Data_Sheet_1_How has the COVID-19 pandemic affected young people?—Mapping knowledge structure and research framework by scientometric analysis.ZIP

Since the outbreak of COVID-19, there has been a large body of literature focusing on the relationship between the COVID-19 pandemic and young people. The purpose of this study is to explore the current research status and the specific mechanism of COVID-19's effects on young people based on related literature. This paper mainly used VOS viewer and CiteSpace software to conduct a scientometric analysis of 5,077 publications retrieved from the Web of Science database. The results show that the main contributors to the field were mainly from North America and Europe, and the trend of research focus was from shallow to deep. The five main research areas in the field were summarized by keyword clustering analysis as follows: lifestyle changes due to lockdown; changes in stress and emotions; psychological illness and trauma; risk perception and practice toward the epidemic; interventions and social support. Finally, they were linked by four pathways to form a framework that integrates the relationships between the five domains and between elements within each of them, revealing the mechanism of COVID-19's effect on young people. In addition, less studied but promising elements are also presented in the framework, such as research on special groups (disadvantaged socioeconomic groups and sexual minority youth) and extreme suicidal tendencies that deserve our further attention.</p

Discrete Element Simulation of Gas–Solid and Gas–Liquid–Solid Flows

Multiphase flow (i.e., gas–solid flow and gas–liquid–solid flow) extensively exists in industries, yet the strong coupling between different phases poses challenges in the discrete element method (DEM)-based model establishment. This work developed a fully coupled framework by combining computational fluid dynamics (CFD) with DEM, with the further extension to incorporate volume-of-fluid (VOF) to study multiphase flow systems. A smoothing method is implemented to allow the grid size to be close to or smaller than the diameter of the particles, benefiting the subsequent interphase and interfacial interactions calculation. Iso-Advector, an advanced VOF-based surface-capturing method, is further introduced to describe interface evolution and interfacial interactions effectively. The integrated model is verified in three benchmark cases, i.e., a quasi-two-dimensional spouted bed, a fully three-dimensional spout-fluid bed, and a dam-break flow. The numerical results agree well with experimental measurements, confirming the model’s reliability in simulating multiphase flow systems

Synthesis of New Branched 2‑Nitroimidazole as a Hypoxia Sensitive Linker for Ligand-Targeted Drugs of Paclitaxel

Because of the low selectivity and efficiency of normal antitumor agents, the strategy of ligand-targeted drugs was put forward. In this paper, we designed and synthesized a new bioreductive linker based on 2-nitroimidazole, which was used in three paclitaxel (PTX) prodrugs. The drug release mechanism via six-membered ring was demonstrated by chemical reduction and nitroreductase assay. Glucose and acetazolamide, which have been reported widely as ligands, were attached to compound <b>7</b> to afford Glu-PTX and AZO-PTX. The prodrugs were considerably stable in phosphate-buffered saline (pH 7.4) and plasma. What is more, PTX releasing could be triggered by nitroreductase rapidly. In in vitro cytotoxicity assay, the prodrugs exhibited moderate selectivity toward hypoxic tumor cells. We considered that the 2-nitroimidazole linker could accelerate the release of prodrugs under hypoxic condition. It was promising in the development of ligand-targeted drugs

Synthesis and Biological Evaluation of Paclitaxel and Camptothecin Prodrugs on the Basis of 2‑Nitroimidazole

Due to the low esterase activity in human plasma, many ester and carbonate prodrugs tested in humans may be less effective than that in preclinical animals. In this letter, PTX and SN-38 were attached to the <i>N</i>-1 position of 2-nitroimidazole via a carbonate linker. Presumably, 2-aminoimidazole may help promote the intramolecular hydrolysis of the carbonate bond. The prodrugs exhibited a considerable stability in buffers at different pH values as well as in human plasma. Furthermore, a rapid reduction was exhibited in the presence of nitroreductase. An <i>in vitro</i> cytotoxicity assay demonstrated that hypoxic conditions could increase the toxicity of prodrugs. Potentially, the compound species may form a new class of promising antitumor agents

MOESM1 of Improved methanol-derived lovastatin production through enhancement of the biosynthetic pathway and intracellular lovastatin efflux in methylotrophic yeast

Additional file 1. Additional figures and tables

Reduction-Triggered Release of CPT from Acid-Degradable Polymeric Prodrug Micelles Bearing Boronate Ester Bonds with Enhanced Cellular Uptake

The aim of this research is to develop a novel type of camptothecin (CPT) prodrug micelles bearing boronate ester bonds as a smart nanosystem with enhanced cellular uptake and controlled drug release based on diblock copolymer abbreviated as PEG-BC-PGlu-ss-CPT. Particularly, boronate ester bond was introduced to achieve acid-triggered de-PEGylation and succeeding boronic acid-mediated enhanced cellular uptake. Besides, CPT was conjugated to the prodrug monomer through a disulfide bond to realize reduction-responsive drug release. The resultant copolymer PEG-BC-PGlu-ss-CPT could self-assemble into spherical nanomicelles in water. The degradation half-life time of PEG-BC-PGlu-ss-CPT copolymer decreased sharply from 96.27 h to only 5.7 h with pH value decreasing from 7.4 to 5.0, indicating the acid-degradable potential, which corresponded to size change monitoring. The cumulative CPT release from prodrug micelles increased significantly from 8.5 ± 1.73 to 82.9 ± 2.29% with an increase of dithiothreitol (DTT) concentration from 20 μM to 10 mM at pH 7.4, illustrating the reduction-responsive drug release property of prodrug micelles. The half maximal inhibitory concentration (IC₅₀) value of prodrug micelles against HepG2 cells decreased from 1.06 to 0.68 μg/mL with the decrement of pH value from 7.4 to 6.0, proving that the utilization of boronate ester bonds was beneficial for enhancing antiproliferative activity. Interestingly, prodrug micelles exhibited enhanced cellular uptake ability against HepG2 cells compared to that of HL7702 cells, further confirming boronic acid-mediated enhanced endocytosis. In brief, this novel type of intelligent prodrug micelles possessed great potential as a smart nanosystem for antitumor drug delivery

Video_1_Danhong Injection Reversed Cardiac Abnormality in Brain–Heart Syndrome via Local and Remote β-Adrenergic Receptor Signaling.mp4

<p>Ischemic brain injury impacts cardiac dysfunction depending on the part of the brain affected, with a manifestation of irregular blood pressure, arrhythmia, and heart failure. Generally called brain–heart syndrome in traditional Chinese medicine, few mechanistic understanding and treatment options are available at present. We hypothesize that considering the established efficacy for both ischemic stroke and myocardial infarction (MI), Danhong injection (DHI), a multicomponent Chinese patent medicine, may have a dual pharmacological potential for treating the brain–heart syndrome caused by cerebral ischemic stroke through its multi-targeted mechanisms. We investigated the role of DHI in the setting of brain–heart syndrome and determined the mechanism by which it regulates this process. We induced Ischemia/Reperfusion in Wistar rats and administered intravenous dose of DHI twice daily for 14 days. We assessed the neurological state, infarct volume, CT scan, arterial blood pressure, heart rhythm, and the hemodynamics. We harvested the brain and heart tissues for immunohistochemistry and western blot analyses. Our data show that DHI exerts potent anti-stroke effects (infarct volume reduction: ^∗∗p < 0.01 and ^∗∗∗p < 0.001 vs. vehicle. Neurological deficit correction: ^∗p < 0.05 and ^∗∗∗p < 0.001 vs. vehicle), and effectively reversed the abnormal arterial pressure (^∗p < 0.05 vs. vehicle) and heart rhythm (^∗∗p < 0.01 vs. vehicle). The phenotype of this brain–heart syndrome is strikingly similar to those of MI model. Quantitative assessment of hemodynamic in cardiac functionality revealed a positive uniformity in the PV-loop after administration with DHI and valsartan in the latter. Immunohistochemistry and western blot results showed the inhibitory effect of DHI on the β-adrenergic pathway as well as protein kinase C epsilon (PKCε) (^∗∗p < 0.01 vs. model). Our data showed the underlying mechanisms of the brain–heart interaction and offer the first evidence that DHI targets the adrenergic pathway to modulate cardiac function in the setting of brain–heart syndrome. This study has made a novel discovery for proper application of the multi-target DHI and could serve as a therapeutic option in the setting of brain–heart syndrome.</p