A cross-species assessment of in silico prediction methods of steady-state volume of distribution using Simcyp Simulators.

Predicting steady-state volume of distribution (V) is a key component of pharmacokinetic predictions and often guided using preclinical data. However, when bottom-up prediction from physiologically-based pharmacokinetic (PBPK) models and observed V misalign in preclinical species, or predicted V from different models varies significantly, no consensus exists for selecting models or preclinical species to improve the prediction. Through systematic analysis of V prediction across rat, dog, monkey, and human, using common methods, a practical strategy for predicting human V, with or without integration of preclinical PK information is warranted.

Integrating machine learning, bioinformatics and experimental verification to identify a novel prognostic marker associated with tumor immune microenvironment in head and neck squamous carcinoma.

Head and neck squamous carcinoma (HNSC), characterized by a high degree of malignancy, develops in close association with the tumor immune microenvironment (TIME). Therefore, identifying effective targets related to HNSC and TIME is of paramount importance. Here, we employed the ESTIMATE algorithm to compute immune and stromal cell scores for HNSC samples from the TCGA database and identified differentially expressed genes (DEGs) based on these scores.

Sialidase NEU3 silencing inhibits angiogenesis of EA.hy926 cells by regulating Wnt/β-catenin signaling pathway.

Angiogenesis significantly drives tumor progression, and the functions of vascular endothelial cells are influenced by various factors. Tumor cells are characterized by abnormal sialylation, and their dynamic balance depends on sialyltransferases and sialidases. NEU3 is a plasma membrane-associated sialidase, vital for the regulation of cell surface sialylation.

Prognostic model based on centrosome-related genes constructed in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor in the epithelium of the head and neck. The role of the centrosome in malignant tumors is crucial. However, research on the centrosome in HNSCC remains largely unexplored.

Discovery of potent dihydro-oxazinoquinolinone inhibitors of GuaB for the treatment of tuberculosis.

Tuberculosis is the leading cause of death from an infectious disease, and is caused by Mycobacterium tuberculosis (M.tb). More than 1 billion people worldwide are thought to harbor an M.

TMEM232 is required for the formation of sperm flagellum and male fertility in mice.

Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes.

Experiences With mHealth Use Among Patient-Caregiver Dyads With Chronic Heart Failure: Qualitative Study.

Background: Chronic heart failure has become a serious threat to the health of the global population, and self-management is key to treating chronic heart failure. The emergence of mobile health (mHealth) provides new ideas for the self-management of chronic heart failure in which the informal caregiver plays an important role. Current research has mainly studied the experiences with using mHealth among patients with chronic heart failure from the perspective of individual patients, and there is a lack of research from the dichotomous perspective.

Induction of interleukin-6 by SPZ1-mediated Wnt5a signaling boosts progression of nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southeast Asia, and in the Guangxi and Guangdong provinces of China. The spermatogenic transcription factor zip 1 (SPZ1) is a member of bHLH zip family, and promotes tumorigenesis in the liver, colon and breast tissues. However, the role of SPZ1 in the progression of NPC is unclear.

Preoperative visit-care for transcatheter aortic valve replacement: a review.

Aim: The aim of this review is to evaluate and summarize the evidence for preoperative visit-care of transcatheter aortic valve replacement (TAVR) and to provide evidence-based support for clinical intervention.

Design: The review presents an evidence summary report, following the standard of the Fudan University Center for Evidence-based Nursing.

Methods: Literature related to preoperative visit-care for transcatheter aortic valve replacement have been retrieved based on the "6S" pyramid model of evidence.

Developing and Validating of the Family Coping Scale for Patients with Chronic Heart Failure.

Background: : Family coping, as an essential part of family management of patients with chronic heart failure (CHF), is an important component of CHF interventions, affecting the health of patients, family members, and the whole family. It is necessary to understand the current situation of family coping in patients with CHF to facilitate the development of family interventions for patients with CHF. This study aims to develop and validate a tool for assessing the family coping scale for patients with CHF.

Barriers and facilitators of the nurse providing evidence-based preoperative visit-care for transcatheter aortic valve replacement: a mixed-methods study based on an evidence application setting.

Background: Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary.

Discovery of GuaB inhibitors with efficacy against infection.

Unlabelled: Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial.

Spatial Pattern of Living Woody and Coarse Woody Debris in Warm-Temperate Broad-Leaved Secondary Forest in North China.

The investigation into the spatial distribution of living woody (LWD) and coarse woody debris (CWD) within forests represents a fundamental methodology for probing the inherent mechanisms governing coexistence and mortality within forest ecosystems. Here, a complete spatial randomness (CSR) null model was employed to scrutinize the spatial pattern, while canonical correspondence analysis (CCA) and the Torus-translation test (TTT) were utilized to elucidate the distribution patterns of LWD and CWD within warm-temperate deciduous broadleaf secondary forests in Dongling Mountains plot, northern China. The results reveal that both LWD and CWD exhibit an aggregated distribution as the predominant pattern in the Dongling Mountains plot, with the proportion and intensity of aggregation diminishing as spatial scale increases.

Promoting γ-aminobutyric acid accumulation to enhances saline-alkali tolerance in tomato.

Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamate decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.

Reinvigoration of cytotoxic T lymphocytes in microsatellite instability-high colon adenocarcinoma through lysosomal degradation of PD-L1.

Compensation and intracellular storage of PD-L1 may compromise the efficacy of antibody drugs targeting the conformational blockade of PD1/PD-L1 on the cell surface. Alternative therapies aiming to reduce the overall cellular abundance of PD-L1 thus might overcome resistance to conventional immune checkpoint blockade. Here we show by bioinformatics analysis that colon adenocarcinoma (COAD) with high microsatellite instability (MSI-H) presents the most promising potential for this therapeutic intervention, and that overall PD-L1 abundance could be controlled via HSC70-mediated lysosomal degradation.

The Sweet Relationship between the Endometrium and Protein Glycosylation.

The endometrium is an important part of women's bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity.

Integrating Dynamic in vitro Systems and Mechanistic Absorption Modeling: Case Study of Pralsetinib.

Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V.