MftG is crucial for ethanol metabolism of mycobacteria by linking mycofactocin oxidation to respiration.

Mycofactocin is a redox cofactor essential for the alcohol metabolism of mycobacteria. While the biosynthesis of mycofactocin is well established, the gene , which encodes an oxidoreductase of the glucose-methanol-choline superfamily, remained functionally uncharacterized. Here, we show that MftG enzymes are almost exclusively found in genomes containing mycofactocin biosynthetic genes and are present in 75% of organisms harboring these genes.

Trends in the incidence and mutational landscape of advanced uterine cancer.

Objective: The aim of this study was to examine disparities in 20-year incidence trends and mutations in advanced-stage uterine cancer in the United States, given poor survival rates.

Methods: Data were obtained from the United States Cancer Statistics for patients from 2001 to 2019 with International Federation of Gynecology and Obstetrics 2009 stage IVA and IVB uterine cancer. SEER∗Stat 8.

Basket study of oral progesterone antagonist onapristone extended-release in combination with anastrozole in progesterone receptor-positive recurrent adult-type granulosa cell tumor of the ovary.

Objective: We sought to determine the safety and efficacy of the oral progesterone antagonist onapristone in combination with anastrozole in patients with recurrent progesterone receptor-positive adult-type granulosa cell tumor of the ovary.

Methods: This was a single-institution phase II study of patients with progesterone receptor-positive adult-type granulosa cell tumor who received at least 1 prior line of chemotherapy. Patients were enrolled from November 2021 to August 2022 and tissue was evaluated for progesterone receptor status via immunohistochemistry.

An evolved, orthogonal ssDNA generator for targeted hypermutation of multiple genomic loci.

Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.

WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals.

Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice and cells, both of which exhibited dramatic mitochondrial changes.

Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear.

Clearing the path for whole-mount labeling and quantification of neuron- and vessel-density in adipose tissue.

White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works indicated that WAT responds to environmental cues by adapting the abundance of these "communication routes", however, high intra-tissue heterogeneity questions the informative value of bulk or single cell analyses and underscores the necessity of whole-mount imaging.

Expression and function of Connexin 43 and Connexin 37 in the murine zona glomerulosa.

The zona glomerulosa (ZG) synthesizes the mineralocorticoid aldosterone. The primary role of aldosterone is the maintenance of volume and electrolyte homeostasis. Aldosterone synthesis is primarily regulated via tightly controlled oscillations in intracellular calcium levels in response to stimulation.

The effects of growth hormone on the outcomes of fertilization and embryo transfer in age-grouped patients with decreased ovarian reserve: a prospective cohort study.

Background: Growth hormone (GH) could improve the outcomes of fertilization and embryo transfer (IVF-ET) in patients with decreased ovarian reserve (DOR), but which age group will benefit the most has remained controversial. This study aims to explore the outcome of IVF-ET among differently aged patients with DOR treated with GH.

Methods: A total of 846 patients with DOR undergoing IVF-ET from May 2018 to June 2023 at the Reproductive Medicine Center of Sichuan Provincial Women's and Children's Hospital were prospectively enrolled.

Genetic association analysis of lipid-lowering drug target genes in chronic kidney disease.

Objective: The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject of debate. This Mendelian randomization (MR) study aims to elucidate the potential effects of lipid-lowering drug targets on CKD development.

Methods: We extracted 11 genetic variants encoding targets of lipid-lowering drugs from published genome-wide association study (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA.

Naxos Disease and Related Cardio-Cutaneous Syndromes.

Naxos disease is a rare autosomal recessive condition combining arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. The first identified causative variant was in the gene encoding the desmosomal protein plakoglobin. Naxos disease exhibits fibro-fatty myocardial replacement with immunohistological abnormalities in cardiac protein and signaling pathways, highlighting the role of inflammation and potential anti-inflammatory treatments.

Analysis of thyroid autoantibodies and the risk of insulin depletion after the clinical onset of acute-onset type 1 diabetes in Japanese patients: the TIDE-J study.

Introduction: Type 1 diabetes is often accompanied by autoimmune thyroid disease. We aimed to investigate the clinical characteristics of Japanese patients with acute-onset type 1 diabetes and thyroid autoantibodies, focusing on decreased endogenous insulin secretion.

Materials And Methods: We examined 80 patients with acute-onset type 1 diabetes, classifying them into two groups with and without thyroid autoantibodies and compared the clinical characteristics of the two groups.

Case report: The case of T-cell acute lymphoblastic leukemia treated with chemotherapy followed by anti-CD7 CAR-T cells using retroviral vector.

CD7-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL). In this study, we reported a case of a 34-year-old male patient with T-ALL who finally developed multi-line drug resistance and refractoriness after multiple lines of high-intensity chemotherapy. After physician evaluation, this patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Transcriptional signature of CD56 NK cells predicts favourable prognosis in bladder cancer.

Human natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56 and CD56 NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56 and CD56 NK cells along with 3 stromal and 18 other immune cell types in the patient tumour transcriptomes from the cancer genome atlas bladder cancer dataset (TCGA-BLCA). Using this computational approach, CD56 NK cells were predicted to be the more abundant tumour-infiltrating NK subset which was also associated with improved patient prognosis.

Upregulation of interferon-γ response genes in monocytes and T cells identified by single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis.

Introduction: Our aim was to investigate the insufficiently understood differences in the immune system between anti-citrullinated peptide antibody (ACPA)-positive (ACPA) and ACPA-negative (ACPA) early rheumatoid arthritis (eRA) patients.

Methods: We performed multiple cytokine assays using sera from drug-naïve ACPA and ACPA eRA patients. Additionally, we conducted single-cell RNA sequencing of CD45 cells from peripheral blood samples to analyze and compare the distribution and functional characteristics of the cell subsets based on the ACPA status.

Epigenetic profiling for prognostic stratification and personalized therapy in breast cancer.

Background: The rising incidence of breast cancer and its heterogeneity necessitate precise tools for predicting patient prognosis and tailoring personalized treatments. Epigenetic changes play a critical role in breast cancer progression and therapy responses, providing a foundation for prognostic model development.

Methods: We developed the Machine Learning-derived Epigenetic Model (MLEM) to identify prognostic epigenetic gene patterns in breast cancer.

Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells.

Background And Purpose: Understanding the cellular and molecular effect of proton radiation, particularly the increased DNA damage complexity at the distal end of the Bragg curve, is current topic of investigation. This work aims to study clonogenic survival and DNA damage foci kinetics of a head and neck squamous cell carcinoma cell line at various positions along a double passively scattered Bragg curve. Complementary studies are conducted to gain insights into the link between cell survival variations, experimentally yielded foci and the number and complexity of double strand breaks (DSBs).

Regional brain iron correlates with transcriptional and cellular signatures in Alzheimer's disease.

Introduction: The link between overload brain iron and transcriptional/cellular signatures in Alzheimer's disease (AD) remains inconclusive.

Methods: Iron deposition in 41 cortical and subcortical regions of 30 AD patients and 26 healthy controls (HCs) was measured using quantitative susceptibility mapping (QSM). The expression of 15,633 genes was estimated in the same regions using transcriptomic data from the Allen Human Brain Atlas (AHBA).

c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.

Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency.

Germline BRCA testing in Denmark following invasive breast cancer: Progress since 2000.

Background And Purpose: Despite advancements in genetic testing and expanded eligibility criteria, underutilisation of germline testing for pathogenic variants in BRCA1 and BRCA2 (BRCA) remains evident among breast cancer (BC) patients. This observational cohort study presents real-world data on BRCA testing within the context of clinical practice challenges, including incomplete family history and under-referral.

Material And Methods: From the Danish Breast Cancer Group (DBCG) clinical database, we included 65,117 females with unilateral stage I-III BC diagnosed in 2000-2017, of whom 9,125 (14%) were BRCA tested.

Advancement of Heart Transplantation in Thai Recipients: Survival Trends and Pharmacogenetic Insights.

Since 1987, King Chulalongkorn Memorial Hospital (KCMH) has performed a substantial number of heart transplants as a specific therapy for advanced-stage heart failure. This descriptive study aimed to analyze post-transplant survival in the recent era compared to earlier periods and examine the pharmacogenetics of related immunosuppressants. Data from all recipients who underwent heart transplants from 1987 to 2021 were retrospectively retrieved from the electronic medical record.

Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).