RESUMO
Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.
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The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.
Assuntos
Antineoplásicos , Proliferação de Células , Neoplasias Colorretais , Depsipeptídeos , Compostos Macrocíclicos , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Depsipeptídeos/farmacologia , Depsipeptídeos/uso terapêutico , Depsipeptídeos/química , Depsipeptídeos/síntese química , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Polymer dots (Pdots) have emerged as a type of attractive electrochemiluminescence (ECL) emitter. However, the low ECL efficiency severely limits their practicability. In this work, we develop a sensitive ECL biosensing strategy for the detection of human papilloma virus subtype (HPV-16) DNA by using target-activated CRISPR/Cas12a to regulate the binding of Pdots-DNA to biosensor and local surface plasmon resonance (LSPR) effect of electrochemically deposited Au nanoparticles (depAuNPs) to enhance the ECL emission of Pdots bound on biosensor. The biosensor is prepared by simply assembling hairpin DNA on depAuNPs modified electrode. In the presence of target DNA, the designed specific CRISPR/Cas12a can be activated to digest single-stranded assistant DNA, which decreases the amount of hairpin DNA opened by assistant DNA to bind Pdots-DNA on the biosensor surface, thus reduces the ECL emission. The integration of target DNA-triggered catalysis and the LSPR effect of depAuNPs greatly improves the sensitivity of ECL analysis. Using HPV-16 DNA as a target model, the proposed method shows a limit of detection (LOD) of 3.2 fM at a signal-to-noise ratio of 3 and a detectable concentration range of 5.0 fM to 50 pM. The high sensitivity, excellent selectivity, good testing stability, and acceptable fabrication reproducibility of the designed ECL biosensing strategy demonstrate its potential application in DNA bioanalysis.
Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Pontos Quânticos , Humanos , Ouro , Polímeros , Reprodutibilidade dos Testes , Sistemas CRISPR-Cas/genética , Técnicas Eletroquímicas/métodos , Medições Luminescentes/métodos , DNA/análise , Limite de Detecção , Técnicas Biossensoriais/métodosRESUMO
Accelerating the charge transfer between electroactive species and the electrode is always a hot topic. Here, we report a finding of Ru(bpy)33+ diffusion-induced acceleration of charge transfer from Ru(bpy)32+-doped silica nanoparticles (RDSNs) to the electrode via electrochemiluminescence (ECL) imaging at a single nanoparticle scale. Ru(bpy)32+ in the electrolyte can act as an enhancer of RDSN ECL emission in the presence of coreactant tripropylamine, which amplifies the RDSN ECL by 478 times at 10 µM free Ru(bpy)32+. According to percolation theory, the diffusion of electro-generated Ru(bpy)33+ near a single RDSN brings much quicker charge transfer to the electrode than electron hopping in RDSN, which is demonstrated by spatial and temporal interaction imaging of the RDSN and the Ru(III) diffusion layer. Taking advantage of this new mechanism, a real-time ECL imaging method has been constructed to monitor the rapid change of cell permeability during surfactant treatment.
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Medições Luminescentes , Nanopartículas , Medições Luminescentes/métodos , Fotometria , Eletrodos , Dióxido de SilícioRESUMO
Self-enhanced electrochemiluminescence (ECL) can be achieved via the confinement of coreactants and ECL emitters in a single nanostructure. This strategy has been used for the design of anodic ECL systems with amine compounds as coreactants. In this work, a novel confinement system was proposed by codoping positively charged ECL emitter tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) and negatively charged coreactant peroxydisulfate (S2O82-) in silica nanoparticles. The codoping process could be performed by introducing S2O82- in cationic poly(diallyldimethylammonium chloride) (PDDA) to form PDDA@S2O82- and then encapsulating it and Ru(bpy)32+ in the Triton X-100 vesicle followed by the hydrolysis of tetraethyl ortosilicate, surface modification, and demulsification. The obtained RuSSNs exhibited good homogeneity, excellent monodispersity, acceptable biocompatibility, and 2.9-fold stronger ECL emission than Ru(bpy)32+-doped silica nanoparticles at an equal amount of nanoparticles in the presence of 0.1 M K2S2O8. Thus, an in situ self-sensitized cathodic ECL imaging method was designed for the monitoring of glycoprotein on living cell membranes. This work provides a new way for the modification, enhancement, and application of nano-ECL emitters in biological analysis.
Assuntos
Medições Luminescentes , Nanopartículas , Medições Luminescentes/métodos , Proteínas de Membrana , Nanopartículas/química , Fotometria , Dióxido de Silício/químicaRESUMO
Midgut receptors play a critical role in the specificity of Cry toxins for individual insect species. Cadherin proteins are essential putative receptors of Cry1A toxins in lepidopteran larvae. Cry2A family members share common binding sites in Helicoverpa armigera, and one of them, Cry2Aa, has been widely reported to interact with midgut cadherin. Here, we studied the binding interaction and functional role of H. armigera cadherin in the mechanism of Cry2Ab toxicity. A region spanning from cadherin repeat 6 (CR6) to the membrane-proximal region (MPR) of cadherin protein was produced as six overlapping peptides to identify the specific binding regions of Cry2Ab. Binding assays showed that Cry2Ab binds nonspecifically to peptides containing CR7 and CR11 regions in a denatured state but binds specifically only to CR7-containing peptides in the native state. The peptides CR6-11 and CR6-8 were transiently expressed in Sf9 cells to assess the functional role of cadherin. Cytotoxicity assays showed that Cry2Ab is not toxic to the cells expressing any of the cadherin peptides. However, ABCA2-expressing cells showed high sensitivity to Cry2Ab toxin. Neither increased nor decreased sensitivity to Cry2Ab was observed when the peptide CR6-11 was coexpressed with the ABCA2 gene in Sf9 cells. Instead, treating ABCA2-expressing cells with a mixture of Cry2Ab and CR6-8 peptides resulted in significantly reduced cell death compared with treatment with Cry2Ab alone. Moreover, silencing of the cadherin gene in H. armigera larvae showed no significant effect on Cry2Ab toxicity, in contrast to the reduced mortality in ABCA2-silenced larvae. IMPORTANCE To improve the efficiency of production of a single toxin in crops and to delay the evolution of insect resistance to the toxin, the second generation of Bt cotton, expressing Cry1Ac and Cry2Ab, was introduced. Understanding the mode action of the Cry proteins in the insect midgut and the mechanisms insects use to overcome these toxins plays a crucial role in developing measures to counter them. Extensive studies have been conducted on the receptors of Cry1A toxins, but relatively little has been done about those of Cry2Ab. By showing the nonfunctional binding of cadherin protein with Cry2Ab, we have furthered the understanding of Cry2Ab receptors.
Assuntos
Toxinas de Bacillus thuringiensis , Helicoverpa armigera , Proteínas de Insetos , Receptores de Superfície Celular , Helicoverpa armigera/crescimento & desenvolvimento , Helicoverpa armigera/metabolismo , Helicoverpa armigera/microbiologia , Animais , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis/química , Toxinas de Bacillus thuringiensis/metabolismo , Receptores de Superfície Celular/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Larva/metabolismo , Técnicas de Silenciamento de Genes , Células Sf9RESUMO
The optical remote sensing techniques are promising for the real-time detection, and identification of different types of hazardous biological materials. However, the received fluorescent spectra from a remote distance suffer from the atmospheric attenuation effect upon the spectral shape. To investigate the influence of atmospheric attenuation on characterizing, and classifying biological agents, the laboratory-measured fluorescence data of fourteen proteins combined with the atmospheric transmission factors of the MODTRAN model were conducted with different detection ranges. The multivariate analysis techniques of principal component analysis (PCA) and linear discriminant analysis (LDA), and the predictors of Random Forest and XGBoost were employed to assess the separability and distinguishability of different spectra recorded. The results showed that the spectral-shift effect on attenuated spectra varied as a function of the detection range, the atmospheric visibility, and the spectral distribution. According to the PCA and LDA analysis, the distribution of decomposed factors changed in the spectral explanatory power with the increasing attenuation effect, which was consistent with the hierarchical clustering results. Random Forest exhibited higher performance in classifying protein samples than that of XGBoost, while the two methods performed similarly in identifying harmful and harmless subgroups of proteins. Fewer subgroups decreased the sensitivity of the classification accuracy to the attenuation effect. Our analysis demonstrated that combining atmospheric transport models to build a fluorescence spectral database is essential for fast identification between spectra, and reduced classification criteria could facilitate the compatibility of spectral database and classification algorithms.
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Algoritmos , Algoritmo Florestas Aleatórias , Análise Discriminante , Análise Multivariada , Análise de Componente PrincipalRESUMO
Macroautophagy/autophagy is critically involved in the process of salivary gland (SG) diseases such as xerostomia, which has a serious impact on quality of life. KRT14+ progenitor cells are found to be the main progenitors for maintaining the ductal homeostasis of the submandibular SGs. In this study, we investigated the role of ATG5 in SG KRT14+ cells in mice and humans. Human labial salivary glands (LSG) from primary Sjogren's syndrome (pSS) and non-pSS patients (normal), and submandibular glands (SMG) from Atg5flox/flox ; Krt14-Cre (cKO) mice were used. ATG5+ KRT14+ and p62+ KRT14+ cells were detected by immunofluorescence staining in LSG. TUNEL, immunofluorescence, immunohistochemistry, and western blot were performed to detect cell death in SMG. Saliva was collected in 12-week-old (12 W) and 32-week-old (32 W) mice, then the concentration of calcium and buffering capacity were detected to analyze the function of SG. We found that LSG from pSS patients showed increased p62 and decreased ATG5 in KRT14+ cells. We further revealed that in 32 W, (1) the function of salivary glands was significantly impaired in cKO mice, (2) cell death increased in cKO mice, but cl-Caspase 3 was not significantly changed, and (3) cleaved gasdermin D increased and was highly expressed in KRT14+ cells of cKO mice. After applying a pyroptosis inhibitor to 32 W mice, the reduced saliva flow rate was rescued. In addition, pyroptosis was also found in KRT14+ cells of pSS patients. Collectively, our results indicate that Atg5 deficiency would induce pyroptosis in mice SG, which could lead to functional impairments of SG.
Assuntos
Síndrome de Sjogren , Humanos , Camundongos , Animais , Síndrome de Sjogren/metabolismo , Piroptose , Qualidade de Vida , Glândulas Salivares/metabolismo , Glândulas Salivares Menores/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Queratina-14/metabolismoRESUMO
BACKGROUND: Evidence is less about the associations between fine particulate matter (PM2.5) components and hypertension. We aimed to examine the long-term effects of PM2.5 components on prevalence of hypertension, diastolic blood pressure (DBP) and systolic blood pressure (SBP). METHODS: We included participants between March 1, and July 31, 2021, from 13 provinces in China. Geocoded residential address was used for exposure assignment. Mixed-effect regression was used to assess 3-year average concentrations of PM2.5 and its components (black carbon, organic matter, nitrate, ammonium, and sulfate) on prevalence of hypertension, DBP and SBP with covariate-adjusted. SHapley Additive exPlanation was used to compare the contribution of PM2.5 components to hypertension, DBP, and SBP. Sex and age subgroup were also analyzed. RESULTS: We enrolled a total of 113,159 participants aged ≥18 years. Long-term exposure to PM2.5 and its components (black carbon, organic matter, nitrate, ammonium, and sulfate) had associations with prevalence of hypertension, with the Odds Ratios and 95% confidence interval (CI) of 1.06 (95%CI: 1.03-1.09), 1.07 (95%CI: 1.04-1.09), 1.07 (95%CI: 1.04-1.10), 1.05 (95%CI: 1.01-1.08), 1.03 (95%CI: 1.00-1.06), and 1.03 (95%CI: 1.00-1.04), respectively. Effects of that except for black carbon on DBP with per interquartile upticks of concentration were 0.23 (95%CI: 0.11-0.35), 0.17 (95%CI: 0.04-0.29), 0.35 (95%CI: 0.21-0.48), 0.40 (95%CI: 0.28-0.52), and 0.25 (95%CI: 0.13-0.26), respectively. Ammonium was associated with SBP, corresponding to an increase of 0.18 (95%CI: 0.01-0.35). Males had higher risks of DBP (Z = 2.54-6.08, P < 0.001). Older people were substantially more affected by PM2.5 and its components. Nitrate showed the highest contribution to hypertension, DBP and SBP compared with other components. CONCLUSIONS: Long-term exposure to PM2.5 and its components had adverse consequences on prevalence of hypertension, DBP and SBP, especially for males and older people. Nitrate contributed the highest to hypertension, DBP and SBP. Findings may have implications for pollution and hypertension control.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hipertensão , Masculino , Humanos , Adolescente , Adulto , Idoso , Poluentes Atmosféricos/toxicidade , Nitratos/análise , Exposição Ambiental/análise , Hipertensão/epidemiologia , Material Particulado/análise , Pressão Sanguínea , China/epidemiologia , Carbono/análise , Poluição do Ar/análiseRESUMO
BACKGROUND: Extensive studies have linked PM2.5 and PM10 with respiratory diseases (RD). However, few is known about causal association between PM1 and morbidity of RD. We aimed to assess the causal effects of PM1 on cause-specific RD. METHODS: Hospital admission data were obtained for RD during 2014 and 2019 in Beijing, China. Negative control exposure and extreme gradient boosting with SHapley Additive exPlanation was used to explore the causality and contribution between PM1 and RD. Stratified analysis by gender, age, and season was conducted. RESULTS: A total of 1,183,591 admissions for RD were recorded. Per interquartile range (28 µg/m3) uptick in concentration of PM1 corresponded to a 3.08% [95% confidence interval (CI): 1.66%-4.52%] increment in morbidity of total RD. And that was 4.47% (95% CI: 2.46%-6.52%) and 0.15% (95% CI: 1.44%-1.78%), for COPD and asthma, respectively. Significantly positive causal associations were observed for PM1 with total RD and COPD. Females and the elderly had higher effects on total RD, COPD, and asthma only in the warm months (Z = 3.03, P = 0.002; Z = 4.01, P < 0.001; Z = 3.92, P < 0.001; Z = 2.11, P = 0.035; Z = 2.44, P = 0.015). Contribution of PM1 ranked first, second and second for total RD, COPD, and asthma among air pollutants. CONCLUSION: PM1 was causally associated with increased morbidity of total RD and COPD, but not causally associated with asthma. Females and the elderly were more vulnerable to PM1-associated effects on RD.
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Poluentes Atmosféricos , Poluição do Ar , Asma , Doença Pulmonar Obstrutiva Crônica , Idoso , Feminino , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Asma/induzido quimicamente , Asma/epidemiologia , China/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Morbidade , Material Particulado/toxicidade , Material Particulado/análise , MasculinoRESUMO
The intramolecular Heck reaction is a well-established strategy for natural product total synthesis. When constructing large rings, this reaction is also referred to as Heck macrocyclization, which has proved a viable avenue to access diverse naturally occurring macrocycles. Less noticed but likewise valuable, it has created novel macrocycles of non-natural origin that neither serve as nor derive from natural products. This review presents a systematic account of the title reaction in forging this non-natural subset of large rings, thereby addressing a topic rarely covered in the literature. Walking through two complementary sections, namely (1) drug discovery research and (2) synthetic methodology development, it demonstrates that beyond the well-known domain of natural product synthesis, Heck macrocyclization also plays a remarkable role in forming synthetic macrocycles, in particular macrocyclic drugs.
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Produtos Biológicos , Compostos Macrocíclicos , Ciclização , Descoberta de DrogasRESUMO
Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure-activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy.
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Antineoplásicos , Fator 1 de Elongação de Peptídeos , Fator 1 de Elongação de Peptídeos/genética , Fator 1 de Elongação de Peptídeos/metabolismo , Biossíntese de Proteínas , Saccharomyces cerevisiae/metabolismo , Ribossomos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/metabolismoRESUMO
A signal-amplified electrochemiluminescent (ECL) sensor chip was developed for sensitive analysis of procalcitonin (PCT). Herein, we first prepared a self-enhanced luminophore, which enhanced ECL responses through intramolecular reactions. Second, Au-Pd bimetallic nanocrystals and mixed-valence Ce-based metal-organic frameworks (MOFs) were introduced as co-reaction promoters to facilitate the reduction of dissolved O2. Based on the synergistic catalysis of Au and Pd, the spontaneous cyclic reaction of Ce(III)/Ce(IV), and the high electrochemical active surface area of Ce(III, IV) MOF, a large number of superoxide anion radicals (O2â¢-) and hydroxyl radicals (OHâ¢) were produced. Therefore, the luminescence efficiency of N-(aminobutyl)-N-(ethylisoluminol)-dissolved O2 (ABEI-O2) systems were greatly improved, providing a new prospect for the application of dissolved O2 in ECL analysis. In addition, the affinity peptide ligands were used for the directional connection of antibodies to provide protection for the bioactivity of the proposed sensor. Finally, the microfluidic technology was applied to ECL analysis to integrate the three-electrode detection system into the self-assembled microfluidic chip, which realized the automation and portability of the detection process. The developed sensor showed high sensitivity for PCT detection with a detection limit of 3.46 fg/mL, which possessed positive significance for the clinical diagnosis of sepsis.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Medições Luminescentes/métodos , Luminol/análogos & derivados , Nanopartículas Metálicas/química , Microfluídica , Pró-Calcitonina/análiseRESUMO
BACKGROUND: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. METHODS: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013-2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. RESULTS: The mean (SD) age was 53.35 (14.66) years, and 6 154 (68.8%) were men. During a median follow-up of 4.82 years, 467 participants developed nephropathy and 90 participants developed retinopathy. One-SD increase in VAI and CVAI levels were significantly associated with an increased risk of nephropathy, and the adjusted hazard ratios (HR) were 1.127 (95% CI 1.050-1.210) and 1.165 (95% CI 1.003-1.353), respectively. On contrary, VAI and CVAI level were not associated with retinopathy after adjusting confounding factors. CONCLUSION: VAI and CVAI are independently associated with the development of nephropathy, but not retinopathy in Chinese adults with diabetes.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Doenças Retinianas , Adiposidade , Adulto , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. METHODS: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0-4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42-5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61-4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. CONCLUSION: This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Rigidez Vascular , Humanos , Pessoa de Meia-Idade , Controle Glicêmico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Pressão SanguíneaRESUMO
Age has been found to be one of the main risk factors for the severity and outcome of COVID-19. However, differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown. In this study, we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups. By antibody response landscape maps, we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age. The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence, disease severity and age of the COVID-19 patients. Furthermore, the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged <50 and high S1 IgG responses are enriched in mild COVID-19 patients aged >60. In addition, high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged >70. These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age, which may facilitate a deeper understanding of the immune responses in COVID-19 patients.
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Fatores Etários , Formação de Anticorpos , COVID-19 , Idoso , Anticorpos Antivirais/sangue , COVID-19/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Peptídeos , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
This work presents a mixed-ligand metal-organic framework (m-MOF) integrated with two ligands, one as a luminophore and the other as a coreactant, on one metal node for self-enhanced electrochemiluminescence (ECL). Both 9,10-di(p-carboxyphenyl)anthracene (DPA) and 1,4-diazabicyclo[2.2.2]octane (D-H2) ligands can be oxidized, generating the cation radicals DPA+⢠and D-H2+â¢, respectively. The latter can be deprotonated to form the neutral radical (D-Hâ¢) and then react with DPA+⢠to produce excited DPA* for ECL emission without exogenous coreactants. As a result of the incorporation into the MOF framework and the intrareticular charge transfer between the two ligands, the ECL intensity of the m-MOF was increased 26.5-fold compared with that of the mixture of DPA and D-H2 in aqueous solution. Moreover, with the process of second oxidation of D-H2, stepwise ECL emission was observed as a result of local excitation in the DPA unit, which was identified through density functional theory calculations. Overall, the implementation of the mixed-ligand approach, which combines the luminophore and coreactant as linkers in reticular materials, enriches the fundamentals and applications of ECL systems.
RESUMO
The controllable growth of metal nanoparticles on nanomaterials is becoming a useful strategy for developing nanocomposites with designated performance. Here, a DNA-controlled strategy for growth of Pt nanoparticles on graphene oxide (GO-PtNPs) to regulate the nanozyme activity and a triplex-hybridization chain reaction (tHCR) for triggering the assembly of DNA probes to amplify the target-induced nanozyme catalytic signal were designed. The tHCR with one linear and two hairpin probes could be specially triggered by a tHCR trigger to form a long double-stranded DNA structure in the presence of target nucleic acid, which hindered the adsorption of these probes on a GO surface, and thus accelerated the growth of PtNPs. The formed GO-PtNPs showed strong catalytic activity toward the oxidation of 3,3,5,5-tetramethylbenzidine, thereby producing an amplified "turn-on" detection signal. The proposed method showed very high sensitivity with the detection limits down to 14.6 pM for mutant KRAS DNA and 21.7 pM for let-7a microRNA. This method was validated with better analytical performance than a general HCR system and could be effectively used for the identification of single-nucleotide polymorphisms, thus providing a novel approach for simple and sensitive detection of nucleic acids.
Assuntos
Colorimetria , DNA de Neoplasias/análise , Grafite/química , Nanopartículas Metálicas/química , Técnicas de Amplificação de Ácido Nucleico , Platina/química , DNA de Neoplasias/genética , MicroRNAs/análise , MicroRNAs/genética , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
The fabrication of heterojunctions or homojunctions between semiconductors is a controllable strategy to facilitate charge separation in photocatalysis. The homophase junctions exhibit atomic-level contact for the fast-speed charge transfer via inducing the built-in electric fields. Herein, a new concept of TiO2 quasi-core-shell homophase junction induced by a Ti3+ concentration difference for remarkably enhancing photocatalytic activity is proposed. Nano anatase TiO2 quasi-core-shell homophase junctions are constructed between the interior with high Ti3+ concentration (quasi-core) and the surface with no detected Ti3+ (quasi-shell). Diverse Ti3+ concentration differences are obtained via regulating the mass ratio of the Ti source. The nano anatase TiO2 quasi-core-shell homophase junctions exhibit improved photocatalytic hydrogen evolution compared with commercial anatase nanoparticles. To be specific, the maximum hydrogen evolution rate of 50.02 mmol/h/g is 25.4 times superior to that of commercial anatase nanoparticles under solar illumination. Besides, the photocatalytic activity remains stable (H2 evolution rate of 49.21 mmol/h/g, activity loss of <2%) after five cycles of catalytic test. The promoted photocatalytic activities are ascribed to the constitution of a built-in electrical field between the quasi-shell and quasi-core induced by the band bending, which accelerates the spatial charge separation and suppresses the recombination of carriers. Moreover, the atomic-level contact at the homophase junction interface provides smooth channels for carrier transfer, resulting in more effective separation and transfer of photogenerated electrons and holes. The synthesis of nano anatase TiO2 quasi-core-shell homophase junctions provides new insights into the efficient separation and transfer of photogenerated carriers for photocatalytic applications.
RESUMO
Multipath is the dominant error source for most fixed Global Navigation Satellite Systems (GNSS) sites and stations. The presence of multipath, particularly the multipath effect on pseudorange measurement, seriously affects positioning accuracy. Unfortunately, multipath effect reduction is still a challenging issue in high-accuracy GNSS positioning applications due to its special properties. To minimize the impact of the multipath effect, this paper focused on pseudorange multipath mitigation. First, the frequency spectrum of the code-minus-carrier divergence (CMCD) for Global Positioning System (GPS), Global Navigation Satellite System (GLONASS), and BeiDou Navigation Satellite System (BDS) satellites observed in different environments were analyzed, where we found that periodic fluctuations appeared in GPS and GLONASS as well as medium earth orbit (MEO) and inclined geosynchronous satellite orbit (IGSO) of BDS satellites in some situations, which manifested as peaks in the frequency domain. The results showed that the location of the frequency peaks in the frequency domain, width, and basic frequency spectrum intensity were different between different satellites and environments, causing difficulty in reducing the error impact. To eliminate such period fluctuations mainly caused by the multipath effect, a novel method based on a frequency domain filter was proposed in this paper. One of the keys of the proposed method was the use of short-time Fourier transformation (STFT) in the GNSS signal data processing to calculate the accurate local frequency spectrum when code-minus-carrier divergence (CMCD) was assumed to be time varying. Once the frequency spectrum was obtained, a new spectrum peak extraction method was used to locate the peak frequency position. By interpolation and inverse Fourier transformation, the influence of the spectrum peaks could be effectively eliminated, thus improving pseudorange precision. The experimental results showed that the periodic multipath effect could be greatly reduced by the proposed method.