The broadband emission of Cr3+-doped CaY2Mg2Ge3O12 and its applications for NIR detectors.

A phosphor-converted light-emitting diode (pc-LED) is a prime light source in smart broadband near-infrared (NIR) spectroscopy. The performance of NIR pc-LEDs crucially depends on the employed NIR luminescent materials. In this study, we synthesized a novel high-efficiency broadband NIR phosphor, CaY2Mg2Ge3O12:Cr3+ (CYMG:Cr3+). Under 450 nm excitation, CYMG:Cr3+ exhibited remarkable broadband NIR emission from 650 to 900 nm with a full width at half maximum (FWHM) of 115 nm. Within the CYMG lattice, the Cr3+ ion occupies Ca/Y sites in the dodecahedron Ca/YO8 and Mg sites in the octahedron MgO6, giving rise to two distinct Cr3+ luminescence centers. Remarkably, the emission at 100 °C remained at 92% of its room temperature intensity and 81% at 150 °C, showcasing its exceptional thermal stability. The internal quantum efficiency (IQE) reached an impressive 81.1%, with an activation energy ΔE of 0.324 eV. Furthermore, we integrated the CYMG:Cr3+ phosphor with a commercial 450 nm blue chip to fabricate a micro NIR pc-LED, which exhibited stable NIR emission across different driving currents, with a NIR output power of 49.65 mW@400 mA and a photoelectric conversion efficiency of 10.52% at 20 mA. All findings highlight CYMG:Cr3+ as a stable and efficient broadband luminescent material for high-performance NIR LEDs.

Machine learning modeling and prognostic value analysis of invasion-related genes in cutaneous melanoma.

In this study, we aimed to develop an invasion-related risk signature and prognostic model for personalized treatment and prognosis prediction in skin cutaneous melanoma (SKCM), as invasion plays a crucial role in this disease. We identified 124 differentially expressed invasion-associated genes (DE-IAGs) and selected 20 prognostic genes (TTYH3, NME1, ORC1, PLK1, MYO10, SPINT1, NUPR1, SERPINE2, HLA-DQB2, METTL7B, TIMP1, NOX4, DBI, ARL15, APOBEC3G, ARRB2, DRAM1, RNF213, C14orf28, and CPEB3) using Cox and LASSO regression to establish a risk score. Gene expression was validated through single-cell sequencing, protein expression, and transcriptome analysis. Negative correlations were discovered between risk score, immune score, and stromal score using ESTIMATE and CIBERSORT algorithms. High- and low-risk groups exhibited significant differences in immune cell infiltration and checkpoint molecule expression. The 20 prognostic genes effectively differentiated between SKCM and normal samples (AUCs >0.7). We identified 234 drugs targeting 6 genes from the DGIdb database. Our study provides potential biomarkers and a risk signature for personalized treatment and prognosis prediction in SKCM patients. We developed a nomogram and machine-learning prognostic model to predict 1-, 3-, and 5-year overall survival (OS) using risk signature and clinical factors. The best model, Extra Trees Classifier (AUC = 0.88), was derived from pycaret's comparison of 15 classifiers. The pipeline and app are accessible at https://github.com/EnyuY/IAGs-in-SKCM.

The Impact of Household Debt on the Health of the Elderly in China: Evidence from China Family Panel Studies.

With the aging of China's population and the expansion of household debt, the health of the elderly has become an important social issue. Based on the 2018 China Family Panel Studies (CFPS) database, we explored the impact of household debt on the health of older adults and the mechanism of transmission. The Oprobit and IV-Oprobit models were employed for our analysis. Results: (1) Household debt had a significant negative impact on both the physical and mental health of older adults. (2) Female older adults were more sensitive to the impact of household debt. Additionally, a higher education level led to an increasing impact of debt on mental health, but physical health was only affected in the low-education group. (3) The impact of household debt had an inverted U-shape relationship with household income, indicating that, as household income increases, the impact on health level first rises and then reduces after peaking at a middling level of income. (4) According to the mechanism analysis, household debt affects the health of the elderly by causing them to return to work and reducing their medical expenditures. Considering the above conclusions, we put forward some policy implications to alleviate the health problems of the elderly.

Enhanced Photoluminescence of Gd3Al4GaO12: Cr3+ by Energy Transfers from Co-Doped Dy3.

LEDs for plant lighting have attracted wide attention and phosphors with good stability and deep-red emission are urgently needed. Novel Cr3+ and Dy3+ co-doped Gd3Al4GaO12 garnet (GAGG) phosphors were successfully prepared through a conventional solid-state reaction. Using blue LEDs, a broadband deep-red emission at 650−850 nm was obtained due to the Cr3+ 4T2 → 4A2 transition. When the Cr3+ concentration was fixed to 0.1 mol, the crystal structure did not change with an increase in the Dy3+ doping concentration. The luminous intensity of the optimized GAGG:0.1Cr3+, 0.01Dy3+ was 1.4 times that of the single-doped GAGG:0.1Cr3+. Due to the energy transfer from Dy3+ to Cr3+, the internal quantum efficiency reached 86.7%. The energy transfer from Dy3+ to Cr3+ can be demonstrated through luminescence spectra and fluorescence decay. The excellent properties of the synthesized phosphor indicate promising applications in the agricultural industry.

A solution for the rational dispatching of concrete transport vehicles.

The amount of concrete needed in the construction of projects is enormous. The concrete dispatching in construction is, however, chaotic and causes grievous waste due to the tight construction schedule, heavy tasks, and improper transport vehicle dispatching by the constructor. This paper proposes a more realistic objective function in the vehicle dispatching algorithm and offers a solution to the rational dispatching of concrete transport vehicles. The analysis of the calculation example validates the feasibility of the built model, which provides more appropriate dispatching and more balanced distribution, meets the needs of the worksite and mixing station to the greatest extent and improves the level of project refinement and process management. Therefore, the model is worth promoting in future practice.

Discovery of Novel cccDNA Reducers toward the Cure of Hepatitis B Virus Infection.

Chronic hepatitis B virus (HBV) infection is a worldwide disease that causes thousands of deaths per year. Currently, there is no therapeutic that can completely cure already infected HBV patients due to the inability of humans to eliminate covalently closed circular DNA (cccDNA), which serves as the template to (re)initiate an infection even after prolonged viral suppression. Through phenotypic screening, we discovered xanthone series hits as novel HBV cccDNA reducers, and subsequent structure optimization led to the identification of a lead compound with improved antiviral activity and pharmacokinetic profiles. A representative compound 59 demonstrated good potency and oral bioavailability with no cellular toxicity. In an HBVcircle mouse model, compound 59 showed excellent efficacy in significantly reducing HBV antigens, DNA, and intrahepatic cccDNA levels.

The Nonlinear Influence of Environmental Regulation on the Transformation and Upgrading of Industrial Structure.

This paper measures the transformation and upgrading of industrial structure from two aspects of rationalization and upgrading of industrial structure, and empirically analyzes the impact of environmental regulation on industrial structure transformation and upgrading by using data of 29 provinces in China from 2004 to 2015. It was found that there is a significant nonlinear effect between environmental regulation and the transformation and upgrading of industrial structure. Specifically, environmental regulation is not conducive to the rational development of industrial structure, but with the continuous improvement of economic development level and human capital level, the inhibitory effect of environmental regulation on the rationalization of industrial structure is gradually weakened. The influence coefficient of environmental regulation on the rationalization of industrial structure is 0.0619~0.2648. Moreover, environmental regulation effectively drives the upgrading of industrial structure, and when the level of economic development and human capital are higher than the threshold, the role of environmental regulation in promoting the high development of industrial structure is gradually enhanced. The influence coefficient of environmental regulation on the upgrading of industrial structure is 0.0540~0.5626. Therefore, it is of great significance to formulate appropriate environmental regulation policies according to local conditions in the transformation and upgrading of industrial structure.

Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.

Aldosterone synthase (CYP11B2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (MR) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (CNS). A benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones CYP11B2 inhibitors. Our systematic structure-activity relationship study enabled us to identify unique structural features that result in high selectivity against the closely homologous cortisol synthase (CYP11B1). We evaluated advanced lead molecules, exemplified by compound 52, in an in vivo cynomolgus monkey acute adrenocorticotropic hormone (ACTH) challenge model and demonstrated a superior 100-fold in vivo selectivity against CYP11B1.

Strategies to approach high performance in Cr3+-doped phosphors for high-power NIR-LED light sources.

Broadband near-infrared (NIR)-emitting phosphors are key for next-generation smart NIR light sources based on blue LEDs. To achieve excellent NIR phosphors, we propose a strategy of enhancing the crystallinity, modifying the micromorphology, and maintaining the valence state of Cr3+ in Ca3Sc2Si3O12 garnet (CSSG). By adding fluxes and sintering in a reducing atmosphere, the internal quantum efficiency (IQE) is greatly enhanced to 92.3%. The optimized CSSG:6%Cr3+ exhibits excellent thermal stability. At 150 °C, 97.4% of the NIR emission at room temperature can be maintained. The fabricated NIR-LED device emits a high optical power of 109.9 mW at 520 mA. The performances of both the achieved phosphor and the NIR-LED are almost the best results until now. The mechanism for the optimization is investigated. An application of the NIR-LED light source is demonstrated.

Antioxidant Capacity, Metal Contents, and Their Health Risk Assessment of Tartary Buckwheat Teas.

Tartary buckwheat tea (TBT) is the most popular and widely consumed buckwheat product in many countries. However, the perfect quality control standards for TBT were still lacking, and the content of heavy metals in TBT and their health risks to consumers were still unknown. In this research, the total phenolic content, total flavonoid content, and antioxidant capacity as well as six metal contents and their health risks in TBT were detected. The results showed that the total phenolic content, total flavonoid content, and antioxidant capacity varied significantly among different types of TBT. Meanwhile, six metal concentrations in TBT leaves and infusions decreased in the order of Zn, Cu, Cr, Ni, Pb, and Cd. Health risk assessment indicated that the heavy metal intake only from TBT would not cause a noncarcinogenic risk to consumers. However, a strong carcinogenic risk of Cr in TBT for consumers should be paid more attention.

Electron-phonon coupling mechanisms of broadband near-infrared emissions from Cr3+ in the Ca3Sc2Si3O12 garnet.

Cr3+ in the Ca3Sc2Si3O12 garnet (CSSG) has the ability to convert blue light to broadband near-infrared (NIR) emissions, which is a promising strategy for next-generation smart NIR light sources based on blue LEDs. The Cr3+ luminescence strongly depends on temperature due to electron-phonon coupling (EPC). We reveal the EPC mechanism of Cr3+ in CSSG for the first time by temperature-dependent photoluminescence measurement from 77 to 573 K and cathodoluminescence using a scanning electron microscope. Cr3+ occupies the Sc3+ site and experiences a weak crystal field in CSSG, manifesting a broad NIR emission in the 700-900 nm range that originates from the 4T2g→4A2g transition. The zero phonon line (ZPL) of the 4T2 state is observed at ∼713 nm with a vibrational energy of ∼310 cm-1. A strong EPC leads to a large Stokes shift (∼2900 cm-1). The Huang-Rhys parameter (S = 4), crystal field strength (Dq/B), and Racah parameters (B and C) are estimated.

YAG:Ce3+ Transparent Ceramic Phosphors Brighten the Next-Generation Laser-Driven Lighting.

Y3 Al5 O12 :Ce3+ (YAG:Ce3+ ) transparent ceramic phosphors (TCPs) are regarded as the most promising luminescent converter for laser-driven (LD) lighting. High-quality YAG:Ce3+ TCPs are still urgent for high efficiency LD lighting devices. YAG:Ce3+ TCPs in a vacuum ambience by using nano-sized raw materials are prepared. Controlling defects by adding nano-sized MgO and SiO2 simultaneously enables a high transmittance nearly 80%. After annealing in air furthermore, the luminous efficiency is enhanced greatly from 106 to 223 lm W-1 , which is the best result reported now for LD lighting. These results demonstrate that the optimizing YAG:Ce3+ TCPs in a fitting strategy will brighten once again in the next-generation LD lighting. Based on scanning electron microscopy (SEM) coupled with a cathodoluminescence system, defects and Ce3+ distributions in grains are identified directly for the first time.

Inhibitory Effect of Sirtuin6 (SIRT6) on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND The imbalance between bone resorption and formation is the basic mechanism underlying osteoporosis in the elderly. Osteogenesis is the differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts. Sirtuin6 (SIRT6) regulates various biological functions, including differentiation. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a non-selective cation channel that can be activated by physical and chemical stimulation. However, experimental data supporting the role of SIRT6 in osteogenic differentiation (OD) of hMSCs are lacking. MATERIAL AND METHODS Differentiation of hMSCs was induced. The expressions of SIRT6, TRPV1, and CGRP were detected by Q-PCR, Western blot, and ELISA, respectively. SIRT6 was overexpressed in hMSCs by transfection. ALP activity and Alizarin Red staining were utilized to detect the effect of SIRT6 on hMSC OD. Then, capsaicin and capsazepine, the TRPV1 agonist and antagonist, respectively, were administrated to assess the role of TRPV1. RESULTS SIRT6 expression was downregulated during hMSC differentiation. SIRT6 overexpression was accompanied by reduced expression of specific genes and alkaline phosphatase (ALP) activity in osteoblasts. Furthermore, TRPV1 channel was also reduced by SIRT6 overexpression via ubiquitinating TRPV1. Capsaicin was utilized in SIRT6-overexpressed cells. Capsaicin therapy counteracted the effect of SIRT6 overexpression on OD, and markedly decreased OD. CONCLUSIONS The SIRT6-TRPV1-CGRP signal axis is the key to regulating OD in hMSCs, which could be a potential therapeutic target for osteoporosis and bone loss-related diseases.

Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor.

Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is in phase 2 clinical trials. This article describes the process of RO-0529 as a potent, selective, and orally bioavailable RSV F protein inhibitor and highlights the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal species. RO-0529 demonstrates single-digit nM EC50 potency against laboratory strains, as well as clinical isolates of RSV in cellular assays, and more than one log viral load reduction in BALB/c mouse model of RSV viral infection. RO-0529 was proven to be a specific RSV F protein inhibitor by identification of drug resistant mutations of D486N, D489V, and D489Y in RSV F protein and the inhibition of RSV F protein-induced cell-cell fusion in cellular assays.

Transparent Ceramics Enabling High Luminous Flux and Efficacy for the Next-Generation High-Power LED Light.

By designing novel chemical compositions and controlling precursor powders, perfect transparent ceramics (TCs) of Gd3Al4GaO12:2%Ce3+ garnets (GAGG:2%Ce3+) were achieved for the first time. Ce3+ distributions in ceramics were revealed by micromorphology and micro-cathodoluminescence. Benefiting from the components that are rich in red emission, warm light with a correlated color temperature of about 2800 K was generated when TC was used in high-power (hp) blue light emitting diodes (LEDs) (∼450 nm, ∼34 W driven at 1 A). The hp LED device shows high brightness with a luminous flux nearly 2100 lm. The luminous efficacy even reaches 388 lm/W, which is the highest value reported till now, indicating that the use of GAGG:2%Ce3+ TCs promises energy saving. We believe that this work will open a new perspective to develop TCs for next-generation hp LED lighting to substitute traditional hp xenon lamps and high-pressure sodium lamps.

Warm White Light with a High Color-Rendering Index from a Single Gd3Al4GaO12:Ce3+ Transparent Ceramic for High-Power LEDs and LDs.

Transparent ceramics (TCs) are promising for high-power (hp) white light-emitting diode (WLED) and laser diode (LD) lighting. However, comfortable warm white light has not been achieved only using a single TC in hp-WLEDs/LDs. Herein, highly transparent Gd3Al4GaO12:Ce3+ (GAGG:Ce3+) TCs (transmittance, T = 55.9-80.2%) were prepared via a solid-state reaction. Ce3+ as a doped activator center in grains plays a positive role in luminescence based on the microstructural investigations by scanning electron microscopy and the cathodoluminescence system. T decreases upon increasing the Ce3+ concentration and/or the ceramic thickness, whereas the luminous efficacy of hp-WLEDs/LDs goes up. For blue hp-LEDs driven at 350 mA or LDs of 2 W, warm white light with a low correlated-color temperature of ∼3000 K was achieved by a single GAGG:Ce3+ TC, benefiting from its broad emission band (full width at half maximum, FWHM = 133-137 nm) and abundant red components (peaking at about 568-574 nm). The color-rendering index of hp-WLEDs reaches 78.9. These results are much better than the performance of the traditional Y3Al5O12:Ce3+ (YAG:Ce3+) TC, indicating that GAGG:Ce3+ TCs are promising color converters for hp-WLEDs/LDs with a comfortable warm white light.

Highly Efficient and Thermally Stable Blue-Green (Ba0.8Eu0.2O)(Al2O3)4.575×(1+ x) Phosphor through Structural Modification.

Exploring phosphors with high quantum efficiency (QE) and thermal stability is an important issue for their application in white light-emitting diodes (LEDs). In this work, the crystal structure and luminescent properties of Eu2+-activated aluminate phosphors with a normal composition (Ba0.8Eu0.2O)(Al2O3)4.575×(1+ x) (short for BA1+ xO:0.2Eu2+) were studied. Although the crystal structures of BA1+ xO:0.2Eu2+ have a same space group, the increase of the Al content will lead to the decrease of cell volume, occupancy of Ba and O6 that is at around Ba1 site, and the increase of the average distance between Eu2+ ions, which are responsible for the modification of luminescent properties. BA1+ xO:0.2Eu2+ exhibits a blue-green emission with an emission peak at around 450 nm and a shoulder at around 490 nm. The increase of Al/(BaEu) ratio results in the increase of both absolute QE and thermal stability. The absolute QE of BA1.5O:0.2Eu2+ is 99.4%, and the emission intensity at 150 °C remains more than 90% of that at room temperature, showing the best performance. Furthermore, all of the external QE values of BA1+ xO:0.2Eu2+ ( x = 0.2-0.5) are higher than 70%. The properties of the LEDs based on the as-prepared phosphor suggest its potential as a candidate for UV LED pumped phosphor-converted white LEDs.

Discovery of Benzoazepinequinoline (BAQ) Derivatives as Novel, Potent, Orally Bioavailable Respiratory Syncytial Virus Fusion Inhibitors.

A novel benzoazepinequnoline (BAQ) series was discovered as RSV fusion inhibitors. BAQ series originated from compound 2, a hit from similarity-based virtual screening. In SAR exploration, benzoazepine allowed modifications in the head moiety. Benzylic sulfonyl on benzoazepine and 6-Me on quinoline were crucial for good anti-RSV activity. Although the basic amine in the head portion was crucial for anti-RSV activity, the attenuated basicity was required to reduce Vss. Introducing oxetane to the head portion led to discovery of compound 1, which demonstrated single-digit nM anti-RSV activity against different RSV strains, reasonable oral exposure in plasma, and 78-fold higher exposure in lung. Compound 1 also displayed 1 log viral reduction in a female BALB/c mice RSV model by b.i.d. oral dosing at 12.5 mg/kg. A single resistant mutant at L138F in fusion protein proved compound 1 to be a RSV fusion inhibitor.

Association between single nucleotide polymorphism rs11057401 of CCDC92 gene and the risk of coronary heart disease (CHD).

BACKGROUND: Given that the CCDC92 (coiled-coil domain containing 92) was important in insulin resistance, we sought to investigate whether the CCDC92 rs825476 SNP is associated with the risk of CHD in Chinese Han population. METHODS: Rs11057401 was genotyped for 817 patients with CHD and 724 age- and sex-matched controls using PCR-based Invader assay with the probe sets designed and synthesized by third wave. RESULTS: Patients were found to have a significantly higher frequency of AA than the controls (23.5% vs. 14.7%, OR = 1.60, p = 0.000), and the frequency of allele A was found to be remarkably higher in the patients than the controls (48.1% vs. 40.3%, OR = 1.19, p = 0.000). Multivariate logistic analysis showed that the incidence of CHD was positively correlated with hyperlipidemia, T2D and rs11057401 AA/AT genotypes. The FPG, TC, and ApoA1 levels in the CHD patients were different among the AA, AT and TT genotypes (P < 0.05), the A allele carriers had higher FPG, TC and lower ApoA1 levels than the A allele non-carriers (P < 0.05). CONCLUSION: The genotypic and allelic frequencies of the rs11057401 SNP were significantly different between the patients with CHD and controls. Subjects with AA genotype or A allele were associated with an increased risk of CHD. The AA/AT genotypes were also associated with increased serum FPG, TC and decreased ApoA1 in CHD.

A two-step solid-state reaction to synthesize the yellow persistent Gd3Al2Ga3O12:Ce3+ phosphor with an enhanced optical performance for AC-LEDs.

By using a two-step solid-state reaction to synthesize the yellow-persistent Gd3Al2Ga3O12:Ce3+ phosphor, both the luminescence and afterglow properties were greatly enhanced. Its internal quantum efficiency reaches as high as 81.9%, indicating its promising application in reducing the flicker effect in AC-LED-based white light systems.