Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.

Vascular remodeling is a complex process involving the coordinated actions of multiple cellular signaling pathways in various cell types, leading to structural and functional changes in blood vessels. These changes can be adaptive, as in wound healing, or maladaptive, as seen in chronic vascular diseases such as atherosclerosis, hypertension, and retinopathy. Exchange proteins directly activated by cAMP (EPACs) are key players in cAMP-mediated cell signaling, distinct from the more traditionally studied protein kinase A pathway.

Clinical performance of a genotyping assay based on a hybrid capture technique in cervical cancer screening in China: a prospective population-based multicentre cohort study.

Objectives: We aimed to assess the clinical performance of DH3, a hybrid capture assay that separately detects human papillomavirus (HPV) 16/18 and 12 other HPV types, for primary screening for cervical cancer in the general population, following Chinese guidelines.

Methods: A total of 9379 eligible women aged 21 to 64 years from three centres underwent baseline screening with DH3 and liquid-based cytology (LBC), and were subsequently followed for 3 years. The diagnostic performance of HPV testing (DH3) and LBC-including sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value-was evaluated for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions.

A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC).

A Nomogram for Predicting Cancer-Specific Survival in Patients With Stage I Vulvar Squamous Cell Carcinoma: A Study Based on the SEER Database and External Validation.

IntroductionVulvar squamous cell carcinoma (VSCC) is a rare but increasingly prevalent gynecological malignancy. This study aimed to identify risk factors for stage I VSCC, which accounts for approximately 70% of VSCC patients, and to develop a nomogram to predict cancer-specific survival (CSS) for this large subgroup.MethodsThis study analyzed the datasets consisting of public training and independent external validation sets of patients diagnosed with stage I VSCC between 2010 and 2019.

Biomechanical evaluation of the triangular support structure of the proximal femoral bionic nail compared to conventional long intramedullary nails for subtrochanteric fractures.

Purpose: The aim of this study was to compare the biomechanical results of long proximal femoral bionic nail (PFBN) and three conventional intramedullary nails in the treatment of subtrochanteric fractures (STFs).

Methods: Using finite element analysis, we compared the therapeutic efficacy of four long intramedullary nails: the PFBN, reconstruction nail (RCN), InterTAN nail (ITN), and proximal femoral nail antirotation (PFNA) for the treatment of Seinsheimer type IIIA and type V STFs. The biomechanical stability of the implants was evaluated by calculating of von Mises stress (VMS), contact pressure and displacement for three loading scenarios.

Efficacy of 5-aminolevulinic acid photodynamic therapy versus observation for cervical low-grade squamous intraepithelial lesion with type 3 transformation zone.

Background: The treatment for patients with cervical low-grade squamous intraepithelial lesion (LSIL) and type 3 transformation zone (TZ) had limitations. The aim of this study was to compare the efficacy of new approach 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and observation in those patients.

Methods: This study retrospectively analyzed data from 236 patients (aged 25-45 years) with cervical LSIL and type 3 TZ.

Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study.

Objective: The concept of constitution in traditional Chinese medicine (TCM) has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia. However, rigorous statistical evidence on the correlation between TCM constitutions-particularly mixed constitutions-and insomnia disorder remains limited. This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.

Structural basis for the substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase.

Helix pomatia AMP deaminase (HPAMPD), an enzyme enriched in the foot muscle of the mollusk H. pomatia, exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is the first member of the adenosine deaminase-related growth factor (ADGF) family to prefer the nucleotide AMP over the nucleoside adenosine.

Multi-analyte approach combining cfDNA sequencing and protein testing for early ovarian cancer detection.

Non-invasive liquid biopsy is a promising strategy for ovarian cancer (OC) detection. We evaluated the feasibility and efficacy of a multi-analyte approach combining circulating tumor DNA (ctDNA) detection with protein biomarkers for early OC detection. At 95% specificity, CA125 and ctDNA alone exhibited an overall sensitivity of 79.

Development and Validation of an Anoikis-Related Gene Signature for Prognostic Prediction in Cervical Cancer.

Background: Cervical cancer still has high incidence and mortality rates worldwide. This study aimed to evaluate the prognostic value of anoikis-related genes (ARGs) and develop a risk scoring model for accurate survival prediction in cervical cancer patients.

Methods: The expression profiles of cervical cancer tissue and survival data were downloaded from TCGA-CESC and CGCI-HTMCP-CC.

GSK-3484862, a DNMT1 degrader, promotes expression in lung cancer cells.

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics.

A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO-interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/nucleoporin 358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex.

Multifaceted roles of Epac signaling in renal functions.

3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli. cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance. Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys.

The biomarker potential of circPOLD1 and its binding protein YBX1 in cervical carcinogenesis.

Background: Cervical cancer progresses through distinct precancerous stages, making early screening and intervention crucial for prevention. However, conventional screening modalities, such as cytology and HPV testing, face challenges related to sensitivity, specificity, and resource dependency. Circular RNAs (circRNAs), owing to their high stability and tissue-specific expression, have emerged as promising biomarkers, though their role in cervical carcinogenesis remains underexplored.

Effect of Tai Chi Softball on Health-Related Outcomes in Elderly Men.

This study aimed to investigate the effects of Tai Chi Softball (TCSB) training on the physical health of older men, with a focus on improvements in muscle strength, flexibility, balance, and blood lipid profiles. A 12-week randomized controlled trial was conducted, recruiting 140 men aged 55-65 years. Participants were randomly assigned to either a Tai Chi Softball group (TCSBG,  = 70) or a control group (CG,  = 70).

Research landscape and trends of internet addiction disorder: A comprehensive bibliometric analysis of publications in the past 20 years.

Background: Internet addiction disorder (IAD) has emerged as a significant public health concern in the digital age, with implications for mental health and social wellbeing. Despite growing recognition, IAD remains a relatively nascent field within academic research.

Methods: We conducted a comprehensive bibliometric analysis to explore the global research landscape and trends of IAD.

Multimeric transcription factor BCL11A utilizes two zinc-finger tandem arrays to bind clustered short sequence motifs.

BCL11A, a transcription factor, is vital for hematopoiesis, including B and T cell maturation and the fetal-to-adult hemoglobin switch. Mutations in BCL11A are linked to neurodevelopmental disorders. BCL11A contains two DNA-binding zinc-finger arrays, low-affinity ZF2-3 and high-affinity ZF4-6, separated by a 300-amino-acid linker.

Digitally Assisted Single-Particle Tracking for Accurate Analysis of Complicated Cargo Transport Dynamics in Microtubule Networks.

Intracellular transport is a fundamental process crucial for cellular function, driven by the coordinated action of motor proteins that move cargo along microtubule tracks. Traditional tracking methods primarily focus on cargo trajectories, often overlooking rotational dynamics and their impact on cargo interactions with the complex microtubule network. To address this limitation, we introduced a digitally assisted single-particle tracking (dSPT) method that significantly advances the angular resolution of intracellular cargo dynamics.

Structural basis of substrate specificity of AMP deaminase and a chimeric ADGF adenosine deaminase.

HPAMPD, an enzyme enriched in the foot muscle of the mollusk , exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is the first member of the adenosine deaminase-related growth factor (ADGF) family to prefer the nucleotide, AMP, over the nucleoside, adenosine. To investigate the substrate selectivity of HPAMPD, we determined its structure in the apo form and in complex with the adenosine analogs pentostatin (2'-deoxycoformycin) and pentostatin-5'-monophosphate.

KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB.

Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits.

SWI/SNF complex-mediated ZNF410 cooperative binding maintains chromatin accessibility and enhancer activity.

The clustering of multiple transcription factor binding sites (TFBSs) for the same TF has proved to be a pervasive feature of cis-regulatory elements in the eukaryotic genome. However, the contribution of binding sites within the homotypic clusters of TFBSs (HCTs) to TF binding and target gene expression remains to be understood. Here, we characterize the CHD4 enhancers that harbor unique functional ZNF410 HCTs genome wide.