Hyaluronic acid modified liposomes with enhanced transdermal delivery of methotrexate for psoriasis treatment.

Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and cutaneous symptoms. Methotrexate (MTX), efficacious in psoriasis, suffers from limited transdermal permeability due to its hydrophilic nature. Liposomal nanomedicine, which offers increased bioavailability and targeted delivery with minimized systemic effects, is a promising approach.

Genomic hallmarks and therapeutic targets of ribosome biogenesis in cancer.

Hyperactive ribosome biogenesis (RiboSis) fuels unrestricted cell proliferation, whereas genomic hallmarks and therapeutic targets of RiboSis in cancers remain elusive, and efficient approaches to quantify RiboSis activity are still limited. Here, we have established an in silico approach to conveniently score RiboSis activity based on individual transcriptome data. By employing this novel approach and RNA-seq data of 14 645 samples from TCGA/GTEx dataset and 917 294 single-cell expression profiles across 13 cancer types, we observed the elevated activity of RiboSis in malignant cells of various human cancers, and high risk of severe outcomes in patients with high RiboSis activity.

Biofilm formation is a risk factor for late and delayed complications of filler injection.

Introduction: Biofilm formation is a major cause of delayed-graft complications. Similarly to implants, dermal fillers carry the risk of biofilm formation, which can lead to the development of nodules, chronic inflammatory reactions, abscesses and other complications. In this study, we investigated the late or delayed complications associated with biofilm formation on dermal fillers.

Shared and divergent contribution of vitamin A and oxytocin to the aetiology of autism spectrum disorder.

Rare genetic variations contribute to the heterogeneity of autism spectrum disorder (ASD) and the responses to various interventions for ASD probands. However, the associated molecular underpinnings remain unclear. Herein, we estimated the association between rare genetic variations in 410 vitamin A (VA)-related genes (VARGs) and ASD aetiology using publicly available mutations (DNMs), rare inherited variants, and copy number variations (CNVs) from about 50,000 ASD probands and 20,000 normal controls (discovery and validation cohorts).

Auxiliary rehabilitation training after calf contouring with botulinum toxin type A injection reduces adverse reactions and improves satisfaction.

Purpose: To analyze the effect of adjuvant rehabilitation training after calf contouring with botulinum toxin type A (BTX-A) injection.

Methods: Clinical data of 48 female beauty seekers who underwent calf contouring at the Plastic Surgery Laser Center of Guangdong Second People's Hospital from January 2021 to June 2022 were retrospectively analyzed. Among them, 24 cases received routine care from January 2021 to December 2021 and were included in a control group, and 24 cases received rehabilitation care with auxiliary rehabilitation training from January 2022 to June 2022 that were in an observation group.

Machine learning modeling identifies hypertrophic cardiomyopathy subtypes with genetic signature.

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.

Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation.

DNA methylation (DNAm) is one of the major epigenetic mechanisms in humans and is important in diverse cellular processes. The variation of DNAm in the human population is related to both genetic and environmental factors. However, the DNAm profiles have not been investigated in the Chinese population of diverse ethnicities.

Risk modeling of single-cell transcriptomes reveals the heterogeneity of immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies. E2F transcription factors play an important role in the tumorigenesis and progression of HCC, mainly through the RB/E2F pathway. Prognostic models for HCC based on gene signatures have been developed rapidly in recent years; however, their discriminating ability at the single-cell level remains elusive, which could reflect the underlying mechanisms driving the sample bifurcation.

An updated overview of experimental and computational approaches to identify non-canonical DNA/RNA structures with emphasis on G-quadruplexes and R-loops.

Multiple types of non-canonical nucleic acid structures play essential roles in DNA recombination and replication, transcription, and genomic instability and have been associated with several human diseases. Thus, an increasing number of experimental and bioinformatics methods have been developed to identify these structures. To date, most reviews have focused on the features of non-canonical DNA/RNA structure formation, experimental approaches to mapping these structures, and the association of these structures with diseases.

Pan-cancer analyses of synonymous mutations based on tissue-specific codon optimality.

Codon optimality has been demonstrated to be an important determinant of mRNA stability and expression levels in multiple model organisms and human cell lines. However, tissue-specific codon optimality has not been developed to investigate how codon optimality is usually perturbed by somatic synonymous mutations in human cancers. Here, we determined tissue-specific codon optimality in 29 human tissues based on mRNA expression data from the Genotype-Tissue Expression project.

Integrative analysis prioritised oxytocin-related biomarkers associated with the aetiology of autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high phenotypic and genetic heterogeneity. The common variants of specific oxytocin-related genes (OTRGs), particularly OXTR, are associated with the aetiology of ASD. The contribution of rare genetic variations in OTRGs to ASD aetiology remains unclear.

Transcriptomic signatures associated with autoimmune thyroiditis in papillary thyroid carcinoma and cancer immunotherapy-induced thyroid dysfunction.

Up to 20% of patients treated with anti-PD-1/PD-L1 inhibitors suffered from thyroid dysfunctions, yet the mediators associated with their occurrence remain unclear. The increasing coincidence of papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) and the high vulnerability of thyroid to immunotherapy motivated us to discover the similarities and their underlying transcriptomic basis. Clinical characteristics analysis of 468 PTC patients from two independent cohorts and meta-analysis of 22,155 PTC patients unveiled a strong negative association between HT and recurrence in PTC patients.

Comprehensive characterization of posttranscriptional impairment-related 3'-UTR mutations in 2413 whole genomes of cancer patients.

The 3' untranslated region (3'-UTR) is the vital element regulating gene expression, but most studies have focused on variations in RNA-binding proteins (RBPs), miRNAs, alternative polyadenylation (APA) and RNA modifications. To explore the posttranscriptional function of 3'-UTR somatic mutations in tumorigenesis, we collected whole-genome data from 2413 patients across 18 cancer types. Our updated algorithm, PIVar, revealed 25,216 3'-UTR posttranscriptional impairment-related SNVs (3'-UTR piSNVs) spanning 2930 genes; 24 related RBPs were significantly enriched.

Promoter Hypermethylation in the Basolateral Amygdala Regulates Reconsolidation of Morphine Reward Memory in Rats.

Impairing reconsolidation may disrupt drug memories to prevent relapse, meanwhile long-term transcription regulations in the brain regions contribute to the occurrence of emotional memories. The basolateral amygdala (BLA) is involved in the drug-cue association, while the nucleus accumbens (NAc) responds to the drug reward. Here, we assessed whether DNA methyltransferases (Dnmts) in these two brain regions function identically in the reconsolidation of morphine reward memory.

Comprehensive evaluation of computational methods for predicting cancer driver genes.

Optimal methods could effectively improve the accuracy of predicting and identifying candidate driver genes. Various computational methods based on mutational frequency, network and function approaches have been developed to identify mutation driver genes in cancer genomes. However, a comprehensive evaluation of the performance levels of network-, function- and frequency-based methods is lacking.

The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis.

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in multiple biological functions in cell development, differentiation, and transcriptional regulation. deficient mice display the defects of murine glucose metabolism. However, the role of TET1 in metabolic homeostasis keeps unknown.

Mapping of de novo mutations in primary biliary cholangitis to a disease-specific co-expression network underlying homeostasis and metabolism.

Primary biliary cholangitis (PBC) is an autoimmune disease involving dysregulation of a broad array of homeostatic and metabolic processes. Although considerable single-nucleotide polymorphisms have been unveiled, a large fraction of risk factors remains enigmatic. Candidate genes with rare mutations that tend to confer more deleterious effects need to be identified.

A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing.

Genetic and epigenetic contributions to various diseases and biological processes have been well-recognized. However, simultaneous identification of single-nucleotide variants (SNVs) and DNA methylation levels from traditional bisulfite sequencing data is still challenging. Here, we develop double strand bisulfite sequencing (DSBS) for genome-wide accurate identification of SNVs and DNA methylation simultaneously at a single-base resolution by using one dataset.

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes.

Neurodevelopmental disorders (NDDs) are a set of complex disorders characterized by diverse and co-occurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown. Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations (DNMs) in 86 genes and 2,385 rare inherited mutations (RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes.

Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders.

The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.

Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes.

AI-Driver: an ensemble method for identifying driver mutations in personal cancer genomes.

The current challenge in cancer research is to increase the resolution of driver prediction from gene-level to mutation-level, which is more closely aligned with the goal of precision cancer medicine. Improved methods to distinguish drivers from passengers are urgently needed to dig out driver mutations from increasing exome sequencing studies. Here, we developed an ensemble method, AI-Driver (AI-based driver classifier, https://github.