Nanolasers with an ultracompact footprint can provide high-intensity coherent light, which can be potentially applied to high-capacity signal processing, biosensing, and subwavelength imaging. Among various nanolasers, those with cavities surrounded by metals have been shown to have superior light emission properties because of the surface plasmon effect that provides enhanced field confinement capability and enables exotic light-matter interaction. In this study, we demonstrated a robust ultraviolet ZnO nanolaser that can operate at room temperature by using silver to dramatically shrink the mode volume. The nanolaser shows several distinct features including an extremely small mode volume, a large Purcell factor, and a slow group velocity, which ensures strong interaction with the exciton in the nanowire.
The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand ("active targeting") is superior to its unlabeled counterpart ("passive targeting"). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8 + T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.
BackgroundThe development and growth of children influence values of liver function tests. This study aims to establish age- and gender-specific pediatric reference intervals of liver function among Han children in Changchun, China.MethodsA total of 1394 healthy Han children, aged 2–14 years, were recruited from communities and schools with informed parental consent in Changchun. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), total bilirubin (TBIL) and direct bilirubin (DBIL) were measured on Hitachi 7600-210 automatic biochemical analyzer. The age- and gender-specific reference intervals were partitioned using Harris and Boyd’s test and calculated using nonparametric rank method. The pediatric reference intervals were validated in five representative hospitals located in different areas in Changchun.ResultsAll the analytes required some levels of age partitioning. Proteins (TP, ALB) and bilirubins (TBIL, DBIL) required no gender partitioning. In contrast, considerable gender partitioning was required for serum ALT, AST, GGT, and ALP. TP, TBIL, and DBIL showed steady increases, and AST showed apparent decreases over time, whereas ALT, GGT, ALP, and ALB demonstrated complex trends of change. ALT and GGT increased sharply in males from 11 to 14 years old. However, ALP declined in females from 13 to 14 years. All five laboratories passed the validation of reference intervals.ConclusionsThere were apparent age or gender variations of the reference intervals for liver function. When establishing pediatric reference intervals, partitioning according to age and gender is necessary.
Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction.
Background: Current evidence about the cardiovascular safety of glucagon-like peptide-1 receptor agonist (GLP-1ra) possesses limited generalizability to real-world patients with type 2 diabetes (T2D) in usual practice. This study aimed to investigate the comparative cardiovascular safety of GLP-1ra in comparisons with dipeptidyl peptidase-4 inhibitor (DPP-4i), sulfonylurea (SU), and insulin in a real-world population with T2D. Methods: Adults with newly-diagnosed T2D were identified from Taiwan's National Health Insurance Research Database in 2003-2014. A prevalent new-user cohort design was adopted to include a broad representation of realworld T2D patients being treated with GLP-1ra. The between-group comparability of baseline patient characteristics was achieved by matching on (1) initiation time of study drugs, (2) prior exposure to glucose-lowering agents, and (3) diabetes severity and complications, comorbidities, and concomitant cardiovascular medications using propensity scores. The primary outcome was a composite of cardiovascular disease (CVD) events and assessed up to the end of 2015. Cox modeling was employed to assess the association between study drugs and outcomes. Results: A total of 3195 GLP-1ra stable users was identified in 2011-2014. 1893, 1829, and 1367 GLP-1ra stable users were 1:1 matched to DPP-4i, SU and insulin users, respectively. Compared to DPP-4i, SU and insulin, the use of GLP-1ra was associated with a lower risk of composite CVD events [hazard ratio (95% confidence interval) 0.73 (0.57-0.96), 0.76 (0.57-1.00), and 0.81 (0.62-1.07), respectively]. Subgroup analyses revealed that GLP-1ra versus DPP-4i yielded a greater cardiovascular benefit in those without established CVD versus those with established CVD. Conclusions: This comparison study extends the supporting evidence for the cardiovascular safety of GLP-1ra to a broad spectrum of real-world T2D patients using GLP-1ra.
Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. In vitro assays indicate that lesinurad is an inducer of CYPs in the order CYP3A > CYP2C8 > CYP2C9 > CYP2C19 > CYP2B6 and an inhibitor of CYP2C8 and CYP2C9. To investigate the drug interaction potential of lesinurad, clinical drug interaction studies were conducted. Open-label studies in volunteers investigated the effects of single-/multiple-dose lesinurad on the pharmacokinetics of sildenafil and amlodipine (CYP3A4 induction), tolbutamide (CYP2C9 inhibition/induction), and repaglinide (CYP2C8 inhibition/induction). There was no apparent induction of CYP2C8 and CYP2C9 following repeated lesinurad administration, although no inhibition of CYP2C9 and modest inhibition of CYP2C8 were observed following single-dose lesinurad. Consistent with in vitro observations, lesinurad (200 mg once daily) was an inducer of CYP3A based on the effects on sildenafil exposure. Sildenafil exposure decreased by approximately 34% for C and AUC when administered with multiple-dose lesinurad 200 mg and allopurinol 300 mg, relative to sildenafil alone. During lesinurad therapy, the possibility of reduced efficacy of concomitant drugs that are CYP3A substrates should be considered and their efficacy monitored because of induction of CYP3A by lesinurad.
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