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A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.
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Corteza Cerebral , Disfunción Cognitiva , Insuficiencia Cardíaca , Imagen por Resonancia Magnética , Humanos , Masculino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/patología , Femenino , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Anciano , Estudios Retrospectivos , Enfermedad CrónicaRESUMEN
Surface plasmon resonance microscopy (SPRM), based on the scattering of single molecules at the interface, is a highly efficient analytical platform widely used in the fields of biology and chemistry. Due to the interference scattering, the imaging pattern exhibits typical parabolic tail and phase transition features, providing a quantitative means of observing the changes in the physical and chemical properties of single molecules. In this work, we reported another unique asymmetric parabolic distribution pattern resulting from polarization conversion in the experiment based on SPRM. This microscopic-level feature is derived from the switching between SPR resonant and nonresonant states. Starting from energy flux theory, we constructed an analysis model and conducted full-wave numerical simulations to verify the experimental results. Furthermore, we demonstrate that the optical rotation induced by chiral thin films can be directly measured through imaging with asymmetric features, providing valuable insights into the field of chiral materials. The quantitative interpretation of asymmetric scattering not only advances the fundamental understanding of the imaging mechanism of SPRM, but also opens up possibilities for utilizing this polarization-sensitive characteristic for single-particle detection and sensing in the future.
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Herein, Zn2+-induced gold cluster aggregation (Zn2+-GCA) as a high-efficiency electrochemiluminescence (ECL) emitter is first employed to construct an ECL biosensor to ultrasensitively detect microRNA-21 (miRNA-21). Impressively, Zn2+ not only can induce the aggregation of monodispersed gold clusters (Au NCs) to limit the ligand vibration of Au NCs for improving ECL emission but also can be utilized as a coreaction accelerator to catalyze the dissociation of coreactant S2O82- into sulfate radicals (SO4â¢-) to improve the interaction efficiency between Zn2+-GCA and S2O82-, resulting in further intense ECL emission. Compared to Au NCs stabilized by bovine serum albumin with ECL efficiency of 0.40%, Zn2+-GCA possessed high ECL efficiency of 10.54%, regarding the [Ru(bpy)3]2+/S2O82- system as a standard. Furthermore, output DNA modified with poly adenine (polyA) obtained from enzyme-free target recycling amplification can be efficiently immobilized on the surface of gold nanoparticles (Au NPs) to reduce the defect of special design, cumbersome operation, and low stability. Thus, an ultrasensitive ECL biosensor based on the Zn2+-GCA/S2O82- ECL system and enzyme-free target recycling amplification achieved ultrasensitive detection of miRNA-21 with the detection limit of 44.7 aM. This strategy presents a new idea to design highly efficient ECL emitters, which is expected to be used in the field of bioanalysis for clinical diagnosis.
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Técnicas Biosensibles , Nanopartículas del Metal , MicroARNs , Oro , Límite de Detección , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , MicroARNs/análisis , ZincRESUMEN
Herein, the novel alloyed silver gold sulfur quantum dots (AgAuS QDs) with highly efficient near-infrared (NIR) electrochemiluminescence (ECL) emission at 707 nm were successfully prepared to construct a biosensing platform for ultrasensitive detection of microRNA-222 (miRNA-222). Interestingly, AgAuS QDs revealed excellent ECL efficiency (34.91%) compared to that of Ag2S QDs (10.30%), versus the standard [Ru(bpy)3]2+/S2O82- system, which benefited from the advantages of abundant surface defects and narrow bandgaps by Au incorporation. Additionally, an improved localized catalytic hairpin self-assembly (L-CHA) system was developed to display an increased reaction speed by improving the local concentration of DNA strands, which addressed the obstacles of time-consuming traditional CHA systems. As a proof of concept, based on AgAuS QDs as an ECL emitter and improved localized CHA systems as a signal amplification strategy, a "signal on-off" ECL biosensor was developed to exhibit a superior reaction rate and excellent sensitivity with a detection limit of 10.5 aM for the target miRNA-222, which was further employed for the analysis of miRNA-222 from cancer cell (MHCC-97L) lysate. This work advances the exploration of highly efficient NIR ECL emitters to construct an ultrasensitive biosensor for the detection of biomolecules in disease diagnosis and NIR biological imaging.
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Técnicas Biosensibles , MicroARNs , Puntos Cuánticos , MicroARNs/análisis , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Oro , Azufre , Límite de DetecciónRESUMEN
In this study, nitrogen-, sulfur-, and fluorine-codoped carbon dots (NSF-CDs) with high electrochemiluminescence (ECL) efficiency were developed as novel emitters to fabricate an ECL biosensor for sensitive detection of matrix metalloproteinase 2 (MMP-2). Impressively, compared to previously reported CDs, NSF-CDs with narrow band gap not only decreased the excitation voltage to reduce the side reaction and the damage on biomolecules but also had hydrogen bonds to vastly enhance the ECL efficiency. Furthermore, an improved exonuclease III (Exo III)-assisted nucleic acid amplification method was established to convert trace MMP-2 into a mass of output DNA, which greatly improved the target conversion efficiency and ECL signal. Hence, the ECL biosensor has realized the sensitive detection of MMP-2 proteins from 10 fg/mL to 10 ng/mL with a limit of detection of 6.83 fg/mL and has been successfully applied in the detection of MMP-2 from Hela and MCF-7 cancer cells. This strategy offered neoteric CDs as ECL emitters for sensitive testing of biomarkers in medical research.
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Técnicas Biosensibles , Puntos Cuánticos , Humanos , Metaloproteinasa 2 de la Matriz , Flúor , Mediciones Luminiscentes/métodos , Nitrógeno/química , Carbono/química , Técnicas Biosensibles/métodos , Azufre/química , Puntos Cuánticos/química , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
Two-dimensional (2D) tin (Sn)-based perovskites have recently received increasing research attention for perovskite transistor application. Although some progress is made, Sn-based perovskites have long suffered from easy oxidation from Sn2+ to Sn4+ , leading to undesirable p-doping and instability. In this study, it is demonstrated that surface passivation by phenethylammonium iodide (PEAI) and 4-fluorophenethylammonium iodide (FPEAI) effectively passivates surface defects in 2D phenethylammonium tin iodide (PEA2 SnI4 ) films, increases the grain size by surface recrystallization, and p-dopes the PEA2 SnI4 film to form a better energy-level alignment with the electrodes and promote charge transport properties. As a result, the passivated devices exhibit better ambient and gate bias stability, improved photo-response, and higher mobility, for example, 2.96 cm2 V-1 s-1 for the FPEAI-passivated films-four times higher than the control film (0.76 cm2 V-1 s-1 ). In addition, these perovskite transistors display non-volatile photomemory characteristics and are used as perovskite-transistor-based memories. Although the reduction of surface defects in perovskite films results in reduced charge retention time due to lower trap density, these passivated devices with better photoresponse and air stability show promise for future photomemory applications.
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Broader spectra, lower reflectivity and higher reliability are the performance requirements for broadband antireflective (BBAR) films. In this work, a BBAR film structure was proposed, which maintains extremely low reflectivity, ultra-wide spectra, low polarization sensitivity and practical reliability. The BBAR film consists of a dense multilayer interference stack on the bottom and a nano-grass-like alumina (NGLA) layer with a gradient low refractive index distribution on the top. The film was deposited by atomic layer deposition, while the NGLA layer was formed by means of a hot water bath on Al2O3 layer. The top NGLA layer has extremely high porosity and ultra-low refractive index, along with extremely fragile structure. To surmount the fragility of NGLA layer, a sub-nano layer of SiO2 was grown by atomic layer deposition to solidify its structure and also to adjust the refractive index with different thicknesses of SiO2. Finally, in the wide wavelength range of 400-1100â nm, the average transmittance of the double-sided coated fused quartz reaches 99.2%. The absorption, light scattering, reliability and polarization characteristics of BBAR films were investigated. An optimized BBAR film with low polarization-sensitivity and improved reliability was realized, which should be potentially promising for application in optical systems.
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Optimizing the atomic layer deposition (ALD) process of films is particularly important in preparing multilayer interference films. In this work, a series of Al2O3/TiO2 nano-laminates with a fixed growth cycle ratio of 1:10 were deposited on Si and fused quartz substrates at 300 °C by ALD. The optical properties, crystallization behavior, surface appearance and microstructures of those laminated layers were systematically investigated by spectroscopic ellipsometry, spectrophotometry, X-ray diffraction, atomic force microscope and transmission electron microscopy. By inserting Al2O3 interlayers into TiO2 layers, the crystallization of the TiO2 is reduced and the surface roughness becomes smaller. The TEM images show that excessively dense distribution of Al2O3 intercalation leads to the appearance of TiO2 nodules, which in turn leads to increased roughness. The Al2O3/TiO2 nano-laminate with a cycle ratio 40:400 has relatively small surface roughness. Additionally, oxygen-deficient defects exist at the interface of Al2O3 and TiO2, leading to evident absorption. Using O3 as an oxidant instead of H2O for depositing Al2O3 interlayers was verified to be effective in reducing absorption during broadband antireflective coating experiments.
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In this work, a novel electrochemiluminescence (ECL) biosensor was developed for ultrasensitive detection of microRNA let-7a (miRNA let-7a) based on MnS:CdS@ZnS core-shell quantum dots (QDs) as ECL luminophores with high ECL efficiency. Impressively, compared to the CdS:Mn@ZnS QDs prepared by ionic doping with ECL efficiency of 0.87%, MnS:CdS@ZnS QDs synthesized by bimetallic clusters (Cd2Mn2O4) doping exhibited high ECL efficiency of up to 15.84% with S2O82- as cathodic coreactant due to the elimination of the dopants size mismatch and "self-purification" effect, which could achieve the surface defect passivation of MnS:CdS@ZnS QDs for effectively improving the ECL emission. Furthermore, with the help of strand displacement amplification (SDA), the trace target miRNA let-7a was able to be converted to a number of output DNA labeled with ferrocene (Fc) to construct an ultrasensitive ECL biosensor. The well-designed ECL biosensor for miRNA let-7a exhibited high stability and excellent sensitivity of a concentration variation from 10 aM to 1 nM and a low detection limit of 4.1 aM, which was further applied to the analysis of miRNA let-7a from cancer cell (MCF-7) lysate. Thus, this strategy provides a novel method to prepare high-efficient ECL emitters for the construction of ECL biosensing platforms in biological fields and clinical diagnosis.
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Técnicas Biosensibles , MicroARNs , Puntos Cuánticos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de Detección , Mediciones Luminiscentes/métodos , MicroARNs/análisis , Sulfuros , Compuestos de ZincRESUMEN
A regio- and chemoselective sulfonylation of propargyl alcohols with sulfinamides in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was developed. It provided straightforward and mild access to multi-substituted allenyl sulfones by using sulfinamides as the sulfonyl sources. This transformation was promoted by HFIP and did not require any catalysts or oxidants, which allowed for the successful conversion of various tertiary and secondary propargyl alcohols into allenyl sulfones in high yields.
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INTRODUCTION: Few studies have investigated the associations of child development with air pollution, land-use type, and maternal mental health simultaneously. Therefore, we evaluated the effect of exposure to air pollutants during several critical periods of life, with adjustment for land-use type and maternal mental status, on child development at 6, 12, and 24 months of age in the Greater Taipei area. METHODS: Participants were selected from an ongoing Taiwanese birth cohort study. We analyzed the data of the participants who had been recruited from January 2011 to April 2014. Self-administered standardized questionnaires were used to collect information on sociodemographic factors, infant development and health, maternal mental status, etc. Air pollution levels in pre- and postnatal periods were estimated using a spatial interpolation technique (ordinary kriging) at children's residential addresses. Land-use types around participants' homes were evaluated using buffer analysis. We used multiple logistic regression analysis to examine the relationships between child development delay and environmental factors. RESULTS: In total, 228, 361, and 441 families completed child development forms at 6, 12, and 24 months of age, respectively. Our results indicated that prenatal exposure to particulate matter with aerodynamic diameter ≤10 µm and O3 and postnatal exposure to NO2 were negatively associated with child development. Traffic-related land-use types, gas stations, and power generation areas around participants' homes were also adversely correlated with child development. Moreover, poor maternal mental health was associated with child development delay. CONCLUSION: Prenatal exposure and postnatal exposure to air pollution were associated with development delay in children under 2 years of age, specifically those under 1 year of age, even after adjustment for land-use type and maternal mental status. Living environment is critical for the development of children under 2 years of age.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Niño , Desarrollo Infantil , Estudios de Cohortes , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Lactante , Salud Materna , Salud Mental , Dióxido de Nitrógeno/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , EmbarazoRESUMEN
ABSTRACT: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2) emerged in Wuhan City. The present study aimed to assess the demographic variables, causes, and patterns of maxillofacial injuries managed at a teaching hospital in Wuhan City during the transmission control measures in the coronavirus disease 2019 (COVID-19) epidemic. In this retrospective study, all patients treated for maxillofacial injuries in the hospital between January 23 and April 7 (2019 and 2020) were involved. Epidemiologic information, including the number of patients, gender, age, etiology, time since injury to the clinic visit, and type of maxillofacial injuries, was recorded. Data of the 2 periods (2019 and 2020) were compared and analyzed. A total of 337 patients had maxillofacial injuries at the 2-time intervals: 74 in 2020 and 263 in 2019. The characteristics of maxillofacial injuries had changes during the transmission control measures in the COVID-19 epidemic, which included the number of patients, gender, age, etiology, time since injury to the clinic visit, and type of maxillofacial injuries. The transmission control measures during the COVID-19 epidemic had a significant impact on the epidemiology of maxillofacial injuries in Wuhan City.
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COVID-19 , Traumatismos Maxilofaciales , China/epidemiología , Hospitales de Enseñanza , Humanos , Traumatismos Maxilofaciales/epidemiología , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan. Epidemiological and clinical characteristics of patients with COVID-19 have been reported, but the relationships between laboratory features and viral load has not been comprehensively described. METHODS: Adult inpatients (≥18 years old) with COVID-19 who underwent multiple (≥5 times) nucleic acid tests with nasal and pharyngeal swabs were recruited from Renmin Hospital of Wuhan University, including general patients (n = 70), severe patients (n = 195), and critical patients (n = 43). Laboratory data, demographic data, and clinical data were extracted from electronic medical records. The fitted polynomial curve was used to explore the association between serial viral loads and illness severity. RESULTS: Viral load of SARS-CoV-2 peaked within the first few days (2-4 days) after admission, then decreased rapidly along with virus rebound under treatment. Critical patients had the highest viral loads, in contrast to the general patients showing the lowest viral loads. The viral loads were higher in sputum compared with nasal and pharyngeal swab (P = .026). The positive rate of respiratory tract samples was significantly higher than that of gastrointestinal tract samples (P < .001). The SARS-CoV-2 viral load was negatively correlated with portion parameters of blood routine and lymphocyte subsets and was positively associated with laboratory features of cardiovascular system. CONCLUSIONS: The serial viral loads of patients revealed whole viral shedding during hospitalization and the resurgence of virus during the treatment, which could be used for early warning of illness severity, thus improve antiviral interventions.
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COVID-19/epidemiología , Coronavirus/patogenicidad , China/epidemiología , Femenino , Humanos , Masculino , Pruebas Serológicas , Carga ViralRESUMEN
BACKGROUND/AIMS: In December 2019, a novel coronavirus emerged in Wuhan City, and a retrospective analysis is necessary to provide clinicians with the characteristics of traumatic dental injuries (TDIs) during the epidemic. The aim of this study was to evaluate the changes in the characteristics of TDIs under the transmission control measures in Wuhan City utilizing an epidemiologic investigation. MATERIALS AND METHOD: In this retrospective study, epidemiologic information, including the number of patients, gender, age, and TDI parameters such as time since injury to the clinic visit, etiology, tooth location, and the type of injury was extracted from the records of patients in the hospital from two periods: period 1 (between January 23, 2020, and April 7, 2020) and period 2 (between January 23, 2019, and April 7, 2019). The data from the two periods were compared and analyzed. RESULT: A total of 158 patients were treated for TDIs (120 in 2019 and 38 in 2020). Males were more likely to suffer from TDIs than females with a ratio of 1.5:1, both in 2020 and 2019. Other than that, there were characteristic changes in TDIs during the transmission control measures in the COVID-19 epidemic, which included the number of patients, age, time since injury to the clinic visit, etiology, tooth location and the type of TDI. CONCLUSION: The transmission control measures during the COVID-19 epidemic had a significant impact on the epidemiology and etiology of TDIs in Wuhan City.
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COVID-19 , Traumatismos de los Dientes , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Pandemias , Prevalencia , Estudios Retrospectivos , SARS-CoV-2 , Traumatismos de los Dientes/epidemiologíaRESUMEN
Purpose: Our previous studies indicate that phorbol 12-myristate 13-acetate (PMA)-treated U937 cells cultured on collagen I-coated dishes express lowered production of pro-inflammatory mediators in parallel through reduced reactive oxygen species (ROS) levels. By contrast, PMA-treated U937 cells on gelatin, the denatured collagen, show enhanced production of pro-inflammatory mediators, mediated by up-regulating autophagy levels. The present study is aimed to investigate the effect of ROS levels in PMA-treated U937 cells cultured on gelatin-coated surface. Material and methods: MTT assay, flow cytometric analysis of ROS and autophagy, biochemical detection of antioxidant levels, enzyme-linked immunosorbent assay, and western blot were used. Results: Gelatin-coating increased ROS levels in PMA-treated U937 cells. Increased ROS levels are involved in the regulation of cell aggregation and the release of pro-inflammatory mediators in gelatin-coated culture. These results lead to the query about the crosstalk between the two positive regulators, the autophagy and ROS. Autophagy induction is attenuated by N-acetyl-L-cysteine treatment, but the treatment with autophagy inhibitor, 3-methyladenine, does not affect ROS levels, suggesting ROS are upstream of autophagy in the regulation axis of differentiated U937 cells on gelatin-coated surface. Further study confirmed that upregulation of autophagy was responsible for ROS-induced cell aggregation and production of pro-inflammatory mediators. Conclusion: The results suggest that gelatin-coating promotes the aggregation of PMA-treated U937 cells and the production of pro-inflammatory mediators by ROS-autophagy signaling pathway.
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Autofagia/efectos de los fármacos , Gelatina/química , Mediadores de Inflamación/metabolismo , Ésteres del Forbol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Agregación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Dinoprostona/metabolismo , Humanos , Interleucina-1beta/metabolismo , Modelos Biológicos , Transducción de Señal/efectos de los fármacos , Porcinos , Factor de Necrosis Tumoral alfa/metabolismo , Células U937RESUMEN
The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.
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Aspartato Aminotransferasas/sangre , Plaquetas/metabolismo , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Periodo Preoperatorio , Pronóstico , Resultado del TratamientoRESUMEN
Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.
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Potenciales de Acción , Globo Pálido/metabolismo , Neuronas/fisiología , Orexinas/metabolismo , Enfermedad de Parkinson/metabolismo , Animales , Benzoxazoles/farmacología , Globo Pálido/citología , Globo Pálido/fisiología , Haloperidol/farmacología , Masculino , Naftiridinas , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antagonistas de los Receptores de Orexina/farmacología , Receptores de Orexina/metabolismo , Orexinas/farmacología , Oxidopamina/toxicidad , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural , Ratas , Ratas Wistar , Urea/análogos & derivados , Urea/farmacologíaRESUMEN
Nanoplastics (NPs, diameter <1 µm) not only have toxicity but also change the toxicity of other pollutants in water. To date, the nanopolystyrene (nano-PS) size effect and its combined toxicity with halogenated polycyclic aromatic hydrocarbons (HPAHs) remain unclear. In this study, the single toxicity, combined toxicity, and mode of action of the binary mixture of polystyrene (PS) and HPAH were examined. At the same time, the nano-PS size effect on combined toxicity was also discussed. According to our results, the 48 h acute toxicity test results showed that 30 nm PS was highly toxic (EC50-48 h = 1.65 mg/L), 200 nm PS was moderately toxic (EC50-48 h = 17.8 mg/L), and 1 µm PS was lowly toxic (EC50-48 h = 189 mg/L). The NP toxicity decreased with increasing size. HPAHs were highly toxic substances to Daphnia magna (EC50-48 h = 0.12-0.22 mg/L). The mode of action of PS and HPAHs was antagonistic according to the toxicity unit method (TU), additive index method (AI), and mixture toxicity index method (MTI). The size effect of nano-PS operates via two mechanisms: the inherent toxicity of nano-PS and the sorption of pollutants by nano-PS. The former impacts the combined toxicity more than the latter. In the binary mixed system, the larger the particle size and the higher the proportion of NPs in the system, the less toxic the system was. Linear interpolation analysis can be used to predict the combined toxicity of a mixed system with any mixing ratio.
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Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Animales , Daphnia magna , Contaminantes Químicos del Agua/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Poliestirenos/toxicidad , Agua , DaphniaRESUMEN
Herein, a new electrochemiluminescence (ECL) biosensor was constructed with highly efficient polymerized carbon dots (PCDs) as ECL emitter and the improved localized catalytic hairpin assembly (L-CHA) as signal amplifier for ultrasensitive detection of microRNA-222 (miRNA-222). Impressively, compared to the traditional carbon dots with inefficient blue region ECL emission, PCDs with N, O co-dope and large conjugated π-system showed high electrical conductivity, narrow band gap and strong radiative transition, which could exhibit high ECL efficiency to improve the sensitivity of detection and long wavelength ECL emission to achieve deep tissue penetration for reducing biological damage. Furthermore, the trace target miRNA-222 could be efficiently converted into large amounts of output DNA labelled with the quencher dopamine (S-DA) through the L-CHA reaction to significantly enhance the target amplification efficiency for further improving the sensitivity of detection. Thus, the ECL biosensor could achieve the ultrasensitive detection of miRNA-222 from 100 aM to 100 pM with the detection limit of 76 aM. Therefore, this work proposed a novel CDs with high ECL efficiency and long wavelength ECL emission, which not only was used to build an ultrasensitive biosensor for biomolecules detection in clinical diagnosis, but also served as a potential emitter for ECL bioimaging.
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Técnicas Biosensibles , MicroARNs , MicroARNs/genética , Carbono , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. The development of efficient methods for rapidly tracing and modulating the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. Thus, we designed and synthesized a series of imidazo[1,2,4] triazole derivatives containing salicylic acid to explore novel scaffolds with inhibitory activities and good fluorescence properties for SHP1. The photophysical properties and inhibitory activities of these imidazo[1,2,4] triazole derivatives (5a-5y) against SHP1PTP were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound 5p exhibited remarkable fluorescence response (P: 0.002) with fluorescence quantum yield (QY) of 0.37 and inhibitory rate of 85.21 ± 5.17% against SHP1PTP at the concentration of 100 µM. Furthermore, compound 5p showed obvious aggregation caused quenching (ACQ) effect and had high selectivity for Fe3+ ions, good anti-interference and relatively low detection limit (5.55 µM). Finally, the cellular imaging test of compound 5p also exhibited good biocompatibility and certain potential biological imaging application. This study provides a potential way to develop molecules with fluorescent properties and bioactivities for SHP1.