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Background: Alzheimer's disease (AD) is a neurodegenerative disorder caused by a complex interplay of various factors. However, a satisfactory cure for AD remains elusive. Pharmacological interventions based on drug targets are considered the most cost-effective therapeutic strategy. Therefore, it is paramount to search potential drug targets and drugs for AD. Objective: We aimed to provide novel targets and drugs for the treatment of AD employing transcriptomic data of AD and normal control brain tissues from a new perspective. Methods: Our study combined the use of a multi-layer perceptron (MLP) with differential expression analysis, variance assessment and molecular docking to screen targets and drugs for AD. Results: We identified the seven differentially expressed genes (DEGs) with the most significant variation (ANKRD39, CPLX1, FABP3, GABBR2, GNG3, PPM1E, and WDR49) in transcriptomic data from AD brain. A newly built MLP was used to confirm the association between the seven DEGs and AD, establishing these DEGs as potential drug targets. Drug databases and molecular docking results indicated that arbaclofen, baclofen, clozapine, arbaclofen placarbil, BML-259, BRD-K72883421, and YC-1 had high affinity for GABBR2, and FABP3 bound with oleic, palmitic, and stearic acids. Arbaclofen and YC-1 activated GABAB receptor through PI3K/AKT and PKA/CREB pathways, respectively, thereby promoting neuronal anti-apoptotic effect and inhibiting p-tau and Aß formation. Conclusions: This study provided a new strategy for the identification of targets and drugs for the treatment of AD using deep learning. Seven therapeutic targets and ten drugs were selected by using this method, providing new insight for AD treatment.
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Doença de Alzheimer , Aprendizado Profundo , Simulação de Acoplamento Molecular , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Humanos , Transcriptoma , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
Nitrogen (N), as the main component of biological macromolecules, maintains the basic process of plant growth and development. GOGAT, as a key enzyme in the N assimilation process, catalyzes α-ketoglutaric acid and glutamine to form glutamate. In this study, six GOGAT genes in wheat (Triticum aestivum L.) were identified and classified into two subfamilies, Fd-GOGAT (TaGOGAT2s) and NADH-GOGAT (TaGOGAT3s), according to the type of electron donor. Subcellular localization prediction showed that TaGOGAT3-D was localized in mitochondria and that the other five TaGOGATs were localized in chloroplasts. Via the analysis of promoter elements, many binding sites related to growth and development, hormone regulation and plant stress resistance regulations were found on the TaGOGAT promoters. The tissue-specificity expression analysis showed that TaGOGAT2s were mainly expressed in wheat leaves and flag leaves, while TaGOGAT3s were highly expressed in roots and leaves. The expression level of TaGOGATs and the enzyme activity of TaGOGAT3s in the leaves and roots of wheat seedlings were influenced by the treatment of N deficiency. This study conducted a systematic analysis of wheat GOGAT genes, providing a theoretical basis not only for the functional analysis of TaGOGATs, but also for the study of wheat nitrogen use efficiency (NUE).
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Regulação da Expressão Gênica de Plantas , Nitrogênio , Proteínas de Plantas , Estresse Fisiológico , Triticum , Triticum/genética , Triticum/metabolismo , Nitrogênio/metabolismo , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glutamato Sintase/genética , Glutamato Sintase/metabolismo , Família Multigênica , Regiões Promotoras Genéticas , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , FilogeniaRESUMO
BACKGROUND: Dyslipidemia is a common complication in patients with diabetes mellitus (DM) that increases the risk of cardiovascular disease. Genetic polymorphisms have been implicated in the development of dyslipidemia. AIM: To investigate the association between polymorphisms of candidate genes involved in lipid metabolism and dyslipidemia in Chinese patients with DM. METHODS: A cross-sectional study was conducted on 1098 Chinese patients with DM recruited from multiple healthcare centers. Demographic and clinical data were collected, and dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Genomic DNA was extracted from blood samples and genotyping for selected polymorphisms of candidate genes (APOE, LPL, CETP, and others) was performed using PCR and DNA sequencing techniques. Statistical analyses were performed using logistic regression models adjusted for potential confounding factors. RESULTS: The study population consisted of 578 males (52.6%) and 520 females (47.4%), with a mean age of 58.4 ± 12.2 years. The prevalence of dyslipidemia was 64.8%. Significant associations were found between dyslipidemia and the APOE rs7412 T/T, APOE rs429358 C/C, LPL rs328 G/G, and CETP rs708272 G/G genotypes after adjusting for covariates. Subgroup analyses showed generally consistent associations across subgroups, although some variations in effect sizes were observed. CONCLUSION: This study identified significant associations between genetic polymorphisms of APOE, LPL, and CETP genes and dyslipidemia in Chinese patients with DM.
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We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.
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Substitutos da Gordura , Ácidos Graxos , Leite Humano , Óleos de Plantas , Software , Triglicerídeos , Humanos , Animais , Óleos de Plantas/química , Ácidos Graxos/química , Leite Humano/química , Camundongos , Triglicerídeos/química , Substitutos da Gordura/química , Óleo de Palmeira/química , Óleo de Soja/química , Óleo de Semente do Linho/química , Óleo de Brassica napus/química , Óleo de Milho/química , Caprilatos/química , Ácido Palmítico/química , Ácido Oleico/químicaRESUMO
MOTIVATION: The technology for analyzing single-cell multi-omics data has advanced rapidly and has provided comprehensive and accurate cellular information by exploring cell heterogeneity in genomics, transcriptomics, epigenomics, metabolomics and proteomics data. However, because of the high-dimensional and sparse characteristics of single-cell multi-omics data, as well as the limitations of various analysis algorithms, the clustering performance is generally poor. Matrix factorization is an unsupervised, dimensionality reduction-based method that can cluster individuals and discover related omics variables from different blocks. Here, we present a novel algorithm that performs joint dimensionality reduction learning and cell clustering analysis on single-cell multi-omics data using non-negative matrix factorization that we named scMNMF. We formulate the objective function of joint learning as a constrained optimization problem and derive the corresponding iterative formulas through alternating iterative algorithms. The major advantage of the scMNMF algorithm remains its capability to explore hidden related features among omics data. Additionally, the feature selection for dimensionality reduction and cell clustering mutually influence each other iteratively, leading to a more effective discovery of cell types. We validated the performance of the scMNMF algorithm using two simulated and five real datasets. The results show that scMNMF outperformed seven other state-of-the-art algorithms in various measurements. AVAILABILITY AND IMPLEMENTATION: scMNMF code can be found at https://github.com/yushanqiu/scMNMF.
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Algoritmos , Análise de Célula Única , Análise de Célula Única/métodos , Análise por Conglomerados , Humanos , Genômica/métodos , Biologia Computacional/métodos , Proteômica/métodos , Metabolômica/métodos , Epigenômica/métodos , MultiômicaRESUMO
Ferroptosis is a newly recognized type of programmed cell death that is implicated in the pathophysiological process of neurological disorders. Our previous studies have revealed that exposure to high concentrations of fluoride for long periods of time induces hippocampal neural injury and cognitive deficits. However, whether ferroptosis is involved in fluoride-induced neuronal death and the underlying mechanism remain unknown. In this study, the results indicated that exposure to high fluoride triggered ferroptosis in SH-SY5Y cells and in the hippocampus of mice. Fluoride exposure accelerated the lysosomal degradation of GPX4 and led to neuronal ferroptosis, while GPX4 overexpression protected SH-SY5Y cells against fluoride-induced neurotoxicity. Intriguingly, the enhanced chaperone-mediated autophagy (CMA) induced by fluoride stimulation was responsible for GPX4 degradation because the inhibition of CMA activity by LAMP2A knockdown effectively prevented fluoride-induced GPX4 loss. Furthermore, mitochondrial ROS (mtROS) accumulation caused by fluoride contributed to CMA activation-mediated GPX4 degradation and subsequent neuronal ferroptosis. Notably, the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or the ROS scavenger N-acetyl-L-cysteine (NAC) alleviated fluoride-evoked hippocampal neuronal death and synaptic injury as well as cognitive deficits in mice. The present studies indicates that ferroptosis is a novel mechanism of fluoride-induced neurotoxicity and that chronic fluoride exposure facilitates GPX4 degradation via mtROS chaperone-mediated autophagy, leading to neuronal ferroptosis and cognitive impairment.
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Autofagia Mediada por Chaperonas , Disfunção Cognitiva , Ferroptose , Fluoretos , Neurônios , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Espécies Reativas de Oxigênio , Animais , Humanos , Camundongos , Autofagia/efeitos dos fármacos , Autofagia Mediada por Chaperonas/fisiologia , Autofagia Mediada por Chaperonas/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Fluoretos/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.
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Transfusão de Eritrócitos , Humanos , China/epidemiologia , Recém-Nascido , Masculino , Feminino , Unidades de Terapia Intensiva Neonatal , Lactente , Recém-Nascido Prematuro , Estudos de Coortes , Lactente Extremamente PrematuroRESUMO
BACKGROUND: The rose is one of the most important ornamental flowers in the world for its aesthetic beauty but can be attacked by many pests such as aphids. Aphid infestation causes tremendous damage on plant tissues leading to harmed petals and leaves. Rose cultivars express different levels of resistance to aphid infestation yet the information remains unclear. Not only that, studies about the transcriptional analysis on defending mechanisms against aphids in rose are limited so far. RESULTS: In this study, the aphid resistance of 20 rose cultivars was evaluated, and they could be sorted into six levels based on the number ratio of aphids. And then, a transcriptome analysis was conducted after aphid infestation in one high resistance (R, Harmonie) and one highly susceptibility (S, Carefree Wonder) rose cultivar. In open environment the majority of rose cultivars had the highest aphid number at May 6th or May 15th in 2020 and the resistance to infestation could be classified into six levels. Differential expression analysis revealed that there were 1,626 upregulated and 767 downregulated genes in the R cultivar and 481 upregulated and 63 downregulated genes in the S cultivar after aphid infestation. Pathway enrichment analysis of the differentially expressed genes revealed that upregulated genes in R and S cultivars were both enriched in defense response, biosynthesis of secondary metabolites (phenylpropanoid, alkaloid, and flavonoid), carbohydrate metabolism (galactose, starch, and sucrose metabolism) and lipid processing (alpha-linolenic acid and linolenic acid metabolism) pathways. In the jasmonic acid metabolic pathway, linoleate 13S-lipoxygenase was specifically upregulated in the R cultivar, while genes encoding other crucial enzymes, allene oxide synthase, allene oxide cyclase, and 12-oxophytodienoate reductase were upregulated in both cultivars. Transcription factor analysis and transcription factor binding search showed that WRKY transcription factors play a pivotal role during aphid infestation in the R cultivar. CONCLUSIONS: Our study indicated the potential roles of jasmonic acid metabolism and WRKY transcription factors during aphid resistance in rose, providing clues for future research.
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Afídeos , Oxilipinas , Animais , Perfilação da Expressão Gênica , Ciclopentanos , Fatores de TranscriçãoRESUMO
As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.
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Doença de Alzheimer , Núcleo Celular , Hialuronan Sintases , Proteínas tau , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Humanos , Proteínas tau/metabolismo , Proteínas tau/genética , Camundongos , Hialuronan Sintases/metabolismo , Hialuronan Sintases/genética , Núcleo Celular/metabolismo , Núcleo Celular/genética , Transcrição Gênica , Fosforilação , Modelos Animais de Doenças , Regulação da Expressão Gênica , Camundongos Transgênicos , UbiquitinaçãoRESUMO
In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%-1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.
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Glicolipídeos , Glicoproteínas , Gotículas Lipídicas , Animais , Glicolipídeos/química , Glicoproteínas/análise , Lipídeos/análise , Digestão , Fosfolipídeos , EmulsõesRESUMO
Adzuki bean (Vigna angularis) is an important legume crop cultivated in over 30 countries worldwide. We developed a high-quality chromosome-level reference genome of adzuki bean cultivar Jingnong6 by combining PacBio Sequel long-read sequencing with short-read and Hi-C technologies. The assembled genome covers 97.8% of the adzuki bean genome with a contig N50 of approximately 16 Mb and a total of 32 738 protein-coding genes. We also generated a comprehensive genome variation map of adzuki bean by whole-genome resequencing (WGRS) of 322 diverse adzuki beans accessions including both wild and cultivated. Furthermore, we have conducted comparative genomics and a genome-wide association study (GWAS) on key agricultural traits to investigate the evolution and domestication. GWAS identified several candidate genes, including VaCycA3;1, VaHB15, VaANR1 and VaBm, that exhibited significant associations with domestication traits. Furthermore, we conducted functional analyses on the roles of VaANR1 and VaBm in regulating seed coat colour. We provided evidence for the highest genetic diversity of wild adzuki (Vigna angularis var. nipponensis) in China with the presence of the most original wild adzuki bean, and the occurrence of domestication process facilitating transition from wild to cultigen. The present study elucidates the genetic basis of adzuki bean domestication traits and provides crucial genomic resources to support future breeding efforts in adzuki bean.
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Genoma de Planta , Estudo de Associação Genômica Ampla , Vigna , Genoma de Planta/genética , Vigna/genética , Cromossomos de Plantas/genética , Domesticação , Variação Genética , Genômica , Produtos Agrícolas/genética , FenótipoRESUMO
High temperature around flowering has a serious impact on the growth and development of maize. However, few maize genes related to flowering under heat stress have been confirmed, and the regulatory mechanism is unclear. To reveal the molecular mechanism of heat tolerance in maize, two maize hybrids, ZD309 and XY335, with different heat resistance, were selected to perform transcriptome and metabolomics analysis at the flowering stage under heat stress. In ZD309, 314 up-regulated and 463 down-regulated differentially expressed genes (DEGs) were detected, while 168 up-regulated and 119 down-regulated DEGs were identified in XY335. By comparing the differential gene expression patterns of ZD309 and XY335, we found the "frontloaded" genes which were less up-regulated in heat-tolerant maize during high temperature stress. They included heat tolerance genes, which may react faster at the protein level to provide resilience to instantaneous heat stress. A total of 1062 metabolites were identified via metabolomics analysis. Lipids, saccharides, and flavonoids were found to be differentially expressed under heat stress, indicating these metabolites' response to high temperature. Our study will contribute to the identification of heat tolerance genes in maize, therefore contributing to the breeding of heat-tolerant maize varieties.
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Melhoramento Vegetal , Zea mays , Zea mays/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Transcriptoma/genéticaRESUMO
Improving the efficiency of the oxygen evolution reaction (OER) is crucial for advancing sustainable and environmentally friendly hydrogen energy. Layered double hydroxides (LDHs) have emerged as promising electrocatalysts for the OER. However, a thorough understanding of the impact of structural disorder and defects on the catalytic activity of LDHs remains limited. In this work, a series of NiAl-LDH models are systematically constructed, and their OER performance is rigorously screened through theoretical density functional theory. The acquired results unequivocally reveal that the energy increase induced by structural disorder is effectively counteracted at the defect surface, indicating the coexistence of defects and disorder. Notably, it is ascertained that the simultaneous presence of defects and disorder synergistically augments the catalytic activity of LDHs in the context of the OER. These theoretical findings offer valuable insights into the design of highly efficient OER catalysts while also shedding light on the efficacy of LDH electrocatalysts.
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Repair of large cranial complex traumas in children is difficult. Notably, children have poorer underlying conditions than adults and are frailer under trauma. In addition, children have more limited treatment options, leading to the need to consider long-term functional and aesthetic outcomes. The present report describes the case of a 2-year-old child weighing 9 kg who experienced a skull fracture with encephalocele after a car accident and had a poor underlying condition. An artificial dura mater combined with bone cement was used to repair the skull, and then a free latissimus dorsi muscle flap (LDMF) combined with a split-thickness skin graft (STSG) was used to cover the wound, allowing the child to overcome the life-threatening situation as soon as possible with a satisfactory outcome. LDMF combined with STSG is an ideal option in repairing head wounds in children. Preoperative imaging and postoperative care also serve an important role in the success of the operation. When the situation is critical, multidisciplinary team treatment can guarantee the safety of the child.
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Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50 % inhibitory concentration (IC50) of â¼5 µM. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virus titer decreased significantly. The time-of-addition assay results showed that VAM could inhibit PEDV replication by blocking viral entry. Importantly, VAM could inhibit PEDV-induced phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) activity and further suppress micropinocytosis, which is required for PEDV entry. In addition, PI3K inhibitor LY294002 showed anti-PEDV activity by blocking viral entry as well. Taken together, VAM possessed anti-PEDV properties against the entry stage of PEDV by inhibiting the macropinocytosis pathway by suppressing the PI3K/Akt pathway. VAM could be considered as a lead compound for the development of anti-PEDV drugs and may be used during the viral entry stage of PEDV infection.
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Infecções por Coronavirus , Fosfatidilinositol 3-Quinases , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Alcaloides de Veratrum , Internalização do Vírus , Animais , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/veterinária , Fosfatidilinositol 3-Quinases/metabolismo , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Suínos , Doenças dos Suínos/tratamento farmacológico , Alcaloides de Veratrum/metabolismo , Alcaloides de Veratrum/farmacologia , Células Vero , Internalização do Vírus/efeitos dos fármacosRESUMO
Accumulating evidence has shown that ultrasound exposure combined with microbubbles can enhance cancer therapy. However, the underlying mechanisms at the tissue level have not been fully understood yet. The conventional cell culture in vitro lacks complex structure and interaction, while animal studies cannot provide micron-scale dynamic information. To bridge the gap, we designed and assembled a 3D vascularized microfluidic cancer model, particularly suitable for ultrasound and microbubble involved mechanistic studies. Using this model, we first studied SonoVue microbubble traveling dynamics in 3D tissue structure, then resolved SonoVue microbubble cavitation dynamics in tissue mimicking agarose gels at a frame rate of 0.675 M fps, and finally explored the impacts of ultrasound and microbubbles on cancer cell spheroids. Our results demonstrate that microbubble penetration in agarose gel was enhanced by increasing microbubble concentration, flow rate and decreasing viscosity of the gel, and little affected by mild acoustic radiation force. SonoVue microbubble exhibited larger expansion amplitudes in 2 %(w/v) agarose gels than in water, which can be explained theoretically by the relaxation of the cavitation medium. The immediate impacts of ultrasound and SonoVue microbubbles to cancer cell spheroids in the 3D tissue model included improved cancer cell spheroid penetration in micron-scale and sparse direct permanent cancer cell damage. Our study provides new insights of the mechanisms for ultrasound and microbubble enhanced cancer therapy at the tissue level.
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Microbolhas , Neoplasias , Animais , Microfluídica , Sefarose , Géis , Meios de Contraste , Neoplasias/terapiaRESUMO
Atomically dispersed metal catalysts with excellent activity and stability are highly desired in heterogeneous catalysis. Herein, we synthesized zeolite-encaged Pd-based pseudo-single atoms via a facile and energy-efficient ligand-protected direct H2 reduction method. Cs-corrected scanning transmission electron microscopy, extended X-ray absorption, and pair distribution function measurements reveal that the metal species are close to atomic-level dispersion and completely confined within the intersectional channels of silicalite-1 (S-1) zeolite with the MFI framework. The Pd@S-1-H exhibits excellent activity and stability in methane combustion reactions with a complete combustion temperature of 390 °C, and no deactivation is observed even after 100 h on stream. The optimized bimetallic 0.8Pd0.2Ni(OH)2@S-1-H catalyst exhibits an excellent H2 generation rate from FA decomposition without any additives, affording a superhigh turnover frequency up to 9308 h-1 at 333 K, which represents the top activity among all of the best heterogeneous catalysts under similar conditions. Significantly, zeolite-encaged metal catalysts are first used for Cr(vi) reduction coupled with formic acid (FA) dehydrogenation and show a superhigh turnover number of 2980 mol(Cr2O72-) mol(Pd)-1 at 323 K, surpassing all of the previously reported catalysts. This work demonstrates that zeolite-encaged pseudo-single atom catalysts are promising in efficient hydrogen storage and pollutant disposal applications.
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With the continuous development of society, the discharge of oily wastewater in daily life and industry has gradually increased, causing considerable damage to the environment, and how to effectively treat oily wastewater is an urgent problem. In this paper, a simple method is proposed to prepare superhydrophobic stainless steel mesh with pH response. The relationship between the ratio of mixed thiols and the surface wettability was explored, as well as the morphology, chemical composition, and pH-responsive mechanism of the stainless steel mesh surface were analyzed, and the separation efficiency, recycling ability, and backwashing ability of the mesh were explored by oil-water separation experiments. It was found that when the molar fraction of 11-mercaptoundecanoic acid and 1-decanethiol in the mixed mercaptan was 2:3, the water contact angle of the surface at this point was 156.5 ± 1°, with pH response characteristics and good oil-water separation efficiency, backwashing and recycling capabilities.
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Seed coat colour is an important quality trait, domestication trait, and morphological marker, and it is closely associated with flavonoid and anthocyanin metabolism pathways. The seed coat colour of the adzuki bean, an important legume crop, influences the processing quality, the commodity itself, and its nutritional quality. In this review, a genetic analysis of different seed coat colours, gene mapping, metabolite content determination, and varietal improvement in adzuki bean are summarized. It provides further insight into gene mapping and cloning of seed coat colour genes and varietal improvements in adzuki beans.
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Cadmium (Cd), a toxic heavy metal, exerts deleterious effects on neuronal survival and cognitive function. NOD-like receptor 3 (NLRP3) inflammasome-dependent pyroptosis has been linked to Cd-induced cytotoxicity. The current research intended to elucidate the role of NLRP3 inflammasome-mediated pyroptosis in Cd-evoked neuronal death and cognitive impairments and the underlying mechanisms. Exposure to 1 mg/kg Cd for 8 weeks led to hippocampal-dependent cognitive deficits and neural/synaptic damage in mice. NLRP3 inflammasome-related protein expression (NLRP3, ASC, and caspase1 p20) and neuronal pyroptosis were significantly upregulated in Cd-treated hippocampi and SH-SY5Y cells. Moreover, pretreatment with the NLRP3 inhibitor MCC950 mitigated Cd-elicited NLRP3 inflammasome activation and subsequent neuronal pyroptosis in SH-SY5Y cells. Furthermore, exposure to Cd downregulated Sirt3 expression, suppressed SOD2 activity by hyperacetylation, and enhanced mtROS accumulation in vivo and in vitro. Notably, Cd-induced NLRP3 inflammasome-dependent neuronal pyroptosis was attenuated by a mtROS scavenger or Sirt3 overexpression in SH-SY5Y cells. In addition, Cd failed to further suppress SOD activity and activate NLRP3 inflammasome-dependent neuronal pyroptosis in Sirt3 shRNA-treated SH-SY5Y cells. Collectively, our findings indicate that Cd exposure induces neuronal injury and cognitive deficits by activating NLRP3 inflammasome-dependent neuronal pyroptosis and that activation of the NLRP3 inflammasome is partially mediated by the Sirt3-mtROS axis.