Rationale And Objectives: Inflammation and immune biomarkers can promote angiogenesis and proliferation and metastasis of esophageal squamous cell carcinoma (ESCC). The degree of pathological grade reflects the tumor heterogeneity of ESCC. The purpose is to develop and validate a nomogram based on enhanced CT multidimensional radiomics combined with inflammatory immune score (IIS) for predicting poorly differentiated ESCC.
View Article and Find Full Text PDFBackground: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.
Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.
Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.
Methods: Patients with ischemic stroke presenting 4.
Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.
Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.
To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging.
View Article and Find Full Text PDFAging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis.
View Article and Find Full Text PDFThe effect of calcium (Ca)-cadmium (Cd) interactions on the plant Cd bioaccumulation process may be closely related to the ecological Ca/Cd stoichiometry in the substrate. However, owing to the complexity of plant absorption, accumulation mechanisms and influencing factors, the mechanism of Ca-mediated Cd bioaccumulation and Cd tolerance in Capsicum is still unclear. In this study, the bioaccumulation, subcellular distribution and chemical forms of Cd in Capsicum were analysed via pot experiments to reveal the Ca-mediated Cd bioaccumulation process and its detoxification mechanism under different Ca/Cd stoichiometric ratios.
View Article and Find Full Text PDF: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). : This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18-49 years.
View Article and Find Full Text PDFBackground: Although the concept of the intrarenal renin-angiotensin system (RAS) in renal disease is well-described in the literature, the precise pathogenic role and mechanism of this local system have not been directly assessed in the absence of confounding influence from the systemic RAS. The present study used novel mouse models of collecting duct (CD)-specific deletion of (pro)renin receptor (PRR) or renin together with pharmacological inhibition of soluble PRR production to unravel the precise contribution of the intrarenal RAS to renal injury induced by unilateral ureteral obstruction.
Methods: We examined the impact of CD-specific deletion of PRR, CD-specific deletion of renin, and S1P (site-1 protease) inhibitor PF429242 treatment on renal fibrosis and inflammation and the indices of the intrarenal RAS in a mouse model of unilateral ureteral obstruction.
Background: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques.
Methods: This was a prospective, single-center, randomized, double-blind clinical trial.
In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness.
View Article and Find Full Text PDFObjectives: To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model.
Methods: The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model.
Many growth factors and cytokines signal by binding to the extracellular domains of their receptors and driving association and transphosphorylation of the receptor intracellular tyrosine kinase domains, initiating downstream signaling cascades. To enable systematic exploration of how receptor valency and geometry affect signaling outcomes, we designed cyclic homo-oligomers with up to 8 subunits using repeat protein building blocks that can be modularly extended. By incorporating a de novo-designed fibroblast growth factor receptor (FGFR)-binding module into these scaffolds, we generated a series of synthetic signaling ligands that exhibit potent valency- and geometry-dependent Ca release and mitogen-activated protein kinase (MAPK) pathway activation.
View Article and Find Full Text PDFBackground: Diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) are two completely different pathologic subtypes of lymphoma with distinctly different clinical presentations and treatment options. Thus, accurately differentiating between the two subtypes has important clinical implications. This study aimed to construct a radiomics model capable of distinguishing between DLBCL and HL based on enhanced computed tomography (CT) for the non-invasive diagnosis of lymphoma subtypes.
View Article and Find Full Text PDFBackground: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain.
Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group).
Introduction: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation (CC).
Methods: This single-blinded, randomized, controlled, and multicenter study was conducted from July 2021 to December 2022 at 7 hospitals.
We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and H/C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states.
View Article and Find Full Text PDFMethadone is cleared predominately by hepatic cytochrome P450 (CYP) 2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interactions.
View Article and Find Full Text PDFLight Sci Appl
November 2023
Low-dimensional materials exhibit unique quantum confinement effects and morphologies as a result of their nanoscale size in one or more dimensions, making them exhibit distinctive physical properties compared to bulk counterparts. Among all low-dimensional materials, due to their atomic level thickness, two-dimensional materials possess extremely large shape anisotropy and consequently are speculated to have large optically anisotropic absorption. In this work, we demonstrate an optoelectronic device based on the combination of two-dimensional material and carbon dot with wide bandgap.
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