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Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-ß (Aß) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aß from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aß. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aß in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aß. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aß after binding to Aß. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Microglia , Mitocôndrias , Simulação de Acoplamento Molecular , Fagocitose , Microglia/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Humanos , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/químicaRESUMO
Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Infecções por Papillomavirus , Animais , Camundongos , Proteínas Hedgehog/genética , Carcinoma de Células Escamosas do Esôfago/genética , Papillomavirus Humano 16/genética , Infecções por Papillomavirus/complicações , Neoplasias Esofágicas/genética , Camundongos NusRESUMO
Three-line hybrid rice has primarily been developed on wild abortive (WA)-type cytoplasmic male sterility (CMS) and has helped increase the yield of rice globally. The development of WA-type CMS lines and hybrids was expedited through the identification and mapping of the fertility restorer gene (Rf) in maintainers. This study observed fertile plants in WA-TianfengA/Zhenshan97B//TianfengB population, indicating that the maintainer line 'Zhenshan97B' should carry Rfs for WA-type CMS. Several advanced backcross populations were generated with the genetic background of the 'WA-TianfengA,' and the pollen fertility levels of the backcrossed individuals in BC3F1, BC4F1 and BC4F2 populations are governed by a new gene, Rf20(t), from 'Zhenshan97B.' Employing bulk segregant analysis of fertile and sterile pools from the BC4F1 population, Rf20(t) was genetically mapped to a candidate region on chromosome 10. Subsequently, Rf20(t) was located between RM24883 and RM24919 through recombination analysis of molecular markers using the BC4F2 population. Implementing a substitution mapping strategy, Rf20(t) was ultimately mapped to a 245-kb region between the molecular markers STS10-122 and STS10-126 and obtained the most likely candidate gene LOC_Os10g02650, which is predicted to encode pentatricopeptide repeat-containing (PPR) protein. These results enhance our understanding of the fertility restoration of WA-type CMS lines, facilitating the development of high-quality pairs of WA-type CMS and maintainer lines.
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Oryza , Humanos , Oryza/genética , Infertilidade das Plantas/genética , Citoplasma/genética , Fertilidade/genética , Genes de PlantasRESUMO
Cisplatin (DDP) based chemotherapy occurs a reduced therapeutic effect on the later treatment of ovarian cancer (OC) due to DDP resistance. Astragaloside II (ASII), a natural product extracted from Radix Astragali, has shown promising anticancer effects. However, the effects of ASII on OC have not been clarified. In this study, we found that ASII inhibited cell growth and promoted cell apoptosis of DDP-resistant OC cells in vitro and in vivo. Further study showed that ASII downregulated multidrug resistance-related protein MDR1 and cell cycle-related protein Cyclin D1 and PCNA, and also upregulated apoptosis-related protein leaved PRAP and cleaved caspase-3. In addition, ASII induced autophagy, characterized by upregulation of LC3II expression, downregulation of p62 expression, and elevation of LC3 punctuation, may be associated with inhibition of the AKT/mTOR signaling pathway. Moreover, the messenger RNA-sequencing was used to identify potential molecules regulated by ASII. In conclusion, these findings indicated that ASII increased sensitivity of DDP in the treatment of OC.
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Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Apoptose , AutofagiaRESUMO
Objective: Autophagy is the catabolic process where the components of eukaryotes experience damage, and the affected or superfluous components undergo self-degradation. However autophagy can promote cancer cell apoptosis or facilitate cell growth. This work aimed to investigat the significance of autophagy-related genes (ARGs) in predicting the prognosis of breast cancer (BC) intervened with Cremastra. Methods: Active ingredients and action targets were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction. Then, the BC transcriptome and clinical data were downloaded in The Cancer Genome Atlas (TCGA), whereas ARGs were collected in the Human Autophagy Database (HADb). Meanwhile, Perl and R software were used for data processing and analysis. Firstly, the transcriptome data of BC were mapped to ARGs to screen the BC-ARGs. Secondly, the above genes were mapped to the action targets of Cremastra, ARGs of Cremastra-intervened BC were then screened out. Moreover, an enrichment analysis of biological function was carried out. Univariate Cox regression was carried out on ARGs of BC for preliminarily selecting the independent prognostic genes and constructing the autophagy prognosis model. These genes were mapped to ARGs involved in Cremastra-intervened BC. Finally, those mapped genes were optimized by multi-factor Cox regression, and the key ARGs and potential compounds were obtained. Finally, all cases were classified as low- or high-risk group based on the median risk score. Receiver operating characteristic (ROC) curve, Kaplan-Meier (K-M) survival, independent prognosis and clinical correlation analyses were conducted for model evaluation and identification of factors to independently predict prognosis. Results: Altogether, 66 active components and 38 targets of the Cremastra-intervened autophagy of BC were screened and the autophagy prognosis model demonstrate good predictive performance. As suggested by the survival curve, low-risk patients had a markedly increased survival rate compared with high-risk patients (P < .01). Besides, the gene expression levels of the high-risk group increased with the increases in patients' risk scores. Upon univariate regression, 34 differentially expressed ARGs related to BC treatment were screened. Multivariate regression identified 4 key ARGs, which were mainly derived from glycosides, lignans, flavonoids, and dibenzyl compounds. Thereafter, key genes were subjected to correlation analysis between clinicopathological features and prognosis, among which BCL2 and TP63, showed independent prognostic value. Conclusions: In this study, an autophagy prognosis model was established, and BCL2 and TP63 were predicted for the Cremastra intervention of BC by Bioinformatics, which will be applied to further work.
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BACKGROUND: The COVID-19 pandemic led many educational institutions to shift to online courses, making blended education a significant trend in teaching. We examined the effectiveness of blended learning in an evidence-based medicine course. METHODS: We compared the examination scores of a blended learning group, an online only group, and a traditional offline group and conducted a questionnaire survey on students' preferences for different learning modes and the reasons for their preferences. A total of 2100 undergraduate students in clinical medicine were included in this cross-sectional study. Examination results were collected, and questionnaires were administered to the study participants. We compared the mean scores and exam pass rates of the three teaching groups using ANOVA and c2test for multiple comparisons. RESULTS: The blended group's exam scores and pass rate were significantly higher than those of the offline and online groups. Furthermore, 71.6% preferred the blended teaching mode. In the survey on " learning effectiveness", the majority of the students believed that blended education could better enhance the initiative of learning, the interest of the course, the pertinence of the learning content, the comprehension of evidence-based medical thinking, and the basic skills of evidence-based practice. Subsequently, in a questionnaire administered to a blended group of students, their foremost reason for liking online instruction was 'flexible in time and space' (99%), followed by 'can be viewed repeatedly, facilitating a better understanding of knowledge points' (98%). Their foremost reason for liking offline teaching was 'helps to create a good learning atmosphere' (97%), followed by 'teachers can control students' learning status in real time' (89%). CONCLUSIONS: This study explored the effectiveness of learning in evidence-based medicine courses by comparing the learning outcomes and personal perceptions of three different teaching modes. This is the first cross-sectional study in which three different teaching models are compared and discussed in an evidence-based medicine course. We also elaborate on the specific instructional protocols for each model. This study shows that using a blended education approach in evidence-based medicine courses can improve students' learning motivation, autonomy, and satisfaction. It also enhances instructional efficiency, thereby improving students' understanding of the course content.
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Educação a Distância , Educação Médica , Estudantes de Medicina , Humanos , Estudos Transversais , Educação a Distância/métodos , Pandemias , AprendizagemRESUMO
With the development of intelligent substations, inspection robots are widely used to ensure the safe and stable operation of substations. Due to the prevalence of grass around the substation in the external environment, the inspection robot will be affected by grass when performing the inspection task, which can easily lead to the interruption of the inspection task. At present, inspection robots based on LiDAR sensors regard grass as hard obstacles such as stones, resulting in interruption of inspection tasks and decreased inspection efficiency. Moreover, there are inaccurate multiple object-detection boxes in grass recognition. To address these issues, this paper proposes a new assistance navigation method for substation inspection robots to cross grass areas safely. First, an assistant navigation algorithm is designed to enable the substation inspection robot to recognize grass and to cross the grass obstacles on the route of movement to continue the inspection work. Second, a three-layer convolutional structure of the Faster-RCNN network in the assistant navigation algorithm is improved instead of the original full connection structure for optimizing the object-detection boxes. Finally, compared with several Faster-RCNN networks with different convolutional kernel dimensions, the experimental results show that at the convolutional kernel dimension of 1024, the proposed method in this paper improves the mAP by 4.13% and the mAP is 91.25% at IoU threshold 0.5 in the range of IoU thresholds from 0.5 to 0.9 with respect to the basic network. In addition, the assistant navigation algorithm designed in this paper fuses the ultrasonic radar signals with the object recognition results and then performs the safety judgment to make the inspection robot safely cross the grass area, which improves the inspection efficiency.
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Ambient particulate matter (PM) can cause adverse health effects via their ability to produce Reactive Oxygen Species (ROS). Water-Soluble Organic Compounds (WSOCs), a complex mixture of organic compounds which usually coexist with Transition Metals (TMs) in PM, have been found to contribute to ROS formation. However, the interaction between WSOCs and TMs and its effect on ROS generation are still unknown. In this study, we examined the ROS concentrations of V, Zn, Suwannee River Fulvic Acid (SRFA), Suwannee River Humic Acid (SRHA) and the mixtures of V/Zn and SRFA/SRHA by using a cell-free 2',7'-Dichlorodihydrofluorescein (DCFH) assay. The results showed that V or Zn synergistically promoted ROS generated by SRFA, but had an antagonistic effect on ROS generated by SRHA. Fluorescence quenching experiments indicated that V and Zn were more prone to form stable complexes with aromatic humic acid-like component (C1) and fulvic acid-like component (C3) in SRFA and SRHA. Results suggested that the underlying mechanism involving the fulvic acid-like component in SRFA more tending to complex with TMs to facilitate ROS generation through π electron transfer. Our work showed that the complexing ability and complexing stability of atmospheric PM organics with metals could significantly affect ROS generation. It is recommended that the research deploying multiple analytical methods to quantify the impact of PM components on public health and environment is needed in the future.
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Substâncias Húmicas , Água , Substâncias Húmicas/análise , Compostos Orgânicos , Material Particulado/química , Espécies Reativas de Oxigênio/químicaRESUMO
Cervical cancer (CC) is the second most common malignancy among women. GEPIA demonstrated that MEF2C-AS1 and its nearby gene MEF2C present downregulation in CC tissues. We attempted to clarify molecular mechanism between MEF2C-AS1 and MEF2C underlying CC progression. RT-qPCR was used to measure expression levels and subcellular distribution of MEF2C-AS1 and MEF2C in CC cell lines. Gain-of-function assays were conducted to reveal roles of MEF2C-AS1 and MEF2C in CC cell behaviors. Bioinformatics, RNA pull down, and RIP assays were performed to assess association of MEF2C-AS1 or MEF2C with miR-20 b-5p in CC cells. Rescue assays were done to assess regulatory function of the MEF2C-AS1-miR-20 b-5p-MEF2C axis in CC cellular processes. MEF2C-AS1 and its nearby gene MEF2C showed downregulation and had a positive expression correlation in CC tissues. MEF2C-AS1 and MEF2C presented downregulation in CC cells, and they majorly distributed in CC cell cytoplasm. MEF2C-AS1 and MEF2C upregulation repressed CC cell proliferative, migratory, and angiogenic abilities. MEF2C-AS1 competitively bound with miR-20 b-5p to upregulate MEF2C in CC cells. The impacts of MEF2C-AS1 elevation on CC cell proliferative, migratory, and angiogenic capabilities were countervailed by miR-20 b-5p overexpression. The impacts of miR-20 b-5p inhibitor on CC cell proliferative, migratory and angiogenic capabilities were countervailed by MEF2C depletion. To sum up, MEF2C-AS1 and its nearby gene MEF2C present downregulation and serve as tumor suppressors in CC cells. MEF2C-AS1 suppresses CC cell malignancy in vitro through sponging miR-20 b-5p to upregulate MEF2C, which may provide a potential new direction for seeking therapeutic plans of CC.
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Fatores de Transcrição MEF2 , MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fenótipo , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Obesity and metabolic disorders caused by energy surplus pose an increasing concern within the global population. Brown adipose tissue (BAT) dissipates energy through mitochondrial non-shivering thermogenesis, thus representing a powerful agent against obesity. Here we explore the novel role of a mitochondrial outer membrane protein, LETM1-domain containing 1 (LETMD1), in BAT. We generated a knockout (Letmd1KO ) mouse model and analyzed BAT morphology, function and gene expression under various physiological conditions. While the Letmd1KO mice are born normally and have normal morphology and body weight, they lose multilocular brown adipocytes completely and have diminished mitochondrial abundance, DNA copy number, cristae structure, and thermogenic gene expression in the intrascapular BAT, associated with elevated reactive oxidative stress. In consequence, the Letmd1KO mice fail to maintain body temperature in response to acute cold exposure without food and become hypothermic within 4 h. Although the cold-exposed Letmd1KO mice can maintain body temperature in the presence of food, they cannot upregulate expression of uncoupling protein 1 (UCP1) and convert white to beige adipocytes, nor can they respond to adrenergic stimulation. These results demonstrate that LETMD1 is essential for mitochondrial structure and function, and thermogenesis of brown adipocytes.
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Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Mitocôndrias/metabolismo , Proteínas Oncogênicas/fisiologia , Receptores de Superfície Celular/fisiologia , Termogênese , Adipócitos Marrons/citologia , Tecido Adiposo Marrom/citologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismoRESUMO
The COVID-19 pandemic is seriously affecting the mental health of adolescents and triggering a series of mental health-related issues. The present study investigates the relationships between conscientiousness, dispositional mindfulness (DM), and adolescents' mental health-related issues including anxiety, depression, and perceived stress during this time. In this study, after obtaining informed consent from participants' parents, 5994 Chinese adolescents voluntarily and anonymously completed an online survey. Conscientiousness was found to be negatively associated with anxiety, depression, and perceived stress. It was found to be positively associated with DM, which, in turn, negatively predicts anxiety, depression, and perceived stress. Conscientiousness is thus related to mental health-related issues, and this relationship is mediated by DM. This mediation effect is stronger in females than in males. These findings provide new and strong evidence for the protective role of conscientiousness and DM in adolescents' mental health-related issues during the COVID-19 pandemic.
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Sox4 participates in the progression of embryo development and regulation of apoptosis in tumors. However, the effect and mechanism of Sox4 in myocardial infarction (MI) remains unclear. Therefore, we aimed at examining the role and molecular mechanism of Sox4 in the process of cardiomyocytes apoptosis during MI. The expression of Sox4 were obviously increased both in MI mice and in neonatal mouse cardiomyocytes treated with H2 O2 . Overexpression of Sox4 promoted cardiomyocyte apoptosis with or without H2 O2 , whereas knocking down of Sox4 alleviated H2 O2 -induced apoptosis in cardiomyocytes. Furthermore, silencing Sox4 by AAV-9 carried short hairpin RNA targeting Sox4 (AAV-9-sh-Sox4) markedly decreased cardiac infarct area, imprfoved cardiac dysfunction, and reversed apoptosis in MI mice. Mechanistically, there is a potential Sox4-binding site in the promoter region of Bim, and forced expression of Sox4 significantly promoted Bim expression in cultured cardiomyocytes with or without H2 O2 , whereas knocking down of Sox4 inhibited the expression of Bim. Further studies showed that silencing Bim attenuated Sox4-induced apoptosis in cardiomyocytes, indicating that Sox4 promoted cardiomyocytes apoptosis through regulation of Bim expression, which can be used as a potential therapeutic target for MI.
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Proteína 11 Semelhante a Bcl-2/genética , Infarto do Miocárdio/genética , Isquemia Miocárdica/genética , Fatores de Transcrição SOXC/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Regulação da Expressão Gênica/genética , Humanos , Peróxido de Hidrogênio/farmacologia , Camundongos , Infarto do Miocárdio/patologia , Isquemia Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: Previous studies using diffusion tensor imaging (DTI)-based connectome analysis revealed improved connectivity in cerebral palsy (CP) patients who underwent autologous umbilical cord blood (UCB) stem-cell therapy. However, the potential mechanism for the connectivity increase remains unclear and needs to be further elucidated. PURPOSE: To develop a technique with improved accuracy for quantitative susceptibility mapping (QSM) with unique sensitivity to myelin, and demonstrate its use in elucidating the underlying mechanism of the observed motor function improvement and brain connectivity increase in CP patients who received autologous UCB stem-cell therapy. STUDY TYPE: Prospective. POPULATION: A cohort of eight pediatric CP patients (2.6 ± 0.6 years of age) with intact corticospinal tracts (CST) from a randomized, placebo-controlled trial of autologous UCB stem-cell therapy in CP children was included in this study. FIELD STRENGTH/SEQUENCE: DTI and 3D spoiled gradient recalled (SPGR) QSM at 3.0T. ASSESSMENT: Pre- and posttreatment magnetic susceptibility (χ) and the rotationally-invariant magnetic susceptibility anisotropy (MSA) along the CST were derived. Behavioral changes were assessed using the 66-item Gross Motor Function Measurement. Changes in χ and MSA were compared between patients with and without substantial behavioral improvements. STATISTICAL TESTS: Two-sample t-tests were performed to assess the differences in the changes of measurements of interest (Δχ, ΔMSA, and ΔFA) between patients who significantly improved and those who did not. RESULTS: Patients who demonstrated posttreatment motor improvements exceeding expectations showed significantly more diamagnetic Δχ in the periventricular region along the CST (P = 0.003). Further analysis on the ΔMSA of this region was significantly increased (P = 0.006) for high responders, along with concurrent FA increase. DATA CONCLUSION: These initial findings suggest that the DTI tract-based QSM method has the potential to characterize white matter changes associated with behavioral improvements in CP children who underwent cord blood stem-cell therapy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
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Paralisia Cerebral , Imagem de Tensor de Difusão , Anisotropia , Encéfalo/diagnóstico por imagem , Terapia Baseada em Transplante de Células e Tecidos , Paralisia Cerebral/diagnóstico por imagem , Paralisia Cerebral/terapia , Criança , Estudos de Viabilidade , Sangue Fetal , Humanos , Estudos Prospectivos , Tratos PiramidaisRESUMO
The effects of immunomodulatory activity of two types of carboxymethyl pachymaran (CMP-1 and CMP-2) on cyclophosphamide (CTX)-induced mice were investigated. Both CMP-1 and CMP-2 were found to restore the splenomegaly and alleviate the spleen lesions and the mRNA expressions of TLR4, MyD88, p65 and NF-κB in spleen were also increased. CMP-1 and CMP-2 could enhance the immunity by increasing the levels of TNF-α, IL-2, IL-6, IFN-γ, Ig-A and Ig-G in serum. In addition, CMP-1 could increase the relative abundance of Bacteroidetes and reduce the relative richness of Firmicutes at the phylum level. CMP-1 and CMP-2 could reduce the relative abundance Erysipelatoclostridum at the genus level. CMP-1 and CMP-2 might enhance the immune function of immunosuppression mice by regulating the gene expression in the TLR4/NF-κB signaling pathway and changing the composition and abundance of the intestinal microbiota. The results suggested that CMP-1 and CMP-2 would be as potential immunomodulatory agents in functional foods.
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Ciclofosfamida/efeitos adversos , Glucanos/química , Hospedeiro Imunocomprometido/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Polissacarídeos/administração & dosagem , Esplenomegalia/tratamento farmacológico , Animais , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Modelos Animais de Doenças , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Alimento Funcional , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/genética , Filogenia , Polissacarídeos/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esplenomegalia/induzido quimicamente , Esplenomegalia/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
This work developed a near-infrared (near-IR) light-activated non-enzymatic signal-off photoelectrochemical (PEC) immunoassay for the ultrasensitive detection of α-fetoprotein (AFP) on the basis of branched polyethylenimine (BPEI)-modified upconversion nanoparticle (UCNP)@CdTe quantum dot (QD) nanostructures by coupling with the synergistic effect of dual-purpose copper ions. Emission light originated from NaYF4:Yb,Er UCNP was directly utilized through the electrostatic bonding of CdTe QDs to excite the separation of electron-hole pairs, resulting in the generation of obvious photocurrent under a 980 nm laser. By using polyclonal antibody-labeled cupric oxide nanoparticle as the secondary antibody, the nanolabel was introduced into the monoclonal anti-AFP antibody-modified microplates in the presence of target AFP. After treatment with acid, the as-released copper ion decreased the photocurrent through the synergistic effect with two issues: one was initially to form coordination with BPEI on the surface of UCNP, and then the near-IR excitation light and upconversion luminescence were attenuated due to the internal filter effect; another was to snatch the electrons flowing from the valence band of CdTe QD as the exciton trapping sites. Under optimal conditions, the dual-purpose Cu2+-activated signal-off PEC immunosensing platform exhibited a dynamic linear range from 10 pg mL-1 to 50 ng mL-1, accompanying the decreasing photocurrent with the increment of AFP concentration at an experimental detection limit of 1.2 pg mL-1. Importantly, good accuracy was achieved by this method in comparison with the results with human AFP ELISA kit for analysis of human serum samples. This dual-purpose Cu2+-activated PEC immunoassay brings a promising, enzyme-free and innovative thinking for the detection of low-abundance biomarkers.
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Cobre/química , Técnicas Eletroquímicas/métodos , Nanoestruturas/química , Processos Fotoquímicos , Polietilenoimina/química , Pontos Quânticos , alfa-Fetoproteínas/análise , Técnicas Biossensoriais , Compostos de Cádmio/química , Humanos , Imunoensaio , Limite de Detecção , Telúrio/químicaRESUMO
This work reports a strategy for glutathione-loaded liposome-encoded magnetic beads initiated by palindromic fragment-mediated single-chain amplification (PFMSCA) for high-precision quantification of a low-abundance aminoglycoside antibiotic (kanamycin; Kana) by using In2O3-ZnIn2S4 (IO-ZIS) as a photoactive matrix. In this strategy, a Kana-recognition region, primer-like palindromic fragment, and polymerization/nicking template are reasonably integrated into one oligonucleotide (hairpin HP1) for target recognition, magnetic separation, and target amplification. Upon target Kana introduction, the Kana-aptamer region in HP1 specifically recognizes the Kana and triggers the palindromic tails intramolecular self-hybridization, amplifying a large number of short fragments in the presence of Klenow fragment polymerase and Nt.BbvCI. The as-generated nick fragments act as a linker to introduce the free hairpin HP2-functionalized glutathione-loaded liposomes (HP2-GLL) onto the surface of the hairpin HP3-modified magnetic beads (HP3-MB), constructing liposome-encoded magnetic beads (HP3-MB-nick-HP2-GLL). Following magnetic separation, the detached glutathione-loaded liposomes (GLL) are lysed by treatment with 1% Triton X-100 to release the glutathione within it, which were then detected as an amplified photocurrent at the IO-ZIS-based photoelectrode. Importantly, this method can be readily carried out by using one oligonucleotide to achieve an exponential amplification effect and open new opportunities for advanced development of robust biodetection systems.
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Técnicas Biossensoriais/métodos , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Sequências Repetidas Invertidas , Processos Fotoquímicos , Eletroquímica , Glutationa/química , Limite de Detecção , Lipossomos/química , Imãs/química , Microesferas , Técnicas de Amplificação de Ácido NucleicoRESUMO
This work presented an innovative and rationally engineered palindromic molecular beacon (PMB) based "Z-scheme" photoelectrochemical (PEC) biosensing protocol for the selective screening of kanamycin (Kana) through DNA hybridization-induced conformational conversion. Interestingly, the ingeniously designed PMB integrated the multifunctional elements including recognition region, primer-like palindromic fragment, and polymerization-nicking template. The cosensitized structures consisted of CdS quantum dot functionalized hairpin DNA2 (QD-HP2) and region-selectively deposited gold nanoparticles onto {001} facets of bismuth oxychloride (BiOCl-Au). Compared with BiOCl-Au alone, the attachment of CdS QDs onto BiOCl-Au (i.e., BiOCl-Au-CdS QDs) exhibited evidently enhanced photocurrent intensity thanks to the synergistic effect of Z-scheme BiOCl-Au-CdS QDs. After incubation with target Kana, Kana-aptamer binding could induce the exposure of PMB region for hairpin DNA1 (HP1). The exposed palindromic tails hybridized with each other (like a molecular machine) to consume the substrates (dNTPs) and fuels (enzyme) for the releasing of numerous nick fragments (Nick). The as-generated nick fragments could specifically hybridize with the complementary region of QD-HP2, thus resulting in decreasing photocurrent because of the increasing spatial distance for electron transfer between two-type photosensitizers. Under optimum conditions, the PMB-based sensing system exhibited satisfying photocurrent responses toward target Kana within the working range from 50 to 5000 fM at a low detection limit of 29 fM. Impressively, the concept of a palindromic fragment-mediated primer-free biosensing strategy offers a new avenue for advanced development of efficient and convenient biodetection systems.
Assuntos
Bismuto/química , Compostos de Cádmio/química , Técnicas Eletroquímicas/métodos , Canamicina/análise , Nanopartículas Metálicas/química , Pontos Quânticos/química , Sulfetos/química , Animais , Antibacterianos/análise , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Técnicas Biossensoriais/métodos , DNA/química , DNA/genética , Técnicas Eletroquímicas/instrumentação , Eletrodos , Contaminação de Alimentos/análise , Ouro/química , Ouro/efeitos da radiação , Sequências Repetidas Invertidas , Luz , Limite de Detecção , Nanopartículas Metálicas/efeitos da radiação , Leite/química , Hibridização de Ácido Nucleico , Fotoquímica/métodosRESUMO
A novel, probabilistically shaped star-CAP-16/32 modulation based on constellation design with honeycomb-like decision regions is proposed in this paper. The proper geometric structural design of the star constellation, along with the probabilistic shaping, is able to achieve better improvement with regards to constellation figure of merit (CFM) and bit error rate (BER) performance. A 25-km standard single-mode fiber (SSMF) data transmission employing the proposed PS star-CAP modulation scheme is successfully demonstrated. Experiment results show that the proposed PS star-CAP-16 in C4,4,4,4 excels the traditional PS star-CAP-16 in C8,8 by 1.5 dB in receiver sensitivity at the BER of 1×10-3 . At the same time, the novel PS star-CAP-32 with entropy of 4.4 bits/symbol defeats the uniform star-CAP-32 by 1.6 dB improvement under the same bit rate.
RESUMO
An innovative visible light-driven photoelectrochemical (PEC) immunosensing system was reasonably established for the sensitive detection of prostate-specific antigen (PSA) by using perovskite metal oxide@gold nanoparticle heterostructures (BaTiO3/Au) as the photoactive materials. When plasmonic Au nanoparticles were directly decorated on BaTiO3, a several times surface plasmon resonance (SPR) enhancement of photocurrent density was induced via the injection of hot electrons from visible light-excited Au nanoparticles into the conduction band of BaTiO3, and the combination of BaTiO3 and Au nanoparticles was employed as a promising platform for developing a photoelectrochemical bioanalysis. As a proof of concept, PSA had been detected by the BaTiO3/Au nanocomposite-based PEC sensor. To design such an immunoassay protocol, a monoclonal anti-PSA capture antibody (cAb)-coated microplate and glucose oxidase/polyclonal anti-PSA detection antibody-modified gold nanoparticles (GOx-Au NP-dAb) were used as the immunoreaction platform and signal probe, respectively. Upon the addition of target PSA, a sandwiched immunocomplex was formed accompanying the immuno-recognition between the antigen and antibody, and then the carried GOx could oxidize glucose to produce H2O2. The photocurrent of the BaTiO3/Au nanocomposite-functionalized electrode amplified with increasing H2O2 concentration since H2O2 is considered as a good hole scavenger. On the basis of the above-mentioned mechanisms and the optimized conditions, the assembled PEC immunosensor was linear with the logarithm of the PSA concentration in the range of 0.01-40 ng mL-1 with a detection limit of 4.2 pg mL-1. It afforded rapid response, good precision, and high stability and specificity, implying its great promise in photoelectrochemical immunoassays. More generally, this system sets up an ideal PEC immunosensing system based on the BaTiO3/Au nanocomposites and represents an innovative and low-cost "signal-on" assay scheme for the practical quantitative screening of low-abundance proteins.
Assuntos
Compostos de Bário/química , Ouro/química , Calicreínas/sangue , Nanopartículas Metálicas/química , Antígeno Prostático Específico/sangue , Titânio/química , Anticorpos Monoclonais/imunologia , Compostos de Bário/efeitos da radiação , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Glucose/análise , Glucose Oxidase/química , Ouro/efeitos da radiação , Humanos , Peróxido de Hidrogênio/química , Imunoensaio/métodos , Calicreínas/imunologia , Luz , Limite de Detecção , Nanopartículas Metálicas/efeitos da radiação , Nanocompostos/química , Nanocompostos/efeitos da radiação , Processos Fotoquímicos , Estudo de Prova de Conceito , Antígeno Prostático Específico/imunologia , Ressonância de Plasmônio de Superfície/métodos , Titânio/efeitos da radiaçãoRESUMO
Aflatoxin B1 (AFB1) pollution is one of the most serious problems for food safety. In this paper, a split-type photoelectrochemical (PEC) immunoassay was designed for sensitive detection of AFB1 in foodstuffs by using amorphous TiO2 with all-inorganic perovskite CsPbBr3 nanocrystals (CsPbBr3/a-TiO2). The a-TiO2 layer not only improved the stability of CsPbBr3 nanocrystals, but also facilitated charge transfer, which resulted in the increasing photocurrent of the nanocomposites. Initially, a competitive-type enzyme immunoreaction was executed on a high-binding microplate between the analyte and alkaline phosphatase (ALP)-labeled AFB1-bovine serum albumin (AFB1-BSA) conjugate. Accompanied by the formation of the immunocomplex, the carried ALP triggered enzymatic hydrolysis to generate ascorbic acid (AA, as an electron donor) for increasing the photocurrent of the CsPbBr3/a-TiO2-modified electrode. Coupling with the competitive enzyme immunoassay, the photocurrent of the modified electrode decreased with the increase of target AFB1 concentration in a dynamic working range from 0.01 ng mL-1 to 15 ng mL-1 with a limit of detection (LOD) of 2.8 pg mL-1 under optimum conditions. Furthermore, the photoelectrochemical immunoassay was also utilized to detect AFB1 in peanut and corn samples, giving acceptable accuracy in comparison with the referenced AFB1 enzyme-linked immunosorbent assay (ELISA) method.