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The low-prevalence effect (LPE) is the finding that target detection rates decline as targets become less frequent in a visual search task. A major source of this effect is thought to be that fewer targets result in lower quitting thresholds, i.e., observers respond target-absent after looking at fewer items compared to searches with a higher prevalence of targets. However, a lower quitting threshold does not directly account for an LPE in searches where observers continuously monitor a dynamic display for targets. In these tasks there are no discrete "trials" to which a quitting threshold could be applied. This study examines whether the LPE persists in this type of dynamic search context. Experiment 1 was a 2 (dynamic/static) x 2 (10%/40% prevalence targets) design. Although overall performance was worse in the dynamic task, both tasks showed a similar magnitude LPE. In Experiment 2, we replicated this effect using a task where subjects searched for either of two targets (Ts and Ls). One target appeared infrequently (10%) and the other moderately (40%). Given this method of manipulating prevalence rate, the quitting threshold explanation does not account for the LPE even for static displays. However, replicating Experiment 1, we found an LPE of similar magnitude for both search scenarios, and lower target detection rates with the dynamic displays, demonstrating the LPE is a potential concern for both static and dynamic searches. These findings suggest an activation threshold explanation of the LPE may better account for our observations than the traditional quitting threshold model.
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BACKGROUND: In single-isocenter multitarget stereotactic body radiotherapy (SBRT), geometric miss risks arise from uncertainties in intertarget position. However, its assessment is inadequate, and may be interfered by the reconstructed tumor position errors (RPEs) during simulated CT and cone beam CT (CBCT) acquisition. This study aimed to quantify intertarget position variations and assess factors influencing it. METHODS: We analyzed data from 14 patients with 100 tumor pairs treated with single-isocenter SBRT. Intertarget position variation was measured using 4D-CT simulation to assess the intertarget position variations (ΔD) during routine treatment process. Additionally, a homologous 4D-CBCT simulation provided RPE-free comparison to determine the impact of RPEs, and isolating purely tumor motion induced ΔD to evaluate potential contributing factors. RESULTS: The median ΔD was 4.3 mm (4D-CT) and 3.4 mm (4D-CBCT). Variations exceeding 5 mm and 10 mm were observed in 31.1% and 5.5% (4D-CT) and 20.4% and 3.4% (4D-CBCT) of fractions, respectively. RPEs necessitated an additional 1-2 mm safety margin. Intertarget distance and breathing amplitude variability showed weak correlations with variation (Rs = 0.33 and 0.31). The ΔD differed significantly by locations (upper vs. lower lobe and right vs. Left lung). Notably, left lung tumor pairs exhibited the highest risk. CONCLUSIONS: This study provide a reliable way to assess intertarget position variation by using both 4D-CT and 4D-CBCT simulation. Consequently, single-isocenter SBRT for multiple lung tumors carries high risk of geometric miss. Tumor motion and RPE constitute a substantial portion of intertarget position variation, requiring correspondent strategies to minimize the intertarget uncertainties.
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Tomografia Computadorizada de Feixe Cônico , Tomografia Computadorizada Quadridimensional , Neoplasias Pulmonares , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiocirurgia/métodos , Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Tomografia Computadorizada de Feixe Cônico/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Masculino , Feminino , Idoso , Simulação por Computador , Pessoa de Meia-IdadeRESUMO
Cortex Morin Radicis (CMR) is the dried root bark of Morus alba. L. It has a variety of effects such as antibacterial, anti-tumour, treatment of cardiovascular diseases or upper respiratory tract disease and so on. The pursuit for drugs selected from Cortex Mori Radicis having improved therapeutic efficacy necessitates increasing research on new assays for screening bioactive compounds with multi-targets. In this work, we applied immobilized ß1-AR and ß2-AR as the stationary phase in chromatographic column to screen bioactive compounds from Cortex Morin Radicis. Specific ligands of the two receptors (e.g. esmolol, metoprolol, atenolol, salbutamol, methoxyphenamine, tulobuterol and clorprenaline) were utilized to characterize the specificity and bioactivity of the columns. We used high performance affinity chromatography coupled with ESI-MS to screen targeted compounds of Cortex Morin Radicis. By zonal elution, we identified morin as a bioactive compound simultaneously binding to ß1-AR and ß2-AR. The compound exhibited the association constants of 3.10 × 104 and 2.60 × 104 M-1 on the ß1-AR and ß2-AR column. On these sites, the dissociation rate constants were calculated to be 0.131 and 0.097 s-1. Molecular docking indicated that the binding of morin to the two receptors occurred on Asp200, Asp121, and Val122 of ß1-AR, Asn312, Thr110, Asp113, Tyr316, Gly90, Phe193, Ile309, and Trp109 of ß2-AR. Likewise, mulberroside C was identified as the bioactive compound binding to ß2-AR. The association constants and dissociation rate constants were calculated to be 1.08 × 104 M-1 and 0.900 s-1. Molecular docking also indicated that mulberroside C could bind to ß2-AR receptor on its agonist site. Taking together, we demonstrated that the chromatographic strategy to identify bioactive natural products based on the ß1-AR and ß2-AR immobilization, has potential for screening bioactive compounds with multi-targets from complex matrices including traditional Chinese medicines.
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Morus , Receptores Adrenérgicos beta 1 , Receptores Adrenérgicos beta 2 , Morus/química , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 1/química , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Cromatografia de Afinidade/métodos , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Flavonoides/químicaRESUMO
CRISPR-Cas system is being used as a powerful genome editing tool with developments focused on enhancing its efficiency and accuracy. Recently, the miniature CRISPR-Cas12f1 system, which is small enough to be easily loaded onto various vectors for cellular delivery, has gained attention. In this study, we explored the influence of temperature conditions on multiplex genome editing using CRISPR-Cas12f1 in an Escherichia coli model. It was revealed that when two distinct targets in the genome are edited simultaneously, the editing efficiency can be enhanced by allowing cells to recover at a reduced temperature during the editing process. Additionally, employing 3'-end truncated sgRNAs facilitated the simultaneous single-nucleotide level editing of three targets. Our results underscore the potential of optimizing recovery temperature and sgRNA design protocols in developing more effective and precise strategies for multiplex genome editing across various organisms.
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Sistemas CRISPR-Cas , Escherichia coli , Edição de Genes , Genoma Bacteriano , Edição de Genes/métodos , Escherichia coli/genética , RNA Guia de Sistemas CRISPR-Cas/genética , Temperatura Baixa , TemperaturaRESUMO
Visual search is speeded when a target is repeatedly presented in an invariant scene context of nontargets (contextual cueing), demonstrating observers' capability for using statistical long-term memory (LTM) to make predictions about upcoming sensory events, thus improving attentional orienting. In the current study, we investigated whether expectations arising from individual, learned environmental structures can encompass multiple target locations. We recorded event-related potentials (ERPs) while participants performed a contextual cueing search task with repeated and non-repeated spatial item configurations. Notably, a given search display could be associated with either a single target location (standard contextual cueing) or two possible target locations. Our result showed that LTM-guided attention was always limited to only one target position in single- but also in the dual-target displays, as evidenced by expedited reaction times (RTs) and enhanced N1pc and N2pc deflections contralateral to one ("dominant") target of up to two repeating target locations. This contrasts with the processing of non-learned ("minor") target positions (in dual-target displays), which revealed slowed RTs alongside an initial N1pc "misguidance" signal that then vanished in the subsequent N2pc. This RT slowing was accompanied by enhanced N200 and N400 waveforms over fronto-central electrodes, suggesting that control mechanisms regulate the competition between dominant and minor targets. Our study thus reveals a dissociation in processing dominant versus minor targets: While LTM templates guide attention to dominant targets, minor targets necessitate control processes to overcome the automatic bias towards previously learned, dominant target locations.
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Atenção , Sinais (Psicologia) , Eletroencefalografia , Potenciais Evocados , Tempo de Reação , Humanos , Atenção/fisiologia , Masculino , Feminino , Potenciais Evocados/fisiologia , Tempo de Reação/fisiologia , Adulto Jovem , Adulto , Eletroencefalografia/métodos , Percepção Visual/fisiologia , Estimulação Luminosa/métodos , Orientação/fisiologia , Memória de Longo Prazo/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown. AIM OF THE STUDY: To explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism. MATERIALS AND METHODS: A randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected. RESULTS: MBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy. CONCLUSION: MBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.
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Medicamentos de Ervas Chinesas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pessoa de Meia-Idade , Masculino , Linhagem Celular Tumoral , Idoso , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Adulto , Farmacologia em RedeRESUMO
Dipicolinic acid (DPA), as a biomarker for Bacillus anthracis, is highly toxic at trace levels. Rapid and on-site quantitative detection of DPA is essential for maintaining food safety and public health. This work develops a dual-channel self-calibrated fluorescence sensor constructed by the YVO4:Eu and Tb-ß-diketone complex for rapid visual detection of DPA. This sensor exhibits high selectivity, fast response time, excellent detection sensitivity, and the detection limit is as low as 4.5 nM in the linear range of 0-16 µM. A smartphone APP and portable ultraviolet lamp can assemble a mobile fluorescence sensor for on-site analysis. Interestingly, adding Cu2+ ions can quench the fluorescence intensity of Tb3+. In contrast, the addition of cysteine can restore the fluorescence, allowing the accurate detection of Cu2+ ions and cysteine in environmental water and food samples. This work provides a portable sensor that facilitates real-time analysis of multiple targets in food and the environment.
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Antraz , Bacillus anthracis , Biomarcadores , Cobre , Cisteína , Análise de Alimentos , Contaminação de Alimentos , Ácidos Picolínicos , Smartphone , Cobre/análise , Cisteína/análise , Bacillus anthracis/isolamento & purificação , Bacillus anthracis/química , Biomarcadores/análise , Contaminação de Alimentos/análise , Antraz/diagnóstico , Análise de Alimentos/instrumentação , Análise de Alimentos/métodos , Ácidos Picolínicos/análise , Espectrometria de Fluorescência/instrumentação , Espectrometria de Fluorescência/métodos , Limite de Detecção , Fluorescência , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodosRESUMO
OBJECTIVES: Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease. METHODS: We performed protein-protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase. RESULTS: We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (-219.8 Kcal/mol) >csgF (-146.52 Kcal/mol) >ompR (-135.68 Kcal/mol) >CsgE (-134.66 Kcal/mol) >CsgG (-113.81 Kcal/mol) >CsgD(-95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets. CONCLUSION: This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.
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Antibacterianos , Asparaginase , Biofilmes , Simulação de Acoplamento Molecular , Salmonella typhi , Biofilmes/efeitos dos fármacos , Asparaginase/farmacologia , Asparaginase/isolamento & purificação , Salmonella typhi/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Desenho de Fármacos , Terapia de Alvo Molecular , Farmacorresistência BacterianaRESUMO
Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi-target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high-efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C-like protease from hosts and viruses, respectively, and exhibit a broad-spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug-binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad-spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs.
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Infecções por Coronavirus , Coronavirus , Animais , Gatos , Camundongos , Suínos , Humanos , Antivirais/química , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Proteases/farmacologia , Inibidores de Proteases/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Artemisia argyi has been used medicinally and eaten for more than 2000 years in China. It is widely reported in treating inflammatory diseases such as eczema, dermatitis, arthritis, allergic asthma and colitis. Although several studies claim that its volatile oil and organic reagent extracts have certain anti-inflammatory effects, the water-soluble fractions and molecular mechanisms have not been studied. AIM OF THE STUDY: To evaluate the therapeutic effect of A. argyi water extract (AAWE) on lipopolysaccharide (LPS)-induced inflammatory responses and to identify the most effective water-soluble subfractions. Moreover, the relevant pharmacological and molecular mechanisms by which the active subfraction mitigates inflammation were further investigated. MATERIALS AND METHODS: Firstly, RAW 264.7 cells stimulated with LPS were treated with AAWE (50, 100, and 200 µg/mL) or the water-soluble subfractions separated by D101 macroporous resin (AAWE1-AAWE4, 100 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated to determine the most effective water-soluble subfractions. Secondly, the chemical components of the active subfraction (AAWE4) were analyzed by UPLC-QTOF-MS. Thirdly, transcriptome and network pharmacology analysis, RT-qPCR and Western blotting assays were conducted to explore the underlying anti-inflammatory mechanism and active compounds of AAWE4. Subsequently, the binding ability of the potential active components in AAWE4 to the core targets was further determined by molecular docking. Eventually, the in vivo anti-inflammatory activity of AAWE4 (1.17, 2.34 and 4.68 g/kg, administered per day for 7 d) was evaluated in mice with LPS-induced systemic inflammation. RESULTS: In this study, AAWE showed excellent anti-inflammatory effects, and its water-soluble subfraction AAWE4 exhibited the strongest inhibitory effect on NO concentration and inflammatory gene mRNA expression after LPS stimulation, indicating that it was the most effective subfraction. Thereafter, four main compounds in AAWE4 were confirmed or tentatively identified by UPLC-QTOF-MS, including three flavonoid glycosides and one phenolic acid. Furthermore, the transcriptome and network pharmacology analysis showed that AAWE4 inhibited inflammation via multiple pathways and multiple targets. Based on the RT-qPCR and Western blotting results, AAWE4 downregulated not only the p38, PI3K, CCL5, MMP9, AP-1, and BCL3 mRNA expression levels activated by LPS but also their upstream and downstream protein expression levels and protein phosphorylation (p-AKT/AKT, p-p38/p38, p-ERK/ERK, p-JNK/JNK). Moreover, four identified compounds (isochlorogenic acid A, vicenin-2, schaftoside and isoschaftoside) could significantly inhibit NO content and the overexpression of inflammatory factors TNF-α, IL-1ß, iNOS and COX-2 mRNA induced by LPS, and the molecular docking confirmed the high binding activity of four active compounds with selected core targets (p38, AKT1, MMP9, and CCL5). In addition, the mRNA expression and immunohistochemical analysis showed that AAWE44 could inhibit lung inflammation via multiple pathways and multiple targets in vivo. CONCLUSIONS: The findings of this study suggest that the water-soluble subfraction AAWE4 from A. argyi ameliorated the inflammation caused by LPS through multiple pathways and multiple targets in vitro and in vivo, providing scientific support for the medicinal use of A. argyi. Importantly, it shows that the A. argyi subfraction AAWE4 can be developed as an anti-inflammatory drug.
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Artemisia , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Extratos Vegetais/farmacologia , Metaloproteinase 9 da Matriz , NF-kappa B/metabolismo , Água , Artemisia/química , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , RNA MensageiroRESUMO
Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). In addition, GeneCards, Disgenet, and GeneMap databases in OMIM were used to determine the disease targets of CI. A total of 88 common targets of DH and CI were selected, a protein-protein interaction (PPI) network was established by Cytoscape, and 19 core targets were screened. These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.
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Carthamus tinctorius , Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Salvia miltiorrhiza , Animais , Ratos , Simulação de Acoplamento Molecular , Infarto Cerebral , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
Benzimidazole nucleus is a predominant heterocycle displaying a wide spectrum of pharmacological activities. The privileged nature of the benzimidazole scaffold has been revealed by its presence in most small molecule drugs and in its ability to bind multiple receptors with high affinity. A literature review of the scaffold reveals several instances where structural modifications of the benzimidazole core have resulted in high-affinity lead compounds against a variety of biological targets. Hence, this structural moiety offers opportunities to discover novel, better, safe and highly potent biological agents. The goal of the present review is to compile the medicinal properties of benzimidazole derivatives with a focus on SAR (Structure-Activity Relationships).
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Chronic heart failure (CHF) is a key part of cardiovascular continuum. Under the guidance of the theory of vessel-collateral doctrine, the present study proposes therapeutic benefits of Qili Qiangxin (QLQX) capsules, an innovative Chinese medicine, on chronic heart failure. The studies show that multiple targets of the drug on CHF, including enhancing myocardial systole, promoting urine excretion, inhibiting excessive activation of the neuroendocrine system, preventing ventricular remodeling by inhibiting inflammatory response, myocardial fibrosis, apoptosis and autophagy, enhancing myocardial energy metabolism, promoting angiogenesis, and improving endothelial function. Investigation on the effects and mechanism of the drug is beneficial to the treatment of chronic heart failure (CHF) through multiple targets and/or signaling pathways. Meanwhile, it provides new insights to further understand other refractory diseases in the cardiovascular continuum, and it also has an important theoretical and practical significance in enhancing prevention and therapeutic effect of traditional Chinese medicine for these diseases.
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Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug.
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Multiple autonomous underwater vehicles (AUVs) have gradually become the trend in underwater operations. Identifying and detecting these new underwater multi-targets is difficult when studying underwater moving targets. A 28-element transducer is used to test the echo of multiple AUVs with different layouts in a lake. The characteristics of the wideband echo signals are studied. Under the condition that the direction of arrival (DOA) is not known, an autofocus coherent signal subspace (ACCSM) method is proposed. The focusing matrix is constructed based on the received data. The spatial spectrum of the array signal of multiple AUVs at different attitudes is calculated. The algorithm estimates the DOA of the echo signals to overcome the shortcomings of traditional wideband DOA estimation and improve its accuracy. The results show that the highlights are not only related to the number of AUVs, but are also modified by scale and attitude. The contribution of the microstructure of the target in the overall echo cannot be ignored. Different parts of the target affect the number of highlights, thus resulting in varying numbers of highlights at different attitude angle intervals. The results have significant implications for underwater multi-target recognition.
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Oat (Avena sativa L.), an annual herbaceous plant belonging to the Gramineae family, is widely grown in various regions including EU, Canada, America, Australia, etc. Due to the nutritional and pharmacological values, oats have been developed into various functional food including fermented beverage, noodle, cookie, etc. Meanwhile, numerous studies have demonstrated that oats may effectively improve metabolic syndrome, such as dyslipidemia, hyperglycemia, atherosclerosis, hypertension, and obesity. However, the systematic pharmacological mechanisms of oats on metabolic syndrome have not been fully revealed. Therefore, in order to fully explore the benefits of oat in food industry and clinic, this review aims to provide up-to-date information on oat and its constituents, focusing on the effects on metabolic syndrome.
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Avena , Síndrome Metabólica , Avena/metabolismo , Síndrome Metabólica/tratamento farmacológico , Grão Comestível , Austrália , CanadáRESUMO
PURPOSE: Robustness to residual setup errors and linac delivery errors of BrainLab Elements single-isocentre-multiple-target stereotactic radiosurgery was evaluated. METHODS: Residual setup errors of 13 patients were evaluated. Linac delivery error was quantified through multi-metastases-Winston-Lutz measurements. PTV margins were calculated using the van Herk recipe. Patient scans were translated and rotated by the median and 95th percentile of the combined uncertainties, and plans were recalculated subsequently. Previous patients' plans were then replanned with the derived margins, effects on GTV coverage and normal brain doses were assessed. RESULTS: Mean (±stdev) coverage of all targets in the original plans were 99.4% (±0.9%) and 98.9% (±1.0%) for 1 and 3-fraction patients respectively. Median geometrical errors did not result in significant differences. A statistically significant reduction in coverage to 91.4% (±10.4%) and 93.0% (±9.6%) was seen under 95th percentile errors. Applying the derived optimal margin of 0.5 mm resulted in 78% of the GTVs retaining a coverage of 98% or above even in the presence of 95th percentile errors, compared to only 30% if no margins were applied. Replanning with margins also caused no significant increase to local normal brain doses, however global dose increases varied according to the number of metastases. CONCLUSIONS: Plans were shown to be robust to average geometrical uncertainties despite targets having no margins, however occurrence of GTV under-coverage increased under 95th percentile scenarios. The margin was proven to substantially improve the target dose coverage with limited change to local normal brain doses, although not all sources of geometrical uncertainty were considered.
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Radiocirurgia , Humanos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , CabeçaRESUMO
Clustered regularly interspaced short palindromic repeat (CRISPR)-based biosensors have been developed to facilitate the rapid and sensitive detection of nucleic acids. However, most approaches using CRISPR-based detection have disadvantages associated with the limitations of CRISPR RNA (crRNA), protospacer adjacent motif (PAM) or protospacer flanking sequence restriction, single channel detection, and difficulty in quantitative detection resulting in only some target sites being detected qualitatively. Here, we aimed to develop a barcode-based Cas12a-mediated DNA detection (BCDetection) strategy, which overcomes the aforementioned drawbacks and enables (1) detection with a universal PAM and crRNA without PAM or crRNA restriction, (2) simultaneous detection of multiple targets in a single reaction, and (3) quantitative detection, which can significantly distinguish copy number differences up to as low as a two-fold limit. We could efficiently and simultaneously detect three ß-thalassemia mutations in a single reaction using BCDetection. Notably, samples from normal individuals, spinal muscular atrophy (SMA) carriers, and SMA patients were significantly and accurately distinguished using the quantitative detection ability of BCDetection, indicating its potential application in ß-thalassemia and SMA carrier screening. Therefore, our findings demonstrate that BCDetection provides a new platform for accurate and efficient quantitative detection using CRISPR/Cas12a, highlighting its bioanalytical applications.
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Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.
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Background: The prominent mitochondrial metabolic changes of the atrium reportedly have significant impact on electrical signals and structural remodeling which play important roles in the occurrence and development of atrial fibrillation (AF). However, the mechanism is not completely known. Objective: This study was aimed to explore the mitochondrial metabolism reprogrammed in AF patients by integrating metabolomics as well as proteomics of human atrium tissues. Methods and Results: Left atrial tissue samples were harvested from 10 non-valvular AF patients and 10 matched samples from healthy donors for transplantation. In metabolomics analysis, 113 metabolites were upregulated and 10 metabolites were downregulated in AF, where multiple pathways related to mitochondrial energy metabolism were enriched. Correlation analysis between the differentially expressed proteins and metabolites identified several hub proteins related to mitochondrial function including Glycerol-3-phosphate dehydrogenase 2 (GPD2), Synemin (SYNM), Plectin (PLEC), with MCC score of 27, 17, 16, respectively, which have the most interactions with the dysregulated metabolites and ranked at the top in network string interactions scored by MCC method. All 330 differentially expressed proteins including 225 upregulated and 105 downregulated molecules were revealed and analyzed, which identified the downregulation of GPD2 (p = 0.02 and FC = 0.77), PLEC (p < 0.001 and FC = 0.71) and SYNM (p = 0.04 and FC = 0.76) in AF patients. Gene Set Variation Analysis (GSEA) showed mitochondrial metabolism-associated pathways including oxidative phosphorylation (NES: -1.73) and ATP biosynthetic process (NES: -2.29), were dramatically diversified in human AF. In GSVA, the expression levels of GPD2, PLEC, and SYNM were demonstrated to be associated with multiple metabolic pathways related to mitochondrial function (e.g., lipid metabolism and AMP activated protein kinase signaling) and cardiac structural and electrical remodeling (e.g., contractile fiber, ion homeostasis), which were proven vital in the development and maintenance of AF. Conclusion: In all, this study provides new insights into understanding the mechanisms of AF progression, especially the reprogramming mitochondrial metabolism, and identifies several genes related to mitochondrial function as novel targets for AF, which may be involved in the occurrence and development of AF.