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Background Secondary structural and functional abnormalities of the neurovascular unit are important pathological mechanisms following traumatic brain injury (TBI). The tumor necrosis factor α (TNF-α)/nuclear factor-κB (NF-κB) pathway regulates neuroinflammation and oxidative damage, which may act as triggers for pathological processes after TBI. However, the role of TNF-α/NF-κB in pericyte-mediated cerebral microcirculation are currently unknown. Methods We assessed the activity and mechanisms of the TNF-α/NF-κB signaling axis on pericyte-mediated microcirculation using the mouse controlled cortical impact model and BV2 cells. Immunofluorescent staining and western blot analysis were used to detect activation of the TNF-α/NF-κB signaling pathway and the expression of inducible nitric oxide synthase (iNOS) to evaluate the effects of the TNF-α specific inhibitor infliximab (IFX). Modified neurological severity scores, Garcia test, Nissl staining, and TUNEL staining were employed to determine the neuroprotective effects of IFX supplementation. The relative blood flow values in the capillary areas surrounding the impinging lesion were observed by Laser speckle contrast imaging. The impact of IFX on pericyte markers was assessed to evaluate whether pericyte damage was dependent on the TNF-α/NF-κB/iNOS axis to gain further insight into the mechanisms underlying the development of the microcirculation disturbance after TBI. Results Microglia were activated after TBI, and the expression of NF-κB, iNOS, a disintegrin and metalloproteinase 17, inflammatory factors, and free radicals increased around the injury areas. After lipopolysaccharide treatment, the expression of TNF-α and downstream NF-κB/iNOS in BV2 cells was significantly upregulated. Pharmacological inhibition of TNF-α via IFX significantly reduced NF-κB p65 phosphorylation and nuclear translocation and downregulated iNOS expression. Meanwhile, we found that specific inhibition of TNF-α reversed pericyte marker loss, and improved pericyte function and cerebral microcirculation perfusion after TBI, which could attenuate inflammation and oxidative damage, reduce neuronal cell damage and apoptosis, and play a neuroprotective role. Conclusion The results of this study suggested that microglia activated and released TNF-α after TBI, which promoted neuroinflammation and oxidative stress by activating downstream NF-κB/iNOS signals, and this led to pericyte-mediated disturbance of the cerebral microcirculation, which may be one of the vital mechanisms of secondary injury in TBI.

Osteoporosis (OP) is a debilitating skeletal abnormality involving bone remodeling and bone cell homeostasis characterized by decreased bone strength and high fracture risk. A novel therapeutic intervention for OP by manipulating cellular autophagy–apoptosis processes to promote skeletal homeostasis are presented. Protective effects of the naturally occurring plant extract Liquiritigenin (LG) were demonstrated in an ovariectomy (OVX)-OP mouse model and preosteoblast MC3T3-E1 cells. Micro-CT and histological staining assessments of skeletal phenotype were applied alongside detection of autophagy activity in osteocytes and MC3T3-E1 cells by transmission electron microscopy (TEM). The effects of LG on chloroquine (CQ)- and the apoptosis-inducing TS-treated osteogenic differentiations and status of lysosomes within MC3T3-E1 cells were analyzed by Neutral red, Alizarin red S and alkaline phosphatase (ALP) staining and Western blot assays. Treatment with LG prevented bone loss, increased osteogenic differentiation in vivo and in vitro, and inhibited osteoclast formation to some extent. TEM analyses revealed that LG can improve auto-lysosomal degradation within osteocytes from OVX mice and MC3T3-E1 cells. The abnormal status of lysosomes associated with CQ and TS treatments was notably alleviated by LG which also reduced levels of apoptosis-induced inhibition of osteogenic differentiation and averted abnormal osteogenic differentiation as a consequence of a blockage in autolysosome degradation. Overall, LG stimulates bone growth in OVX mice through increased osteogenic differentiation and regulation of autophagy-apoptosis mechanisms, presenting an auspicious natural therapy for OP.

In view of the difficulty of kerosene-air detonation faced by the application of rotating detonation to aviation engines, in order to improve the kerosene detonation activity, the atmospheric pressure gliding arc plasma is used to conduct secondary adjustment of the pre-combustion cracking products. The results show that the components with larger molecular weight in the pre-combustion cracking products, such as ethylene and methane, can be cracked into highly active species of hydrogen and acetylene by gliding arc plasma. With the increase of the fuel ratio of pre-combustion cracking, the plasma has a more significant effect on the adjustment of high active components. However, as the flow rate of the cracking gas treated by plasma increases, the adjustment effect is obviously reduced.

Monitoring of ambient volatile organic compounds (VOCs) was conducted within typical residential-commercial area in the city of Xi'an in northwest China during typical ozone (O3) episodes, to investigate the major contributors to the characteristic of ambient VOCs and their impact on O3 production. In the residential-commercial area, diurnal variation of VOCs was highly impacted by vehicle exhaust, fuel evaporation, and local solvent use. Relative higher contributions (up to 60%) of VOCs from solvent use to the ozone formation potential were found. The present findings highlight the urgent need for restrictions on the emission of VOCs from solvent use and non-vehicle-traffic-related sources, such as oil storage.

Development of new photosensitizers (PSs) with high singlet oxygen quantum yield and minimal side effects is of great interest in photodynamic therapy (PDT). Herein, a facile strategy to significan...

Heterogeneous two-dimensional layered membranes reconstructed from natural or synthetic van der Waals materials enable novel ion transport mechanisms by coupling with the chemistry and optoelectron...

Ionic liquids (ILs) have attracted increasing attention since last few decades due to their high molecular design abilities and wide applications in different fields. In this study, four novel fluorescent isoquinolino [2,1-a]quinoxalin-5-ium ILs were designed and synthesized via a two-step process including a simple dual Schiff's base formation and a subsequent [RhCp∗Cl2]2-catalyzed oxidative C–H activation/annulation reaction. The as-synthesized ILs were extensively characterized using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, HSQC-NMR, HMBC-NMR and HR-MS. Their photophysical properties were determined by steady-state fluorescence spectroscopy. The results demonstrate that all these ILs showed dual or triple emissions, large stokes shift (90 nm) and mechanochromic behaviors. Basing on solvatochromism and titration experiments, it is thought that the emission bands of the ILs are raised from their local excited states, charge transfer states or excited state proton transfer of cations, while the substitute effect of these quinoxaline derived ILs on their stokes shifts is negligible.

The diastereoselectivity of conventional polyene cyclization reactions is highly dependent on the configuration of the internal alkenes, where E-polyenes provide trans-decalins, while Z-polyenes of...

Designing highly active and selective metal nanocatalysts for use in liquid chemical hydrides is highly attractive but remains a critical challenge. Herein, bimetallic NiPt nanoparticles (NPs) immobilized on lanthanum oxycarbonate (NiPt/La2O2CO3) have been facilely synthesized via an alkali-assisted reduction method. The introduction of NaOH is the key factor to the formation of the well-dispersed and ultrafine NiPt NPs (2.8 nm). The obtained Ni0.6Pt0.4/La2O2CO3 exhibits an extraordinarily high catalytic activity and 100% H2 selectivity for hydrous hydrazine dehydrogenation, providing a turnover frequency value (TOF) high up to 490 h-1 at 298 K. Additionally, the NiPt/La2O2CO3 prepared with NaOH demonstrates higher catalytic performance and lower activation energy than that of NiPt/La2O2CO3_N prepared without NaOH. Moreover, the NiPt/La2O2CO3 also shows an outstanding catalytic efficiency (TOF = 1200 h-1) for dehydrogenation of hydrazine borane at 298 K. The efficient catalytic performance may be attributed to the small size effect, the strong metal-support interaction, and the NaOH promotion effect. This alkali-assisted reduction method provides a new perspective for preparing of highly efficient catalysts in clean energy application.

Supported palladium is the most promising catalyst for catalytic combustion/oxidation of unburned methane generated in vehicles and thermal power generation. The development of a stable catalyst in the presence of high concentrations of water vapor is a challenging task. Herein, core–shell Pd@silicalite-1 catalysts were synthesized with a two-step seed-directed hydrothermal growth method. Firstly, we demonstrate that Fourier transform infrared spectroscopy of CO adsorption (CO-FTIR) is a facile, sensitive, and definite method to probe the completeness of the zeolite shell for metal@zeolite materials. CO-FTIR method is based on the CO access to metal surface because the structure directing agent (SDA) retained in the pores of zeolite shell in the fresh metal@zeolite materials will block the transport of CO. More importantly, for catalysts with complete shell, Pd@S-x (x = 1.5, 2.0) catalyst show no deactivation for 200 h in practical wet conditions (10% H2O, 500 °C). To the best of our knowledge, this is one of the scare Pd catalysts which show 200 h stability in these practical conditions. Pd@S-2.0 shows negligible low temperature water absorption which lead to its high catalytic stability in wet conditions.

No consensus has been reached on the role of reducible and irreducible supports on the reaction pathway of CO oxidation over supported metal catalysts. Here, colloidal ligand-free Pt nanoparticles were deposited on Al2O3 and CeO2 to investigate the support effect in CO oxidation by in situ diffuse reflectance Fourier-transform infrared spectroscopy (DRIFTS) and mass spectrometry (MS). On Pt/Al2O3, the carbonate-like intermediates accumulate and do not decompose to CO2 at the ignition temperature (150 °C) or above; the conversion of CO to CO2 follows classic Langmuir−Hinshelwood (L–H) mechanism with direct reaction of CO and O2 on Pt. Whereas for Pt/CeO2, the CO conversion to bidentate carbonate (b-CO32−) species followed by decomposition to CO2 is a main reaction pathway leading to its high reactivity at low temperature (75 °C). CeO2 facilitates the activation of oxygen to produce the carbonate-like intermediates and further decomposition to CO2, which resulted in a lower ignition temperature.

Cryptorchidism-caused adult infertility is a common component of idiopathic reasons for male infertility. Retinoic acid (RA) has a vital effect on the spermatogenesis process. Here, we found that the expression of c-Kit, Stra8, and Sycp3 could be up-regulated via the activation of retinoic acid receptor α (RARα) after RA supplementation in neonatal cryptorchid infertile rats. We also demonstrated that the protein expression of PI3K, p-Akt/pan-Akt, and p-mTOR/mTOR was higher in cryptorchid than in normal testes, and could be suppressed with RA in vivo. After RA treatment in infertile cryptorchid testis in vivo, the levels of the autophagy proteins LC3 and Beclin1 increased and those of P62 decreased. Biotin tracer indicated that the permeability of blood-testis barrier (BTB) in cryptorchid rats decreased after RA administration. Additionally, after blocking the RARα with AR7 (an RARα antagonist) in testicle culture in vitro, we observed that compared with normal testes, the PI3K-Akt-mTOR signaling pathway and the autophagy pathway was increased and decreased, respectively, which were coincident with cryptorchisd testes in vivo. Additionally, the appropriate concentrations of RA treatment could depress the PI3K-Akt-mTOR signaling pathway and improve the autophagy pathway. The results confirmed that RA can rehabilitate BTB function and drive key protein levels in spermatogonial differentiation through depressing the PI3K-Akt-mTOR signaling pathway via RARα.

Pd modified electrodes possess problems such as easy agglomeration and low electrolytic ability, and the use of manganese dioxide (MnO2) to facilitate Pd reduction of organic pollutants is just started. However, there is still a limited understanding of how to match the Pd load and MnO2 to realize optimal dechlorination efficiency at minimum cost. Here, a Pd/MnO2/Ni foam cathode was successfully fabricated and applied for the efficient electrochemical dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP). The optimal electrocatalytic hydrodechlorination (ECH) performance with 2,4,6-TCP dechlorination efficiency (92.58% in 180 min) was obtained when the concentration of PdCl2 precipitation was 1 mmol/L, the deposition time of MnO2 was 300 s and cathode potential was −0.8 V. Performance influenced by the exogenous factors (e.g., initial pH and coexisted ions) were further investigated. It was found that the neutral pH was the most favorable for ECH and a reduction in dechlorination efficiency (6% ∼ 47.6%) was observed in presence of 5 mmol/L of NO 2 − , NO 3 − , S2− or SO 3 2 − . Cyclic voltammetry (CV) and quenching experiments verified the existence of three hydrogen species on Pd surface, including adsorbed atomic hydrogen (H*ads), absorbed atomic hydrogen (H*abs), and molecular hydrogen (H2). And the introduction of MnO2 promoted the generation of atomic H*. Only adsorbed atomic hydrogen (H*ads) was confirmed that it truly facilitated the ECH process. Besides H*ads induced reduction, the direct reduction by cathode electrons also participated in the 2,4,6-TCP dechlorination process. Pd/MnO2/Ni foam cathode shows excellent dechlorination performance, fine stability and recyclable potential, which provides strategies for the effective degradation of persistent halogenated organic pollutants in groundwater.

The wide application of molecular beacon probes in specific DNA detection, especially in the fast prototyping of pathogen DNA detection kits in point-of-care diagnostics, has been hindered by the nonflexible choice of target sequences and the unstable fluorophore output. We developed an in vitro DNA detection system consisting of a pair of dCas9 proteins linked to split halves of luciferase, named the Paired dCas9 (PC) reporter. Co-localization of the reporter pair to a ~46 bp target sequence defined by two single guide RNAs (sgRNAs) activated luciferase which subsequently generated highly intensified luminescent signals. Combined with an array design and statistical analyses, the PC reporter system could be programmed to access sequence information across the entire genome of the pathogenic Mycobacterium tuberculosis H37Rv strain. These findings suggest great potential for the PC reporter in effective and affordable in vitro nucleic acid detection technologies. In this article we highlighted the systems design from our previous research work on the PC reporter (Zhang et al, 2015) with a focus on methodology.

Peracetic acid (PAA)-based system is becoming an emerging advanced oxidation process (AOP) for effective removal of organic contaminants from water. Various approaches have been tested to activate PAA, while no previous researches reported the application of metal-organic frameworks (MOFs) materials for PAA activation. In this study, zeolitic imidazole framework (ZIF)-67, a representative MOFs, was facile synthesized via direct-mixing method at room temperature, and tested for PAA activation and sulfachloropyridazine (SCP) degradation. The as-synthesized ZIF-67 exhibited excellent performance of PAA activation and SCP degradation with 100% of SCP degraded within 3 min, owing to the specific MOFs structure and abundant Co2+ sites. The pseudo-first-order kinetic model was applied to fit the kinetic data, with rate constant k1 of ZIF-67 activated PAA system 34.2 and 156.5 times higher than those of conventional Co3O4 activated PAA and direct oxidation by PAA. Radical quenching experiments and electron paramagnetic resonance (EPR) analysis indicated that CH3C(O)OO• played a major role in this PAA activation system. Then, the Fukui index based on density functional theory (DFT) calculation was used to predict the possible reaction sites of SCP for electrophilic attack by CH3C(O)OO•. In addition, the degradation pathway of SCP was proposed based on Fukui index values and intermediates detection, which mainly included the S-N bond cleavage and SO2 extrusion and followed by further oxidation, dechlorination, and hydroxylation. Therefore, ZIF-67 activated PAA is a novel strategy and holds strong potential for the removal of emerging organic contaminants (EOCs) from water.

Background: Vitexin is the main bioactive compound of hawthorn (Crataegus pinnatifida), a famous traditional Chinese medicine, and vitexin for injection is currently in phase I clinical trial in China. Objective: This investigation systematically evaluated the metabolism and toxicokinetics of vitexin in rats and dogs. Methods: Rats and beagle dogs were administrated different doses of vitexin, and then the plasma concentration, tissue distribution, excretion, metabolism, pharmacokinetics and plasma protein binding were investigated. Results : The elimination half-life (t1/2) values in rats after a single intravenous dose of 3, 15 and 75 mg/kg were estimated as 43.53±10.82, 22.86±4.23, and 21.17±8.64 min, and the values of the area under the plasma concentration-time curve (AUC0→∞) were 329.34±144.07, 974.79±177.27, and 5251.49±786.98 mg•min/L, respectively. The plasma protein binding rate in rats was determined as about 65% by equilibrium dialysis after 72 hr. After 24 hr of intravenous administration, 16.30%, 3.47% and 9.72% of the given dose were excreted in urine, feces and bile, respectively. The metabolites of the vitexin were hydrolyzed via deglycosylation. The pharmacokinetics of dogs after intravenous administration revealed t1/2, AUC0-∞ and mean residence time (MRT0-∞) values of 20.43±6.37 min, 227.96±26.68 mg•min/L and 17.12±4.33 min, respectively. The no-observed-adverse- effect level (NOAEL) was 50 mg/kg body weight/day. There was no significant accumulation effect at 8 or 20 mg/kg/day in dogs over 92 days of repeated administration. For the 50 mg/kg/- day dose group, the exposure (AUC, Cmax) decreased significantly with prolonged administration. This trend suggests that repeated administration accelerates vitexin metabolism. Conclusion: The absorption of vitexin following routine oral administration was very low. To improve the bioavailability of vitexin, the development of an injectable formulation would be a suitable alternative choice.

Bưởi là loài cây không chỉ có giá trị cao về mặt dinh dưỡng mà còn có giá trị cao về mặt kinh tế và được trồng phổ biến ở Việt Nam. Ngoài ra, tinh dầu bưởi chứa nhiều hợp chất có hoạt tính sinh học cao. Tinh dầu bưởi được chiết xuất bằng phương pháp chưng cất lôi cuốn hơi nước và thành phần hóa học được phân tích bằng phương pháp GC-MS. Thành phần chính của tinh dầu gồm limonene (91,19%), b-myrcene (2,92%), a-phellandrene (1,98%) và a-pinene (1,19%). Hoạt tính kháng vi sinh vật của tinh dầu được khảo sát với vi khuẩn Gram dương (Bacillus cereus, Staphylococcus aureus), Gram âm (Escherichia coli) và nấm mốc Aspergillus flavus ở nồng độ 5, 10, 25 và 50% bằng phương pháp khuếch tán giếng thạch. Tinh dầu có khả năng kháng B. cereus, S. aureus và E. coli với đường kính vòng kháng khuẩn lần lượt là 8,3–11,3, 10,3–18,7 và 9,0–11,7 mm và ức chế sự phát triển của A. flavus (18,9–65,0%).

A series of ZnO-ZrO2 solid solutions with different Zn contents were synthesized by the urea co-precipitation method, which were coupled with H-ZSM-5 zeolite to form bifunctional catalysts. As a new benzene alkylation reagent, syngas was used instead of methanol to realize the efficient conversion of syngas and benzene into toluene and xylene. A suitable ratio of ZnO-ZrO2 led to the significant improvement in the catalytic performance, and a suitable amount of acid helped to increase the selectivity of toluene/xylene and reduce the selectivity of the by-products ethylbenzene and C9+ aromatics. The highest benzene conversion of 89.2% and toluene/xylene selectivity of 88.7% were achieved over 10% ZnO-ZrO2H hence, the conversion of benzene is higher. H-ZSM-35 and H-MOR zeolites exhibited small eight-membered-ring channels, which were not conducive to the passage of benzene; hence, the by-product ethylbenzene exhibits a higher selectivity. The distance between the active centers of the bifunctional catalysts was the main factor affecting the catalytic performance, and the powder mixing method was more conducive to the conversion of syngas and benzene.

A linear supramolecular polymer with controllable features based on twisted cucurbit[14]uril (tQ[14]) and cucurbit[8]uril (Q[8]) was firstly fabricated via an effective self-sorting strategy. Herein we designed a monomer, 1-butyl-1′-(naphthalen- 2-ylmethyl)-4,4′-bipyridinium bromide (BNB), that contains bipyridyl, aliphatic butyl and aromatic naphthyl groups, simultaneously. Two host molecules, tQ[14] and Q[8] were employed to develop an effective strategy for constructing a linear supramolecular polymer with controllable features. The alkyl groups on both sides of BNB could insert into the two cavities of tQ[14], the naphthyl part of BNB via π-π stacking in Q[8] cavity, serving as the driving force for supramolecular polymerization. Through self-sorting of the monomer, tQ[14] and Q[8], led to the formation of the linear supramolecular polymer. Depolymerization could be achieved by addition of adamantane hydrochloride (AH) which driven two BNB guest molecules out of the Q[8] cavity. This self-sorting strategy has great potential, not only for designing supramolecular polymer materials with different controllable structures through introduction of multiple functional groups, but also for broadening the application of twisted cucurbit[14]uril in supramolecular chemistry.

Sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by SARS-CoV2, HIV-1, and other viruses. In HIV-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cART) has benefited tremendously from the development of sensitive HIV-1 DNA and RNA quantitation assays. Simian immunodeficiency virus (SIV) infection of Rhesus macaques is similar in many key aspects to human HIV-1 infection and consequently this non-human primate (NHP) model has and continues to prove instrumental in evaluating HIV prevention, treatment and eradication approaches. Cell and tissue associated HIV-1 viral nucleic acids have been found to serve as useful predictors of disease outcome and indicators of treatment efficacy, highlighting the value of and the need for sensitive detection of viruses in cells/tissues from infected individuals or animal models. However, viral nucleic acid detection and quantitation in such sample sources can often be complicated by high nucleic acid input (that is required to detect ultralow level viruses in, for example, cure research) or inhibitors, leading to reduced detection sensitivity and under-quantification, and confounded result interpretation. Here, we present a step-by-step procedure to quantitatively recover cell/tissue associated viral DNA and RNA, using SIV-infected Rhesus macaque cells and tissues as model systems, and subsequently quantify the viral DNA and RNA with an ultrasensitive SIV droplet digital PCR (ddPCR) assay and reverse transcription ddPCR (RT-ddPCR) assay, respectively, on the Raindance ddPCR platform. The procedure can be readily adapted for a broad range of applications where highly sensitive nucleic acid detection and quantitation are required.

Background: Rituximab represents a drug used for standard Non-Hodgkin’s B-cell lymphoma therapy; however, it displays limited clinical efficacy. Antibody-drug conjugate (ADC) is one of the potential strategies to increase the antitumor activity of an antibody, with improved cytotoxicity directly resulting from the delivery of a molecular warhead. Currently, the warhead monomethyl auristatin E (MMAE) has been widely applied in the study of ADCs, conjugated to a carbamate-based linker (MCVC- PABC). However, the hydrophobic drug-linker (MC-VC-PABC-MMAE) may lead to ADC aggregation, ultimately resulting in decreased activity. Objective: In this study, we developed a hydrophilic drug-linker MC-VC-PABQ-AE linked to rituximab. If the replacement of the tertiary amine in AE for a secondary amine in MMAE represents a characteristic modification, the change of antitumor activity of two corresponding anti-CD20 ADC is unknown, requiring further verification. Method: The structural elucidation of MC-VC-PAB-AE was displayed by high-resolution mass spectra. The average drug antibody ratio (DAR) of rituximab-VC-AE/MMAE ADCs was performed by HICHPLC. The cell cycle arrest analysis of two ADCs was detected by flow cytometry and the antitumor activity of two ADCs was evaluated in vitro against Ramos and Daudi cells. Results: The average drug antibody ratio (DAR) of two ADCs was approximately 4.0. The activities of rituximab-VC-AE could be increased in CD20 positive B-lymphoma cell lines, most notably due to the higher cell viability inhibitory rates and apoptosis rates compared to rituximab-VC-MMAE. Conclusions: A hydrophilicity linker of ADC was developed and studied. Rituximab-VC-AE may potentially be used against CD20-positive cells, and the therapeutic efficacy and safety bring about further investigations.

Achieving high-quality perovskite films with uniform morphology and homogeneous crystallinity is challenging owing to the coffee ring effect (CRE) in the spray-coating technologies. In this study, an evaporation/spray-coating two-step deposition method is used to fabricate Cs0.19FA0.81PbI2.5Br0.5 light harvesters for perovskite solar cells (PSCs). Considering the solid-liquid reaction, we establish a reaction-dependent regulating strategy that inhibits CRE successfully and prepare a high-quality perovskite layer, wherein the solvent for the FAI/Br solution during the spraying process is changed from isopropanol to n-butyl alcohol (NBA). The retarded-drying-enhanced spreading of the NBA solution inhibits contact line pinning to suppress the capillary flows and increases the reaction between metal halides (CsI/PbI2) and organic salts (FAI/Br), which result in a reduction in the accumulation of solutes in the periphery effectively inhibiting CRE. Consequently, we obtain a high performance Cs0.19FA0.81PbI2.5Br0.5 PSC with a power conversion efficiency (PCE) of 19.17%. An enlarged perovskite film (10 × 10 cm2) containing 40 sub-cells is prepared. The average PCE of these devices is 18.33 ± 0.56%, proving the reliability of the “coffee ring” regulating strategy. This study provides an effective approach for CRE controlment in spraying technology to achieve high repeatability devices with good performance.

Kernel size, one of the traits that determine wheat yield, is controlled by multiple quantitative trait loci. Polish wheat (Triticum polonicum) has elongated and plump kernel and is a valuable material for breeding high-yielding wheat cultivars. However, genes or loci determining kernel length (KL) in Polish wheat are unknown. We identified and validated a major KL gene, KL-PW, at the P1 locus in Polish wheat. KL-PW is VRT-A2, which encodes a MIKC-type MADS-box protein (MADS55). An insertion/deletion mutation in intron 1 of VRT-A2PW led to an alternatively spliced transcript, VRT-A2PW2. Quantitative PCR analysis showed that VRT-A2PW was more highly expressed in developing seeds than was VRT-A2Ailanmai. Brassinosteroid (BR) sensitivity experiment and the expression of BR-related genes indicated that VRT-A2PW functions as a positive regulator of BR responses. VRT-A2PW significantly increased KL of wheat. These findings not only reveal the molecular basis of KL-PW in controlling KL, but also provide a valuable genetic resource for increasing kernel size in wheat.

Oxidation remediation is a commonly used technology for PAHs contaminated soil presently, but the overestimate of efficiency due to ongoing remediation by residual oxidants during extraction and testing has not been paid enough attention. In this study, persulfate was activated by Fe(II) to investigate the effects of residual oxidants on PAHs removal during detection process and the elimination effects of adding Na2SO3 and extending sampling time on residual oxidants. Results verified that the residual oxidants removed PAHs in extraction process, making the results lower than the actual values: the detection recovery rate η of ∑PAHs and 3-6 ring PAHs ranged from 24.3% (25% Na2S2O8 treatment) to 87.4% (5% Na2S2O8+4/4Fe2+ treatment), 20.1%-99.0%, 28.9%-87.9%, 20.8%-89.4%, and 18.6%-76.9%, respectively. After adding Na2SO3, the accuracy of detection results increased significantly: the η of ∑PAHs and 3-6 ring PAHs increased to 64.1%-96.5%, 58.8%-95.5%, 73.8%-114.4%, 60.6%-95.6%, and 45.4%-77.1%, respectively. After 49 days of adding oxidants, residual oxidants had no considerable effect on the detection of PAHs, indicating it was appropriate to start soil remediation verification sampling49 days after the remediation was completed. The observed results will help scientific evaluation of the remediation effects of chemical oxidation on organic contaminated soil.

Numerous approaches have been used to modify graphitic carbon nitride (g-C3N4) for improving its photocatalytic activity. In this study, we demonstrated a facial post-calcination method for modified graphitic carbon nitride (g-C3N4-Ar/Air) to direct tuning band structure, i.e., bandgap and positions of conduction band (CB)/valence band (VB), through the control of atmospheric condition without involving any additional elements or metals or semiconductors. The synthesized g-C3N4-Ar/Air could efficiently degrade sulfamethazine (SMT) under simulated solar light, i.e., 99.0% removal of SMT with rate constant k1 = 2.696 h−1 within 1.5 h (4.9 times than pristine g-C3N4). Material characterizations indicated that the damaged/partial-collapsed structure and decreased nanosheet-interlayer distance for g-C3N4-Ar/Air resulted in the shift of band structure due to the denser stacking of pristine g-C3N4 through oxidative exfoliation and planarization by air calcination. In addition, the bandgap of g-C3N4-Ar/Air was slightly shrunk from 2.82 eV (pristine g-C3N4) to 2.79 eV, and the CB was significantly upshifted from -0.44 eV (pristine g-C3N4) to -0.81 eV, suggesting the powerful ability for donating the electrons for O2 to form •O2−. Fukui index (f –) based on theoretical calculation indicated that the sites of SMT molecule with high values, i.e., N9, C4 and C6, preferred to be attacked by •O2− and •OH, which is confirmed by the intermediates’ analysis. The tuning method for graphitic carbon nitride provides a simple approach to regulate the charge carrier lifetime then facilitate the utilization efficiency of solar light, which exhibits great potential in efficient removal of emerging organic contaminants from wastewater.

Background Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. Objective Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. Design Cross-sectional. Setting All 288 MVMs on the market in the United States in the National Institutes of Health’s Dietary Supplement Label Database in 2018 labeled for children 1 to Main outcome measures Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. Statistical analyses Number of products and percent DV per day provided by each micronutrient in each product. Results The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children’s diets. Conclusions A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

Carbon aerogels with nanoporous structure are attractive for thermal insulation under extreme conditions, but their practical applications are usually plagued by the inherent brittleness and easy-oxidation characteristic at high temperature. Herein, silica-modified carbon aerogels (SCAs) with extraordinarily high strength are prepared via a facile sol-gel polymerization of phenolic resin and siloxane, followed by ambient pressure drying and carbonization. The resulting SCAs possess medium-high density of ∼ 0.5 g·cm-3 and mesoporous structure with the mean pore size of 33 nm. During carbonization process, the siloxane could be gradually transformed into the amorphous SiO2 particles and crystalline SiC particles, which are coated on the surface of carbon nanoparticle and consequently improve the oxidation-resistance of carbon aerogels. Due to the density-porosity trade-off, the SCAs have high compressive strength of 10.0 MPa and satisfied thermal conductivities of 0.118 W·m-1·K-1 at 25 °C and 0.263 W·m-1·K-1 at 1000 °C. Furthermore, needled carbon fiber-reinforced SCAs (CF-SCAs) with ultrahigh compressive strength of 210.5 MPa are prepared, which exhibit good thermal conductivities of 0.207 W·m-1·K-1 at 25 °C and 0.407 W·m-1·K-1 at 1000 °C. The ultrahigh mechanical strength, good oxidation-resistance, good thermal insulation as well as the facile preparation make the SACs great promising in high-temperature insulations especially under harsh conditions.

The exploration of efficient bifunctional electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) under alkaline conditions is an important way to promote the development of electrolytic water technology. Herein, the reduced graphene oxide-supported MoO42- modified amorphous cobalt metaphosphate cubes (a-Co(PO3)2/MoO4/rGO) as bifunctional OER/HER catalyst is prepared by anion exchange and phosphating, using the Prussian blue analogue (PBA) as a precursor. The resulting composite exhibits the low overpotentials (η) that of 290 and 50 mV for OER and HER in 1.0 M KOH solution at 10 mA cm-2, respectively. The electrochemical test and density functional theory (DFT) results reveal that the MoO42--modified optimizes the adsorption/desorption energy of H* of Co(PO3)2, thus enhance the HER activity. Benefiting from efficient HER and OER performances, an efficient and stable alkaline water electrolysis operation using a-Co(PO3)2/MoO4/rGO used as bifunctional catalyst can be carried out, which can deliver a current density (j) of 20 mA cm−2 at 1.65 V cell voltage and work continuously for 24 h.

0-3 composites containing high permittivity ceramic particles and high breakdown strength polymer have aroused extensive concern for energy-storage application. In this research, flexible composite films were fabricated through incorporating of strontium titanate (SrTiO3) platelets (P-ST) and poly(vinylidene fluoride) (PVDF), and the effect of P-ST content on the dielectric and energy storage performances were researched systematically. It was found that at the relatively low electric field of 350 MV/m, the composite with 1 wt% P-ST exhibited an increased discharged energy density of 9.48 J/cm3, exceeding most of the current reports at the same electric field. And the distribution of local electric field and local polarization of composite films were simulated by COMSOL Multiphysics. This work provided a reference for polymer-based composite films featuring high energy storage property at relatively low applied electric field, which could reduce the possibility of failure for capacitors.

In order to investigate the effects of plasticizers on the binding energy, solubility parameter and mechanical properties of pBAMO-b-GAP copolymer (the copolymer of 3,3’-bis(azidomethy) oxetane and glycidyl azide polymer), the related copolymer/plasticizer mixed systems were established by molecular dynamics simulations. Besides, the mechanical properties of the formulas based on pBAMO-b-GAP containing the three energetic plasticizers were also studied experimentally. The results showed that all involved energetic plasticizers could be miscible with the pBAMO-b-GAP. The order of binding energy was theoretically found to be pBAMO-b-GAP / BuNENA > pBAMO-b-GAP/ TMETN > pBAMO-b-GAP/ DIANP which was consistent with the trends of the experimental tensile strength values of three mixed materials. Excitedly, the DIANP showed strongest effects among the three plasticizers on improving the toughness of the copolymer according to the calculation of Cauchy pressure and experimental value of elongation. For the pBAMO-b-GAP copolymer, the DIANP could be a promising plasticizer and compolymer/plasticizer mixed system was suitable used as binder in azido polyether-based propellants.

Background Ginseng, officially known as Panax ginseng Meyer, has been traditionally used as a medicinal herb, particularly in Asia. Ginseng is propagated from seeds; however, seed germination is challenging, especially in its natural environment on farms. The seeds typically exhibit morphophysiological dormancy and require release from both morphological and physiological dormancy before germination. Although some studies have proposed methods for increasing seed germination rates, the underlying mechanisms of its dormancy release process remain unclear. Here, we investigated metabolic alterations during dehiscence in P. ginseng to determine their potential roles in dormancy release. Methods We compared the ginseng seed metabolome before and after dehiscence and the ginsenoside and phytosterol compositions of the seeds in both periods in the presence of related enzymes. Results After seed dehiscence, the sugar, amino acid, and squalene concentrations were significantly altered, phytosterols associated with the stigmasterol biosynthesis pathway were increased, while ginsenoside and brassinosteroid levels were not significantly altered. In addition, squalene epoxidase, cycloartenol synthase, 24-methylenesterol C-methyltransferase, and the stigmasterol biosynthesis pathway were activated. Conclusion Overall, our findings suggest that morphological activities that facilitate ginseng seed growth are the primary phenomena occurring during the dehiscence process. This study improves the understanding of P. ginseng germination processes and promotes further research of its germination and cultivation.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.

This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy.

Oysters are widely distributed worldwide, but are mainly concentrated in tropics and subtropics. Total lipid (TL), fatty acid (FA) composition of TL and polar lipid (PoL) fractions, phospholipid (PL) class, and molecular species composition in soft tissues of Crassostrea lugubris were investigated for the first time from Vietnam. Phosphatidylglycolic acid (PGA) is the new phospholipid class first identified in marine species in general and Crassostrea lugubris in particular. Main eight classes of PL were determined in PoL fraction: diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), ceramide aminoethylphosphonate (CAEP), CAEP with hydroxylated FAs (CAEP‐OH), and lysophosphatidylcholine. PE and PC accounted for approximately 63% of total known PL. Polyunsaturated FAs accounted for more than 30% of TL. Ninety molecular species of glycerophospholipids, including PGA, PE, PC, PS, PI, DPG, and PG, and sphingophosphonolipids (CAEP) were identified in PoL. Alkenyl‐acyl forms of glycerophospholipids were predominated in the molecular species of PGA, PE, and PS. PGA 38:1 (p18:0/20:1), PE 40:6 (p18:0/22:6 and p18:1/22:5), PC 30:0 (14:0/16:0), PS 38:1 (p18:0/20:1), PI 40:5 (20:1/20:4), PG 32:0 (16:0/16:0), DPG 88:24 (22:6/22:6/22:6/22:6), and CAEP 34:2 (d18:2/16:0) were major molecular species., This study presented a first structural characterization and quantification of phospholipid molecular species, in general, and phosphoglycolic acid, in particular, of Vietnamese oyster. Eight molecular species of PGA were found using HPLC‐HRMS. Other types of glycerophospholipid were identified, including PE, PC, PS, PI, DPG, and PG.

The avalanche ruggedness of power devices becomes a crucial issue to ensure the safe operation of the power conversion systems, particularly under the extreme temperature conditions. In this article, the avalanche capability of SiC planar/trench MOSFETs is systematically evaluated and analyzed over the temperature range of 90 to 340 K. Importantly, the essential mechanisms and temperature dependence of avalanche failure under cryogenic conditions are further explored by combining many analysis methods such as TCAD simulations, the unclamped inductive switching characterizations, and the transient junction temperature prediction. The highest avalanche energy density of 171.24 mJ/mm2 at 90K indicates the great application potential of SiC planner mosfet in cryogenic electronics. Moreover, the safe avalanche operation boundary (AOB) model is established over the cryogenic temperature range. The relevant analysis method and AOB model can be used to accurately evaluate and quantitatively predict the avalanche capability of SiC planar/trench mosfet s for the cryogenic converter design.

Thin film lithium niobate on insulator (LNOI), as an emerging photonic material, provides a promising platform to realize compact, high-speed, and high-efficient electro-optic (EO) modulators. However, due to the large coupling loss caused by the large mode field mismatch between standard single mode fibers and the LNOI waveguides, edge or grating couplers are indispensable to LNOI modulators. In this paper, we propose a novel edge coupler employing staircase structure. The proposed coupler is feasible with i-line lithography and avoids high precise alignment. Moreover, such coupler can be applied to wafer-scale manufacture with low cost. The simulation results show that a low input/output coupling loss of 1.14 dB/1.62 dB can be achieved at 1.55 m wavelength for transverse electric (TE) polarized light signals. Specifically, benefited from the novel staircase design, the proposed edge coupler shows a unique property of polarization extinction ratio larger than 10 dB, which will further improve the modulation efficiency and depth of the EO modulators based on X-cut LNOI.

Sorafenib-mediated chemotherapy is currently the first choice for hepatocellular carcinoma (HCC) that cannot be surgically excised, and can significantly improve the survival of patients. However, its poor water solubility restricts its bioavailability, and long-term single use of it does not achieve satisfactory HCC therapy effects. Herein, we report a novel cascaded copper-based metal-organic framework (MOF) therapeutic nanocatalyst using HKUST-1 by integrating cyclooxygenase-2 (COX-2) inhibitor meloxicam (Mel) and chemotherapeutic agent sorafenib (Sol) to amplify HCC therapy. This HKUST-1 nanocatalyst can be degraded by glutathione (GSH) into a Fenton-like agent to trigger chemodynamic therapy (CDT). CDT-mediated cytotoxic reactive oxygen species (ROS) can activate ferroptosis by accumulating lipid peroxides (LPO). Alternatively, GSH depletion not only deactivates glutathione peroxidase 4 (GPX4) to trigger ferroptosis, but also leads to oxidative stress amplification. Moreover, Sol can also activate ferroptosis by inhibiting system XC-, resulting in cascade-amplified ferroptosis mediated HCC therapy. Furthermore, the down-regulation of COX-2 can induce PINK1/Parkin-mediated mitophagy to further act synergistically with Sol-mediated chemotherapy. Therefore, this HKUST-1 nanocatalyst provides a novel strategy to regulate GSH and COX-2 levels for amplified chemo/chemodynamic and ferroptosis-mediated HCC therapy.

Since the early years of the 21st century, the whole world has faced two very urgent problems: the depletion of fossil energy sources and climate change due to environmental pollution. Among the solutions sought, 2,5-Dimethylfuran (DMF) emerged as a promising solution. DMF is a 2nd generation biofuel capable of mass production from biomass. There have been many studies confirming that DMF is a potential alternative fuel for traditional fuels (gasoline and diesel) in internal combustion engines, contributing to solving the problem of energy security and environmental pollution. However, in order to apply DMF in practice, more comprehensive studies are needed. Not out of the above trend, this paper analyzes and discusses in detail the characteristics of DMF's combustible laminar flame and its instability under different initial conditions. The evaluation results show that the flame characteristics of DMF are similar to those of gasoline, although the burning rate of DMF is much higher than that of gasoline. This shows that DMF can become a potential alternative fuel in internal combustion engines.

Background: Lipopolysaccharide (LPS) desensitization, which is characterized by hyporesponsiveness and a form of immunosuppression, is important in the negative regulation of responses to LPS and inflammatory disease such as sepsis. However, effect of IL-33 in the desensitization to LPS remains unclear. Methods: We used RNA-sequencing technology to analyze changes in mRNA in bone-marrow-derived macrophages (BMDMs) stimulated with LPS. Changes in expression and secretion of inflammatory cytokines were detected by qPCR and ELISA, respectively. Mechanisms were further studied through p65 phosphorylation detection. Results: IL-33 expression was significantly increased in LPS-treated macrophages, indicating its involvement in LPS-induced inflammation. Exogenous IL-33 increased the inflammatory response and ameliorated LPS desensitization by increasing the secretion of proinflammatory cytokines. It also activated p65 phosphorylation in resistant cells. Conclusion: IL-33 can enhance the inflammatory response induced by LPS and ameliorate LPS desensitization possibly by activating the NF-κB pathway in mouse macrophages.

The derivation of protective values for aquatic life can be enhanced by the development and use of bioavailability models. Recent advances to metals bioavailability modeling are applicable to other analyte groups and should be widely considered. In this study, we conduct a meta-analysis of available aquatic toxicity literature for fluoride to evaluate the utility of hardness, alkalinity, and chloride as toxicity modifying factors (TMFs) in empirical bioavailability models of freshwater taxa. The resulting optimal multiple linear regression (MLR) model predicting acute fluoride toxicity to the invertebrate Hyalella azteca included all three TMFs (Observed versus Predicted LC50, R 2 = 0.88) and the optimal model predicting toxicity to the fish Oncorhynchus mykiss included alkalinity and hardness (R 2 = 0.37). At >20 mg/L chloride, the preliminary final acute values (FAVs) for fluoride were within one order of magnitude and ranged from approximately 18.1 to 56.3 mg/L, depending on water chemistry. Sensitivity of H. azteca to low chloride conditions increased model uncertainty when chloride

Owing to the varied mechanisms of ORR/OER, exploiting cost-effective bifunctional catalysts with robust ORR/OER activities and excellent performances in Zn-air batteries is still a challenge. In this work, the Co/CoO@NSC bifunctional catalyst is obtained by using Zn-MOF@Co-MOF as self-template. The Co/CoO@NSC composite has interconnected porous architecture with intact metal@carbon structure, exhibiting superior electrocatalytic activities toward ORR and OER that can be comparable with the Pt/C and RuO2 catalysts, respectively. The Co/CoO@NSC-based aqueous Zn-air battery achieves a high specific capacity (759.7 mAh/g) and energy density (990.5 Wh/kg), and ultra-long rechargeable property (more than 400 h/1200 cycles). The Co/CoO@NSC-based solid-state Zn-air battery also delivers an excellent performance with a long cycle life (more than 143 h/858 cycles). Most importantly, the newly synthesized and recharged Co/CoO@NSC-based solid-state Zn-air battery can be used to light up a 2 V LED lamp for more than 28 h, demonstrating the superior practicability as rechargeable power source.

Aluminum-Vanadium (AlV) alloy is essential for high-performance titanium material. Calcium fluoride (CaF2) is currently used in AlV production and has inevitable drawbacks in terms of product quality and environmental impact. In order to avoid its potential hazards, lime (CaO) as an alternative flux material in producing AlV alloy has been investigated in laboratory and by industrial trials in the present study. The samples were analyzed by Electron Probe X-ray Micro-analyzer (EPMA) and X-ray Diffraction (XRD), regarding the phases formed and corresponding compositions. A slag with good fluidity can protect inner alloy from being oxidized and also promotes the separation between slag and alloy, with a goal to reduce alloy inclusions in slag to enhance the yield. The results showed that using CaO as flux with appropriate amount greatly improved the yield and quality of the AlV alloy and avoided environmental pollutions caused by fluoride evaporations.

The graphitic carbon nitride is considered as the promising anode of lithium ion battery due to its high theoretical capacity (>1000 mAh g−1) and easy synthesis method. But the electrochemical inactivity and the structural collapse during cycles lead to its poor electrochemical performance in practice. Here, an interesting molten salt method is used to obtain the KCl-preintercalated carbon nitride nanosheets with abundant N vacancies and pyridinic-N. The KCl as a prop enhances the interlayer distance and the structural stability. And the N vacancy and the pyridinic-N increase the conductivity, the active sites and the reversibility of Li+ storage. Thus, the optimized electrode shows a higher specific discharge capacity (389 mAh g−1 at 0.1 A g−1) and a longer cyclic life (66% capacity retention after 10 K cycles at 3.0 A g−1) compared to those of bulk g-C3N4.

Background Psoriasis is a chronic, complicated, and recurrent inflammatory skin disease. However, the precise molecular mechanisms remain largely elusive and the present treatment is unsatisfactory. Objective This study aimed to unravel the functions of long noncoding RNA (lncRNA) AGAP2-AS1 and its biological mechanism in psoriasis pathogenesis, hinting for the new therapeutic targets in psoriasis. Methods The expression of AGAP2-AS1 in the skin tissue of psoriasis patients and healthy controls were detected by qRT-PCR and RNAscope®. Cell Counting Kit‑8 (CCK8) and clone formation assays were utilized to assess proliferation. Methylated RNA immunoprecipitation (MeRIP) was performed to detect the N6-methyladenosine (m6A) modification. RNA immunoprecipitation (RIP) was used to detect the interaction of AGAP2-AS1 with YTH domain family 2(YTHDF2). The relationships among AGAP2-AS1, miR-424-5p and AKT3 were examined by dual-luciferase reporter assay and RIP assay. Results We found that AGAP2-AS1 level was upregulated in the skin tissue of psoriasis patients than that of healthy controls and AGAP2-AS1 could promote proliferation and inhibit apoptosis of keratinocytes. Methyltransferase like 3(METTL3)-mediated m6A modification suppressed the expression of AGAP2-AS1 via YTHDF2-dependent AGAP2-AS1 stability. Thus, downregulation of METTL3 resulted in the upregulation of AGAP2-AS1 in psoriasis. AGAP2-AS1 functioned as a competitive endogenous RNA by sponging miR-424-5p to upregulate AKT3, activate AKT/mTOR pathway, as well as promote cell proliferation in keratinocytes. Conclusion AGAP2-AS1 is upregulated in the skin tissue of psoriasis patients and m6A methylation was involved in its upregulation. AGAP2-AS1 promotes keratinocyte proliferation through miR-424-5p/AKT/mTOR axis and may be a promising target for psoriasis therapy.

Background The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder. Stress and immune alterations can impact this system, through cortisol- and cytokine-induced activation. In addition, there is emerging evidence that the kynurenine pathway is associated with suicidality. There have been no studies to date exploring the immune-kynurenine system in social anxiety disorder (SAD), and indeed very limited human studies on the kynurenine pathway in any clinical anxiety disorder. Methods We investigated plasma levels of several kynurenine pathway markers, including kynurenine (KYN), tryptophan (TRYP) and kynurenic acid (KYNA), along with the KYN/TRYP and KYNA/KYN ratios, in a cohort of 32 patients with SAD and 36 healthy controls. We also investigated a broad array of both basal and lipopolysaccharide (LPS)-stimulated blood cytokine levels including IFN-γ, interleukin (IL)-10, IL-1β, IL-2, IL-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α. Results SAD patients had elevated plasma KYNA levels and an increased KYNA/KYN ratio compared to healthy controls. No differences in KYN, TRYP or the KYN/TRYP ratio were seen between the two groups. SAD patients with a history of past suicide attempt showed elevated plasma KYN levels and a higher KYN/TRYP ratio compared to patients without a history of suicide attempt. No differences were seen in basal or LPS-stimulated pro-inflammatory cytokine levels between the patients and controls. However, unstimulated IL-10, an anti-inflammatory cytokine, was significantly lower in the SAD group. A significant sex influence was evident with SAD males having lower levels of IL-10 compared to healthy males but no difference seen between SAD females and healthy females. Conclusions The peripheral kynurenine pathway is altered in SAD and preferentially directed towards KYNA synthesis. Additionally, kynurenine pathway activation, as evidenced by elevated KYN and KYN/TRYP ratio, is evident in SAD patients with a history of past suicide attempt. While no differences in pro-inflammatory cytokines is apparent in SAD patients, lower anti-inflammatory IL-10 levels are seen in SAD males. Further investigation of the role of the immune-kynurenine pathway in SAD and other clinical anxiety disorders is warranted.

Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI., Graphical abstract Image 1, Highlights • Alginate (ALG) alone has a limited vascularized ability in vivo. • ALG with 20% hyaluronic acid (HA) could attenuate LV remodeling and promote angiogenesis. • ALG-HA with lyophilized platelet-rich fibrin (Ly-PRF) could make further improvement in angiogenesis. • The Ly-PRF is promising for further clinical application because of autologous source and definite therapeutic effects.

Two coumarin-triarylimidazole hybrid derivatives having a N,N-diethylamine at 7-position and triaryl-substituted imidazole at 3-position on the coumarin core, 3-(1-(4-(tert-butyl)phenyl)-4,5-diphenyl-1H-imidazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (C-IM-Bu) and 3-(1-(4-cyanophenyl)-4,5-diphenyl-1H-imidazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (C-IM-CN), were successfully synthesized for application in organic-light emitting. Their photophysical and electrochemical properties, thermal stability and electroluminescent properties were investigated. The results showed that these compounds have excellent thermal stability, and exhibit strong blue-green emission in dichloromethane solution and green emission in thin solid films. Further, the solution-processed doped devices based on the compounds were fabricated, in which the devices fabricated from C-IM-CN exhibited the best device performance with a turn-on voltage of 3.6 V, a maximum brightness of 6896 cd/m2, a maximum current efficiency of 6.39 cd/A and a maximum external quantum efficiency of 2.92%.