Roadmap on Perovskite Light-Emitting Diodes

In recent years, the field of metal-halide perovskite emitters has rapidly emerged as a new community in solid-state lighting. Their exceptional optoelectronic properties have contributed to the rapid rise in external quantum efficiencies (EQEs) in perovskite light-emitting diodes (PeLEDs) from <1% (in 2014) to approaching 30% (in 2023) across a wide range of wavelengths. However, several challenges still hinder their commercialization, including the relatively low EQEs of blue/white devices, limited EQEs in large-area devices, poor device stability, as well as the toxicity of the easily accessible lead components and the solvents used in the synthesis and processing of PeLEDs. This roadmap addresses the current and future challenges in PeLEDs across fundamental and applied research areas, by sharing the community's perspectives. This work will provide the field with practical guidelines to advance PeLED development and facilitate more rapid commercialization.Comment: 103 pages, 29 figures. This is the version of the article before peer review or editing, as submitted by an author to Journal of Physics: Photonics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Coronavirus disease 2019 epidemic prediction in Shanghai under the “dynamic zero-COVID policy” using time-dependent SEAIQR model

It’s urgently needed to assess the COVID-19 epidemic under the “dynamic zero-COVID policy” in China, which provides a scientific basis for evaluating the effectiveness of this strategy in COVID-19 control. Here, we developed a time-dependent susceptible-exposed-asymptomatic-infected-quarantined-removed (SEAIQR) model with stage-specific interventions based on recent Shanghai epidemic data, considering a large number of asymptomatic infectious, the changing parameters, and control procedures. The data collected from March 1st, 2022 to April 15th, 2022 were used to fit the model, and the data of subsequent 7 days and 14 days were used to evaluate the model performance of forecasting. We then calculated the effective regeneration number (Rt) and analyzed the sensitivity of different measures scenarios. Asymptomatic infectious accounts for the vast majority of the outbreaks in Shanghai, and Pudong is the district with the most positive cases. The peak of newly confirmed cases and newly asymptomatic infectious predicted by the SEAIQR model would appear on April 13th, 2022, with 1963 and 28,502 cases, respectively, and zero community transmission may be achieved in early to mid-May. The prediction errors for newly confirmed cases were considered to be reasonable, and newly asymptomatic infectious were considered to be good between April 16th to 22nd and reasonable between April 16th to 29th. The final ranges of cumulative confirmed cases and cumulative asymptomatic infectious predicted in this round of the epidemic were 26,477 ∼ 47,749 and 402,254 ∼ 730,176, respectively. At the beginning of the outbreak, Rt was 6.69. Since the implementation of comprehensive control, Rt showed a gradual downward trend, dropping to below 1.0 on April 15th, 2022. With the early implementation of control measures and the improvement of quarantine rate, recovery rate, and immunity threshold, the peak number of infections will continue to decrease, whereas the earlier the control is implemented, the earlier the turning point of the epidemic will arrive. The proposed time-dependent SEAIQR dynamic model fits and forecasts the epidemic well, which can provide a reference for decision making of the “dynamic zero-COVID policy”

circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3

Abstract Background Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa. Methods circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients’ clinical and biological information. Results CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038–0.723; P = 0.017). Conclusions This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy

Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucose-induced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A2B siRNA. The expression of the adenosine A2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2

The stack of ¹³C NMR spectra of WS010117 and its four metabolites (in DMSO-d₆).

<p>The stack of ¹³C NMR spectra of WS010117 and its four metabolites (in DMSO-d₆).</p

Structure Elucidation of the Metabolites of 2', 3', 5'-Tri-<i>O</i>-Acetyl-<i>N</i>₆-(3-Hydroxyphenyl) Adenosine in Rat Urine by HPLC-DAD, ESI-MS and Off-Line Microprobe NMR

<div><p>2', 3', 5'-tri-<i>O</i>-acetyl-<i>N₆</i>-(3-hydroxyphenyl) adenosine (also known as WS070117) is a new adenosine analog that displays anti-hyperlipidemic activity both <i>in vitro</i> and <i>in vivo</i> experiments as shown in many preliminary studies. Due to its new structure, little is known about the metabolism of WS070117. Hence, the <i>in vivo</i> metabolites of WS070117 in rat urine following oral administration were investigated. Identification of the metabolites was conducted using the combination of high-performance liquid chromatography (HPLC) coupled with diode array detector (DAD), ion trap electrospray ionization-mass spectrometry (ESI-MS), and off-line microprobe nuclear magnetic resonance (NMR) measurements. Seven metabolites were obtained as pure compounds at the sub-milligram to milligram levels. Results of structure elucidation unambiguously revealed that the phase I metabolite, <i>N₆</i>-(3-hydroxyphenyl) adenosine (M8), was a hydrolysate of WS070117 by hydrolysis on the three ester groups. <i>N₆</i>-(3-hydr-oxyphenyl) adenine (M7), also one of the phase I metabolites, was the derivative of M8 by the loss of ribofuranose. In addition to two phase I metabolites, there were five phase II metabolites of WS070117 found in rat urine. 8-hydroxy-<i>N₆</i>-(3-hydroxy-phenyl) adenosine (M6) was the product of M7 by hydrolysis at position 8. The other four were elucidated to be <i>N₆</i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenine (M2), <i>N₈</i>-hydroxy-<i>N₆</i>-(3-<i>O</i>-sulfophenyl) adenine (M3), <i>N₆</i>-(3-<i>O-β</i>-D-glucuronyphenyl) adenosine (M4), and <i>N₆</i>-(3-<i>O</i>- sulfophenyl) adenosine (M5). Phase II metabolic pathways were proven to consist of hydroxylation, glucuronidation and sulfation. This study provides new and valuable information on the metabolism of WS070117, and also demonstrates the HPLC/MS/off-line microprobe NMR approach as a robust means for rapid identification of metabolites.</p></div

The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.

<p>The retention time, predicted elemental compositions, observed mass and calculated mass, characteristic fragment ions, and description of metabolites of WS070117 in rat urine.</p

Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.

<p>Structures of WS070117 metabolites in rat urine and the proposed metabolic pathways.</p