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Plant can recruit beneficial microbes to enhance their ability to resist disease. Selenium is well established as a beneficial element in plant growth, but its role in mediating microbial disease resistance remained poorly understood. Here, we investigated the correlation between selenium, oilseed rape rhizosphere microbes and Sclerotinia sclerotiorum. Soil application of 0.5 and 1.0 mg/kg selenium significantly increased the resistance of oilseed rape to Sclerotinia sclerotiorum compared with no selenium application, and the disease inhibition rate was higher than 20%. The disease resistance of oilseed rape was related to rhizosphere microorganisms, and beneficial bacteria isolated from the rhizosphere inhibited Sclerotinia stem rot. Burkholderia cepacia, and synthetic community enhanced plant disease resistance through transcriptional regulation and activated plant-induced systemic resistance to protect plants. Besides, inoculation of isolated bacteria optimized the bacterial community structure of leaves and enriched beneficial microorganisms such as Bacillus, Pseudomonas and Sphingomonas. Bacillus isolated from the leaves were sprayed on the detached leaves, and it also performed a significant inhibition effect on Sclerotinia sclerotiorum. Overall, our results suggested that selenium drive plant rhizosphere microorganisms to increase resistance to Sclerotinia sclerotiorum in oilseed rape.
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Janus heterostructures consisting of multiple jointed components with distinct properties have gained growing interest in the photoredox catalytic field. Herein, we have developed a facile low-temperature method to gain anisotropic one-dimensional Au-tipped CdS (Au-CdS) nanorods (NRs), followed by assembling Ru molecular co-catalyst (RuN5) onto the surface of the NRs. The CdS NRs decorated with plasmonic Au nanoparticles (NPs) and RuN5 complex harness the virtues of metal-semiconductor and inorganic-organic interface, giving directional charge transfer channels, spatially separated reaction sites, and enhanced local electric field distribution. As a result, the Au-CdS-RuN5 can act as an efficient dual-function photocatalyst for simultaneous H2 evolution and valorization of biomass-derived alcohols. Benefiting from the interfacial charge decoupling and selective chemical bond activation, the optimal all-in-one Au-CdS-RuN5 heterostructure shows greatly enhanced photoactivity and selectivity as compared to bare CdS NRs, along with a remarkable apparent quantum yield of 40.2 % at 400â nm. The structural evolution and working mechanism of the heterostructures are systematically analyzed based on experimental and computational results.
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PURPOSE: Orbital [99mTc]TcDTPA orbital single-photon emission computed tomography (SPECT)/CT is an important method for assessing inflammatory activity in patients with Graves' orbitopathy (GO). However, interpreting the results requires substantial physician workload. We aim to propose an automated method called GO-Net to detect inflammatory activity in patients with GO. MATERIALS AND METHODS: GO-Net had two stages: (1) a semantic V-Net segmentation network (SV-Net) that extracts extraocular muscles (EOMs) in orbital CT images and (2) a convolutional neural network (CNN) that uses SPECT/CT images and the segmentation results to classify inflammatory activity. A total of 956 eyes from 478 patients with GO (active: 475; inactive: 481) at Xiangya Hospital of Central South University were investigated. For the segmentation task, five-fold cross-validation with 194 eyes was used for training and internal validation. For the classification task, 80% of the eye data were used for training and internal fivefold cross-validation, and the remaining 20% of the eye data were used for testing. The EOM regions of interest (ROIs) were manually drawn by two readers and reviewed by an experienced physician as ground truth for segmentation GO activity was diagnosed according to clinical activity scores (CASs) and the SPECT/CT images. Furthermore, results are interpreted and visualized using gradient-weighted class activation mapping (Grad-CAM). RESULTS: The GO-Net model combining CT, SPECT, and EOM masks achieved a sensitivity of 84.63%, a specificity of 83.87%, and an area under the receiver operating curve (AUC) of 0.89 (p < 0.01) on the test set for distinguishing active and inactive GO. Compared with the CT-only model, the GO-Net model showed superior diagnostic performance. Moreover, Grad-CAM demonstrated that the GO-Net model placed focus on the GO-active regions. For EOM segmentation, our segmentation model achieved a mean intersection over union (IOU) of 0.82. CONCLUSION: The proposed Go-Net model accurately detected GO activity and has great potential in the diagnosis of GO.
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Visible-light-driven C-C bond formation utilizing ketyl radical (Cketyl ) species has attracted increasing attention recently, as it provides a direct route for the synthesis of complex molecules. However, the most-developed homogeneous photocatalytic systems for the generation and utilization of ketyl radicals usually entail noble metal-based (e. g., Ru and Ir) photosensitizers, which suffer from not only high cost but also potential degradation and hence pose challenges in product separation and purification. In contrast, readily accessible, inexpensive, and recyclable semiconductors represent a class of attractive and alternative photocatalysts but remain much less explored for photocatalytic ketyl radical initiated C-C bond formation. This work demonstrates that a wide range of industrially important chemicals, including substituted chromanes and tertiary alcohols, can be produced on ZnIn2 S4 under visible light irradiation through intramolecular cyclization (Cketyl -Csp2 ) and intermolecular cross-coupling (Cketyl -Csp3 ) reactions, respectively, using ketyl radicals. A suite of experimental studies aided by computational investigation were carried out to shed light on the mechanistic insights of these two types of ketyl radical initiated C-C coupling reactions on ZnIn2 S4 .
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Hidrolasas , Luz , Ciclización , Fármacos Fotosensibilizantes , SemiconductoresRESUMEN
During our previous study, strain NEAU-J3T was classified as representing a novel genus 'Wangella' within the family Micromonosporaceae. Nevertheless, it is a great pity the name cannot be validated as the proposed genus name is illegitimate (Principle 2 of the ICNP). In this study, we describe Jidongwangia as a novel genus within the family Micromonosporaceae and a polyphasic approach was used to provide evidence to support the classification. The G+C content of the genomic DNA of the type strain is 71.6â%. Digital DNA-DNA hybridization and average nucleotide identity (ANI) values could be used to differentiate NEAU-J3T from its related type strains. The phenotypic, genetic and chemotaxonomic data also indicated that NEAU-J3T occupies a branch separated from those of known genera in the family Micromonosporaceae. Therefore, NEAU-J3T represents a novel species of a novel genus in the family Micromonosporaceae, for which the name Jidongwangia harbinensis gen. nov., sp. nov. is proposed. The type strain of Jidongwangia harbinensis is NEAU-J3T (= CGMCC 4.7039T = DSM 45747T).
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Ácidos Grasos , Micromonosporaceae , Ácidos Grasos/química , ADN Bacteriano/genética , Composición de Base , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Técnicas de Tipificación Bacteriana , ChinaRESUMEN
The simultaneous utilization of electrons and holes to couple photocatalytic H2 production with selective biomass transformation has attracted immense interest toward achieving sustainability in the fields of energy and chemical industry. In this study, by assembling highly dispersed Ni(OH)2 onto ZnIn2S4 (ZIS), efficient H2 evolution along with highly selective photocatalytic oxidation of furfuryl alcohol (FA) to furfural (FF) in pure water was achieved under anaerobic conditions. The H2 production and FA conversion rates over the optimal Ni-ZIS sample reached about 686 and 583 µmol g-1 h-1, respectively, about 4.9 and 1.7 folds as those of pure ZIS. Moreover, the formation of by-products with C-C coupling was dramatically suppressed over Ni-ZIS, resulting in higher selectivity for FF (97%), which is about 2.7-fold that of pure ZIS (36%). Deep mechanistic studies were conducted to reveal the structural evolution and cocatalyst effects of Ni(OH)2. This study not only offers a feasible paradigm for modifying the surface of catalysts to tune the photoactivity and selectivity for product-oriented alcohol oxidation coupled with efficient H2 production in water but also reveals the working mechanism of the deposited Ni(OH)2 over ZIS toward coupling reactions.
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The direction estimation of the coherent source in a uniform circular array is an essential part of the signal processing area of the array, but the traditional uniform circular array algorithm has a low localization accuracy and a poor localization effect on the coherent source. To solve this problem, this paper proposes a two-dimensional direction of arrival (DOA) estimation for the coherent source in broadband. Firstly, the central frequency of the coherent sound source is estimated using the frequency estimation method of the delayed data, and a real-valued beamformer is constructed using the concept of the multiloop phase mode. Then, the cost function in the beam space is obtained. Finally, the cost function is searched in two dimensions to locate the sound source. In this paper, we simulate the DOA of the sound source at different frequencies and signal-to-noise ratios and analyze the resolution of the circular array. The simulation results show that the proposed algorithm can estimate the direction of arrival with high precision and achieve the desired results.
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Myocardial infarction (MI) has the characteristics of high mortality rate, strong suddenness and invisibility. There are problems such as the delayed diagnosis, misdiagnosis and missed diagnosis in clinical practice. Electrocardiogram (ECG) examination is the simplest and fastest way to diagnose MI. The research on MI intelligent auxiliary diagnosis based on ECG is of great significance. On the basis of the pathophysiological mechanism of MI and characteristic changes in ECG, feature point extraction and morphology recognition of ECG, along with intelligent auxiliary diagnosis method of MI based on machine learning and deep learning are all summarized. The models, datasets, the number of ECG, the number of leads, input modes, evaluation methods and effects of different methods are compared. Finally, future research directions and development trends are pointed out, including data enhancement of MI, feature points and dynamic features extraction of ECG, the generalization and clinical interpretability of models, which are expected to provide references for researchers in related fields of MI intelligent auxiliary diagnosis.
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Electrocardiografía , Infarto del Miocardio , Humanos , Infarto del Miocardio/diagnóstico , Reconocimiento en PsicologíaRESUMEN
A novel lignin-degrading actinobacterium, designated NEAU-G5T, was isolated from pumpkin rhizosphere soil collected from field in Mudanjiang, Heilongjiang Province, northeast China, and characterized using polyphasic approach. The prior 16S rRNA gene sequence similarities and phylogenic analysis showed that strain NEAU-G5T exhibited close phylogenetic relatedness to Nocardia miyunensis NBRC 108239T (98.82â%), Nocardia nova NBRC 15556T (98.75â%), Nocardia jiangxiensis NBRC 101359T (98.68â%) and Nocardia macrotermitis RB20T (98.61â%). Morphological and chemotaxonomic characteristics indicated that strain NEAU-G5T could be assigned to the genus Nocardia. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and an unidentified lipid. The predominant menaquinone was MK-8(H4, ω-cycl). The major fatty acids (>10â%) were identified as C16â:â0, C18â:â1 ω9c, 10-methyl C18â:â0 and C18â:â0. Mycolic acids were present. The genomic DNA G+C content of strain NEAU-G5T was 68âmol%. Moreover, based on digital DNA-DNA hybridization and average nucleotide identity values, strain NEAU-G5T could be differentiated from its reference strains. In addition, an azure B plate decolorization test and genomic analysis indicated that strain NEAU-G5T had the ability to degrade lignin. On the basis of polyphasic characteristics, strain NEAU-G5T represents a novel species of the genus Nocardia, with the name Nocardia albiluteola sp. nov. The type strain is NEAU-G5T (=CCTCC AA 2021018T=DSM 110547T).
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Actinobacteria , Cucurbita , Nocardia , Actinobacteria/genética , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Lignina , Filogenia , ARN Ribosómico 16S/genética , Rizosfera , Análisis de Secuencia de ADN , Suelo , Microbiología del SueloRESUMEN
A Gram-stain-positive, aerobic actinobacterium, designated strain NEAU-24T, was isolated from saline-alkali soil collected from Daqing City, Heilongjiang Province, PR China. Strain NEAU-24T was found to produce abundant substrate mycelia but no aerial hyphae. The substrate mycelia formed irregular pseudosporangia consisting of nuciform spores, and the surface of the spores was smooth. 16S rRNA gene sequence analysis showed that strain NEAU-24T clustered with Pseudosporangium ferrugineum 3-44-a(19)T, Couchioplanes caeruleus subsp. azureus DSM 44103T and C. caeruleus subsp. caeruleus DSM 43634T within the family Micromonosporaceae and was most closely related to P. ferrugineum 3-44-a(19)T (99.17 %). The strain contained meso-diaminopimelic acid as the cell-wall diamino acid and MK-9(H6) as the menaquinone. The whole cell sugar profile consisted of glucose, galactose, xylose and arabinose. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, phosphatidylinositol and an unidentified lipid. The major fatty acids were summarized as C16â:â0, C15â:â0, C17â:â0, iso-C16â:â0 and iso-C17â:â0. The low digital DNA-DNA hybridization and average nucleotide identity values could differentiate strain NEAU-24T from its related type strains. The phenotypic, genetic and chemotaxonomic data also indicated that strain NEAU-24T occupied a branch separated from those of known genera in the family Micromonosporaceae. In addition, genomic analysis confirmed that strain NEAU-24T had the potential to produce chitinase. Therefore, strain NEAU-24T represents a novel species of a new genus and species in the family Micromonosporaceae, for which the name Nucisporomicrobium flavum gen. nov., sp. nov. is proposed. The type strain of Nucisporomicrobium flavum is NEAU-24T (=CCTCC AA 2020016T=JCM 33973T).
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Micromonosporaceae , Rizosfera , ARN Ribosómico 16S/genética , Suelo/química , Microbiología del Suelo , Álcalis , Filogenia , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Ácidos Grasos/química , Análisis de Secuencia de ADNRESUMEN
A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC50 = 0.88 ± 0.78 µM), which was better than that of Huperzine-A, and its inhibitory effect on BuChE was weak (IC50 = 10.0 ± 1.30 µM), which indicated that compound 10q was a dominant AChE inhibitor. In addition, the result of molecular docking study displayed that 10q could simultaneously bind to CAS and PAS sites of AChE, which was consistent with the mixed inhibition mode shown by the enzymatic kinetics study of 10q. Furthermore, the molecular properties of the target compounds were predicted online using the molinspiration server and pkCSM, The results exhibited that compound 10q had drug-like properties that satisfied the Lipinski's rule of five. Based on the bioactivity and molecular properties, compound 10q for further development was valuable.
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Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Diseño de Fármacos , Humanos , Simulación del Acoplamiento Molecular , Pirimidinas/farmacología , Relación Estructura-ActividadRESUMEN
Heterogeneous photocatalysis is less common but can provide unique avenues for inducing novel chemical transformations and can also be utilized for energy transductions, i.e., the energy in the photons can be captured in chemical bonds. Here, we developed a novel heterogeneous photocatalytic system that employs a lead-halide perovskite nanocrystal (NC) to capture photons and direct photogenerated holes to a surface bound transition metal Cu-site, resulting in a N-N heterocyclization reaction. The reaction starts from surface coordinated diamine substrates and requires two subsequent photo-oxidation events per reaction cycle. We establish a photocatalytic pathway that incorporates sequential inner sphere electron transfer events, photons absorbed by the NC generate holes that are sequentially funneled to the Cu-surface site to perform the reaction. The photocatalyst is readily prepared via a controlled cation-exchange reaction and provides new opportunities in photodriven heterogeneous catalysis.
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Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Coenzima A Ligasas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Coenzima A Ligasas/genética , Ferroptosis/efectos de los fármacos , Técnicas de Inactivación de Genes , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones Endogámicos BALB C , Pronóstico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change. METHODS: A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion. RESULTS: Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI. CONCLUSION: Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.
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Tornillos Pediculares , Fusión Vertebral , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Esclerosis/diagnóstico por imagen , Esclerosis/patología , Fusión Vertebral/efectos adversosRESUMEN
Opportunistic beamforming (OBF) is a potential technique in the fifth generation (5G) and beyond 5G (B5G) that can boost the performance of communication systems and encourage high user quality of service (QoS) through multi-user selection gain. However, the achievable rate tends to be saturated with the increased number of users, when the number of users is large. To further improve the achievable rate, we proposed a multi-antenna opportunistic beamforming-based relay (MOBR) system, which can achieve both multi-user and multi-relay selection gains. Then, an optimization problem is formulated to maximize the achievable rate. Nevertheless, the optimization problem is a non-deterministic polynomial (NP)-hard problem, and it is difficult to obtain an optimal solution. In order to solve the proposed optimization problem, we divide it into two suboptimal issues and apply a joint iterative algorithm to consider both the suboptimal issues. Our simulation results indicate that the proposed system achieved a higher achievable rate than the conventional OBF systems and outperformed other beamforming schemes with low feedback information.
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Solar-driven syngas production by CO2 reduction provides a sustainable strategy to produce renewable feedstocks. However, this promising reaction often suffers from tough CO2 activation, sluggish oxidative half-reaction kinetics and undesired by-products. Herein, we report a function-oriented strategy of deliberately constructing black phosphorus quantum dots-ZnIn2 S4 (BP/ZIS) heterostructures for solar-driven CO2 reduction to syngas, paired with selectively oxidative C-N bond formation, in one redox cycle. The optimal BP/ZIS heterostructure features the enhanced charge-carrier separation and enriched active sites for cooperatively photocatalytic syngas production with a tunable ratio of CO/H2 and efficient oxidation of amines to imines with high conversion and selectivity. This prominent catalytic performance arises from the efficient electronic coupling between black phosphorus quantum dots and ZnIn2 S4 , as well as the optimized adsorption strength for key reaction intermediates, as supported by both experimental and theoretical investigations. We also demonstrate a synergistic interplay between CO2 reduction and amine dehydrogenation oxidation, rather than simply collecting these two single half-reactions in this dual-functional photoredox system.
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Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.
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Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Ciclo Celular/genética , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Hepáticas/genética , Oncogenes/genética , Fosfoinositido Fosfolipasa C/genética , Adulto , Apoptosis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Supervivencia sin Enfermedad , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Masculino , Recurrencia Local de Neoplasia/genética , Pronóstico , ARN Mensajero/genéticaRESUMEN
Lately, heterogeneous semiconductor materials have been explored as an emerging type of efficient photocatalyst for photoredox organic synthesis. Among these semiconductors, lead halide perovskite materials demonstrate unique properties towards excellent charge separation and charge transfer, extremely long charge carrier migration, high efficiency in visible light absorption, and long excited states lifetimes, etc., as proved in ground-breaking solar cell applications, garnering necessary merits for an efficient catalytic system for photoredox organic reactions. Here, the latest progress in heterogeneous semiconductor materials towards this endeavor is examined, with particular emphasis on lead halide perovskite nanocrystals (NCs) in photocatalytic organic synthesis.
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A series of new 4-arylthiazole-2-amine derivatives as acetylcholinesterase inhibitors (AChEIs) were designed and synthesized, Furthermore, their inhibitory activities against acetylcholinesterase in vitro were tested by Ellman spectrophotometry, and the results of inhibitory activity test showed that most of them had a certain acetylcholinesterase inhibitory activity in vitro. Moreover, the IC50 value of compound 4f was to 0.66 µM, which was higher than that of Rivastigmine and Huperzine-A as reference compounds, and it had a weak inhibitory effect on butyrylcholinesterase. The potential binding mode of compound 4f with AChE was investigated by the molecular docking, and the results showed that 4f was strongly bound up with AChE with the optimal conformation, in addition, their binding energy reached -11.27 Kcal*mol-1. At last, in silico molecular property of the synthesized compounds were predicted by using Molinspiration online servers. It can be concluded that the lead AChEIs compound 4f presented satisfactory drug-like characteristics.
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Acetilcolinesterasa/metabolismo , Aminas/síntesis química , Inhibidores de la Colinesterasa/síntesis química , Fármacos Neuroprotectores/síntesis química , Tiazoles/química , Alcaloides/farmacología , Alcaloides/normas , Aminas/farmacología , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Diseño de Fármacos , Humanos , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/farmacología , Rivastigmina/farmacología , Rivastigmina/normas , Sesquiterpenos/farmacología , Sesquiterpenos/normas , Relación Estructura-ActividadRESUMEN
BACKGROUND: This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). METHODS: A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis. RESULTS: In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway. CONCLUSION: GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.