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MAIN CONCLUSION: Based on phenotypic, physiological and proteomic analysis, the possible mechanism by which Ds-26-16 regulates salt tolerance in Arabidopsis seedlings was revealed. Functional and mechanistic characterization of salt tolerance genes isolated from natural resources is crucial for their application. In this study, we report the possible mechanism by which Ds-26-16, a gene from Dunaliella, and its point mutation gene EP-5, enhance salt tolerance in Arabidopsis seedlings. Both Ds-26-16 and EP-5 transgenic lines displayed higher seed germination rates, cotyledon-greening rates, soluble sugar contents, decreased relative conductivity and ROS accumulation when germinating under 150 mM NaCl conditions. Comparative proteomic analysis revealed that there were 470 or 391 differentially expressed proteins (DEPs) in Ds-26-16 or EP-5, respectively, compared with the control (3301) under salt stress. The GO and KEGG enrichment analyses showed the DEPs in Ds-26-16 vs. 3301 and EP-5 vs. 3301 were similar and mainly enriched in photosynthesis, regulation of gene expression, carbohydrate metabolism, redox homeostasis, hormonal signal and defense, and regulation of seed germination. Thirty-seven proteins were found to be stably expressed under salt stress due to the expression of Ds-26-16, and eleven of them contain the CCACGT motif which could be bound by the transcription factor in ABA signaling to repress gene transcription. Taken together, we propose that Ds-26-16, as a global regulator, improves salt-tolerance by coordinating stress-induced signal transduction and modulating multiple responses in Arabidopsis seedlings. These results provide valuable information for utilizing natural resources in crop improvement for breeding salt-tolerant crops.
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Arabidopsis , Clorofíceas , Plântula/genética , Arabidopsis/metabolismo , Tolerância ao Sal/genética , Proteômica , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética , Germinação/genéticaRESUMO
BACKGROUND: Accurate prediction of fluid responsiveness is important for postoperative critically ill elderly patients. The objective of this present study was to evaluate the predictive values of peak velocity variation (ΔVpeak) and passive leg raising (PLR)-induced changes in ΔVpeak (ΔVpeak PLR ) of left ventricular outflow tract (LVOT) to predict fluid responsiveness in postoperative critically ill elderly patients. METHOD: Seventy-two postoperative elderly patients with acute circulatory failure who were mechanically ventilated with sinus rhythm were enrolled in our study. Pulse pressure variation (PPV), ΔVpeak, and stroke volume (SV) were collected at baseline and after PLR. An increase of >10% in SV after PLR defined fluid responsiveness. Receiver operating characteristic (ROC) curves and grey zones were constructed to assess the ability of ΔVpeak and ΔVpeak PLR to predict fluid responsiveness. RESULTS: Thirty-two patients were fluid responders. The areas under the ROC curves (AUC) for baseline PPV and ΔVpeak to predict fluid responsiveness was 0.768 (95% CI, 0.653 - 0.859; p < 0.001) and 0.899 (95% CI, 0.805 - 0.958; p < 0.001) with grey zones of 7.63% to 12.66% included 41 patients (56.9%) and 9.92% to 13.46% included 28 patients (38.9%). ΔPPV PLR predicted fluid responsiveness with an AUC of 0.909 (95% CI, 0.818 - 0.964; p < 0.001), and the grey zone was 1.49% to 2.93% included 20 patients (27.8%). ΔVpeak PLR predicted fluid responsiveness with an AUC of 0.944 (95% CI, 0.863 - 0.984; p < 0.001), and the grey zone was 1.48% to 2.46% included 6 patients (8.3%). CONCLUSIONS: PLR-induced changes in peak velocity variation of blood flow in the LVOT accurately predicted fluid responsiveness with a small grey zone in postoperative critically ill elderly patients.Trial registration: ChiCTR2200059954.
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Activated alkyl halides have been extensively explored to generate alkyl radicals with Ru- and Ir- photocatalysts for 1,2-difunctionalization of alkenes, but unactivated alkyl bromides remain challenging substrates due to their strong reduction potential. Here we report a three-component 1,2-difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (e.g., amines and indoles) using a trinuclear gold catalyst [Au3(tppm)2](OTf)3. It can achieve the 1,2-aminoalkylation and 1,2-alkylarylation readily. This protocol has a broad reaction scope and excellent functional group compatibility (>100 examples with up to 96% yield). It also affords a robust formal [2+2+1] cyclization strategy for the concise construction of pyrrolidine skeletons under mild reaction conditions. Mechanistic studies support an inner-sphere single electron transfer pathway for the successful cleavage of inert C-Br bonds.
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Exploration of elementary reactions in organometallic catalysis is an important method with which to discover new reactions. In this article, we report a gold(I)-catalyzed iodo-alkynylation of benzyne involving the merging of challenging migratory insertion and an oxidative addition process in gold catalytic cycle. A wide range of structurally diverse alkynyl iodides are good coupling partners in this iodo-alkynylation transformation. Both aliphatic and aromatic alkynyl iodides can react with benzynes smoothly to afford highly functionalized 1,2-disubstituted aromatics in moderate to good yields. Its good functional group compatibility and late-stage application of complex molecules demonstrate its synthetic robustness. Studies of the mechanism reveals the feasibility of oxidative addition and the DFT calculations demonstrate the possible migratory insertion of benzyne into Au(III)-carbon bonds in the Au(I)/Au(III) redox catalytic cycle, representing an important step towards an elementary reaction in gold chemistry research.
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Adverse male reproduction caused by phthalate ester (PAE) exposure has been well documented in vivo. However, existing evidence from population studies remains inadequate to demonstrate the impact of PAE exposure on spermatogenesis and underlying mechanisms. Our present study aimed to explore the potential link between PAE exposure and sperm quality and the possible mediation by sperm mitochondrial and telomere in healthy male adults recruited from the Hubei Province Human Sperm Bank, China. Nine PAEs were determined in one pooled urine sample prepared from multiple collections during the spermatogenesis period from the same participant. Sperm telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined in sperm samples. The sperm concentration and count per quartile increment in mixture concentrations were -4.10 million/mL (-7.12, -1.08) and -13.52% (-21.62%, -4.59%), respectively. We found one quartile increase in PAE mixture concentrations to be marginally associated with sperm mtDNAcn (ß = 0.09, 95% CI: -0.01, 0.19). Mediation analysis showed that sperm mtDNAcn significantly explained 24.6% and 32.5% of the relationships of mono-2-ethylhexyl phthalate (MEHP) with sperm concentration and sperm count (ß = -0.44 million/mL, 95% CI: -0.82, -0.08; ß = -1.35, 95% CI: -2.54, -0.26, respectively). Our study provided a novel insight into the mixed effect of PAEs on adverse semen quality and the potential mediation role of sperm mtDNAcn.
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Photonic crystal fibre (PCF) embedded with functional materials has demonstrated diverse applications ranging from ultrafast lasers, optical communication to chemical sensors.[ 1] Many efforts have been made to fabricating carbon nanotube (CNT) based optical fibres by ex-situ transfer method, however, often suffer poor uniformity and coverage.[ 2] Here, we report the direct growth of CNTs on the inner walls of PCFs by the chemical vapour deposition method. A two-step growth method was developed to control the narrow diametre distribution of CNTs to ensure desirable nanotube optical transitions. In the as-fabricated CNTs embedded fibre, third-harmonic generation has been enhanced by â¼15 times compared with flat CNT film on fused silica. We further demonstrated a dual-wavelength all-fibre mode-locked ultrafast laser (â¼1561 nm and â¼1064 nm) by integrating the 1.36±0.15 nm-diametre CNTs into two kinds of photonic bandgap PCF (HC-1550 and HC-1060) as saturable absorbers, using their S11 (â¼ 0.7 eV) and S22 (â¼ 1.2 eV) interband transition respectively. The fibre laser showed stable output of â¼10 mW, â¼800 fs pulse width and â¼71 MHz repetition rate at 1561 nm wavelength. Our results can enable the large-scale applications of CNTs in PCF-based optical devices. This article is protected by copyright. All rights reserved.
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K (lysine) acetyltransferase (KAT) 5, which is a member of the KAT family of enzymes, has been found to act as a regulatory factor in various types of cancer. However, the role of KAT5 in anaplastic thyroid carcinoma (ATC) and its underlying mechanism is still elusive. The expression levels of KAT5 and kinesin family member 11 (KIF11) in ATC cells were assessed utilizing reverse transcription-quantitative PCR and western blot analyses. The cell proliferative ability was assessed via Cell Counting Kit-8 assay and using 5-ethynyl-2'-deoxyuridine staining. Flow cytometry and western blot analyses were applied for the assessment of cell apoptosis. Cell autophagy was investigated by employing western blot analysis and immunofluorescence staining. In addition, the enrichment of histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II (RNA pol II) was analyzed by chromatin immunoprecipitation assay. It was shown that KAT5 expression was markedly increased in ATC cells. KAT5 depletion suppressed the cell proliferative capability but promoted the induction of apoptosis and autophagy. In addition, the autophagy inhibitor 3-methyladenine reversed the effects of KAT5 deficiency on the proliferative and apoptotic activities of 8505C cells. With regard to the mechanism, it was found that KAT5 inhibited the expression of KIF11 by repressing the enrichment of H3K27ac and RNA pol II. Upregulation of KIF11 expression reversed the effects of KAT5 silencing on the proliferative activity, apoptosis and autophagy of 8505C cells. In conclusion, the results indicated that KAT5 induced autophagy and promoted apoptosis of ATC cells by targeting KIF11, which may provide a promising target for the treatment of ATC.
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Piezoelectric Laterally Vibrating Resonators (LVRs) have attracted significant attention as a potential technology for next-generation wafer-level multi-band filters. Piezoelectric bilayer structures such as Thin-film Piezoelectric-on-Silicon (TPoS) LVRs which aim to increase the quality factor (Q) or aluminum nitride and silicon dioxide (AlN/SiO2) composite membrane for thermal compensation have been proposed. However, limited studies have investigated the detailed behaviors of the electromechanical coupling factor (K2) of these piezoelectric bilayer LVRs. Herein, AlN/Si bilayer LVRs are selected as an example, we observed notable degenerative valleys in K2 at specific normalized thicknesses using two-dimensional finite element analysis (FEA), which has not been reported in the previous studies of bilayer LVRs. Moreover, the bilayer LVRs should be designed away from the valleys to minimize the reduction in K2. Modal-transition-induced mismatch between electric and strain fields of AlN/Si bilayer LVRs are investigated to interpret the valleys from energy considerations. Furthermore, the impact of various factors, including electrode configurations, AlN/Si thickness ratios, the Number of Interdigitated Electrode (IDT) Fingers (NFs), and IDT Duty Factors (DFs), on the observed valleys and K2 are analyzed. These results can provide guidance for the designs of piezoelectric LVRs with bilayer structure, especially for LVRs with a moderate K2 and low thickness ratio.
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Bioluminescence has been drawing broad attention due to its high signal-to-noise ratio and high bioluminescence quantum yields, which has been widely applied in the fields of biomedicine, bioanalysis, and so on. Among numerous bioluminescent substrates, coelenterazine is famous for its wide distribution. However, the oxygenation reaction mechanism of coelenterazine is far from being completely understood. In this paper, the formation and decomposition mechanisms of coelenterazine dioxetanone were investigated via density functional theory (DFT) and time-dependent (TD) DFT approaches. The results showed that the oxygenation reaction first occurred along the triplet-state potential energy surface (PES), after the intersystem crossing (ISC), second jumped to the diradical-state PES, and ultimately formed coelenterazine dioxetanone. For the decomposition mechanism of dioxetanone, the computational results showed that the chemiexcitation of neutral dioxetanone was more efficient than that of other dioxetanone species. Moreover, the diradical properties and the degree of ionic character are modified by the counter ions.
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BACKGROUND: In traditional Chinese medicine, Gynostemma pentaphyllum (G. pentaphyllum) is widely used to treat conditions associated with hyperlipidemia, and its therapeutic potential has been demonstrated in numerous studies. However, the mechanism of lipid metabolism in hyperlipidemic by G. pentaphyllum, especially heat-processed G. pentaphyllum is not yet clear. PURPOSE: The aim of this study was to investigate the therapeutic mechanism of gypenosides from heat-processed G. pentaphyllum (HGyp) in hyperlipidemic mice by means of a lipidomics. METHODS: The content of the major components of HGyp was determined by ultra-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (UPLC-ESI-MS). An animal model of hyperlipidaemia was constructed using C57BL/6J mice fed with high-fat diet. HGyp was also administered at doses of 50, 100 and 200 mg/kg, all for 12 weeks. Serum parameters were measured, histological sections were prepared and liver lipidome analysis using UPLC-MS coupled with multivariate statistical analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the genes and proteins associated with lipid lowering in HGyp. RESULTS: HGyp reduced body weight, serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) and hepatic lipid accumulation in hyperlipidemic obese mice. To explore specific changes in lipid metabolism in relation to HGyp administration, lipid analysis of the liver was performed. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that HGyp altered lipid metabolism in HFD mice. In particular, fatty acids (FA), triglycerides (DG), TG and ceramides (CER) were significantly altered. Eleven lipids were identified as potential lipid biomarkers, namely TG (18:2/20:5/18:2), TG (18:2/18:3/20:4), DG (18:3/20:0/0:0), Cer (d18:1/19:0), Cer (d16:1/23:0), Ceramide (d18:1/9Z-18:1), PS (19:0/18:3), PS (20:2/0:0), LysoPC (22:5), LysoPE (0:0/18:0), PE (24:0/16:1). Western blot and qRT-PCR analysis showed that these metabolic improvements played a role by down-regulating genes and proteins related to fat production (SREBP1, ACC1, SCD1), up-regulating genes and proteins related to lipid oxidation (CPTA1, PPARα) and lipid transport decomposition in the bile acid pathway (LXRα, PPARγ, FXR, BSEP). CONCLUSION: The lipid-lowering effect of gypenosides from heat-processed G. pentaphyllum is regulate lipid homeostasis and metabolism.
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Hiperlipidemias , Lipidômica , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Gynostemma/química , Cromatografia Líquida , Temperatura Alta , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Fígado , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , TriglicerídeosRESUMO
Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes Fusarium wilt of banana, necessitating urgent measures to control this disease. However, the molecular mechanisms underlying Foc TR4 virulence remain elusive. Phosphomannose isomerase is a key enzyme involved in the biosynthesis of GDP mannose, an important precursor of fungal cell walls. In this study, two phosphomannose isomerases were identified in the Foc TR4 genome, of which only Focpmi1 was highly expressed throughout all developmental stages. Generated null mutants in Foc TR4 showed that only the ΔFocpmi1 mutant required exogenous mannose for growth, indicating that Focpmi1 is the key enzyme involved in GDP mannose biosynthesis. The Focpmi1 deficient strain was unable to grow without exogenous mannose and exhibited impaired growth under stress conditions. The mutant had reduced chitin content in its cell wall, rendering it vulnerable to cell wall stresses. Transcriptomic analysis revealed up- and down-regulation of several genes involved in host cell wall degradation and physiological processes due to the loss of Focpmi1. Furthermore, Focpmi1 was also found to be crucial for Foc TR4 infection and virulence, making it a potential antifungal target to address the threats posed by Foc TR4.
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Reticular chemistry provides opportunities to design solid-state electrolytes (SSEs) with modular tunability. However, SSEs based on modularly designed crystalline metal-organic frameworks (MOFs) often require liquid electrolytes for interfacial contact. Monolithic glassy MOFs can have liquid processability and uniform lithium conduction, which is promising for the reticular design of SSE without liquid electrolytes. Here, we develop a generalizable strategy for the modular design of noncrystalline SSEs based on a bottom-up synthesis of glassy MOFs. We demonstrate such a strategy by linking polyethylene glycol (PEG) struts and nanosized titanium-oxo clusters into network structures termed titanium alkoxide networks (TANs). The modular design allows the incorporation of PEG linkers with different molecular weights, which give optimal chain flexibility for high ionic conductivity, and the reticular coordinative network provides a controlled degree of cross-linking that gives adequate mechanical strength. This research shows the power of reticular design in noncrystalline molecular framework materials for SSEs.
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Specific biomarkers of ferroptosis after peripheral nerve injury (PNI) are still under debate. In this study, 52 differentially expressed ferroptosis-related genes (DE-FRGs) were retrieved from publicly accessible sequencing data of intact and injured samples of rats with sciatic nerve crush injury. Functional enrichment analyses revealed that adipogenesis, mitochondrial gene sets, and pathways of MAPK, p53, and CD28 family were predominantly engaged in ferroptosis after PNI. Next, Cdkn1a, Cdh1, Hif1a, Hmox1, Nfe2l2, and Tgfb1 were investigated as new ferroptosis-associated hub genes after PNI. Subsequently, clustering correlation heatmap shows six hub genes are linked to mitochondria. The immunofluorescence assay at 0, 1, 4, 7, and 14 days indicated the temporal expression patterns of Tgfb1, Hmox1, and Hif1a after PNI were consistent with ferroptosis validated by PI and ROS staining, while Cdh1, Cdkn1a, and Nfe2l2 were the opposite. In summary, this study identified six hub genes as possible ferroptosis-related biomarkers for PNI, which may offer therapeutic targets for peripheral nerve regeneration and provide a therapeutic window for ferroptosis.
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Lignin has many potential applications and is a biopolymer with a three-dimensional network structure. It is composed of three phenylpropane units, p-hydroxyphenyl, guaiacyl, and syringyl, connected by ether bonds and carbon-carbon bonds, and it contains a large number of phenol or aldehyde structural units, resulting in complex lignin structures. This limits the application of lignin. To expand the application range of lignin, we prepared lignin thermoplastic phenolic resins (LPRs) by using lignin instead of phenol; these LPRs had molecular weights of up to 1917 g/mol, a molecular weight distribution of 1.451, and an O/P value of up to 2.73. Due to the complex structure of the lignin, the synthetic lignin thermoplastic phenolic resins were not very tough, which greatly affected the performance of the material. If the lignin phenolic resins were toughened, their application range would be substantially expanded. Polybutylene succinate (PBS) has excellent processability and excellent mechanical properties. The toughening effects of different PBS contents in the LPRs were investigated. PBS was found to be compatible with the LPRs, and the flexible chain segments of the small PBS molecules were embedded in the molecular chain segments of the LPRs, thus reducing the crystallinities of the LPRs. The good compatibility between the two materials promoted hydrogen bond formation between the PBS and LPRs. Rheological data showed good interfacial bonding between the materials, and the modulus of the high-melting PBS made the LPRs more damage resistant. When PBS was added at 30%, the tensile strength of the LPRs was increased by 2.8 times to 1.65 MPa, and the elongation at break increased by 31 times to 93%. This work demonstrates the potential of lignin thermoplastic phenolic resins for industrial applications and provides novel concepts for toughening biobased aromatic resins with PBS.
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Materiais Biocompatíveis , Lignina , Lignina/química , Materiais Biocompatíveis/química , Fenóis , Resinas SintéticasRESUMO
Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.
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Background: The application of robotic-assisted radical resection in perihilar cholangiocarcinoma (pCCA) remains poorly defined. This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute. Methods: Between July 2017 and July 2022, pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The short-term outcomes were compared by using propensity-scored matching (PSM) analysis. Results: Eighty-six pCCA patients were enrolled. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robotic-assisted and open groups, respectively. There were no significant disparities in the clinicopathological features between the two groups. The robotic-assisted group had significantly longer operation time (median: 548 vs 353 min, P = 0.004) and larger total number of lymph nodes examined (median: 11 vs 5, P = 0.010) than the open group. The robotic-assisted group tended to have a lower intraoperative blood loss (median: 125 vs 350 mL, P = 0.067), blood transfusion rates (30.0% vs 70.0%, P = 0.056), and post-operative overall morbidities (30.0% vs 70.0%, P = 0.056) than the open group, even though the differences were not statistically significant. There were no significant differences in the negative resection margin, post-operative major morbidities, or post-operative length-of-stay between the robotic-assisted and open groups (all P > 0.05). Conclusions: Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery. Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.
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OBJECTIVE: To assess whether velocity-time integral (VTI) variation and peak velocity (Vpeak) variation of the left ventricular outflow tract (LVOT) accurately could predict fluid responsiveness in postoperative critically ill patients mechanically ventilated at low tidal volumes. DESIGN: A prospective, single-center, observational study. SETTING: A surgical intensive care unit at a tertiary hospital. PARTICIPANTS: Sixty postoperative critically ill patients with deep sedation and mechanical ventilation (tidal volume <8 mL/kg) were included in this study. INTERVENTIONS: Passive leg raising (PLR). MEASUREMENT AND MAIN RESULTS: Pulse pressure variation (PPV), VTI variation, and Vpeak variation were measured at baseline and after PLR by transthoracic echocardiography. The fluid responsiveness was defined as an increase (>10%) in stroke volume after PLR. Thirty-two (53.3%) patients were fluid responders. The areas under the receiver operating characteristic (AUROC) curves for PPV were 0.797, and the gray zone was large and included 58.3% of patients. Both VTI variation and Vpeak variation predicted fluid responsiveness with the AUROC of 0.919 and 0.905; meanwhile, the best cutoff values were 12.51% (sensitivity of 71.9%; specificity of 75.0%) and 11.76% (sensitivity of 81.3%; specificity of 89.3%). The gray zones of VTI variation and Vpeak variation were from 7.41% to 11.88% (contained 23.3% patients) and from 9.96% to 13.10% (contained 28.3% patients). CONCLUSIONS: In postoperative critically ill patients mechanically ventilated with tidal volume <8 mL/kg, the VTI variation and Vpeak variation of LVOT accurately could predict fluid responsiveness, and VTI variation showed more accuracy than Vpeak variation in predicting fluid responsiveness.
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Estado Terminal , Respiração Artificial , Humanos , Volume de Ventilação Pulmonar , Velocidade do Fluxo Sanguíneo , Estudos Prospectivos , Hidratação , Pressão Sanguínea , Volume Sistólico , HemodinâmicaRESUMO
Involving eight electron transfer process and multiple intermediates of nitrate (NO3 - ) reduction reaction leads to a sluggish kinetic and low Faradaic efficiency, therefore, it is essential to get an insight into the reaction mechanism to develop highly efficient electrocatalyst. Herein, a series of reduced-graphene-oxide-supported RuCu alloy catalysts (Rux Cux /rGO) are fabricated and used for the direct reduction of NO3 - to NH3 . It is found that the Ru1 Cu10 /rGO shows the ammonia formation rate of 0.38 mmol cm-2 h-1 (loading 1 mg cm-2 ) and the ammonia Faradaic efficiency of 98% under an ultralow potential of -0.05 V versus Reversible Hydrogen Electode (RHE), which is comparable to Ru catalyst. The highly efficient activity of Ru1 Cu10 /rGO can be attributed to the synergetic effect between Ru and Cu sites via a relay catalysis, in which the Cu shows the exclusively efficient activity for the reduction of NO3 - to NO2 - and Ru exhibits the superior activity for NO2 - to NH3 . In addition, the doping of Ru into Cu tunes the d-band center of alloy and effectively modulates the adsorption energy of the NO3 - and NO2 - , which promotes the direct reduction of NO3 - to NH3 . This synergetic electrocatalysis strategy opens a new avenue for developing highly efficient multifunctional catalysts.
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Spring viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus infecting the common carp, yet neither a vaccine nor effective therapies are available to treat spring viremia of carp (SVC). Like all negative-sense viruses, SVCV contains an RNA genome that is encapsidated by the nucleoprotein (N) in the form of a ribonucleoprotein (RNP) complex, which serves as the template for viral replication and transcription. Here, the three-dimensional (3D) structure of SVCV RNP was resolved through cryo-electron microscopy (cryo-EM) at a resolution of 3.7 Å. RNP assembly was stabilized by N and C loops; RNA was wrapped in the groove between the N and C lobes with 9 nt nucleotide per protomer. Combined with mutational analysis, our results elucidated the mechanism of RNP formation. The RNA binding groove of SVCV N was used as a target for drug virtual screening, and it was found suramin had a good antiviral effect. This study provided insights into RNP assembly, and anti-SVCV drug screening was performed on the basis of this structure, providing a theoretical basis and efficient drug screening method for the prevention and treatment of SVC. IMPORTANCE Aquaculture accounts for about 70% of global aquatic products, and viral diseases severely harm the development of aquaculture industry. Spring viremia of carp virus (SVCV) is the pathogen causing highly contagious spring viremia of carp (SVC) disease in cyprinids, especially common carp (Cyprinus carpio), yet neither a vaccine nor effective therapies are available to treat this disease. In this study, we have elucidated the mechanism of SVCV ribonucleoprotein complex (RNP) formation by resolving the 3D structure of SVCV RNP and screened antiviral drugs based on the structure. It is found that suramin could competitively bind to the RNA binding groove and has good antiviral effects both in vivo and in vitro. Our study provides a template for rational drug discovery efforts to treat and prevent SVCV infections.
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Modelos Moleculares , Rhabdoviridae , Ribonucleoproteínas , Proteínas Virais , Ribonucleoproteínas/química , Ribonucleoproteínas/metabolismo , Rhabdoviridae/química , Rhabdoviridae/efeitos dos fármacos , Proteínas Virais/química , Proteínas Virais/metabolismo , Estrutura Quaternária de Proteína , Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos , Microscopia Crioeletrônica , Suramina/farmacologiaRESUMO
In high-cold regions, alfalfa is susceptible to cold damage during the seed germination. The effects of discontinuous low temperature stress and plant growth regulators (PGRs) on alfalfa were studied in response to the high day/night temperature differentials in the area. The experiments included seed germination, seedling cold tolerance and plant recovery. Variable temperatures (VT) of 0 °C/15 °C, 5 °C/20 °C and 10 °C/25 °C were set and seeds were soaked with alginate oligosaccharides (AOS), brassinolide (BR) and diethyl aminoethyl hexanoate (DA-6) during the germination period. Parameters such as seed germination and mean germination time (MGT), phenylalanine ammonia-lyase (PAL) activity and oligomeric proanthocyanidins (OPC) content of early seedlings, dry matter accumulation and root crown of the restored plants were analysed. The results showed that low variable-temperature (LVT) stress prolonged the MGT but had little inhibitory effect on germination percentage. Early seedlings adapted to LVT stress by regulating their own water and OPC content, PAL activity and other parameters. LVT induced early alfalfa seedlings to increase their underground biomass by shortening root length and increasing root diameter, and those that had accumulated more underground biomass had faster growth rates and higher total biomass when the ambient temperature rose. AOS also promoted an increase in root crown diameter and root dry weight. This research proved that LVT stress and AOS during the germination process can lead to better growth of alfalfa in high cold regions.