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.

Clinicopathologic stratification demonstrates survival differences between endometrial carcinomas with mismatch repair deficiency and no specific molecular profile: a cohort study.

Objective: Endometrial carcinomas with mismatch repair deficiency (MMRd) and no specific molecular profile (NSMP) are considered to have intermediate prognoses. However, potential prognostic differences between these molecular subgroups remain unclear due to the lack of standardized control for clinicopathologic factors. This study aims to evaluate outcomes of MMRd and NSMP endometrial carcinomas across guideline-based clinicopathologic risk groups.

Liquid biopsy for diagnosing epithelial ovarian cancer: quantification of cell-free DNA and p53 mutational analysis.

Objective: To isolate and quantify cell-free DNA, analysis for p53 mutations, and correlation with tumor burden in women with epithelial ovarian cancer compared with benign and borderline epithelial ovarian tumors.

Methods: In this case-control study, plasma samples of eligible women collected 1 hour before surgery and based on final histopathology, women with epithelial ovarian cancer recruited as cases and borderline, and benign ovarian tumors as controls. Cell-free DNA extracted from plasma serum and quantified using Nanodrop Spectrophotometer.

Genomic Footprints of Hybridisation in North Atlantic Eels (Anguilla anguilla and A. rostrata).

Understanding interspecific introgressive hybridisation and the biological significance of introgressed variation remains an important goal in population genomics. European (Anguilla anguilla) and American eel (A. rostrata) represent a remarkable case of hybridisation.

Cell-Free Systems to Mimic and Expand Metabolism.

Cell-free synthetic biology incorporates purified components and/or crude cell extracts to carry out metabolic and genetic programs. While protein synthesis has historically been the primary focus, more metabolism researchers are now turning toward cell-free systems either to prototype pathways for cellular implementation or to design new-to-nature reaction networks that incorporate environmentally relevant substrates or new energy sources. The ability to design, build, and test enzyme combinations has accelerated efforts to understand metabolic bottlenecks and engineer high-yielding pathways.

Measuring XNA polymerase fidelity in a hydrogel particle format.

Growth in the development of engineered polymerases for synthetic biology has led to renewed interest in assays that can measure the fidelity of polymerases that are capable of synthesizing artificial genetic polymers (XNAs). Conventional approaches require purifying the XNA intermediate of a replication cycle (DNA → XNA → DNA) by denaturing polyacrylamide gel electrophoresis, which is a slow, costly, and inefficient process that requires a large-scale transcription reaction and careful extraction of the XNA strand from the gel slice. In an effort to streamline the assay, we developed a purification-free approach in which the XNA transcription and reverse transcription steps occur inside the matrix of a hydrogel-coated magnetic particle.

Telomemore enables single-cell analysis of cell cycle and chromatin condensation.

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites.

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.

Influenza A virus NS2 protein acts on vRNA-resident polymerase to drive the transcription to replication switch.

The heterotrimeric RNA-dependent RNA polymerase (RdRp) of influenza A virus catalyzes viral RNA transcription (vRNA→mRNA) and replication (vRNA→cRNA→vRNA) by adopting different conformations. A switch from transcription to replication occurs at a relatively late stage of infection. We recently reported that the viral NS2 protein, expressed at later stages from a spliced transcript of the NS segment messenger RNA (mRNA), inhibits transcription, promotes replication and plays a key role in the transcription-to-replication switch.

A novel ADP-directed chaperone function facilitates the ATP-driven motor activity of SARS-CoV helicase.

Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability.

Histidine Tags in Human Recombinant Alpha B-Crystallin (HSPB5) Proteins Are Detrimental for Zinc Binding Studies.

The stability of α-crystallin, the major protein of the mammalian eye lens and a molecular chaperone, is one of the most crucial factors for its survival and function. The chaperone-like activity and stability of α-crystallin dramatically increased in the presence of Zn. Each subunit of α-crystallin could bind multiple zinc atoms through inter-subunit bridging and cause enhanced stability.

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.

Endocrine alterations in patients with pachydermoperiostosis.

Context: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO) usually due to biallelic loss-of-function variants in HPGD and SLCO2A1, has some features overlapping with acromegaly and often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.

Objective: To assess the genetic and endocrine characteristics of PHO patients referred to endocrine centres with a possible diagnosis of acromegaly.

Microbial surveillance versus cytokine responsiveness in native and non-native house sparrows.

The success of introduced species often relies on flexible traits, including immune system traits. While theories predict non-natives will have weak defences due to decreased parasite pressure, effective parasite surveillance remains crucial, as infection risk is rarely zero and the evolutionary novelty of infection is elevated in non-native areas. This study examines the relationship between parasite surveillance and cytokine responsiveness in native and non-native house sparrows, hypothesizing that non-natives maintain high pathogen surveillance while avoiding costly inflammation.

Limiting cap-dependent translation increases 20S proteasomal degradation and protects the proteomic integrity in autophagy-deficient skeletal muscle.

Postmitotic skeletal muscle critically depends on tightly regulated protein degradation to maintain proteomic stability. Impaired macroautophagy/autophagy-lysosomal or ubiquitin-proteasomal protein degradation causes the accumulation of damaged proteins, ultimately accelerating muscle dysfunction with age. While studies have demonstrated the complementary nature of these systems, their interplay at the organism levels remains poorly understood.

Precision Medicine in Colorectal Cancer: Targeted Therapies and Biomarker Insights.

The current review delves into the transformative role of precision medicine in addressing Colorectal Cancer [CRC], a pressing global health challenge. It examines closely signalling pathways, genetic and epigenetic modifications, and microsatellite in-stability. The primary focus is on elucidating biomarkers revolutionizing CRC diagnosis and treatment.

Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N-acetyltransferase 2 genetic polymorphism.

Objective: Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N-hydroxylation via CYP1A2 followed by O-acetylation via N-acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.

Labor onset and delivery mode in women with congenital heart disease-A nationwide cohort study.

Introduction: More women with congenital heart disease (CHD) are pursuing pregnancy. Their cardiac condition may impact the pregnancy and necessitate interventions during childbirth. We aimed to investigate labor onset and delivery mode in women with CHD relative to women without heart disease and explore the time trends of induced labor and cesarean deliveries.

IGF2BP3 is upregulated in endometrial cancer and tightly regulates the growth of drug-resistant endometrial cancer cells via HMGA1.

Objective: Endometrial cancer (EC) is a malignant tumor with various histological subtypes and molecular phenotypes. The evaluation of drug resistance is important for cancer treatment. Progesterone resistance is the major challenge in EC.

Nuclear blebs are associated with destabilized chromatin packing domains.

Disrupted nuclear shape is associated with multiple pathological processes including premature aging disorders, cancer-relevant chromosomal rearrangements, and DNA damage. Nuclear blebs (i.e.

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.

Comprehensive Hematological and molecular Characterization of hemoglobin Hekinan [α27(B8)Glu→Asp(α1), :c.84G > T] in a Large Thai cohort.

Background: Hemoglobin (Hb) Hekinan is a prevalent α-globin variant frequently missed in thalassemia screening centers using high-performance liquid chromatography (HPLC) or capillary electrophoresis. This study aims to investigate the hematological and molecular characteristics of Hb Hekinan in a large cohort.

Methods: Hb variants were identified using isoelectric focusing (IEF) and HPLC.

PP2A Attenuates Thoracic Aneurysm and Dissection in Mouse Models of Marfan Syndrome.

Background: Recent studies show that hyperactivation of mTOR (mammalian target of rapamycin) signaling plays a causal role in the development of thoracic aortic aneurysm and dissection. Modulation of PP2A (protein phosphatase 2A) activity has been shown to be of significant therapeutic value. In light of the effects that PP2A can exert on the mTOR pathway, we hypothesized that PP2A activation by small-molecule activators of PP2A could mitigate AA progression in Marfan syndrome (MFS).