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Combination therapy has exhibited substantial potential compared to monotherapy. However, due to the explosive growth in the number of cancer drugs, the screening of synergistic drug combinations has become both expensive and time-consuming. Synergistic drug combinations refer to the concurrent use of two or more drugs to enhance treatment efficacy. Currently, numerous computational methods have been developed to predict the synergistic effects of anticancer drugs. However, there has been insufficient exploration of how to mine drug and cell line data at different granularity levels for predicting synergistic anticancer drug combinations. Therefore, this study proposes a granularity-level information fusion strategy based on the hypergraph transformer, named HypertranSynergy, to predict synergistic effects of anticancer drugs. HypertranSynergy introduces synergistic connections between cancer cell lines and drug combinations using hypergraph. Then, the Coarse-grained Information Extraction (CIE) module merges the hypergraph with a transformer for node embeddings. In the CIE module, Contranorm is a normalization layer that mitigates over-smoothing, while Gaussian noise addresses local information gaps. Additionally, the Fine-grained Information Extraction (FIE) module assesses fine-grained information's impact on predictions by employing similarity-aware matrices from drug/cell line features. Both CIE and FIE modules are integrated into HypertranSynergy. In addition, HypertranSynergy achieved the AUC of 0.93${\pm }$0.01 and the AUPR of 0.69${\pm }$0.02 in 5-fold cross-validation of classification task, and the RMSE of 13.77${\pm }$0.07 and the PCC of 0.81${\pm }$0.02 in 5-fold cross-validation of regression task. These results are better than most of the state-of-the-art models.
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Antineoplásicos , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular , Terapia Combinada , Combinação de MedicamentosRESUMO
Recent developments of deep learning methods have demonstrated their feasibility in liver malignancy diagnosis using ultrasound (US) images. However, most of these methods require manual selection and annotation of US images by radiologists, which limit their practical application. On the other hand, US videos provide more comprehensive morphological information about liver masses and their relationships with surrounding structures than US images, potentially leading to a more accurate diagnosis. Here, we developed a fully automated artificial intelligence (AI) pipeline to imitate the workflow of radiologists for detecting liver masses and diagnosing liver malignancy. In this pipeline, we designed an automated mass-guided strategy that used segmentation information to direct diagnostic models to focus on liver masses, thus increasing diagnostic accuracy. The diagnostic models based on US videos utilized bi-directional convolutional long short-term memory modules with an attention-boosted module to learn and fuse spatiotemporal information from consecutive video frames. Using a large-scale dataset of 50 063 US images and video frames from 11 468 patients, we developed and tested the AI pipeline and investigated its applications. A dataset of annotated US images is available at https://doi.org/10.5281/zenodo.7272660.
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Inteligência Artificial , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Fluxo de TrabalhoRESUMO
Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.
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Alelos , Cromossomos de Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Fenótipo , Pleiotropia Genética , Melhoramento VegetalRESUMO
Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 µM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch.
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DNA , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Bibliotecas de Moléculas Pequenas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Humanos , DNA/química , DNA/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/antagonistas & inibidores , Descoberta de Drogas , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: Physical activity (PA) plays an important role in the process of several chronic diseases. It may be also associated with the incidence of sarcopenia. This study aimed to determine the association of PA from different components including frequency, duration, intensity, and volume with the incidence of sarcopenia in middle-aged and older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study in 2011 and 2015. A total of 3,760 individuals aged ≥ 40 years were involved in this study. Sarcopenia was diagnosed using muscle mass, strength and physical performance according to the Asian Working Group for Sarcopenia. PA information including frequency, duration, intensity, and volume was obtained by a self-reported questionnaire. Logistic regression analysis was employed to examine the association between PA and the incidence of sarcopenia at 4-year follow-up. RESULTS: The incidence of sarcopenia was 5.9% during the 4-year follow-up. Compared to sedentary individuals, those taking 1-2 days or more per week, or a minimum of 10 min each time on vigorous-intensity PA (VPA) had a lower incidence of sarcopenia. Adults spending 3 days or more each week, a minimum of 30 min each time, or 150 min or more per week on moderate-intensity PA (MPA) had a lower presence of sarcopenia than sedentary adults. Adults taking 3 days or more per week, at least 30 min each time, or 150 min or more each week on light-intensity PA (LPA) tended to have a lower incidence of sarcopenia than sedentary individuals. Sensitivity analyses confirmed the robustness of the findings after removing persons with hypertension, dyslipidemia, or diabetes. CONCLUSIONS: These findings suggest that the frequency, duration, and volume of VPA or MPA are negatively associated with the presence of sarcopenia. Participation in LPA tends to have a lower incidence of sarcopenia in middle-aged and older adults.
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Sarcopenia , Humanos , Pessoa de Meia-Idade , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Estudos Longitudinais , Incidência , Exercício Físico/fisiologia , China/epidemiologiaRESUMO
OBJECTIVES: Although there have been studies on the association of handgrip strength or walking speed alone with cognitive abilities, few studies have determined the combined associations of handgrip strength and walking speed with cognitive function. Therefore we aimed to explore the independent and combined associations of handgrip strength and walking speed with cognitive function in Chinese older adults using a nationally representative sample. METHOD: This cross-sectional study included 4,577 adults aged 60 and older. Handgrip strength was measured using a dynamometer and walking speed was assessed using a 2.5-meter walking test. Both handgrip strength and walking speed were organized into low, normal, and high tertiles according to the sample distribution. Cognitive function was measured using the Telephone Interview for Cognitive Status. RESULTS: Handgrip strength and walking speed were significantly associated with cognitive function. Participants with low handgrip strength or low walking speed separately had a higher rate of lower cognitive function (adjusted odds ratio (OR): 1.22 (95% CI: 1.04 - 1.44) for low handgrip strength; 1.54 (95% CI: 1.31 - 1.81) for low walking speed). Those with both low handgrip strength and low walking speed had an additively higher rate of lower cognitive function (adjusted OR: 1.72 (95% CI: 1.32 - 2.24)). CONCLUSION: Having low handgrip strength or low walking speed is associated with a greater likelihood of lower cognitive function and vice versa. The concurrence of having low handgrip strength and low walking speed has an additive effect on cognitive function in older adults.
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BACKGROUND: Identifying treatment targets for sarcopenia is a public health concern. This study aimed to examine the association of nocturnal sleep duration and midday napping with the presence of sarcopenia in middle-aged and older adults, utilizing data from the China Health and Retirement Longitudinal Study in 2011 and 2015. METHODS: A sum of 7,926 individuals (≥40 years) took part in this study. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia. A self-reported questionnaire was used to collect data on nocturnal sleep duration and midday napping. Nocturnal sleep duration was categorized into three groups: short sleepers (<6 h), normal sleepers (6-8 h), and long sleepers (>8 h). Midday napping was coded as a dichotomous outcome (yes/no). RESULTS: The incidence of sarcopenia was 5.3% during the 4-year follow-up. Short sleep duration (<6 h) was substantially linked to an increased incidence of sarcopenia (OR: 1.50, 95% CI: 1.21-1.87) as compared to nocturnal sleep length (6-8 h). Adults with midday napping had a lower risk of developing sarcopenia than non-nappers (OR: 0.78, 95% CI: 0.63-0.95). We further found that short sleepers with midday napping did not have a significantly higher risk of subsequent diagnosis of sarcopenia compared to normal sleepers without midday napping. CONCLUSION: These findings imply that short sleep duration in middle-aged and older persons is related to an increased incidence of sarcopenia. However, the adverse effect of short sleep duration on sarcopenia can be compensated by midday napping.
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Sarcopenia , Sono , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Sarcopenia/epidemiologia , Masculino , Incidência , Feminino , Sono/fisiologia , Idoso , China/epidemiologia , Fatores de Tempo , Adulto , Idoso de 80 Anos ou mais , Fatores de Risco , Duração do SonoRESUMO
Room-temperature sodium-sulfur (RT Na-S) batteries, noted for their low material costs and high energy density, are emerging as a promising alternative to lithium-ion batteries (LIBs) in various applications including power grids and standalone renewable energy systems. These batteries are commonly assembled with glass fiber membranes, which face significant challenges like the dissolution of polysulfides, sluggish sulfur conversion kinetics, and the growth of Na dendrites. Here, we develop an amorphous two-dimensional (2D) iron tin oxide (A-FeSnOx) nanosheet with hierarchical vacancies, including abundant oxygen vacancies (Ovs) and nano-sized perforations, that can be assembled into a multifunctional layer overlaying commercial separators for RT Na-S batteries. The Ovs offer strong adsorption and abundant catalytic sites for polysulfides, while the defect concentration is finely tuned to elucidate the polysulfides conversion mechanisms. The nano-sized perforations aid in regulating Na ions transport, resulting in uniform Na deposition. Moreover, the strategic addition of trace amounts of Ti3C2 (MXene) forms an amorphous/crystalline (A/C) interface that significantly improves the mechanical properties of the separator and suppresses dendrite growth. As a result, the task-specific layer achieves ultra-light (~0.1â mg cm-2), ultra-thin (~200â nm), and ultra-robust (modulus=4.9â GPa) characteristics. Consequently, the RT Na-S battery maintained a high capacity of 610.3â mAh g-1 and an average Coulombic efficiency of 99.9 % after 400â cycles at 0.5â C.
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The flexibility of protein structure is related to various biological processes, such as molecular recognition, allosteric regulation, catalytic activity, and protein stability. At the molecular level, protein dynamics and flexibility are important factors to understand protein function. DNA-binding proteins and Coronavirus proteins are of great concern and relatively unique proteins. However, exploring the flexibility of DNA-binding proteins and Coronavirus proteins through experiments or calculations is a difficult process. Since protein dihedral rotational motion can be used to predict protein structural changes, it provides key information about protein local conformation. Therefore, this paper introduces a method to improve the accuracy of protein flexibility prediction, DihProFle (Prediction of DNA-binding proteins and Coronavirus proteins flexibility introduces the calculated dihedral Angle information). Based on protein dihedral Angle information, protein evolution information, and amino acid physical and chemical properties, DihProFle realizes the prediction of protein flexibility in two cases on DNA-binding proteins and Coronavirus proteins, and assigns flexibility class to each protein sequence position. In this study, compared with the flexible prediction using sequence evolution information, and physicochemical properties of amino acids, the flexible prediction accuracy based on protein dihedral Angle information, sequence evolution information and physicochemical properties of amino acids improved by 2.2% and 3.1% in the nonstrict and strict conditions, respectively. And DihProFle achieves better performance than previous methods for protein flexibility analysis. In addition, we further analyzed the correlation of amino acid properties and protein dihedral angles with residues flexibility. The results show that the charged hydrophilic residues have higher proportion in the flexible region, and the rigid region tends to be in the angular range of the protein dihedral angle (such as the ψ angle of amino acid residues is more flexible than rigid in the range of 91°-120°). Therefore, the results indicate that hydrophilic residues and protein dihedral angle information play an important role in protein flexibility.
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Coronavirus , Proteínas de Ligação a DNA , Proteínas de Ligação a DNA/química , Conformação Proteica , Aminoácidos/química , Sequência de AminoácidosRESUMO
The formation and maintenance of synapses are precisely regulated, and the misregulation often leads to neurodevelopmental or neurodegenerative disorders. Besides intrinsic genetically encoded signaling pathways, synaptic structure and function are also regulated by extrinsic factors, such as nutrients. O-GlcNAc transferase (OGT), a nutrient sensor, is abundant in the nervous system and required for synaptic plasticity, learning, and memory. However, whether OGT is involved in synaptic development and the mechanism underlying the process are largely unknown. In this study, we found that OGT-1, the OGT homolog in C. elegans, regulates the presynaptic assembly in AIY interneurons. The insulin receptor DAF-2 acts upstream of OGT-1 to promote the presynaptic assembly by positively regulating the expression of ogt-1. This insulin-OGT-1 axis functions most likely by regulating neuronal activity. In this study, we elucidated a novel mechanism for synaptic development, and provided a potential link between synaptic development and insulin-related neurological disorders.
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Caenorhabditis elegans , Insulina , Animais , Insulina/metabolismo , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Transdução de SinaisRESUMO
The inert C(sp3)-H bond and easy overoxidation of toluene make the selective oxidation of toluene to benzaldehyde a great challenge. Herein, we present that a photocatalyst, constructed with a small amount (1 mol %) of amorphous BiOCl nanosheets assembled on TiO2 (denoted as 0.01BOC/TiO2), shows excellent performance in toluene oxidation to benzaldehyde, with 85% selectivity at 10% conversion, and the benzaldehyde formation rate is up to 1.7 mmol g-1 h-1, which is 5.6 and 3.7 times that of bare TiO2 and BOC, respectively. In addition to the charge separation function of the BOC/TiO2 heterojunction, we found that the amorphous structure of BOC endows its abundant surface oxygen vacancies (Ov), which can further promote the charge separation. Most importantly, the surface Ov of amorphous BOC can efficiently adsorb and activate O2, and amorphous BOC makes the product, benzaldehyde, easily desorb from the catalyst surface, which alleviates the further oxidation of benzaldehyde, and results in the high selectivity. This work highlights the importance of the microstructure based on heterojunctions, which is conducive to the rational design of photocatalysts with high performance in organic synthesis.
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Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1ß and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment.
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Lesão Pulmonar Aguda , Ferroptose , Humanos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/tratamento farmacológico , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Inflamação/genética , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Heme Oxigenase-1/metabolismoRESUMO
Liquid fluidity is a most key prerequisite for a broad range of technologies, from energy, fluid machineries, microfluidic devices, water, and oil transportation to bio-deliveries. While from thermodynamics, the liquid fluidity gradually diminishes as temperature decreases until completely solidified below icing points. Here, self-driven droplet motions are discovered and demonstrated occurring in icing environments and accelerating with both moving distances and droplet volumes. The self-driven motions, including self-depinning and continuous wriggling, require no surface pre-preparation or energy input but are triggered by the overpressure spontaneously established during icing and then continuously accelerated by capillary pulling of frosts. Such self-driven motions are generic to a broad class of liquid types, volumes, and numbers on various micro-nanostructured surfaces and can be facilely manipulated by introducing pressure gradients spontaneously or externally. The discovery and control of self-driven motions below icing points can greatly broaden liquid-related applications in icing environments.
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An outbreak of coronavirus disease 2019 (COVID-19) was reported in Yongchuan district of Chongqing, China in March 2022, while the source was unknown. We aimed to investigate the origin and transmission route of the virus in the outbreak. We conducted field investigations for all cases and collected their epidemiological and clinical data. We performed gene sequencing and phylogenetic analysis for the cases, and draw the epidemic curve and the case relationship chart to analyze interactions and possible transmission mode of the outbreak. A total of 11 cases of COVID-19, including 5 patients and 6 asymptomatic cases were laboratory-confirmed in the outbreak. The branch of the virus was Omicron BA.2 which was introduced into Yongchuan district by a traveler in early March. Patient F and asymptomatic case G had never contact with other positive-infected individuals, but close contact with their pet dog that sniffed the discarded cigarette butts and stepped on the sputum of patient B. Laboratory test results showed that the dog hair and kennel were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the 10 isolates were highly homologous to an epidemic strain in a province of China. The investigation suggested that the contaminated dog by SARS-CoV-2 can act as a passive mechanical carrier of the virus and might transmit the virus to humans through close contact. Our findings suggest that during the COVID-19 pandemic, increasing hygiene measures and hand washing after close contact with pets is essential to minimize the risk of community spread of the virus.
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COVID-19 , Cães , Humanos , Animais , COVID-19/epidemiologia , SARS-CoV-2/genética , Pandemias , Filogenia , China/epidemiologiaRESUMO
The melting of metals at high temperatures is common and important in many fields, e.g., metallurgy, refining, casting, welding, brazing, even newly developed batteries, and nuclear fusion, which is thus of great value in modern industrialization. However, the knowledge of the wetting behaviors of molten metals on various substrate surfaces remains insufficient, especially when the temperature is over 1000 °C and with microstructured metal substrate surfaces. Herein, we selected molten cerium (Ce) on a tantalum (Ta) substrate as an example and investigated in detail its wetting at temperatures up to 1000 °C by modulating the microstructures of the substrate surfaces via laser processing. We discovered that the wetting states of molten Ce on Ta surfaces at temperatures over 900 °C could be completely altered by modifying the laser-induced surface microstructures and the surface compositions. The molten Ce turned superlyophilic with its contact angle (CA) below 10° on the only laser-microstructured surfaces, while it exhibited lyophobicity with a CA of about 135° on the laser-microstructured plus oxidized ones, which demonstrated remarkably enhanced resistance against the melt with only tiny adhesion in this circumstance. In contrast, the CA of molten Ce on Ta substrate surfaces only changed from â¼25 to â¼95° after oxidization without laser microstructuring. We proved that modulating the substrate surface microstructures via laser together with oxidization was capable of efficiently controlling various molten metals' wetting behaviors even at very high temperatures. These findings not only enrich the understanding of molten metal high-temperature wettability but also enable a novel practical approach to control the wetting states for relevant applications.
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INTRODUCTION: The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta. METHODS: This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization. RESULTS: Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta. CONCLUSION: Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.
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COVID-19 , SARS-CoV-2 , Humanos , Masculino , Adulto , Feminino , COVID-19/diagnóstico , Plaquetas , Estudos RetrospectivosRESUMO
Hematite is a common iron oxide in natural environments, which has been observed to influence the transport and fate of arsenate by its association with hematite. Although oxygen vacancies were demonstrated to exist in hematite, their contributions to the arsenate immobilization have not been quantified. In this study, hematite samples with tunable oxygen vacancy defect (OVD) concentrations were synthesized by treating defect-free hematite using different NaBH4 solutions. The vacancy defects were characterized by positron annihilation lifetime spectroscopy, Doppler broadening of annihilation radiation, extended X-ray absorption fine structure (EXAFS), thermogravimetric mass spectrometry (TG-MS), electron paramagnetic resonance (EPR), and X-ray photoelectron spectroscopy (XPS). The results revealed that oxygen vacancy was the primary defect type existing on the hematite surface. TG-MS combined with EPR analysis allowed quantification of OVD concentrations in hematite. Batch experiments revealed that OVDs had a positive effect on arsenate adsorption, which could be quantitatively described by a linear relationship between the OVD concentration (Cdef, mmol m-2) and the enhanced arsenate adsorption amount caused by defects (ΔQm, µmol m-2) (ΔQm = 20.94 Cdef, R2 = 0.9813). NH3-diffuse reflectance infrared Fourier transform (NH3-DRIFT) analysis and density functional theory (DFT) calculations demonstrated that OVDs in hematite were beneficial to the improvement in adsorption strength of surface-active sites, thus considerably promoting the immobilization of arsenate.
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Arseniatos , Compostos Férricos , Compostos Férricos/química , AdsorçãoRESUMO
Determining the interaction of drug and target plays a key role in the process of drug development and discovery. The calculation methods can predict new interactions and speed up the process of drug development. In recent studies, the network-based approaches have been proposed to predict drug-target interactions. However, these methods cannot fully utilize the node information from heterogeneous networks. Therefore, we propose a method based on heterogeneous graph convolutional neural network for drug-target interaction prediction, GCHN-DTI (Predicting drug-target interactions by graph convolution on heterogeneous net-works), to predict potential DTIs. GCHN-DTI integrates network information from drug-target interactions, drug-drug interactions, drug-similarities, target-target interactions, and target-similarities. Then, the graph convolution operation is used in the heterogeneous network to obtain the node embedding of the drugs and the targets. Furthermore, we incorporate an attention mechanism between graph convolutional layers to combine node embedding from each layer. Finally, the drug-target interaction score is predicted based on the node embedding of the drugs and the targets. Our model uses fewer network types and achieves higher prediction performance. In addition, the prediction performance of the model will be significantly improved on the dataset with a higher proportion of positive samples. The experimental evaluations show that GCHN-DTI outperforms several state-of-the-art prediction methods.
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Desenvolvimento de Medicamentos , Redes Neurais de Computação , Desenvolvimento de Medicamentos/métodos , Interações MedicamentosasRESUMO
With pyrite (FeS2) and polycaprolactone (PCL) as electron donors, three denitrification systems, namely FeS2-based autotrophic denitrification (PAD) system, PCL-supported heterotrophic denitrification (PHD) system and split-mixotrophic denitrification (PPMD) system, were constructed and operated under varying hydraulic retention times (HRT, 1-48 h). Compared with PAD or PHD, the PPMD system could achieve higher removals of NO3--N and PO43--P, and the effluent SO42- concentration was greatly reduced to 7.28 mg/L. Similarly, the abundance of the dominant genera involved in the PAD (Thiobacillus, Sulfurimonas, and Ferritrophicum, etc.) or PHD (Syntrophomonas, Desulfomicrobium, and Desulfovibrio, etc.) process all increased in the PPMD system. Gene prediction completed by PICRUSt2 showed that the abundance of the functional genes involved in denitrification and sulfur oxidation all increased with the increase of HRT. This also accounted for the increased contribution of autotrophic denitrification to total nitrogen removal in the PPMD system. In addition, the analysis of metabolic pathways disclosed the specific conversion mechanisms of nitrogen and sulfur inside the reactor.
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Desnitrificação , Nitratos , Processos Autotróficos , Nitrogênio , Enxofre , Reatores BiológicosRESUMO
Winter wheat line Tianmin 668 was crossed with susceptible cultivar Jingshuang 16 to develop 216 recombinant inbred lines (RILs) for dissecting its adult-plant resistance (APR) and all-stage resistance (ASR) against powdery mildew. The RIL population was genotyped on a 16K genotyping by target sequencing single-nucleotide polymorphism array and phenotyped in six field trials and in the greenhouse. Three loci-QPmtj.caas-2BL, QPmtj.caas-2AS, and QPmtj.caas-5AL-conferring APR to powdery mildew were detected on chromosomes 2BL, 2AS, and 5AL, respectively, of Tianmin 668. The effect of resistance to powdery mildew for QPmtj.caas-2BL was greater than that of the other two loci. A Kompetitive allele-specific PCR marker specific for QPmtj.caas-2BL was developed and verified on 402 wheat cultivars or breeding lines. Results of virulence and avirulence patterns to 17 Blumeria graminis f. sp. tritici isolates, bulked segregant analysis-RNA-sequencing, and a genetic linkage mapping identified a resistance allele at locus Pm4 in Tianmin 668 based on the seedling phenotypes of the RIL population. The PCR-based DNA sequence alignment and cosegregation of the functional marker with the phenotypes of the RIL population demonstrated that Pm4d was responsible for the ASR to isolate Bgt1 in Tianmin 668. The dissection of genetic loci for APR and ASR may facilitate the application of Tianmin 668 in developing powdery mildew-resistant wheat cultivars.