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Introduction: Coronavirus disease 2019 occurred unexpectedly in late December 2019, it was difficult to immediately develop an effective vaccine or propose targeted medical interventions in the early stages of the outbreak. At this point, non-pharmaceutical interventions (NPIs) are essential components of the public health response to COVID-19. How to combine different NPIs in the early stages of an outbreak to control the spread of epidemics and ensure that the policy combination does not incur high socio-economic costs became the focus of this study. Methods: We mainly used the fuzzy set qualitative comparative analysis to assess the impact of different combinations of NPIs on the effectiveness of control in the COVID-19 pandemic early stage, using open datasets containing case numbers, country populations and policy responses. Results: We showed that the configuration of high morbidity results includes one, which is the combination of non-strict face covering, social isolation and travel restrictions. The configuration of non-high morbidity results includes three, one is strict mask wearing measures, which alone constitute sufficient conditions for interpreting the results; the second is strict testing and contact tracing, social isolation; the third is strict testing and contact tracing, travel restriction. The results of the robustness test showed that the number, components and consistency of the configurations have not changed after changing the minimum case frequency, which proved that the analysis results are reliable. Conclusion: In the early stages of the epidemic, the causes of high morbidity are not symmetrical with the causes of non-high morbidity. Strict face covering is the most basic measure required to prevent and control epidemics, and the combination of non-strict face covering and containment is the most important factor leading to poor prevention and control, and the combination of strict containment and proactive pursuit is the way to achieve superior prevention and control, timely and proactive containment strategies have better prevention and control, and should mobilize the public to cooperate.
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COVID-19 , Lógica Difusa , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , SARS-CoV-2 , Pandemias/prevención & control , Trazado de Contacto , Control de Enfermedades Transmisibles , Salud Pública , Aislamiento Social , Salud Global , Investigación Cualitativa , Máscaras/estadística & datos numéricosRESUMEN
Aggregation-induced emission (AIE) materials are attracting great attention in biomedical fields such as sensors, bioimaging, and cancer treatment, et al. due to their strong fluorescence emission in the aggregated state. In this contribution, a series of tetraphenylene-acetonitrile AIE compounds with D-A-D' structures were synthesized by Suzuki coupling reaction and Knoevenagel condensation, and their relationship of chemical structure and fluorescence properties was investigated in detail, among which TPPA compound was selected as the monomer owing to the longest emission wavelength at about 530â¯nm with low energy band gap ΔE 3.09â¯eV of neutral TPPA and 1.43â¯eV of protonated TPPA. Novel amphiphilic AIE PEG-TA copolymers were prepared by RAFT polymerization of TPPA and PEGMA with about 1.44×104 Mw and narrow PDI, and the molar ratio of TPPA in the PEG-TA1 and PEG-TA2 copolymers was about 23.4â¯% and 29.6â¯%. The as-prepared PEG-TA copolymers would self-assembled in aqueous solution to form core-shell structures with a diameter of 150-200â¯nm, and their emission wavelength could reversibly convert from 545â¯nm to 650â¯nm with excellent pH sensitivity. The CLSM images showed that the PEG-TA FONs and PTX drugs-loaded PTX-TA FONs could be endocytosed by cells and mainly enriched in the cytoplasm, and CCK-8 results showed that the PEG-TA FONs had excellent biocompatibility but PTX-TA FONs had high inhibition ratio for A549 cells, moreover, the flow cytometry also showed that PTX-TA FONs could result in the apoptosis of A549 cells with some extent anti-tumor effect.
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BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by the presence of hyperphosphorylated and misfolded tau aggregates in neurons and glia. Recent studies have illuminated the prion-like cell-to-cell propagation of tau via exosomes. Recognizing the potential significance of excretion through urine as a crucial pathway for eliminating pathological tau from the central nervous system, this study aimed to investigate whether exosomes derived from the urine of PSP-Richardson's syndrome (PSP-RS) patients can elicit tau pathology and PSP-like symptoms in mice. METHODS: Urinary exosomes obtained from PSP-RS patients and normal controls (NCs) were stereotactically injected into the bilateral globus pallidus of mouse brains. Behavioral analyses were conducted every 3 months post-injection. After 6 months, mice were sacrificed for pathological evaluation. RESULTS: Elevated levels of phosphorylated tau and neural cell markers were observed in urinary exosomes from PSP-RS patients compared to NCs. At the 6-month mark post-injection, tau inclusions were evident in the brains of mice receiving urinary exosomes from PSP-RS patients, with widespread distribution in both injection sites and distant brain regions (cortex, hippocampus, and substantia nigra). Tau pathology manifested in neurons and astrocytes. Moreover, mice injected with urinary exosomes from PSP-RS patients exhibited impaired motor coordination and balance, mirroring PSP motor symptoms. CONCLUSION: Our findings indicate that urinary exosomes from PSP-RS patients can induce tau pathology and trigger PSP-like motor symptoms in mice. This leads to the hypothesis that exosomes may play a role in the pathogenesis of PSP.
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Background: The elderly represents the population group with the highest rate of sedentary behavior. Sedentary behavior has an adverse impact on the elderly, which might be related to depression. Methods: We queried PubMed, EMBASE, Web of Science, and MEDLINE to collect literature data. The odds ratio (OR) and corresponding 95% confidence interval (CI) were adopted for the pooled measurements. Sub-group analyses were conducted through stratified meta-analyses based on study design, depression indicator, adjustment for physical activity, sedentary behavior indicator, and type. Sensitivity analyses were performed to test the robustness of the results, and publication bias was assessed through a funnel plot. Results: Seven cross-sectional studies and five cohort studies were included in our meta-analysis. The overall pooled OR was 1.38 (95%CI: 1.16-1.65; P < 0.01), which indicated that sedentary behavior was positively associated with depression in older adults. Sub-group analysis showed that different study designs, depression indicators, sedentary behavior indicators, adjustment for physical activity, sedentary behavior indicator, and type produced different results. In the cross-sectional studies (OR = 1.45, 95%CI: 1.15-1.84), CES-D scale (OR = 1.54, 95%CI: 1.13-2.10), self-reported (OR = 1.39, 95%CI: 1.04-1.87), watching TV (OR = 1.75, 95%CI: 1.02-3.02), and not adjusted for physical activity (OR = 1.37, 95%CI: 1.14-1.65) groups, there was a strong correlation between sedentary behavior and depression in the elderly. Conclusion: Sedentary behavior is associated with depression in the elderly. As a preventive strategy, we should consider reducing their sedentary time and appropriately increasing physical activity.
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Objective: The aim of this study is to understand the job burnout of village doctors during the COVID-19 epidemic and its influencing factors, and to provide a reference for effectively alleviating the job burnout of village doctors. Methods: A cross-sectional survey was conducted among village doctors in S province in December 2021. The survey included a general information questionnaire and the CMBI Burnout Scale. Epidata was used for dual input, and descriptive analysis, t-test, chi-square test, and binary Logistic regression for statistical analysis were used. Results: A total of 993 village doctors participated in the survey. Most of them were male village doctors (62.84%), with an average age of 46.57 (SD = 7.50). Village doctors believed that the impact of the epidemic on work was serious, with a score of 3.87 ± 0.91. The economic support was small, with a score of 2.31 ± 0.99. The development space was low, with a score of 2.62 ± 0.98. The overall incidence of burnout was 53.47%. In the burnout group, 54.05% were mild, 33.14% were moderate, and 12.81% were severe. The high degree of difficulty in using WeChat (OR = 1.436, 95%CI: 1.229-1.679), high work pressure (OR = 1.857, 95%CI: 1.409-2.449), high risk of practice (OR = 1.138, 95%CI: 1.004-1.289), less economic support (OR = 0.825, 95%CI: 0.684-0.995), less technical support (OR = 0.696, 95%CI: 0.565-0.858), and poor emotional support (OR = 0.632, 95%CI: 0.513-0.780) were more likely to have job burnout. Conclusion: Burnout is a common phenomenon among village doctors during the COVID-19 pandemic, which needs to be prevented and alleviated by various measures.
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Agotamiento Profesional , COVID-19 , Médicos , Humanos , COVID-19/epidemiología , COVID-19/psicología , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Médicos/psicología , Médicos/estadística & datos numéricos , China/epidemiología , SARS-CoV-2 , PandemiasRESUMEN
BACKGROUND: Village doctors are the main health service providers in China's rural areas. Compared with other rural groups, they will have a sense of relative deprivation, which has an impact on their practice mentality and job stability. This study aims to analyze the changes and causes of relative deprivation among village doctors, so as to improve the stability of them. METHODS: The data were collected from two surveys conducted in Shandong Province in 2015 and 2021. In 2015, 322 village doctors were surveyed and 307 questionnaires were collected, with a recovery rate of 95.3%. In 2021, 394 village doctors were surveyed and 366 questionnaires were collected, with a recovery rate of 92.9%. Descriptive and univariate analysis were used to compare the changes before and after the survey. RESULTS: The scores of vertical deprivation of village doctors increased from 2.77 ± 0.81 in 2015 to 3.04 ± 0.83 in 2021, with a statistically significant difference (P < 0.001). The reference group selected by village doctors changed from village teachers to ordinary villagers. Compared to village teachers, the horizontal deprivation score of village doctors increased from 3.47 ± 0.87 to 3.97 ± 0.77, with a statistically significant difference (P < 0.001). Compared to villagers, only the professional reputation deprivation score increased, from 2.38 ± 0.93 to 2.68 ± 0.76, with a statistically significant difference (P < 0.05). CONCLUSIONS: As time goes by, village doctors fail to reach the expected level in terms of economic income, social status, professional reputation and living standards, resulting in a sense of relative deprivation. This may have a negative impact on village doctors' work motivation and behavior, and will fail to guarantee the sustainability of the team. We should pay attention to this unbalanced mentality of village doctors.
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Médicos , Humanos , Estudios Transversales , China/epidemiología , Femenino , Masculino , Adulto , Médicos/psicología , Médicos/estadística & datos numéricos , Encuestas y Cuestionarios , Persona de Mediana Edad , Satisfacción en el Trabajo , Agentes Comunitarios de Salud , Servicios de Salud Rural/estadística & datos numéricos , Población Rural/estadística & datos numéricosRESUMEN
Objectives: The proportion of middle-aged and older adult people exposed to the Internet continues to grow. Internet use may have an impact on the mental health of the older adult, especially loneliness. This study analyzed the relationship between Internet use and presence of loneliness. Methods: A total of 550 person aged 45 years and above were randomly selected from a province in eastern China at the end of 2022. The outcome variable was presence of loneliness, as measured by self-report. Descriptive analysis, chi-square test and binary logistic analysis were used to analyze the data. Results: 58.3% of respondents use the Internet. Internet use could reduce the possible of reported loneliness in middle-aged and older adult people (OR = 0.652, 95%CI: 0.465, 0.940), and residence played a moderating role in the relationship between them. Middle-aged and older adults who used the Internet for 1-3 h (OR = 0.464, 95%CI: 0.275, 0.784) and 3-5 h (OR = 0.484, 95%CI: 0.247, 0.946) were less likely to felt lonely than those who used the Internet for less than 1 h per day. In addition, middle-aged and older adult people using the Internet to contact relatives and friends (OR = 0.488, 95%CI:0.292, 0.818), read the news (OR = 0.485, 95%CI:0.277, 0.848), assets management (OR = 0.297, 95%CI:0.109, 0.818) were less likely to report loneliness, while those who made online payment (OR = 3.101, 95%CI:1.413, 6.807) were more likely to report loneliness. Conclusion: There is a significant negative correlation between Internet use and presence of loneliness, but different Internet duration and content have different effects on loneliness in middle-aged and older adult people. We should pay attention to the impact of Internet use on loneliness in middle-aged and older adult people.
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Uso de Internet , Soledad , Persona de Mediana Edad , Humanos , Anciano , Soledad/psicología , Emociones , Internet , ChinaRESUMEN
In this contribution, a novel AIE monomers 2-(4-styrylphenyl)- 1,2-diphenylvinyl)styryl)pyridine (SDVPY) with smart fluorescent pH-sensitivity basing on tetraphenylethylene-pyridine were successfully synthesized for the first time, subsequently, a series of amphiphilic copolymers PEG-PY were achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of SDVPY and poly(ethylene glycol) methacrylate (PEGMA), which would self-assemble in water solution to form core-shell nanoparticles (PEG-PY FONs) with about 150 nm diameter. The PEG-PY FONs showed obvious fluorescence response to Fe3+, HCO3- and CO32- ions in aqueous solution owing to their smart pH-sensitivity and AIE characteristics, and their maximum emission wavelength could reversibly change from 525 nm to 624 nm. The as-prepared PEG-PY FONs showed also prospective application in cells imaging with the variable fluorescence for different pH cells micro-environment. When PEG-PY copolymers self-assembled with the anti-tumor drug paclitaxel (PTX), the obtained PY-PTX FONs could effectively deliver and release PTX with pH-sensitivity, and could be easily internalized by A549 cells and located at the cytoplasm with high cytotoxicity, which was further confirmed by the Calcein-AM/PI staining of dead and alive A549 cells. Moreover, the flow cytometry results indicated that the PY-PTX FONs could obviously induce the apoptosis of A549 cells, which further showed the great potential of PY-PTX FONs in the application of tumors therapy.
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Metacrilatos , Nanopartículas , Neoplasias , Estilbenos , Humanos , Polietilenglicoles , Polímeros , Colorantes , Paclitaxel/farmacología , Concentración de Iones de Hidrógeno , Piridinas/farmacología , Microambiente TumoralRESUMEN
BACKGROUND: Population migration in China has increasingly included middle-aged and older populations. Relatedly, the lack of mental health education among China's older migrants is still an important but neglected problem. This study aimed to understand the current situation of mental health education received by the older migrant population in China and to explore related influencing factors. METHODS: This cross-sectional study included 5729 older migrants who participated in the 2017 China Migrants Dynamic Survey. The independent variables included four components: demographic and socioeconomic characteristics, migration factors, public health service utilization, and social integration factors. Data were analyzed using the chi-square test for single factors and a binary logistic regression model for multiple factors. RESULTS: A total of 1749 older migrants received mental health education, for a receipt rate of 30.53%. Regression analysis showed that older migrant individuals who had an average monthly household income > 3000 CNY, self-rated their health as healthy, had chronic diseases, had heard of National Basic Public Health Services, had established health records, received ≥2 types of health education were willing to integrate into the local population, and were highly involved in the community were more likely to receive mental health education. Older migrants who were ≥ 70 years old, had an elementary school education or below, had difficulties in the local community, had migrated ≥11 years prior, moved for their offspring, and moved across provinces were less likely to receive mental health education. CONCLUSIONS: The older migrant population does not receive sufficient mental health education. Mental health interventions should be tailored to the characteristics of older migrants to increase their mental health literacy and meet their psychological needs.
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Migrantes , Persona de Mediana Edad , Humanos , Anciano , Estudios Transversales , Factores Socioeconómicos , Educación en Salud , China/epidemiologíaRESUMEN
BACKGROUND: Village doctors in China are not only the gatekeepers of rural residents' health but also the net bottom of the medical security system. However, emotional labour is increasingly threatening the stability of the rural primary medical system. In addition, the ongoing coronavirus disease 2019 (COVID-19) pandemic has further exposed the vulnerability of human resources in China's rural health system. This study aims to evaluate the current situation of emotional labour among village doctors and explore the impact of emotional labour on job burnout during the COVID-19 pandemic in China. METHODS: A cross-sectional survey was conducted in December 2021 in Shandong Province. We used structured questionnaires to collect data, including sociodemographic characteristics, emotional labour, and job burnout. Data were analysed by t test, analysis of variance (ANOVA), Pearson correlation analysis, and hierarchical multiple linear regression. RESULTS: A total of 1,093 village doctors from Shandong Province participated in the study. More than half of the participants were male (62.40%) and were between 41 and 50 years old (53.43%). The total mean score of emotional labour was 3.17 ± 0.67, of which the surface acting (SA) score was 2.28 ± 0.90, and the deep acting (DA) score was 3.91 ± 0.93. There were significant differences in SA according to gender and work content (P < 0.05) and in DA according to gender, age, education level, and work content (P < 0.05). Pearson correlation analysis showed that SA was positively correlated with job burnout (P < 0.001), and DA was negatively correlated with job burnout (P < 0.001). Hierarchical multiple linear regression analysis revealed that 29% of the variance in job burnout is attributable to SA (ß = 0.530, P < 0.001) and DA (ß = -0.154, P < 0.001). CONCLUSION: Village doctors in Shandong Province performed moderate levels of emotional labour during the COVID-19 pandemic. SA had a significant positive effect on job burnout, while DA had a significant negative effect on job burnout among village doctors. Administrators should enhance training on emotional labour for village doctors to play a positive role in alleviating their job burnout.
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Agotamiento Profesional , COVID-19 , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Estudios Transversales , Pandemias , Satisfacción en el Trabajo , COVID-19/epidemiología , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Agotamiento Psicológico , China/epidemiologíaRESUMEN
Objective@#To investigate HPV vaccine hesitation and associated factors among female college students in Weifang, and to provide a suggestions for improving the coverage rate of HPV vaccine among female college students.@*Methods@#The questionnaire of HPV vaccine hesitancy of female college students was designed. By adopting the stratified sampling method, the survey was conducted among female students at one medical university and three nonmedical universities in Weifang. Chi-square test and Logistic regression were used to analyze the influencing factors of vaccine hesitation.@*Results@#Female college students who had high risk perception toward vaccine (OR=4.15, 95%CI=1.55-11.10) and those who were angry about the sideeffects of the vaccine (OR=3.63, 95%CI=1.95-6.75) were hesitate to vaccinate against HPV. Female college students who believed long protection period of HPV vaccine (OR=0.08, 95%CI=0.04-0.17), that women had a high probability of cervical cancer (OR=0.44, 95%CI=0.21-0.90) and that the knowledge of HPV vaccine scored >6 (OR=0.31, 95%CI=0.15-0.67) were more likely to receive HPV vaccine.@*Conclusion@#High risk perception of vaccines and anger at vaccine adverse reactions are important factors affecting HPV vaccines for female college students. Our findings call for strategic role of the state, school-based health education as well as medical professional guidance in lowering HPV vaccination hesitation among fenale college sutdents.
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This paper describes a triplex DNA nanotweezer to specifically capture melamine (MEL). The triplex-forming oligonucleotide (TFO) arm can be switched from the open state to the closed state once MEL binds to the abasic site (AP site) in duplex via the bifacial hydrogen bonding with thymines. Following this nanotweezer operation, the AP site-bound fluorophore is translocated to the terminal triplet to subsequently light up the nanotweezer. The TFO arm is found to be pivotal for permitting the AP site binding. The synergic processes of target competition and fluorophore translocation support a high selectivity for the MEL assay even against the inherent adenosine and the MEL hydrolysis products. Chelerythrine is employed as the fluorescent probe. The detection limit of MEL was estimated to be about 140 nM assuming a signal-to-noise ratio of 3. It was applied to the determination of MEL in spiked milk samples without any separation procedure. Conceivably, this method opens a new avenue towards highly selective triplex-based sensors by making use of other commercially available DNA modifications for recognizing other analytes. Graphical abstract Schematic presentation of a triplex nanotweezer with an open-to-close conversion upon the abasic site binding of melamine. The assay is based on a synergic fluorophore translocation. The corresponding duplex otherwise shows no binding with melamine. Chelerythrine (CHE) with a yellow-green emission peaking at 544 nm is employed as the fluorescent probe.
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Relative to the individual intensity-dependent strategy, the multicolor fluorescence sensor has promise to achieve a high signaling contrast. In this work, we develop a cucurbituril-based supramolecular and multicolor DNA recognition rationale via indicator competition assay (ICA). Alkaloids of coptisine (COP) and palmatine (PAL) are identified as the proof-of-principle indicators with a lighting-up fluorescence upon supramolecular complexation to cucurbit[7]uril (CB[7]). With an introduced abasic site (AP site) as the contestant, DNAs having pyrimidines opposite this site can compete for COP with CB[7] to bring an emission color change from green to yellow brown, while those having purines opposite the AP site do not compete for COP and still have the green emission, indicative of a high selectivity for the multicolor nucleotide transversion recognition. However, because of the relatively weaker binding of PAL with CB[7], the AP site-containing DNA can take away PAL from its CB[7] complex and resultantly bring a blue-to-green emission color change independent of the AP site-opposite nucleotide identity, dissimilar to the remaining blue color for the fully matched DNA without the AP site, suggesting a preferable strategy for the AP site biomarker detection. Our method demonstrates a new way to develop an ICA-based multicolor DNA sensor with the supramolecular cucurbituril complexation to ensure a highly selective performance.
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Alcaloides de Berberina/química , Bioensayo/métodos , Hidrocarburos Aromáticos con Puentes/química , ADN/química , Indicadores y Reactivos/química , Espectrometría de Fluorescencia/métodos , Sitios de Unión , Color , FluorescenciaRESUMEN
Efficient structuring of DNA by small molecules is very crucial in developing DNA-based novel switches with an ideal performance. In this work, we found that inverting only the polarity of the 3' terminal guanine of the thrombin-binding aptamer (3iTBA) totally eradicates the original TBA G-quadruplex (G4) structure in K+. The unstructured 3iTBA can be further refolded upon specifically interacting with small molecules of natural isoquinoline alkaloids (IAs) due to their fruitful binding patterns with variant nucleic acid structures. We identified that 3iTBA can serve as a topology selector for planar IAs. Nitidine (NIT), owing to the planar aromatic ring and coplanar substituents, is the most efficient to restructure the 3iTBA random coil toward the anti-parallel G4 conformation. However, common metal ions can't realize this structuring. The topology selector competency of 3iTBA toward IAs' planarity can be visualized using gold nanoparticles (AuNPs) as the chromogenic readout. Our work expands the G4 repertoire by exploring the polarity inversion regulation and provides a new approach to switch nucleic acid structures toward a small molecule structure-sensitive sensor.
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Molecularly imprinted polymers (MIPs) provide versatile sensor platforms to recognize targets by shape complementarity. However, the rigid structure of the classic MIPs compromises the signal transduction with necessary polymer and target modifications. Herein, we tried to use a flexible DNA that has a perfectly structured folding as the soft molecularly imprinted polymer (SMIP) for a straightforward sensor. As a proof of concept, the guanosine SMIP recognition was achieved by removal of a guanosine from a G-quadruplex-forming sequence (G4). The G4 folding structure with such an apurinic site (AP site) provides a well-defined MIP binding accommodation for guanosine according to the shape complementarity. The guanosine binding at the AP site subsequently leads to a conformation change suitable for remote readout using a G4-specific fluorescent ligand. The G4 sequence and AP site position were optimized for this SMIP behavior. Due to the G4 compact structure and the remaining hydrogen bonding pattern, nucleosides other than guanosine and negatively charged nucleotides exhibit no binding with the AP site, suggesting a high selectivity in the SMIP recognition. The proposed rationale was then convinced by the alkaline phosphatase-catalyzed GMP hydrolysis. Our work will inspire more interest in exploring nucleic acids as the SMIP frameworks due to their variant conformations and well-established molecular engineering.
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Técnicas Biosensibles/métodos , G-Cuádruplex , Guanosina/análisis , Impresión Molecular , Polímeros/química , Fluorescencia , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
Selective nucleotide recognition for biosensor evolution requires rational probe design toward the binding-pattern-susceptible readout but without serious poison in selectivity from the context sequences. In this work, we synthesized a dual-function (trihydroxyphenyl)porphyrin (POH3) to target the abasic site (AP site) in ds-DNA using the trihydroxyphenyl substituent and the tetrapyrrole macrocycle as the recognition unit (RU) and the fluorescent signal unit (SU), respectively. RU and SU are separated from each other but are prototropically allosteric. We found that an appropriate pH favors formation of the nonfluorescent quinine/pyrrole (O-NH) conformer of POH3. However, the complementary hydrogen bonding of RU in O-NH with the target cytosine opposite the AP site switches on the SU fluorescence through prototropic allostery toward the phenol/isopyrrole (OH-N) conformer, while the bases thymine, guanine, and adenine totally silence this allostery, suggesting a superb selectivity in single-nucleotide polymorphism (SNP) analysis. The role of the prototropic allostery in achieving such SNP selectivity is also evidenced using porphyrins with other hydroxyl substituent patterns. Because of the SU separation from RU, SU is not directly involved in the interaction with the AP site, and thus, the turn-on selectivity is also realized for DNA with flanking guanine, the most easily oxidized base in DNA. This tolerance to the flanking base identity has seldom been achieved in previous studies. Additionally, other DNA structures cannot bring this allostery, indicating that the combination recipe of the AP site design and the prototropically allosteric probe will find wide applications in DNA-based sensors.
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Sitio Alostérico , Sondas de ADN/normas , ADN/química , Secuencia de Bases , Conformación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , Porfirinas/química , Sensibilidad y EspecificidadRESUMEN
The rapid identification of biomacromolecule structure that has a specific association with chiral enantiomers especially from natural sources will be helpful in developing enantioselective sensor and in speeding up drug exploitation. Herein, owing to its existence also in living cells, apurinic/apyrimidinic site (AP site) was first engineered into ds-DNA duplex to explore its competence in enantiomer selectivity. An AP site-specific fluorophore was utilized as an enantioselective discrimination probe to develop a straightforward chiral sensor using natural tetrahydropalmatine (L- and D-THP) as enantiomer representatives. We found that only L-THP can efficiently replace the prebound fluorophore to cause a significant fluorescence increase due to its specific binding with the AP site (two orders magnitude higher in affinity than binding with D-THP). The AP site binding specificity of L-THP over D-THP was assessed via intrinsic fluorescence, isothermal titration calorimetry, and DNA stability. The enantioselective performance can be easily tuned by the sequences near the AP site and the number of AP sites. A single AP site provides a perfect binding pocket to differentiate the chiral atom-induced structure discrepancy. We expect that our work will inspire interest in engineering local structures into a ds-DNA duplex for developing novel enantioselective sensors.
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Alcaloides de Berberina/química , ADN/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia , Estereoisomerismo , Temperatura de TransiciónRESUMEN
LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.
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Antioxidantes/farmacocinética , Depuradores de Radicales Libres/farmacología , Radicales Libres/metabolismo , Polifenoles/farmacocinética , Té/química , Animales , Antioxidantes/farmacología , Área Bajo la Curva , Catequina/análogos & derivados , Catequina/farmacocinética , Cromatografía Liquida , Depuradores de Radicales Libres/sangre , Depuradores de Radicales Libres/farmacocinética , Inyecciones Intravenosas , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Polifenoles/sangre , Polifenoles/farmacología , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.