Comprehensive analysis of single-cell transcriptomics and genetic factors reveals the mechanisms and preventive strategies for the progression from pulmonary fibrosis to lung cancer.

Background: Pulmonary fibrosis (PF) leads to excessive deposition of fibrous connective tissue in the lungs, increasing the risk of lung cancer due to the enhanced activity of fibroblasts (FBs). Fibroblast-mediated collagen fiber deposition creates a tumor-like microenvironment, laying the foundation for tumorigenesis. Clinically, numerous cases of lung cancer induced by pulmonary fibrosis have been observed.

Optimization of ultracentrifugation-based method to enhance the purity and proteomic profiling depth of plasma-derived extracellular vesicles and particles.

Circulating extracellular vesicles and particles (EVPs) are being investigated as potential biomarkers for early cancer detection, prognosis, and disease monitoring. However, the suboptimal purity of EVPs isolated from peripheral blood plasma has posed a challenge of in-depth analysis of the EVP proteome. Here, we compared the effectiveness of different methods for isolating EVPs from healthy donor plasma, including ultracentrifugation (UC)-based protocols, phosphatidylserine-Tim4 interaction-based affinity capture (referred to as "PS"), and several commercial kits.

Ragas: integration and enhanced visualization for single cell subcluster analysis.

Summary: Subcluster analysis is a powerful means to improve clustering and characterization of single cell RNA-Seq data. However, there are no existing tools to systematically integrate results from multiple subclusters, which creates hurdles for accurate data quantification, visualization, and interpretation in downstream analysis. To address this issue, we developed Ragas, an R package that integrates multi-level subclustering objects for streamlined analysis and visualization.

Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner.

Genetic variants can alter the profile of heritable molecules such as small RNAs in sperm and oocytes, and in this manner ancestral genetic variants can have a significant effect on offspring phenotypes even if they are not themselves inherited. Here we show that wild type female mice descended from ancestors with a mutation in the mammalian germ cell gene have hepatic metabolic defects that persist over multiple generations. We find that genetically wild type females descended from mutants have transcriptional dysregulation of critical hepatic metabolic genes, which persist over multiple generations and pass through both female and male lineages.

The levels of IL1RN is a factor influencing the onset of rheumatoid arthritis in non-alcoholic fatty liver disease.

With the improvement of global dietary conditions, non-alcoholic fatty liver disease (NAFLD) has gradually become prevalent. As the number of NAFLD patients increases, the coexistence of diseases associated with it has come into focus. In this study, based on immune phenotypes, intercellular communication activities, and clinical manifestations of NAFLD patients, IL1RN was identified as a central pro-inflammatory factor.

RNA m6A modifications regulate crosstalk between tumor metabolism and immunity.

In recent years, m6A modifications in RNA transcripts have arisen as a hot topic in cancer research. Indeed, a number of independent studies have elaborated that the m6A modification impacts the behavior of tumor cells and tumor-infiltrating immune cells, altering tumor cell metabolism along with the differentiation and functional activity of immune cells. This review elaborates on the links between RNA m6A modifications, tumor cell metabolism, and immune cell behavior, discussing this topic from the viewpoint of reciprocal regulation through "RNA m6A-tumor cell metabolism-immune cell behavior" and "RNA m6A-immune cell behavior-tumor cell metabolism" axes.

An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes.

Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN . Thus, defective removal of mitochondria from mature red blood cells (Mito RBCs), a feature of SLE, contributes to IFN production by myeloid cells .

Transcriptomic analyses of patient peripheral blood with hemoglobin depletion reveal glioblastoma biomarkers.

Peripheral blood is gaining prominence as a noninvasive alternative to tissue biopsy to develop biomarkers for glioblastoma (GBM); however, widely utilized blood-based biomarkers in clinical settings have not yet been identified due to the lack of a robust detection approach. Here, we describe the application of globin reduction in RNA sequencing of whole blood (i.e.

Fatigue behavior of zirconia with microgrooved surfaces produced using femtosecond laser.

Femtosecond laser is a promising surface treatment tool for zirconia implant. In this study, the fatigue behavior of zirconia specimens with microgrooved surfaces formed by femtosecond laser is reported. One hundred sixty CAD/CAM zirconia bars (20 mm × 4 mm × 1.

Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect inflammatory responses. While n-3 PUFAs are generally considered beneficial for cardiovascular disease and obesity, the effects on asthma, the most common inflammatory lung disease are unclear. While prenatal dietary n-3 PUFAs decrease the risk for childhood wheezing, postnatal dietary n-3 PUFAs can worsen allergic airway inflammation.

Chloride intracellular channel 1 promotes esophageal squamous cell carcinoma proliferation via mTOR signalling.

Objectives: To investigate the clinical significance of Chloride Intracellular Channel 1 (CLIC1) expression in esophageal squamous cell carcinoma (ESCC) and its functional contribution and molecular mechanisms to the progression of ESCC.

Methods: CLIC1 expression was analyzed by immunohistochemistry (IHC) in a cohort of 86 ESCC tissue specimens and paired normal adjacent esophageal tissues. Associations between clinicopathological features of ESCC and CLIC1 expression were determined.

Dysregulated DNA methylation in the pathogenesis of Fabry disease.

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A and subsequent accumulation of glycosphingolipids with terminal α-D-galactosyl residues. The molecular process through which this abnormal metabolism of glycosphingolipids causes multisystem dysfunction in Fabry disease is not fully understood. We sought to determine whether dysregulated DNA methylation plays a role in the development of this disease.

Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis.

The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis.

Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.

Emerging evidence supports that mitochondrial dysfunction contributes to systemic lupus erythematosus (SLE) pathogenesis. Here we show that programmed mitochondrial removal, a hallmark of mammalian erythropoiesis, is defective in SLE. Specifically, we demonstrate that during human erythroid cell maturation, a hypoxia-inducible factor (HIF)-mediated metabolic switch is responsible for the activation of the ubiquitin-proteasome system (UPS), which precedes and is necessary for the autophagic removal of mitochondria.

Screening for SARS-CoV-2 via PCR and serological testing in asymptomatic healthcare workers.

The prevalence and seroconversion rate of SARS-CoV-2 infection among asymptomatic health care workers in the US is unclear. Our study utilized real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing and serological evaluation to detect IgG antibodies specific to SARS-CoV-2 antigens in asymptomatic health care workers. A total of 197 subjects with a mean age of 35 years were recruited into the study.

Surgical treatment for cryptoglandular and Crohn's perianal fistulas: Protocol of an umbrella review.

Introduction: A high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review.

In Esophageal Squamous Cells From Eosinophilic Esophagitis Patients, Th2 Cytokines Increase Eotaxin-3 Secretion Through Effects on Intracellular Calcium and a Non-Gastric Proton Pump.

Background & Aims: In upper airway cells, T helper 2 cytokines that signal through interleukin-4 (IL-4) receptor-α have been shown to stimulate eotaxin-3 secretion via a nongastric proton pump (ngH,KATPase). To seek novel targets for eosinophilic esophagitis (EoE) treatments, we evaluated ngH,KATPase expression in EoE squamous cells, and explored molecular pathways involved in eotaxin-3 secretion by IL-4 receptor-α signaling.

Methods: ngH,KATPase expression in EoE cells was evaluated by quantitative real-time polymerase chain reaction and Western blotting.

Identifying intracellular signaling modules and exploring pathways associated with breast cancer recurrence.

Exploring complex modularization of intracellular signal transduction pathways is critical to understanding aberrant cellular responses during disease development and drug treatment. IMPALA (Inferred Modularization of PAthway LAndscapes) integrates information from high throughput gene expression experiments and genome-scale knowledge databases to identify aberrant pathway modules, thereby providing a powerful sampling strategy to reconstruct and explore pathway landscapes. Here IMPALA identifies pathway modules associated with breast cancer recurrence and Tamoxifen resistance.

Cerina: systematic circRNA functional annotation based on integrative analysis of ceRNA interactions.

Circular RNAs, a family of covalently circularized RNAs with tissue-specific expression, were recently demonstrated to play important roles in mammalian biology. Regardless of extensive research to predict, quantify, and annotate circRNAs, our understanding of their functions is still in its infancy. In this study, we developed a novel computational tool: Competing Endogenous RNA for INtegrative Annotations (Cerina), to predict biological functions of circRNAs based on the competing endogenous RNA model.

Occurrence and distribution of PAHs and microbial communities in nearshore sediments of the Knysna Estuary, South Africa.

This study investigated the polycyclic aromatic hydrocarbons (PAHs) occurrence, and their impact on the microbial community and PAH-degrading genera and genes in the Knysna Estuary of South Africa. The results reveal that the estuary exhibits low PAH levels (114.1-356.

Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation.

Background: Eosinophils and mast cells are key effectors of allergy. When they accumulate in the esophagus, their myoactive, pro-inflammatory, and cytotoxic products potentially could cause achalasia-like motility abnormalities and neuronal degeneration. We hypothesized that there is an allergy-mediated form of achalasia.