Single-cell transcriptomic analysis reveals characteristic feature of macrophage reprogramming in liver Mallory-Denk bodies pathogenesis.

Chronic liver diseases are highly linked with mitochondrial dysfunction and macrophage infiltration. Mallory-Denk bodies (MDBs) are protein aggregates associated with hepatic inflammation, and MDBs pathogenesis could be induced in mice by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Here, we investigate the macrophage heterogeneity and the role of macrophage during MDBs pathogenesis on DDC-induced MDBs mouse model by single-nucleus RNA sequencing (snRNA-seq).

A pan-genome perspective on the evolutionary dynamics of polyphyly, virulence, and antibiotic resistance in serovar Mbandaka highlights emerging threats to public health and food safety posed by cloud gene families.

serovar Mbandaka, a prevalent foodborne pathogen, poses a threat to public health but remains poorly understood. We have determined the phylogenomic tree, genetic diversity, virulence, and antimicrobial resistance (AMR) profiles on a large genomic scale to elucidate the evolutionary dynamics within the Mbandaka pan-genome. The polyphyletic nature of this serovar is characterized by two distinct phylogenetic groups and inter-serovar recombination boundaries, that potentially arising from recombination events at the H2-antigen loci.

Capture primed pluripotency in guinea pig.

Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency.

The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells.

The nuclear matrix, a proteinaceous gel composed of proteins and RNA, is an important nuclear structure that supports chromatin architecture, but its role in human pluripotent stem cells (hPSCs) has not been described. Here we show that by disrupting heterogeneous nuclear ribonucleoprotein U (HNRNPU) or the nuclear matrix protein, Matrin-3, primed hPSCs adopted features of the naive pluripotent state, including morphology and upregulation of naive-specific marker genes. We demonstrate that HNRNPU depletion leads to increased chromatin accessibility, reduced DNA contacts and increased nuclear size.

[Application value of surface respiratory muscle electromyography and its ratio to tidal volume in the assessment of airway hyperresponsiveness in bronchial asthma patients].

To explore the application value of surface respiratory muscle electromyography and its ratio to tidal volume in the assessment of airway hyperresponsiveness in bronchial asthma patients. A case-control study was conducted to retrospectively analyze the data of 29 asthma patients who visited the outpatient department of respiratory medicine of the First Affiliated Hospital of Guangzhou Medical University from October 2015 to May 2017 and 27 non-asthmatic subjects who were recruited as the control group.Changes in surface respiratory muscle electromyography (parasternal, EMG, diaphragmatic, EMG), and its ratio to tidal volume (EMG/VT, EMG/VT) before and after the histamine challenge test were compared between the asthma group and the control group; and their receiver operating characteristic (ROC) curves were plotted.

[Influence of Methylenetetrahydrofolate Reductase Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients].

Objective: To investigate the effect of genetic polymorphism of (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients.

Methods: Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included, and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed.

Results: Among the 58 pediatric patients, the number of CC, CT, and TT genotypes for was 33, 19 and 6, respectively.

Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression.

Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation.

Pan-cancer analysis of the potential of PEA3 subfamily genes as tumor markers.

Polyomavirus enhancer activator 3 (PEA3), an ETS transcription factor, has been documented to regulate the development and metastasis of human cancers. Nonetheless, a thorough analysis examining the relationship between the PEA3 subfamily members and tumour development, prognosis, and the tumour microenvironment (TME) across various cancer types has not yet been conducted. The expression profiles and prognostic significance of the PEA3 subfamily were evaluated using data from the GEO, TCGA, and PrognoScan databases, in conjunction with COX regression analyses and the Kaplan-Meier Plotter.

BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation.

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells).

Biocompatible, biodegradable, and anticancer alginate-quercetin ureteral stent via co-axial extrusion technique.

Ureteral stents (US) are used as interventional medical implants in the treatment and surgery of urinary tract infections (UTIs). This study reported a new formulation of alginate-quercetin (AQ) based US through a co-axial extrusion procedure for the first time to afford a 26 cm long US with 3.2×1.

The impact of gut microbiota in full-term pregnant women on immune regulation during pregnancy: A prospective, exploratory study.

Aim: This study aims to investigate the correlation between gut microbiota and both placental local immune function and the maternal systemic immune system in pregnant women.

Methods: Twenty-six pregnant women were included in this study, utilizing high-throughput sequencing for gut microbiota analysis. Immune cells and cytokine levels were measured in placental tissue and peripheral venous blood.

Lycorine protects motor neurons against TDP-43 proteinopathy-induced degeneration in cross-species models with amyotrophic lateral sclerosis.

Aggregation of TAR-DNA binding protein-43 (TDP-43) is a pathological feature present in nearly 97 % cases of amyotrophic lateral sclerosis (ALS), making it an attractive target for pathogenic studies and drug screening. Here, we have performed a high-throughput screening of 1500 compounds from a natural product library and identified that lycorine, a naturally occurring alkaloid, significantly decreases the level of TDP-43 in a cellular model. We further demonstrate that lycorine reduces the level of TDP-43 both through inhibiting its synthesis and by promoting its degradation by the ubiquitin-proteasome system (UPS).

Tropism of adeno-associated virus serotypes in mouse lungs via intratracheal instillation.

Background: Gene therapy holds great potential for treating various acquired and inherited pulmonary diseases. Adeno-associated viral (AAV) vectors have been thought to be primary candidates for gene delivery in patients with pulmonary diseases. However, the tropism of AAVs in the lungs remains largely unknown.

AHR suppresses cisplatin-induced apoptosis in ovarian cancer cells by regulating XIAP.

X-linked inhibitor of apoptosis protein (XIAP) plays a crucial role in cisplatin-induced apoptosis in ovarian cancer, whereas the molecular mechanism of how its expression is dysregulated remains unclear. Here, we report that the aryl hydrocarbon receptor (AHR) acts as a competitive endogenous RNA (ceRNA) of XIAP and can regulate its expression. Overexpression of AHR 3'UTR decreased, while AHR knockdown increased, the cisplatin-induced apoptotic rate in ovarian cancer cells.

Targeting METTL3 as a checkpoint to enhance T cells for tumour immunotherapy.

Background: Immunotherapy has emerged as a crucial treatment modality for solid tumours, yet tumours often evade immune surveillance. There is an imperative to uncover novel immune regulators that can boost tumour immunogenicity and increase the efficacy of immune checkpoint blockade (ICB) therapy. Epigenetic regulators play critical roles in tumour microenvironment remodelling, and N6-methyladenosine (mA) is known to be involved in tumourigenesis.

Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms.

Induced pluripotent stem cells (iPSCs) technology holds great potential in both scientific research and clinical applications. It enables the generation of naïve and primed iPSCs from various cell types through different strategies. Despite extensive characterizations of transcriptional and epigenetic factors, the intricacies of chromatin landscape dynamics during naïve and primed reprogramming, particularly in humans, remain poorly understood.

Nodularin-R Synergistically Enhances Abiraterone Against Castrate- Resistant Prostate Cancer via PPP1CA Inhibition.

Clinically, most prostate cancer (PCa) patients inevitably progress to castration-resistant prostate cancer (CRPC) with poor prognosis after androgen deprivation therapy (ADT), including abiraterone, the drug of choice for ADT. Therefore, it is necessary to explore the resistance mechanism of abiraterone in depth. Genome-wide CRISPR/Cas9 knockout technology was used to screen CRPC cell line 22Rv1 for abiraterone-resistant genes.

Biomechanical impact of progressive meniscal extrusion on the knee joint: a finite element analysis.

Background: While measuring meniscal extrusion quantitatively is an early risk factor for knee osteoarthritis (KOA), the biomechanics involved in this process are not well understood. This study aimed to investigate the effects of varying degrees of medial and lateral meniscal extrusion and their material softening on knee osteoarthritis progression.

Methods: Finite element analysis (FEA) was utilized to simulate varying degrees of meniscal extrusion (1-5 mm) in 72 knee joint models, representing progressive meniscal degeneration and material softening due to injury.

Low-intensity pulsed ultrasound promotes cell viability of hUSCs in volumetric bioprinting scaffolds via PI3K/Akt and ERK1/2 pathways.

The study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) on human urinary-derived stem cells (hUSCs) viability within three-dimensional (3D) cell-laden gelatin methacryloyl (GelMA) scaffolds. hUSCs were integrated into GelMA bio-inks at concentrations ranging from 2.5% to 10% w/v and then bioprinted using a volumetic-based method.

Can hypoxic exercise retard cellular senescence? A narrative review.

Background: Senescent cells are defined as normal cells that have undergone irreversible division arrest due to various factors. These cells have been found to play a pivotal role in aging and the development of chronic diseases. Numerous studies demonstrated that physical exercise is effective in anti-aging and anti-chronic diseases.

Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression.

Cervical cancer (CC) is the most common cancer in women. This study aims to explore the molecular mechanism of lactate secreted by CC cells modulating macrophage polarization in CC via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical squamous cell carcinoma (CESC) were collected to assess H3K18la level and macrophage infiltration.

Advancements in Targeting Macrophage Senescence for Age-Associated Conditions.

Macrophages, a critical subset of innate immune cells, play a pivotal role in cytokine production during disease progression, tissue injury, and pathogen invasion. Their intricate involvement in the manifestation of chronic low-grade inflammation associated with the aging process is widely acknowledged. Notably, in aged tissues, macrophages exhibit an altered phenotype characterized by an augmented synthesis of pro-inflammatory cytokines and chemokines, a profile intimately associated with a phenomenon known as inflammaging.