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BACKGROUND This retrospective study evaluated the effects of specific COVID-19 preventive measures, including the use of medical masks, nucleic acid testing, and patient isolation, on respiratory infections, disease severity, and seasonal patterns among children in Hohhot, located in northern China. Understanding these alterations is pivotal in developing effective strategies to handle pediatric respiratory infections within the context of continuous public health initiatives. MATERIAL AND METHODS At the First Hospital of Hohhot, throat swabs were collected from 605 children with community-acquired respiratory between January 2022 and March 2023 for pathogen infection spectrum detection using microarray testing. RESULTS Among the patients, 56.03% were male, and their average age was 3.45 years. SARS-CoV-2 infections were highest between October 2022 and January 2023. Influenza A peaked in March 2023, and other pathogens such as respiratory syncytial virus and influenza B virus disappeared after December 2022. The proportion of mixed infections was 41.94% among SARS-CoV-2 patients, while other pathogens had mixed infection rates exceeding 57.14%. Before December 2022, the mean WBC count for Streptococcus pneumoniae and Haemophilus influenzae was 8.83×109/L, CRP was 18.36 mg/L, and PCT was 1.11 ng/ml. After December 2022, these values decreased significantly. Coughing, difficulty breathing, running nose, and lower respiratory tract infection diagnoses decreased in December 2022, except for SARS-CoV-2 infections. CONCLUSIONS SARS-CoV-2 peaked around November 2022, influenza A peaked in March 2023, and other pathogens like respiratory syncytial virus and influenza B virus were greatly reduced after December 2022. Inflammatory markers and respiratory symptoms decreased after December 2022, except for SARS-CoV-2.
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COVID-19 , Influenza Humana , Infecções Respiratórias , Humanos , Criança , Masculino , Pré-Escolar , Feminino , COVID-19/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estudos Retrospectivos , SARS-CoV-2 , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , China/epidemiologia , Vírus Sinciciais Respiratórios , Vírus da Influenza B , Gravidade do PacienteRESUMO
Huanglongbing (HLB), a devastating citrus disease caused by Candidatus Liberibacter asiaticus, is efficiently vectored by the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae). Tamarixia radiata (Waterston) plays a crucial role as an ectoparasitoid, preying on D. citri nymphs. By collecting and identifying headspace volatiles from fifth instar nymphs of D. citri using a gas chromatograph-mass spectrometer (GC-MS), we obtained a collection of 9 volatile compounds. These compounds were subsequently chosen to investigate the electrophysiological and behavioral responses of female T. radiata. At a concentration of 10 µg/µl, 9 compounds were compared with cis-3-hexen-1-ol (control), resulting in trans-2-nonenal inducing the highest relative electroantennogram (EAG) value, followed by hexanal, heptanal, n-heptadecane, tetradecanal, n-tetradecane, n-pentadecane, 1-tetradecanol, and 1-dodecanol. The top 5 EAG responses of female T. radiata to these compounds were further investigated through EAG dose-response experiments. The results showed positive dose-responses as concentrations increased from 0.01 to 10 µg/µl. In Y-tube olfactometer bioassays, female T. radiata exhibited a preference for specific compounds. They were significantly attracted to tetradecanal at a concentration of 10 µg/µl and trans-2-nonenal at 0.01 µg/µl, while no significant attraction was observed toward hexanal, heptanal, or n-heptadecane. Our report is the first to demonstrate that volatiles produced by D. citri nymphs attract T. radiata, which suggests that this parasitoid may utilize nymph volatiles to locate its host.
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Hemípteros , Ninfa , Compostos Orgânicos Voláteis , Animais , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Hemípteros/fisiologia , Feminino , Vespas/fisiologia , Fenômenos Eletrofisiológicos , Comportamento Animal/efeitos dos fármacos , Antenas de Artrópodes/fisiologia , Antenas de Artrópodes/efeitos dos fármacosRESUMO
The development of precisely engineered vehicles for intracellular delivery and the controlled release of payloads remains a challenge. DNA-based nanomaterials offer a promising solution based on the A-T-G-C alphabet-dictated predictable assembly and high programmability. Herein, we present a self-immolative DNA nanogel vaccine, which can be tracelessly released in the intracellular compartments and activate the immune response. Three building blocks with cytosine-rich overhang domains are designed to self-assemble into a DNA nanogel framework with a controlled size. Two oligo agonists and one antigen peptide are conjugated to the building blocks via an acid-labile chemical linker. Upon internalization into acidic endosomes, the formation of i-motif configurations leads to dissociation of the DNA nanogel vaccine. The acid-labile chemical linker is cleaved, releasing the agonists and antigen in their traceless original form to activate antigen-presenting cells and an immune response. This study presents a novel strategy for constructing delivery platforms for intracellularly stimuli-triggered traceless release of therapeutics.
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Neoplasias , Vacinas de DNA , Humanos , Nanogéis , Imunoterapia , DNA/uso terapêutico , DNA/químicaRESUMO
"Subitizing" defines a phenomenon whereby approximately four items can be quickly and accurately processed. Studies have shown the close association between subitizing and math performance, however, the mechanism for the association remains unclear. The present study was conducted to investigate whether form perception assessed on a serial figure matching task is a potential non-numerical mechanism between subitizing ability and math performance. Three-hundred and seventy-three Chinese primary school students completed four kinds of dot comparison tasks, serial figure matching task, math performance tasks (including three arithmetic computation tasks and math word problem task), and other cognitive tasks as their general cognitive abilities were observed as covariates. A series of hierarchical regression analyses showed that after controlling for age, gender, nonverbal matrix reasoning, and visual tracking, subitizing comparison (subitizing vs. subitizing, subitizing vs. estimation) still contributed to simple addition or simple subtraction but not to complex subtraction ability or math word problem. After taking form perception as an additional control variable, the predictive power of different dot comparison conditions disappeared. A path model also showed that form perception fully mediates the relation between numerosity comparison (within and beyond the subitizing range) and arithmetic performance. These findings support the claim that form perception is a non-numerical cognitive correlate of the relation between subitizing ability and math performance (especially arithmetic computation).
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Matemática , Humanos , Masculino , Feminino , Criança , Cognição/fisiologia , Resolução de Problemas/fisiologia , Conceitos Matemáticos , Reconhecimento Visual de Modelos/fisiologia , Aptidão/fisiologiaRESUMO
Although selenium (Se) reserves are crucial for the development and exploitation of Se-rich resources in karst soil areas, research on these reserves is still limited. A comprehensive study was conducted in a typical karst region known for its Se richness. A total of 12,547 surface soil samples, 134 deep soil samples, and 60 soil profiles from various locations were systematically collected. The findings showed that the Se content in the surface soil ranged from 0.073 to 9.04 mg/kg, with a baseline level of 0.84 mg/kg. This underscores the high background level and moderate variability in the region. Surface soil Se exhibited a notable positive correlation with deep soil Se, and an inverse correlation with pH (p < 0.01). One-way analysis of variance indicated that land formations and soil structure were the primary determinants affecting the concentration of Se in the topsoil (p = 0.000), with parent rock type and land-use type following closely (p = 0.003). In addition, the study included an investigation of soil Se variations with depth using 60 soil profiles. Through this analysis, it was revealed that Se content exhibited an exponential change with depth. Multiple integrations were employed to derive formulas for calculating Se reserves in the 0-200 cm depth range. Following these calculations, the estimations of Se stockpile across diverse types of source materials, varieties of soils, and land management methods were determined, highlighting the findings using a passive construction. This paper lays the groundwork for advancing the extraction and application of Se.
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Selênio , Solo , Selênio/análise , China , Solo/química , Poluentes do Solo/análise , Monitoramento Ambiental , Concentração de Íons de HidrogênioRESUMO
Under a pH value lower than the pKa of adenine (3.5), adenine-rich sequences (A-strand) form a unique parallel A-motif duplex due to the protonation of A-strand. At a pH above 3.5, deprotonation of adenines leads to the dissolution of A-motif duplex to A-strand single coil. This pH-reconfigurable A-motif duplex has been developed as a novel pH-responsive DNA hydrogel, termed A-hydrogel. The hydrogel state is achieved at pH 1.2 by the A-motif duplex bridging units, which are cross-linked by both reverse Hoogsteen interaction and electrostatic attraction. Hydrogel-to-solution transition is triggered by pH 4.3 due to the deprotonation-induced separation of A-motif duplex. The A-hydrogel system undergoes reversible hydrogel-solution transitions by subjecting the system to cyclic pH shifts between 1.2 and 4.3. An anti-inflammatory medicine, sulfasalazine (SSZ), which intercalates into A-motif duplex, is loaded into A-hydrogel. Its pH-controlled release from A-hydrogel is successfully demonstrated. The strong acid-induced A-hydrogel may fill the gap that other mild acid-responsive DNA hydrogels cannot do, such as protection of orally delivered drug in hostile stomach environment against strong acid (pH ~ 1.2) and digestive enzymes.
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DNA , Hidrogéis , Concentração de Íons de HidrogênioRESUMO
Parkinson's disease (PD) is a common neurodegenerative motor disorder characterized by a dramatic reduction in pars compacta of substantia nigra dopaminergic neurons and striatal dopamine (DA) levels. Mutations or deletions in the PARK7/DJ-1 gene are associated with an early-onset familial form of PD. DJ-1 protein prevents neurodegeneration via its regulation of oxidative stress and mitochondrial function as well as its roles in transcription and signal transduction. In this study, we investigated how loss of DJ-1 function affected DA degradation, ROS generation and mitochondrial dysfunction in neuronal cells. We showed that loss of DJ-1 significantly increased the expression of monoamine oxidase (MAO)-B but not MAO-A in both neuronal cells and primary astrocytes. In DJ-1-knockout (KO) mice, MAO-B protein levels in the substantia nigra (SN) and striatal regions were significantly increased. We demonstrated that the induction of MAO-B expression by DJ-1 deficiency depended on early growth response 1 (EGR1) in N2a cells. By coimmunoprecipitation omics analysis, we found that DJ-1 interacted with receptor of activated protein C kinase 1 (RACK1), a scaffolding protein, and thus inhibited the activity of the PKC/JNK/AP-1/EGR1 cascade. The PKC inhibitor sotrastaurin or the JNK inhibitor SP600125 completely inhibited DJ-1 deficiency-induced EGR1 and MAO-B expression in N2a cells. Moreover, the MAO-B inhibitor rasagiline inhibited mitochondrial ROS generation and rescued neuronal cell death caused by DJ-1 deficiency, especially in response to MPTP stimulation in vitro and in vivo. These results suggest that DJ-1 exerts neuroprotective effects by inhibiting the expression of MAO-B distributed at the mitochondrial outer membrane, which mediates DA degradation, ROS generation and mitochondrial dysfunction. This study reveals a mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the crosslinks among pathogenic factors, mitochondrial dysfunction and oxidative stress in PD pathogenesis.
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Doenças Neurodegenerativas , Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Monoaminoxidase/farmacologia , Regulação para Cima , Espécies Reativas de Oxigênio/metabolismo , Neurônios Dopaminérgicos/metabolismo , Transdução de Sinais , Doenças Neurodegenerativas/metabolismo , Receptores de Quinase C Ativada/genética , Receptores de Quinase C Ativada/metabolismo , Receptores de Quinase C Ativada/farmacologia , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismoRESUMO
Metal contamination in agricultural soils has received widespread attention; however, the status of beryllium (Be) contamination in agricultural soils has been inadequately studied. This research was conducted to determine the enrichment level and major sources of Be contamination in the agricultural soil in Qingcheng District, Qingyuan City, and to quantify the potential ecological risk and human health risk (PER and HHR) of Be by integrating geological mineral and remote-sensing image maps. The results of principal component analysis followed by multiple linear regression (PCA-MLR) suggest that Be, Sn, Zn, Pb, As, and Cd are mainly derived from anthropogenic activities; V, Ti, Sc, Cr, and Co are mainly derived from medium acidic granites; Al and Si are mainly derived from geological sources; and K and Na are mainly derived from calcium-alkaline materials. Anthropogenic activities are priority material sources owing to the highest contribution. Be contamination poses a slight PER, and the PER level of agricultural soil was moderate. The HHR caused by Be is negligible. The results of this study can serve as the basis for promoting agricultural soil protection and developing and implementing agricultural policies to reduce environmental pollution in the study area.
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In this study, the phytoremediation efficiency of Arabidopsis halleri L. in response to mechanical injury were compared between those irrigated with magnetized water and those irrigated with normal water. Under normal irrigation treatment, wounding stress increased malondialdehyde (MDA) concentrations and hydrogen peroxide (H2O2) levels in A. halleri leaves significantly, by 46.7-86.1% and 39.4-77.4%, respectively, relative to those in the intact tissues. In addition, wounding stresses decreased the content of Cd in leaves by 26.8-52.2%, relative to the control, indicating that oxidative damage in plant tissues was induced by mechanical injury, rather than Cd accumulation. There were no significant differences in MDA and H2O2 between A. halleri irrigated with magnetized water and with normal water under wounding conditions; however, the activities of catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) in the leaves of plants treated with magnetized water were significantly increased by 25.1-56.7%, 47.3-183.6%, and 44.2-109.4%, respectively. Notably, under the magnetic field, the phytoremediation effect of 30% wounded A. halleri nearly returned to normal levels. We find that irrigation with magnetized water is an economical pathway to improve the tolerance of A. halleri to inevitable mechanical injury and may recover its phytoremediation effect.
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An acid-resistant DNA hydrogel that is stable in an extremely acidic environment with pH as low as 1.2 has not been reported before, largely due to the instability of DNA-hybridized structures. To achieve this, adenine (A)-rich and cytosine (C)-rich oligonucleotides are rationally designed and integrated to form copolymers with acrylamide monomers via free-radical polymerization. In an acidic environment (pH 1.2-6.0), the generated copolymers form a hydrogel state, which is cross-linked by parallel A-motif duplex configurations (pH 1.2-3.0) and quadruplex i-motif structures (pH 4.0-6.0) due to the protonation of A and C bases, respectively. Specifically, the protonated A-rich sequences under pH 1.2-3.0 form a stable parallel A-motif duplex cross-linking unit through reverse Hoogsteen interaction and electrostatic attraction. Hemi-protonated C bases under mildly acidic pH (4.0-6.0) form quadruplex i-motif cross-linking configuration via Hoogsteen interaction. Under physiological pH, both A and C bases deprotonated, resulting in the separation of A-motif and i-motif to A-rich and C-rich single strands, respectively, and thereby the dissociation of the DNA hydrogel into the solution state. The acid-resistant and physiological pH-responsive DNA hydrogel was further developed for oral drug delivery to the hostile acidic environment in the stomach (pH 1.2), duodenum (pH 5.0), and small intestine (pH 7.2), where the drug would be released and absorbed. As a proof of concept, insulin was encapsulated in the DNA hydrogel and orally administered to diabetic rats. In vitro and in vivo studies demonstrated the potential usage of the DNA hydrogel for oral drug delivery.
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Diabetes Mellitus Experimental , Hidrogéis , Ácidos , Animais , DNA/química , Concentração de Íons de Hidrogênio , Insulina/farmacologia , RatosRESUMO
BACKGROUND Lower respiratory tract infection (LRTI) in children is due to various pathogens. Appropriate diagnosis and early treatment are important for reducing the mortality rate of LRTI. Data on the epidemiology profiles of LRTI are scarce in northern China. The aim of this study was to provide data on the pathogen pattern of LRTI in hospitalized children in Hohhot, Inner Mongolia, China. MATERIAL AND METHODS From July 2019 to June 2020, nasopharyngeal swabs were collected from 265 children in Hohhot with LRTI, and pathogens were detected with RT-PCR and PCR. The correlations among procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) with acute respiratory infections were evaluated. RESULTS The highest prevalence of LRTI was detected in 2- to 6-year-old children (149, 56.2%) in winter. Eleven respiratory pathogens were evaluated, and respiratory syncytial virus, Streptococcus pneumoniae and Haemophilus influenza were the most common pathogens in this region. Single viruses, bacteria, mycoplasma, and multiple pathogens were identified in 24.2, 15.8, 5.3, and 54.7% of patients, respectively. The mean blood biomarker values of patients with LRTI were significantly different from those of healthy children. Furthermore, The AUCs were 0.90, 0.74, and 0.84 for bacteria, virus, and mycoplasma PCT values, which were significantly higher than that of WBC and CRP. CONCLUSIONS This evaluation of the regional pattern of pathogens in children with acute respiratory infections and the correlation with blood biomarkers provides valuable information for the prevention and treatment of LRTI in children.
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Infecções Respiratórias , Vírus , Bactérias , Criança , China/epidemiologia , Humanos , Lactente , Pró-Calcitonina , Vírus Sinciciais Respiratórios , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologiaRESUMO
A total of 511 topsoils and 139 deep soil samples were collected to analyze the distribution characteristics, regional differentiation factors, and contamination sources of Cd in Shantou City, and to assess its environmental, ecological, and human health risks. We used a combination of multivariate statistics and geostatistics to quantify the distribution and level of Cd contamination in the study area, and an absolute principal component scores-multiple linear regression model to resolve the sources of contamination and their contribution values, combined with the health risk model to assess the human health risk from each source. The result exhibited that the average value of soil Cd content was 0.100 mg/kg, which was lower than the threshold value of soil environmental quality standard, but higher than the 0.070 mg/kg background value of soil. The high-value areas of surface Cd content in the study area were distributed in the western, northern, and northeastern parts of Shantou, and the source of Cd in the soil was a mix of anthropogenic and natural contamination. The non-carcinogenic and carcinogenic risks of heavy metal Cd exposure pathways are: oral ingestion > dermal contact > inhalation. The human health risk posed by Cd is below the reference threshold, indicating that the Cd contents in the soil have no unacceptable health risk to the residents. Among industrial sources, natural sources, and unknown sources with potential carcinogenic and non-carcinogenic risks, natural sources were the main source of contamination for adults and children. Among the different soil types, paddy, and red soils had relatively high Cd content, and among the different soil-forming parent materials, the Cd content in soils developed on Quaternary sediments was significantly higher than that other parent materials. Among the different land use types, the Cd content of soil for construction land was the highest. This study provides a scientific foundation and reference for the prevention of soil Cd contamination in Shantou City and the analysis of soil contamination sources in areas with similar contamination patterns.
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Metais Pesados , Poluentes do Solo , Adulto , Cádmio/análise , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análiseRESUMO
Pomelo is rich in bioactive compounds (carotenoids, phenolics and essential oil) in the early stage of fruit development, but it is often wasted in the cultivation and management process. To gain an insight into the carotenoid metabolism pathway in pomelo, the carotenoid profiles and the expression patterns of carotenogenic genes were investigated in two genotypes of pomelo during early fruit development. The results showed that a higher carotenoid content was observed in honey pomelo as compared with golden pomelo, which may be related to different gene regulation mechanisms. Lutein, α-carotene, and ß-carotene were the main carotenoids in pomelo young fruit, and lutein was the highest one. The accumulation of carotenoids during fruit early development in honey pomelo is related to the transcriptional regulation of ZISO and LUT5. In golden pomelo, the rate-limiting gene for carotenoids is PDS and ZDS. In addition, the expression of seven genes except CRTISO in honey pomelo was higher than that in golden pomelo. The results are helpful to further clarify the regulatory mechanism of carotenoid accumulation during early fruit development and provide a direction for the high-value utilization of young fruits in pomelo.
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Carotenoides/metabolismo , Citrus/genética , Citrus/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genótipo , Luteína/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
OBJECTIVE: To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction. METHODS: Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power. RESULTS: The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%. CONCLUSION: CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.
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Citocromo P-450 CYP2C19 , Citocromo P-450 CYP3A , Infarto do Miocárdio , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Frequência do Gene , Genótipo , Humanos , Infarto do Miocárdio/genéticaRESUMO
Numerous studies have demonstrated an association between approximate number system (ANS) acuity and mathematical performance. Studies have also shown that ANS acuity can predict the longitudinal development of mathematical achievement. Visual form perception in the current investigation was proposed to account for the predictive role of ANS acuity in the development of mathematical achievement. One hundred and eighty-eight school children (100 males, 88 females; mean age = 12.2 ± 0.3 years) participated in the study by completing five tests: numerosity comparison, figure matching, mental rotation, nonverbal matrix reasoning, and choice reaction time. Three years later, they took a mathematical achievement test. We assessed whether the early tests predicted mathematical achievement at the later date. Analysis showed that the ANS acuity measured via numerosity comparison significantly predicted mathematical achievement 3 years later, even when controlling for individual differences in mental rotation, nonverbal matrix reasoning, and choice reaction time, as well as age and gender differences. Hierarchical regression and mediation analyses further showed that the longitudinal predictive role of ANS acuity in mathematical achievement was interpreted by visual form perception measured with a figure-matching test. Together, these results indicate that visual form perception may be the underlying cognitive mechanism that links ANS acuity to mathematical achievement in terms of longitudinal development.
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Logro , Percepção de Forma , Criança , Cognição , Feminino , Humanos , Masculino , Conceitos Matemáticos , Matemática , Percepção VisualRESUMO
Many living organisms undergo conspicuous or abrupt changes in body structure, which is often accompanied by a behavioral change. Inspired by the natural metamorphosis, robotic systems can be designed as reconfigurable to be multifunctional. Here, a tissue-engineered transformable robot is developed, which can be remotely controlled to assume different mechanical structures for switching locomotive function. The soft robot is actuated by a muscular tail fin that emulates the swimming of whales and works as a cellular engine powered by the synchronized contraction of striated cardiac microtissue constructs. For a transition of locomotive behavior, the robot can be optically triggered to transform from a spread to a retracted form, which effectively changes the bending stiffness of the tail fins, thus minimizing the propulsion output from the "tail fin" and effectively switching off the engine. With the unprecedented controllability and responsiveness, the transformable robot is implemented to work as a cargo carrier for programmed delivery of chemotherapeutic agents to selectively eradicate cancer cells. It is believed that the realization of the transformable concept paves a pathway for potential development of intelligent biohybrid robotic systems.
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Coração , Robótica/instrumentação , Engenharia Tecidual , Fenômenos Biomecânicos , Desenho de EquipamentoRESUMO
The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution â hydrogel â solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.
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DNA/química , Hidrogéis/química , DNA/metabolismo , Hidrogéis/metabolismo , NanotecnologiaRESUMO
We demonstrate a long-term stable, all-fiber, erbium-doped femtosecond laser mode-locked by a black phosphorus saturable absorber. The saturable absorber, fabricated by scalable and highly controllable inkjet printing technology, exhibits strong nonlinear optical response and is stable for long-term operation against intense irradiation, overcoming a key drawback of this material. The oscillator delivers self-starting, 102 fs stable pulses centered at 1555 nm with 40 nm spectral bandwidth. This represents the shortest pulse duration achieved from black phosphorus in a fiber laser to date. Our results demonstrate the great potential for black phosphorus as an excellent candidate for long-term stable ultrashort pulse generation.
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Chemotherapeutic drugs currently used in clinical settings have high toxicity, low specificity, and short half-lives. Herein, polypyrrole-based anticancer drug nanocapsules were prepared by tailoring the size of the nanoparticles with a template method, controlling drug release by means of an aromatic imine, increasing nanoparticle stability through PEGylation, and improving tumor-cell selectivity by folate mediation. The nanoparticles were characterized by TEM and dynamic light scattering. α-Folate receptor expression levelsof tumor cells and normal cells were investigated by western blot and quantitative polymerase chain reaction analyses. Flow cytometry and fluorescence imaging were used to verify the cell uptake of the different-sized nanoparticles. From the different-sized polypyrrole nanoparticles, the optimally functionalized nanoparticles of 180â nm hydrodynamic diameter were chosen and further usedfor inâ vitroandinâ vivotests. The nanoparticles showed excellent biocompatibility and the drug-loaded nanoparticles exhibited effective inhibition of tumor cell growth inâ vitro. Moreover, the drug-loaded nanoparticles showed substantially enhanced accumulation in tumor regions and effectively inhibitedinâ vivotumor growth. Furthermore, the nanoparticles showed reduced doxorubicin-induced toxicity andno significant side effects in normal organs of tumor-bearing mice, as measured by body-weight shifts and evaluationof drug distribution. Overall, the functionalized nanoparticles are promising nanocarriers for tumor-targeting drug delivery.
Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Nanoestruturas/química , Polímeros/química , Pirróis/química , Animais , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Doxorrubicina/toxicidade , Portadores de Fármacos/síntese química , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Imagem Óptica , Espectroscopia Fotoeletrônica , Polietilenoglicóis/química , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual , Titânio/química , Transplante HeterólogoRESUMO
The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-ß-cyclodextrin (ß-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between ß-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.