RESUMO
Artificial solid-state nanochannels featuring precise partitions present a highly promising platform for biomarker detection. While the significance of probes on the outer surface (POS) has been relatively overlooked in the past, our research highlights their crucial role in biosensing. Furthermore, the contribution of POS on the bullet-shaped asymmetric nanochannels has not been extensively explored until now. Here, we fabricated a series of bullet-shaped nanochannels, each featuring a distinct asymmetric structure characterized by different tip- and base-pore diameters. These nanochannels were further modified with explicit distributions at the inner wall (PIW), the outer surface (POS), and their combination (POS + PIW) for lysozyme sensing. The impact of diameters, structural asymmetry, and surface charge density on the sensing efficacy of POS and PIW was thoroughly examined through experimental investigations and numerical simulations. POS demonstrates great individual sensing performance for lysozyme within a broad concentration range, spanning from 10 nM to 1 mM. Furthermore, it improves the sensitivity when combined with PIW, particularly within the nanochannels featuring the smaller base-pore diameter, resulting in a 2-fold increase in sensing performance for POS + PIW compared to PIW at a concentration of 10 nM. These findings are substantiated by numerical simulations that closely align with the experimental parameters. The contributions of POS are notably amplified in the presence of smaller base pores and a higher degree of asymmetry within the bullet-shaped nanochannels. These findings elucidate the mechanism underlying the role of POS within bullet-shaped asymmetric nanochannels and open up new avenues for manipulating and enhancing the sensing efficiency.
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Nanoestruturas , Nanoestruturas/química , Muramidase , ProteínasRESUMO
Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.
Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Diabetes Mellitus Experimental , Transdução de Sinais , Cicatrização , Quinases Associadas a rho , Animais , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Cicatrização/efeitos dos fármacos , Humanos , Diabetes Mellitus Experimental/metabolismo , Masculino , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , FemininoRESUMO
BACKGROUND: The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap. METHODS: A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL. RESULTS: This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)). CONCLUSIONS: This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.
Assuntos
Exercício Físico , Metabolismo dos Lipídeos , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos , Humanos , Exercício Físico/fisiologia , Triglicerídeos/sangue , Medicina Esportiva , HDL-Colesterol/sangue , Colesterol/sangue , Masculino , LDL-Colesterol/sangue , Terapia por ExercícioRESUMO
Environmental exposure to the cadmium (Cd) has been shown to be a risk factor for colorectal cancer (CRC) progression, but the exact mechanism has not been fully elucidated. In this study, we found that chronic Cd (3⯵M) exposure promoted the proliferation, adhesion, migration, and invasion of CRC cells in vitro, as well as lung metastasis in vivo. RNA-seq and TCGA-COAD datasets revealed that decreased hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) expression may be a crucial factor in Cd-induced CRC progression. Further analysis using qRT-PCR and tissue microarrays from CRC patients showed that HADHB expression was significantly reduced in CRC tissues compared to adjacent normal tissues, and low HADHB expression was associated with adverse clinical features and poor overall survival, either directly or through TNM stage. Furthermore, HADHB was found to play an important role in the Cd-induced malignant metastatic phenotype of CRC cells and lung metastasis in mice. Mechanistically, we discovered that chronic Cd exposure resulted in hypermethylation of the HADHB promoter region via inhibition of DNA demethylase tet methylcytosine dioxygenase 2 (TET2), which then led to decreased HADHB expression and activation of the FAK signaling pathway, and ultimately contributed to CRC progression. In conclusion, this study provided a new potential insight and evaluable biomarker for Cd exposure-induced CRC progression and treatment.
Assuntos
Cádmio , Neoplasias Colorretais , Proteínas de Ligação a DNA , Dioxigenases , Progressão da Doença , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/induzido quimicamente , Humanos , Dioxigenases/genética , Animais , Camundongos , Cádmio/toxicidade , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Linhagem Celular Tumoral , Masculino , Proliferação de Células/efeitos dos fármacos , Feminino , Camundongos Nus , Metilação de DNA/efeitos dos fármacos , Movimento Celular/efeitos dos fármacosRESUMO
BACKGROUND: Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. METHODS: This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. RESULTS: According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. CONCLUSION: The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.
Assuntos
Currículo , Aprendizagem Baseada em Problemas , Humanos , Feminino , Aprendizagem Baseada em Problemas/métodos , Aprendizagem , Estudantes , Inquéritos e Questionários , EnsinoRESUMO
Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.
Assuntos
Hiperuricemia , Ácido Oxônico , Plantago , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Animais , Ratos , Ácido Oxônico/efeitos adversos , Masculino , Plantago/química , Ácido Úrico/sangue , Extratos Vegetais/farmacologia , Rim/metabolismo , Rim/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Xantina Oxidase/metabolismoRESUMO
Seed dormancy and germination determine the beginning of the life cycle of plants, and the phytohormone ABA plays a crucial role in regulation of seed dormancy and germination. However, the upstream regulatory mechanism of ABA metabolism during dormancy releasing is still remain elusive. In this paper, we present a novel mechanism of OsNAC2 in controlling ABA metabolism and regulation of seed dormancy. OsNAC2 highly expressed during seed development and germination, and overexpression of OsNAC2 strengthened seed dormancy and suppressed germination. Moreover, exogenous phytohormone treatment showed that OsNAC2 acted upstream of GA signaling and downstream of ABA signaling. Additionally, overexpression of OsNAC2 inhibited ABA degradation and increased ABA content during early germination. Further molecular analysis revealed that OsNAC2 directly bound to the ABA metabolism genes promoter and inhibits their transcription in rice protoplasts. These finding could help us explain the genetic regulation mechanism of ABA metabolism during dormancy release and germination in rice.
Assuntos
Oryza , Dormência de Plantas , Dormência de Plantas/genética , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Germinação/genética , Sementes/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Urban ecosystem services (UES), as an important concept in nature-based solutions, can effectively mitigate adverse environmental burdens and have great potential in addressing environmental justice issues. However, few studies linking UES with environmental justice have considered both supply and demand sides of UES, particularly at the spatial scale of residential walking space. Against this backdrop, we investigated the distributional justice of supply and demand for urban cooling, flood mitigation, air purification, and outdoor recreation in residential walking spaces in Shanghai among socially vulnerable groups (i.e., elderly residents, children, females, low-income residents, no-hukou residents, and ethnic minorities). We found that (1) the UES supply of residential walking space was much lower than that of non-residential walking space, while the UES demand was much higher than that of non-residential walking space. (2) Higher proportions of ethnic minorities, no-hukou residents, and females in Shanghai were positively correlated with several UES demands but were not positively correlated with ES supply, indicating a higher possibility of unsatisfied UES demand for these disadvantaged groups. Future urban blue-green space planning should pay more attention to the spatial allocation of blue-green space, especially placing more blue-green space around residential walking spaces with high UES demand and with a high proportion of socially disadvantaged groups.
Assuntos
Ecossistema , Justiça Ambiental , Criança , Feminino , Humanos , Idoso , China , Parques Recreativos , Pobreza , CidadesRESUMO
Studies of the ecosystem services (ES) and human wellbeing (HWB) relationship have proliferated in recent decades, but few have examined how ES affect HWB over time in a region (i.e., the temporal ES-HWB relationship) and how this relationship varies between regions. Thus, this study was intended to address these questions using data from Inner Mongolia. We first quantified multiple indicators of ES and objective HWB from 1978 to 2019, and then quantified their temporal relationship with correlation analysis over the entire duration and during four development periods, respectively. Our results showed that, depending on the time periods of analysis, geographic locations, and indicators, the temporal ES-HWB relationship varied substantially in both correlation strength and directionality (r values ranged from -0.93 to +1). Specifically, food-related provisioning services and cultural services often showed significant positive relationships with income, consumption, and basic living needs (r values ranged from +0.43 to +1), but erratic relationships with equity, employment, and social relationships (r values ranged from -0.93 to +0.96). Also, the positive correlations between food-related provisioning services and HWB were generally weaker in the urbanized regions. Cultural services and HWB were more strongly correlated in later development periods, whereas the relationship between regulating services and HWB was quite variable in space and time. The variations in the relationship over different development periods may be attributable to changing environmental and socioeconomic conditions, while the variations between regions were likely due to spatial heterogeneity of influencing factors. Our findings have an important policy implication for Inner Mongolia and beyond: sustainable management based on the ES and HWB relationship must be temporally adaptive and spatially tailored.
Assuntos
Ecossistema , Emprego , Humanos , Renda , Políticas , China , Conservação dos Recursos NaturaisRESUMO
The immobilization of proteins on nanoparticles has received much attention in recent years. Among different approaches, enzymatic protein immobilization shows unique advantages because of its site-specific connection. OaAEP1 is a recently engineered peptide ligase which can specifically recognize an N-terminal GL residue (NH2-Gly-Leu) and a C-terminal NGL amino acid residue (Asn-Gly-Leu-COOH) and ligates them efficiently. Herein, we report OaAEP1-mediated protein immobilization on synthetic magnetic nanoparticles. Our work showed that OaAEP1 could mediate C-terminal site-specific protein immobilization on the amino-functionalized Fe3O4 nanoparticles. Our work demonstrates a new method for site-specific protein immobilization on nanoparticles.
Assuntos
Enzimas Imobilizadas , Enzimas Imobilizadas/químicaRESUMO
Although root nodules are essential for biological nitrogen fixation in legumes, the cell types and molecular regulatory mechanisms contributing to nodule development and nitrogen fixation in determinate nodule legumes, such as soybean (Glycine max), remain incompletely understood. Here, we generated a single-nucleus resolution transcriptomic atlas of soybean roots and nodules at 14 days post inoculation (dpi) and annotated 17 major cell types, including six that are specific to nodules. We identified the specific cell types responsible for each step in the ureides synthesis pathway, which enables spatial compartmentalization of biochemical reactions during soybean nitrogen fixation. By utilizing RNA velocity analysis, we reconstructed the differentiation dynamics of soybean nodules, which differs from those of indeterminate nodules in Medicago truncatula. Moreover, we identified several putative regulators of soybean nodulation and two of these genes, GmbHLH93 and GmSCL1, were as-yet uncharacterized in soybean. Overexpression of each gene in soybean hairy root systems validated their respective roles in nodulation. Notably, enrichment for cytokinin-related genes in soybean nodules led to identification of the cytokinin receptor, GmCRE1, as a prominent component of the nodulation pathway. GmCRE1 knockout in soybean resulted in a striking nodule phenotype with decreased nitrogen fixation zone and depletion of leghemoglobins, accompanied by downregulation of nodule-specific gene expression, as well as almost complete abrogation of biological nitrogen fixation. In summary, this study provides a comprehensive perspective of the cellular landscape during soybean nodulation, shedding light on the underlying metabolic and developmental mechanisms of soybean nodule formation.
Assuntos
Ascomicetos , Medicago truncatula , Fixação de Nitrogênio/genética , Glycine max/fisiologia , Nodulação/genética , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/metabolismo , Transcriptoma/genética , Citocininas/metabolismo , Medicago truncatula/genética , Medicago truncatula/metabolismo , Simbiose/genética , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nitrogênio/metabolismoRESUMO
Nanochannel technology has emerged as a powerful tool for label-free and highly sensitive detection of protein folding/unfolding status. However, utilizing the inner walls of a nanochannel array may cause multiple events even for proteins with the same conformation, posing challenges for accurate identification. Herein, we present a platform to detect unfolded proteins through electrical and optical signals using nanochannel arrays with outer-surface probes. The detection principle relies on the specific binding between the maleimide groups in outer-surface probes and the protein cysteine thiols that induce changes in the ionic current and fluorescence intensity responses of the nanochannel array. By taking advantage of this mechanism, the platform has the ability to differentiate folded and unfolded state of proteins based on the exposure of a single cysteine thiol group. The integration of these two signals enhances the reliability and sensitivity of the identification of unfolded protein states and enables the distinction between normal cells and Huntington's disease mutant cells. This study provides an effective approach for the precise analysis of proteins with distinct conformations and holds promise for facilitating the diagnoses of protein conformation-related diseases.
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The nanofluidic ionic signal is governed by the interactions between ion species and the surface charge, surface wettability, and pore diameter of nanofluidic membranes. However, the effect of surface wettability on the ionic detection signal across the nanofluidic membrane remains poorly explored, limited nanofluidic applications in biochemical sensing. Here, we investigate the effect of surface wettability of the nanofluidic membrane on the ionic signal for the detection of hydrophobic drug molecules using a heterogeneous nanofluidic system. This ionic signal can be tuned by light or the presence of certain ions due to the tailoring of hydrophobic interactions between the ion species and membrane surface. Compared with traditional nanofluidic membranes whose ionic signal is governed by surface charge, the regulation mechanism reported here mainly dependents on specific hydrophobic interactions, which shows a more sensitive ionic signal to environments. By virtue of the mechanism, the selective detection of the three drug molecules was realized owing to their different hydrophobic interactions with membrane surfaces. These findings have implications for understanding mass transport in nanofluidic devices and biological components and porous media involving surface wettability in nanofluidic systems.
Assuntos
Molhabilidade , Íons , PorosidadeRESUMO
Solid-state nanopores, inspired by biological nanopores, have the advantages of good mechanical properties, stability, and easy modification. They have attracted wide attention in the fields of sequencing, sensing, molecular sieving, nanofluidic devices, nanoelectrochemistry, and energy conversion. Because of the ion/molecule transport characteristic of the pore, the research on solid-state nanopores mainly focuses on the functional modification of its inner wall. In recent years, the outer surface of nanopores has also attracted the attention of researchers, and the functional elements on the outer surface have the functions of anti-interference and ionic signal enhancement. In this perspective, we review research progress of inner wall and outer surface distinguished solid-state nanopores, highlight their processing and advantages, summarize their functions and applications in sensing, and give insight into further research.
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Nanoporos , Nanotecnologia , Íons , Cromatografia LíquidaRESUMO
Graphene oxide (GO) has been widely reported as a supercapacitor electrode. Especially, GO is usually utilized to composite with electrochemical active materials, such as transition-metal oxide/hydroxide/sulfide, due to its considerable conductivity and mechanical strength. However, the ideal design and treatment for compositing GO with active materials are still challenging. Herein, an Ni-metal-organic framework (MOF) was self-assembled on GO nanosheets via the solvothermal method and was subsequently etched into the Ni(OH)2-GO composite electrode material through a gentle hydrolysis strategy. The GO support enables fast electron transport within the composite material, and the nickel hydroxide growth on GO nanosheets can prevent their aggregation, guaranteeing rapid ion migration. The improved Ni(OH)2-GO battery-type electrode features outstanding stability (capacity retention of 108% at 8000 cycles) and a considerable specific capacity (SC) of 1007.5 C g-1 at a current density of 0.5 A g-1. Compared with MOF-derived Ni(OH)2 obtained through hydrolysis, Ni(OH)2-GO only contains 7.41% wt GO, while its SC is almost 50% higher. An asymmetric supercapacitor has an energy density of 65.22 W h kg-1 and a power density of 395.27 W kg-1 utilizing p-phenylenediamine-functional reduced GO as the negative electrode, and it can maintain 73.08% capacity during 8000 cycles at a current density of 5 A g-1.
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Polygonum cuspidatum Sieb. et Zucc. is a traditional and popular Chinese medicine with a wide spectrum of pharmacological effects such as anti-bacterial, anti-inflammatory, and anti-tumor activities together with other health effects like lowering lipids, preventing diabetes, and regulating the immune system. It is of great significance to explore the complex chemical constituents and metabolic process of Polygonum cuspidatum in vivo to further clarify the effective substances. However, studies on its metabolism in vivo were not comprehensive in previous literature. In this study, ultra-high performance liquid chromatography coupled with Quadrupole-Exactive Orbitrap mass spectrometry was used to comprehensively identify the chemical constituents in Polygonum cuspidatum and further analyze its metabolic profile in rats. Compared with reference substances, various databases, and literature retrieval, 62 compounds were inferred from the Polygonum cuspidatum extract. Furthermore, a total of 119 compounds, including 44 prototype compounds and 75 metabolites, were annotated in rat plasma, urine, and feces. The main metabolic pathways of Polygonum cuspidatum in rats included hydrogenation reduction, hydroxylation, dehydration, methylation, sulfation, and glucuronidation. This is the first systematic study on the chemical constituents of Polygonum cuspidatum and its metabolic profile in vivo, which contributes to finding its bioactive components and seeking its therapeutic targets.
Assuntos
Fallopia japonica , Ratos , Animais , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , MetabolomaRESUMO
PMP-HPLC, FT-IR, and HPSEC fingerprints of 10 batches of polysaccharides from Saposhnikoviae Radix with different production areas and harvest times have been prepared, and the chemometrics analysis was performed. The anti-allergic activity of 10 batches of Saposhnikoviae Radix polysaccharide (SP) was evaluated, and the spectrum-effect relationship of the 10 batches of SP was analyzed by gray correlation degree with the chromatographic fingerprint as the independent variable. The results showed that the PMP-HPLC, HPSEC, and FT-IR fingerprints of 10 batches of SP had a high similarity. Two monosaccharides (rhamnose and galactose), the polysaccharide fragment Mn = 8.67 × 106~9.56 × 106 Da, and the FT-IR absorption peak of 892 cm-1 can be used as the quality control markers of SPs. All 10 batches of SP could significantly inhibit the release of ß-HEX in RBL-231 cells, and the polysaccharides harvested from Inner Mongolia in the winter had the best anti-allergic activity. The spectrum-effect relationship model showed that the monosaccharide composition and molecular weight were related to the anti-allergic activity of the SPs. Multiple fingerprints combined with spectrum-effect relationship analysis can evaluate and control the quality of SPs from the aspects of overall quality and efficacy, which has more application value.
Assuntos
Antialérgicos , Medicamentos de Ervas Chinesas , Antialérgicos/análise , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Monossacarídeos/análise , Raízes de Plantas/química , Polissacarídeos/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The grafting density of probes at sensor interface plays a critical role in the performance of biochemical sensors. However, compared with macroscopic interface, the effects of probe grafting density at nanometric confinement are rarely studied due to the limitation of precise grafting density regulation and characterization at the nanoscale. Here, we investigate the effect from the grafting density of DNA probes on ionic signal for nucleic acid detection in a cylindrical nanochannel array (with diameter of 25 nm) by combing experiments and theories. We set up a theoretical model of charge distribution from close to inner wall of nanochannels at low probe grafting density to spreading in whole space at high probe grafting density. The theoretical results fit well with the experimental results. A reverse of ionic output from signal-off to signal-on occurs with increasing probe grafting density. Low probe grafting density offers a high current change ratio that is further enhanced using long-chain DNA probes or the electrolyte with a low salt concentration. This work develops an approach to enhance performance of nanochannel-based sensors and explore physicochemical properties in nanometric confines.
Assuntos
Sondas de DNA/química , DNA/química , Nanoestruturas/química , Análise de Sequência com Séries de Oligonucleotídeos , Eletrodos , Modelos Teóricos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Probe-modified nanopores/nanochannels are one of the most advanced sensors because the probes interact strongly with ions and targets in nanoconfinement and create a sensitive and selective ionic signal. Recently, ionic signals have been demonstrated to be sensitive to the probe-target interaction on the outer surface of nanopores/nanochannels, which can offer more open space for target recognition and signal conversion than nanoconfined cavities. To enhance the ionic signal, we investigated the effect of grafting density, a critical parameter of the sensing interface, of the probe on the outer surface of nanochannels on the change rate of the ionic signal before and after target recognition (ß). Electroneutral peptide nucleic acids and negatively charged DNA are selected as probes and targets, respectively. The experimental results showed that when adding the same number of targets, the ß value increased with the probe grafting density on the outer surface. A theoretical model with clearly defined physical properties of each probe and target has been established. Numerical simulations suggest that the decrease of the background current and the aggregation of targets at the mouth of nanochannels with increasing probe grafting density contribute to this enhancement. This work reveals the signal mechanism of probe-target recognition on the outer surface of nanochannels and suggests a general approach to the nanochannel/nanopore design leading to sensitivity improvement on the basis of relatively good selectivity.
Assuntos
Nanoporos , Ácidos Nucleicos Peptídicos , DNA , Íons , Modelos TeóricosRESUMO
Nanochannels have advantage in sensitive analyses due to the confinement effects on ionic signal in nano- or sub-nanometric confines but could realize further gains by optimizing signal mechanism. Making target recognitions on the outer surface of nanochannels has been verified to improve target recognitions and signal conversions by maximizing surfaces accessible to targets and ions, but until recently, the signal mechanism has been still unclear. Using electroneutral peptide nucleic acid (PNA) and negative-charged DNA, we verified a dominant space charge effect on an ionic signal on the outer surface of nanochannels. A typical exponential increase of the ionic signal with the charge density on the outer surface has been demonstrated through the PNA-PNA, PNA-DNA, DNA-DNA hybrid, DNA cleavage, and hybridization chain reaction. These results challenge the essential role of steric hindrance on the ionic signal and describe a new ion passageway surrounded and accelerated by the stern layer of charged species on the nanochannel outer surface.