

Objectives: Here we aim to investigate the role of GRB2 in SSc.

Induced skin aging by blue-light irradiation in human skin fibroblasts via TGF-β, JNK and EGFR pathways.

Background: Studies indicate that blue light (BL) irradiation can damage human skins, but the impact of BL irradiation on skin aging is unknown.

Objectives: This study aimed to give an insight to phenotypic characteristics and molecular mechanism of blue light-induced skin aging, and thus provide a theoretical basis for the precise protection of photodermatosis.

Methods: The effect of BL on skin photoaging in mice was evaluated by non-invasive measurement equipment and histopathology analysis.

Enhancement of Zyxin Promotes Skin Fibrosis by Regulating FAK/PI3K/AKT and TGF-β Signaling Pathways via Integrins.

Skin fibrosis is a common pathological manifestation in systemic sclerosis (SSc), keloid, and localized scleroderma (LS) characterized by fibroblast activation and excessive extracellular matrix (ECM) deposition. However, few effective drugs are available to treat skin fibrosis due to its unclear mechanisms. In our study, we reanalyzed skin RNA-sequencing data of Caucasian, African, and Hispanic SSc patients from the Gene Expression Omnibus (GEO) database.

WDFY4 polymorphisms in Chinese patients with anti-MDA5 dermatomyositis is associated with rapid progressive interstitial lung disease.

Objectives: Anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+DM), is susceptible to development of rapidly progressive interstitial lung disease (RPILD), which has been predominantly reported in East Asia. A Japanese genome-wide study has identified a WDFY4 variant rs7919656 linkage. We sought to evaluate this genetic marker and exploit its possible clinical relevance in Chinese MDA5+DM.

Integrated proteogenomic characterization of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes.

Insights into male androgenetic alopecia using comparative transcriptome profiling: hypoxia-inducible factor-1 and Wnt/β-catenin signalling pathways.

Background: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region.

Objectives: To identify biological differences among HF subpopulations.

Methods: Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay.

LDLR dysfunction induces LDL accumulation and promotes pulmonary fibrosis.

Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients.

Targeted Bisulfite Sequencing Reveals DNA Methylation Changes in Zinc Finger Family Genes Associated With KRAS Mutated Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking.

Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma.

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients' paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a "cancer-primed" premalignant thyrocyte population with normal morphology but altered transcriptomes.

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia.

High altitude is an extreme environment that imposes hypoxic pressure on physiological processes, and natives living at high altitudes are more adaptive in certain physiological processes. So far, epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood. Here, we recruit 32 Tibetan elite alpinists (TEAs), who have successfully mounted Everest (8848 m) at least five times.

DNA hypermethylation contributes to colorectal cancer metastasis by regulating the binding of CEBPB and TFCP2 to the CPEB1 promoter.

Background: Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised.

Methods: We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104).