TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer.

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan-Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial-mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer.

Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions.

Atenolol, a cardioselective ß1-blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single-center, randomized, open, single-dose, 2-preparation, 2-cycle, 2-sequence, double-crossover trial with a 7-day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty-eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration-time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration-time profiles for both formulations were similar, and Cmax, AUC0-t, and AUC0-∞ were within the BE range of 80%-125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development.

Identification of crucial anoikis-related genes as novel biomarkers and potential therapeutic targets for lung adenocarcinoma via bioinformatic analysis and experimental verification.

Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasis. The aim of this study was to develop an anoikis-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for LUAD. Through differentially expressed analysis, univariate Cox, LASSO Cox regression, and random forest algorithm analysis, we established a 4 anoikis-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of LUAD patients in the TCGA and GEO databases, respectively. The low and high-risk score LUAD patients stratified by the model showed different tumor mutation burden, tumor microenvironment, gemcitabine sensitivity and immune checkpoint expressions. Through immunohistochemical analysis of clinical LUAD samples, we found that the 4 anoikis-related genes (PLK1, SLC2A1, ANGPTL4, CDKN3) were highly expressed in the tumor samples from clinical LUAD patients, and knockdown of these genes in LUAD cells by transfection with small interfering RNAs significantly inhibited LUAD cell proliferation and migration, and promoted anoikis. In conclusion, we developed an anoikis-based stratified model and a multivariable-based nomogram of LUAD, which could predict the survival of LUAD patients and guide clinical treatment.

Magnetically controlled nanorobots induced oriented and rapid clearance of the cytokine storm for acute lung injury therapy.

Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe3O4 nanoparticles (Fe3O4NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe3O4NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.

Ephrin-A4 Ligand (EFNA4) Predicts Poor Prognosis of Hepatocellular Carcinoma and Promotes Tumor Proliferation.

Background/Aims: Primary hepatocellular carcinoma (HCC) is one of the most lethal tumor diseases in the world. Receptor tyrosine kinases (RTKs) are thought to play a vital role in HCC and Ephrin-A4 ligand (EFNA4) is a membrane-bound molecule that can activate RTKs through erythropoietin-producing hepatocellular (Eph) receptors. However, the specific role of EFNA4 remains unknown. The aim of our study was to explore the prognostic value of EFNA4 expression in HCC. Methods: Bioinformatics analyses were conducted to probe the expression levels and prognostic value of EFNA4 in HCC. The quantitative real-time polymerase chain reaction, immunohistochemical and western blot were used to confirm the expression of EFNA4 in paired clinical specimens of HCC. Colony formation assay was used to confirm the proliferation of tumor cell. Results: The expression of EFNA4 is generally elevated in various cancers. Especially, EFNA4 was upregulated in tumor tissue and associated with clinical stage in HCC patients. HCC patients with lower levels of EFNA4 possessed better survival and progression-free survival times. Colony formation assay indicated that the overexpression of EFNA4 promoted tumor cell proliferation. Conclusion: These results demonstrated that EFNA4 played as an oncogenic gene and a prognostic biomarker for HCC patients.

Study on the migration characteristics of bioaerosols and optimization of ventilation patterns in a negative pressure isolation ward considering different patient postures.

Due to the serious global harm caused by the outbreak of various viral infectious diseases, how to improve indoor air quality and contain the spread of infectious bioaerosols has become a popular research subject. Negative pressure isolation ward is a key place to prevent the spread of aerosol particles. However, there is still limited knowledge available regarding airflow patterns and bioaerosol diffusion behavior in the ward, which is not conducive to reducing the risk of cross-infection between health care workers (HCWs) and patients. In addition, ventilation layout and patient posture have important effects on aerosol distribution. In this study, the spatial and temporal characteristics as well as dispersion patterns of bioaerosols under different ventilation patterns in the ward were investigated using the computational fluid dynamics (CFD) technique. It is concluded that changes in the location of droplet release source due to different body positions of the patient have a significant effect on the bioaerosol distribution. After optimizing the layout arrangements of exhaust air, the aerosol concentration in the ward with the patient in both supine and sitting positions is significantly reduced with particle removal efficiencies exceeding 95%, that is, the ventilation performance is improved. Meanwhile, the proportion of aerosol deposition on all surfaces of the ward is decreased, especially the deposition on both the patient's body and the bed is less than 1%, implying that the risk of HCWs being infected through direct contact is reduced.

Pharmacokinetic and Bioequivalence Evaluation of Two Cefprozil Dispersible Tablets in Healthy Chinese Volunteers.

This study aimed to assess the bioequivalence of 2 cefprozil dispersible tablet formulations (250 mg) in healthy Chinese volunteers under fasting and fed conditions and to determine the pharmacokinetics of cefprozil. A randomized, single-dose, open-label, 2-formulation, 2-period study was conducted. The elimination period for this study was 7 days. Forty-eight healthy volunteers received 250-mg cefprozil dispersible tablets in each study period under both test and reference conditions. The test and the reference cefprozil were bioequivalent in healthy Chinese volunteers, and there was no significant food effect in individuals receiving either formulation. No serious adverse event was recorded, and no volunteers withdrew from the study.

Bibliometric Analysis of Exercise and Chronic Obstructive Pulmonary Disease.

Background: Chronic Obstructive Pulmonary Disease (COPD) is the leading cause of death in the world. Pulmonary rehabilitation includes, but is not limited to, exercise training and education, which aim to improve the physical and psychological conditions of patients with chronic respiratory diseases through self-management interventions. Objective: The aim of this study was to perform a bibliometric analysis of studies on exercise and COPD published from 2000 to 2021 using VOSviewer and CiteSpace. Methods: All included literature was obtained from the Web of Science core collection. VOSviewer was used to analyze country or region, institution, major co-cited journals, and keywords. CiteSpace was used to analyze centrality, author and co-cited authors, journals, the strongest citation bursts of references, and keywords. Results: A total of 1889 articles meeting the criteria were obtained. The United States has the largest number of publications. The American Journal of Respiratory and Critical Care Medicine is the most influential in this field, and the most published research institution is Queen's University. Denis E. O'Donnell has made significant contributions to exercise and COPD research. Association, impact, and statement are hot spots of research in this field. Conclusion: A bibliometric analysis of exercise interventions for COPD over the past 22 years provides direction for future research.

Cell Membrane-Camouflaged Nanoparticles Mediated Nucleic Acids Delivery.

Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery.

A bibliometric analysis of COVID-19 and physical activity.

BACKGROUND: Due to the huge impact of coronavirus disease 2019 (COVID-19) on a global scale, the level of physical activity during confinement has become a widespread concern. This study summarizes the development of performance and research trends in COVID-19 and physical activity over the last 3 years. METHODS: Research publications on COVID-19 and physical activity in the past 3 years were downloaded from the Web of Science database. CiteSpace and VOSviewer software were used to analyze the authors, published outputs, journals, cited authors, countries and institutions, co-cited journals, cited references, and keywords. Statistical and centrality analyses were used to identify the active authors, core journals, basic references, hot topics, and cutting-edge fields. RESULTS: A total of 1331 papers was retrieved. SMITH L was a prolific author in the field of exercise intervention in COVID-19 with 11 publications. International Journal of Environmental Research and Public Health was the most productive journal (179 publications) and the most cited journal (1324). The most productive countries and institutions in this field were the USA (322 publications) and Harvard Medical School (21 publications). The four hot keywords in COVID-19 and physical activity research were physical activity, exercise, health, and mental health. CONCLUSIONS: This study provides researchers with directions to intervene in changing levels of physical activity during the COVID-19 pandemic and valuable information for researchers in the field of sports medicine to identify potential collaborators, collaborating institutions, hot issues, and research frontiers.