Endocrine disrupting and carcinogenic effects of decabromodiphenyl ether

BackgroundDecabromodiphenyl ether (BDE209), an essential industrial flame retardant that is widely used, has recently been reported to be increasing in human serum. Due to the structural similarity between BDE209 and thyroid hormones, its toxic effects on the thyroid are of particular concern.MethodsOriginal articles in the PubMed database were collected using the terms “BDE209”, “decabromodiphenyl ether”, “endocrine disrupting”, “thyroid”, “carcinogenesis”, “polybrominated diphenyl ethers”, “PBDEs,” and their synonyms from inception up to October of 2022.ResultsOf the 748 studies initially identified, 45 were selected, which emphasized the adverse effects of BDE209 on endocrine system. BDE209 may have a toxic effect not only on thyroid function but also on thyroid cancer tumorigenesis at multiple levels, such as by directly interfering with the TR, hypothalamic-pituitary-thyroid (HPT) axis, enzyme activity, and methylation. However, it is impossible to draw a definitive conclusion on the exact pathway of thyroid toxicity from BDE209.ConclusionsAlthough the toxic effects of BDE209 on the thyroid have been well investigated, its tumorigenic effects remain unclear and further research is necessary

Case Report: Pericardial patch repair of mitral annulus and mitral valve for a left atrial dissection caused by parasitic infective endocarditis

IntroductionLeft atrial dissection is a rare event, typically associated with cardiac manipulation. We report the first case of a left atrial dissection caused by parasitic infectious endocarditis, which required the use of patch repair for the damaged mitral annulus and valve.Case PresentationTo treat heart failure in a 43-year-old man with left atrial dissection, we performed a patch repair of the mitral annulus and valve using autologous pericardium.ConclusionWe encourage novel surgery for complicated infectious endocarditis

Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification

<p>Supplementary files.</p&gt

Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification

<p>Supplementary files.</p&gt

Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification

<p>All necessary files, including scripts, input files, configuration files, and output files use in the paper: Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification. For more details, please check this paper.</p&gt

SEPepQuant enhances the detection of possible isoform regulations in shotgun proteomics

Abstract Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key limitations of existing methods, providing more comprehensive isoform-level characterization, identifying hundreds of isoform-level regulation events, and facilitating streamlined cross-study comparisons. Our analysis provides solid evidence to support a widespread role of protein isoform regulation in normal and disease processes, and SEPepQuant has broad applications to biological and translational research

Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation

ABSTRACT The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions

Multi‐omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple‐negative breast cancer

Abstract Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as “disulfidptosis.” However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan‐cancer at multi‐omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (GYS1), was identified as a promising target for triple‐negative breast cancer and validated via in vitro and in vivo experiments. In conclusion, our study elucidated the complex molecular phenotypes and clinicopathological correlations of disulfidptosis regulators in tumors, laying a solid foundation for the development of disulfidptosis‐targeting strategies for cancer treatment

Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations

Abstract Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive “big-data” processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain