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1.
Nano Lett ; 24(36): 11202-11209, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39207943

RESUMEN

Reverse electron transfer (RET), an abnormal backward flow of electrons from complexes III/IV to II/I of mitochondria, causes the overproduction of a reduced-type CoQ to boost downstream production of mitochondrial superoxide anions that leads to ischemia-reperfusion injury (IRI) to organs. Herein, we studied low-coordinated gold nanoclusters (AuNCs) with abundant oxygen-binding sites to form an electron-demanding trapper that allowed rapid capture of electrons to compensate for the CoQ/CoQH2 imbalance during RET. The AuNCs were composed of only eight gold atoms that formed a Cs-symmetrical configuration with all gold atoms exposed on the edge site. The geometry and atomic configuration enhance oxygen intercalation to attain a d-band electron deficiency in frontier orbitals, forming an unusually high oxidation state for rapid mitochondrial reverse electron capture under a transient imbalance of CoQ/CoQH2 redox cycles. Using hepatic IRI cells/animals, we corroborated that the CoQ-like AuNCs prevent inflammation and liver damage from IRI via recovery of the mitochondrial function.


Asunto(s)
Electrones , Oro , Nanopartículas del Metal , Oxígeno , Oro/química , Nanopartículas del Metal/química , Oxígeno/química , Oxígeno/metabolismo , Transporte de Electrón , Sitios de Unión , Animales , Ubiquinona/química , Ubiquinona/análogos & derivados , Mitocondrias/metabolismo , Daño por Reperfusión/metabolismo , Oxidación-Reducción , Humanos , Ratones
2.
Opt Lett ; 49(12): 3300-3303, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875605

RESUMEN

Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.

3.
Chemistry ; 30(22): e202304114, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38311596

RESUMEN

Lithium-selenium (Li-Se) batteries are promising energy storage devices. However, the long-term durability and high-rate performance of the Se cathode have been limited by significant volume expansion and the troublesome shuttle effect of polyselenides during repeated charging/discharging processes. To revolutionize these issues, we applied a top-down strategy through the in-situ trapping of amorphous Se within bubble-like carbon (BLC) frameworks, which can radically minimize the presence of surface-absorbed Se while enhancing Se loading capacity. This ingenious technique successfully encapsulates all Se species within carbon nanoshells, creating a distinct half-filled core-shell structure known as Se@void@BLC. This in-situ trapping approach ensures the efficient management of Se volume changes during repeated discharge and charge cycles. Moreover, an extraordinary Se loading capacity of up to 65.6 wt% is reached. Using the Se@void@BLC as cathode for Li-Se battery, we achieve a high initial Columbic efficiency of 84.2 %, a high reversible capacity of 585 mAh g-1, and an ultralow capacity decay of only 0.0037 % per cycle during 4000 cycles at 10 A g-1.

4.
Langmuir ; 40(29): 15107-15116, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38989541

RESUMEN

The release of radioactive iodine into the environment poses a significant threat, as it can contaminate soil, water, and food chains, leading to detrimental effects on ecosystems and biodiversity. Hence, employing the adsorption method proves to be a simple yet effective approach for treating radioactive waste. N/O-codoped ultrathin porous biochar, synthesized from casein using NaHCO3 activation, emerges as a potential candidate for adsorption materials. The saturation level of I2 adsorption in 100 mg L-1 iodine-cyclohexane solution is 73 mg·g-1 at 20 min. The density functional theory (DFT) calculations and experiments attribute this phenomenon to the presence of graphite nitrogen (NG) and C-OH groups on the biochar surface. Furthermore, the pseudo-first-order model fits better with the experimental values, suggesting that the adsorption of iodine by the adsorbent is primarily physisorption-based. The Freundlich isotherm is suitable for iodine adsorption of biochar, owing to the abundance of adsorption sites within the porous structure, particularly at the edges, which enhance the adsorption activity. Significantly, the study highlights that NG adsorptive sites exhibit 1.5 times higher adsorption activity compared to C-OH adsorptive sites, underscoring the essential role of NG in iodine adsorption for electron transfer. Overall, these findings underscore the potential of N/O-codoped ultrathin porous biochar in effectively mitigating the presence of radioactive I2, showcasing its promise in addressing environmental challenges associated with radioactive contamination.

5.
Anal Bioanal Chem ; 416(4): 945-957, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38051414

RESUMEN

Histamine causes allergic reactions and can serve as an indicator for assessing food quality. This study designed and developed a dispersive micro solid-phase extraction (D-µSPE) method that combined the advantages of dispersive liquid-liquid extraction and solid-phase extraction (SPE). Molecularly imprinted polymers (MIPs) were employed as the solid phase in the D-µSPE method to extract histamine in wine samples. We used microwave energy to significantly reduce the synthesis time, achieving an 11.1-fold shorter synthesis time compared to the conventional MIP synthetic method. Under optimized D-µSPE conditions, our results showed that the dispersive solvent could effectively increase the adsorption performance of MIPs in wine samples by 97.7%. To improve the sensitivity of histamine detection in gas chromatography-mass spectrometry, we employed the microwave-assisted tandem derivatization method to reuse excess derivatization reagents and reduce energy consumption and reaction time. Calibration curves were constructed for wine samples spiked with 0-400 nmol histamine using the standard addition method, resulting in good linearity with a coefficient of determination of 0.999. The intra- and inter-batch relative standard deviations of the slope and intercept were < 0.7% and < 5.3%, respectively. The limits of quantitation and detection were 0.4 nmol and 0.1 nmol, respectively. The developed method was successfully applied to analyze the histamine concentration in 10 commercial wine samples. In addition, the AGREEprep tool was used to evaluate the greenness performance of the developed method, which obtained a higher score than the other reported methods.


Asunto(s)
Impresión Molecular , Vino , Vino/análisis , Cromatografía Líquida de Alta Presión/métodos , Histamina/análisis , Polímeros/química , Extracción en Fase Sólida/métodos , Impresión Molecular/métodos
6.
Anal Chem ; 95(17): 7006-7013, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37083199

RESUMEN

Herein, an electrochemiluminescence (ECL) and electrochemical (EC) dual-mode biosensor platform with a self-powered DNAzyme walking machine was established for accurate and sensitive detection of miRNA-21. By employing a magnesium ion (Mn2+)-dependent DNAzyme cleavage cycling reaction, the walking machine was built by assembling DNAzyme walking strands and ferrocene (Fc)-labeled substrate strands on the Au nanoparticles and graphitic carbon nitride nanosheet (g-C3N4 NS)-covered electrode. The DNAzyme walking strand was first prohibited by a blocker strand. After the addition of target miRNA-21 and Mn2+, the DNAzyme walker could be activated and produce autonomous movements along the electrode track fueled by Mn2+-dependent DNAzyme-catalyzed substrate cleavage without additional energy supply. Notably, each walking step resulted in the cleavage of a substrate strand and the release of a Fc-labeled DNA strand fragment, allowing us to acquire an extreme ECL signal recovery of g-C3N4 inhibited by Fc. Meanwhile, numerous Fc-labeled DNA fragments escaped from the surface of the electrode, directly producing an obvious decrease in the square wave voltammetry (SWV) signal from Fc on the same sensing platform. This work not only avoided difficultly assembling various signal indicators but also significantly improved the sensitivity through using self-powered DNAzyme-walker amplification. Moreover, the proposed design employed the same reaction to produce two signal output modes, which could eliminate the interference from diverse reactive pathways on the outcome to mutually improve the accuracy. Therefore, the dual-mode miRNA-21 biosensor exhibited wide detection ranges of 100 aM to 100 nM with low detection limits of 54.3 and 78.6 aM by ECL and SWV modes, respectively, which provided an efficient and universal biosensing approach with extensive applications in early disease diagnosis and bioanalysis.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , Nanopartículas del Metal , MicroARNs , Técnicas Biosensibles/métodos , ADN/metabolismo , ADN Catalítico/metabolismo , Técnicas Electroquímicas/métodos , Oro , Límite de Detección , MicroARNs/análisis , Mediciones Luminiscentes
7.
Ecotoxicol Environ Saf ; 264: 115405, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37657390

RESUMEN

Due to the lack of statistical methods, few studies have investigated the spatial autocorrelated distribution in the association between short-term exposure to PM2.5 and mortality and used a statistical manner to explore the association-clustered regions, which play important roles in identifying high-sensitivity/susceptibility regions. The Sichuan Basin (SCB) is one of the most PM2.5-polluted areas, and the extreme economic imbalance may cause considerable spatial heterogeneity and clustering in PM2.5-mortality association. In this work, we used a recently proposed strategy by us to investigate the spatially autocorrelated and clustered association between daily PM2.5 and cardiorespiratory mortality from 2015 to 2019 in 130 counties of the SCB. First, generalized additive models were independently constructed to obtain the county-level association estimations. Then, an estimation-error-based spatial scan statistic was used to detect the association-clustered regions. Third, multivariate conditional meta autoregression was used to obtain the spatially autocorrelated association distribution, based on which the attributable deaths were mapped and their inequality was evaluated using the Gini coefficient and Lorenz curve. Results showed that two significantly association-clustered regions were detected. One is mainly located in the megacity Chengdu where PM2.5 presented a significantly stronger association with no threshold effect at low-level PM2.5 but a threshold at high-level PM2.5. In the other cluster, a threshold effect at low-level PM2.5 but no threshold at high-level PM2.5 were found. The mortality risk at low/middle-level PM2.5 decreased from Chengdu as the center to the surrounding areas. A total of 29,129 (2.0 %) deaths were attributable to the excess PM2.5 exposure. The attributable deaths also decreased from Chengdu as the center to the surrounding areas with Gini coefficients of 0.43 and 0.3 for absolute and relative attributable deaths, respectively. This novel strategy provided a new epidemiological perspective regarding the association and implicated that Chengdu is significantly deserving of more attention regarding PM2.5-related health loss.


Asunto(s)
Material Particulado , China , Análisis por Conglomerados , Material Particulado/efectos adversos
8.
Eur Arch Otorhinolaryngol ; 280(2): 789-795, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36030468

RESUMEN

OBJECTIVES: To assess the performance of DeepSurv, a deep learning-based model in the survival prediction of laryngeal squamous cell carcinoma (LSCC) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: In this large population-based study, we developed and validated a deep learning survival neural network using pathologically diagnosed patients with LSCC from the SEER database between January 2010 and December 2018. Totally 13 variables were included in this network, including patients baseline characteristics, stage, grade, site, tumor extension and treatment details. Based on the total risk score derived from this algorithm, a three-knot restricted cubic spline was plotted to exhibit the difference of survival benefits from two treatment modalities. RESULTS: Totally 6316 patients with LSCC were included in the study, of which 4237 cases diagnosed between 2010 and 2015 were selected as the development cohort, and the rest (2079 cases diagnosed from 2016 to 2018) were the validation cohort. A state-of-the-art deep learning-based model based on 23 features (i.e., 13 variables) was generated, which showed more superior performance in the prediction of overall survival (OS) than the tumor, node, and metastasis (TNM) staging system (C-index for DeepSurv vs TNM staging = 0.71; 95% CI 0.69-0.74 vs 0.61; 95% CI 0.60-0.63). Interestingly, a significantly nonlinear association between total risk score and treatment effectiveness was observed. When the total risk score ranges 0.1-1.5, surgical treatment brought more survival benefits than nonsurgical one for LSCC patients, especially in 70.5% of patients staged III-IV. CONCLUSIONS: The deep learning-based model shows more potential benefits in survival estimation for patients with LSCC, which may potentially serve as an auxiliary approach to provide reliable treatment recommendations.


Asunto(s)
Carcinoma de Células Escamosas , Aprendizaje Profundo , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Pronóstico , Estadificación de Neoplasias , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias Laríngeas/patología
9.
Hu Li Za Zhi ; 70(5): 7-12, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-37740259

RESUMEN

Higher education is becoming increasingly internationalized, and English as a medium of instruction (EMI) for academic content has become commonplace in countries where English is not a native language. However, concerns are growing that the fast-growing trend of EMI lacks sufficient consideration of the related challenges with regard to implementation and impact. As a complex phenomenon, EMI requires increased awareness of its positive and negative implications for teachers and students. The attitudes and perspectives of teachers and students play a significant role in influencing the promotion and effectiveness of EMI teaching. Nevertheless, internationalization is essential for the advancement of nursing education. Therefore, it is imperative to understand the perspectives and challenges faced by teachers and students with regard to EMI and their readiness to embrace it. Therefore, in this article, we first define EMI and describe the reasons for its introduction and then discuss the challenges that teachers and students involved with EMI face in order to provide a reference for nursing education policymakers and academic institutions tasked with EMI development and implementation.


Asunto(s)
Aprendizaje , Estudiantes , Humanos , Lenguaje , Internacionalidad
10.
Mol Pharm ; 19(11): 4299-4310, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36281715

RESUMEN

Weight loss by increasing energy consumption of thermogenic adipocytes to overcome obesity remains a challenge. Herein, we established a transdermal device that was based on the local and temporarily controlled delivery of succinate (SC), a tricarboxylic acid cycle metabolic intermediate to stimulate the thermogenesis pathway of uncoupling protein 1 (UCP1) and accelerate energy dissipation of brown adipose tissue (BAT) under the dorsal interscapular skin, further initiating the consumption of fatty acids by systemic metabolism. SC microneedle patches significantly suppressed weight gain and fat accumulation of remote organs, including liver and peripheral white adipose tissue (WAT) in high-fat diet-induced obese mice. mRNA expression levels of Ucp1 in BAT and other browning markers in WAT were significantly elevated in the mice that were treated with SC microneedle. Thus, the energy dissipation of BAT using UCP1-mediated thermogenesis accelerated by the transdermal delivery of SC may become a potential and effective strategy for preventing obesity.


Asunto(s)
Adipocitos Marrones , Ácido Succínico , Ratones , Animales , Adipocitos Marrones/metabolismo , Metabolismo Energético , Termogénesis/genética , Dieta Alta en Grasa/efectos adversos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratones Endogámicos C57BL
11.
Stat Med ; 41(15): 2939-2956, 2022 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-35347729

RESUMEN

Most spatial models include a spatial weights matrix (W) derived from the first law of geography to adjust the spatial dependence to fulfill the independence assumption. In various fields such as epidemiological and environmental studies, the spatial dependence often shows clustering (or geographic discontinuity) due to natural or social factors. In such cases, adjustment using the first-law-of-geography-based W might be inappropriate and leads to inaccuracy estimations and loss of statistical power. In this work, we propose a series of data-driven Ws (DDWs) built following the spatial pattern identified by the scan statistic, which can be easily carried out using existing tools such as SaTScan software. The DDWs take both the clustering (or discontinuous) and the intuitive first-law-of-geographic-based spatial dependence into consideration. Aiming at two common purposes in epidemiology studies (ie, estimating the effect value of explanatory variable X and estimating the risk of each spatial unit in disease mapping), the common spatial autoregressive models and the Leroux-prior-based conditional autoregressive (CAR) models were selected to evaluate performance of DDWs, respectively. Both simulation and case studies show that our DDWs achieve considerably better performance than the classic W in datasets with clustering (or discontinuous) spatial dependence. Furthermore, the latest published density-based spatial clustering models, aiming at dealing with such clustering (or discontinuity) spatial dependence in disease mapping, were also compared as references. The DDWs, incorporated into the CAR models, still show considerable advantage, especially in the datasets for common diseases.


Asunto(s)
Programas Informáticos , Análisis por Conglomerados , Simulación por Computador , Geografía , Humanos , Análisis Espacial
12.
BMC Infect Dis ; 22(1): 878, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36418982

RESUMEN

BACKGROUND: Obstetrical infection is one of the causes of maternal death and a difficult problem for many clinicians. Changes in the demographic and obstetric background of pregnant women following the Universal Two-Child Policy may have an impact on some fertility phenomena. And with the increase in the number of deliveries, the limited medical resources become more scarce. How will China's health system quickly adapt to the growing needs and expectations for maternal health and ensure the provision of qualified and accessible medical services? In addition, what social support measures should be provided to reduce preventable obstetric complications? Given the relatively low per capita share of medical resources in China, how should China deal with the impact of the Universal Two-Child Policy? Therefore, more studies based on the change of fertility policy are needed. We try to analyze the epidemiological characteristics and risk factors of obstetric infection before and after the Universal Two-Child Policy, with a view to providing reference for the prevention and control of obstetric infection in regions after the change of fertility policy, and also hope to make corresponding contributions to the solution of the above problems through relevant studies. METHODS: The subjects of the survey were 268,311 pregnant women from Hebei Province Maternal Near Miss Surveillance System (HBMNMSS) of Hebei Women and Children's Health Center from January 1, 2013 to December 31, 2017. We analyzed the region, time and population distribution characteristics of obstetric infection, compared the epidemiological factors of obstetric infection before and after the Universal Two-Child Policy, and analyzed the relevant risk factors of obstetric infection. RESULTS: The incidence of obstetric infection increased nearly twice after the Universal Two-Child Policy. The incidence of obstetric infection was highest in Chengde (1.9%), a city with a northward geographical distribution, Baoding (1.6%), Cangzhou (1.5%) followed; The higher the hospital grade, the higher the incidence; The incidence of obstetric infections in hospitals at all levels has increased; The age of onset before the Universal Two-Child Policy was (27.82 ± 5.047) years old, and the age after the Universal Two-Child Policy was (28.97 ± 4.880) years old; The incidence of obstetric infections is higher in winter. The rate of abortion-related infection (increased from 0.61 to 1.65%) and the rate of pregnant women with high school education (increased from 0.35 to 0.74%) increased significantly. The results of multivariate Logistic regression analysis after the Universal Two-Child Policy showed that anemia (OR = 1.249, 95%CI: 1.071-1.458), chronic hypertension (OR = 1.934, 95%CI: 1.375-2.722), mild preeclampsia (OR = 2.103, 95%CI: 1.323-3.344) and severe preeclampsia (OR = 2.228, 95%CI: 1.703-2.916) were independent risk factors for obstetric infection. Gestational age ≥ 37 weeks was a protective factor. CONCLUSION: After the Universal Two-Child Policy, the prevention and control of obstetric infections should be strengthened, especially for abortion-related infections and elderly maternal with obstetric complications and complication in high-grade hospitals in winter. Educational background is also one of the factors that should be considered in the prevention of obstetric sensation. Prolonging gestational age is helpful to reduce the incidence of obstetric infection.


Asunto(s)
Preeclampsia , Embarazo , Anciano , Femenino , Humanos , Adulto Joven , Adulto , Lactante , Estudios Retrospectivos , Factores de Riesgo , Políticas , China/epidemiología
13.
Anal Bioanal Chem ; 414(16): 4717-4726, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35589864

RESUMEN

A new fluorescent probe TPE-GHK was synthesized containing a tetrastyrene (TPE) derivative as fluorophore and classical tripeptide (Gly-His-Lys-NH2) as a receptor based on the aggregation-induced emission (AIE) mechanism. TPE-GHK displayed high selectivity and rapid fluorescent "turn-on" response to Hg2+ among other competitive metal ions. The 2:1 complex binding mechanism of TPE-GHK toward Hg2+ was verified by fluorometric titration, Job's plots, and ESI-HRMS spectra. The fluorescent emission showed a good linear response in the range of 0-1.0 µM with the low detection limit of 28.6 nM. Meanwhile, TPE-GHK exhibited the excellent biocompatibility and low toxicity and was successfully applied in monitoring Hg2+ in living CAKI 2 cells, which demonstrated its potential application in environment and biological science. More importantly, TPE-GHK could be used to detect Hg2+ in two real water samples and also was successfully designed as test strips.


Asunto(s)
Colorantes Fluorescentes , Mercurio , Iones , Péptidos , Espectrometría de Fluorescencia , Agua
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 109-113, 2022 Jan.
Artículo en Zh | MEDLINE | ID: mdl-35048609

RESUMEN

OBJECTIVE: To investigate the relationship between sleep duration and depressive symptoms in older people in China, and to explore whether there are gender differences in the relationship. METHODS: Accessing the data from China Health and Retirement Longitudinal Study (CHARLS) for 2015 and 2018, we covered in the study a total of 2898 respondents, including 1684 males (58.1%) and 1214 females (41.9%). The 10-item form of Center for Epidemiological Studies Depression Scale (CES-D) was used to measure the depressive symptoms of the older people. The effects of sleep duration on depressive symptoms of older people in China were analyzed with the logistic model. Based on the depressive and non-depressive subgroups in 2018, the differences of health factor variables and sleep duration between 2015 and 2018 were studied. Adjustments were made for health factors presenting statistical differences in 2018 to further explore the stability of the analysis results. RESULTS: Among the female older people, those with short sleep duration and those with long sleep duration had increased risks of developing depressive symptoms [odds ratio ( OR)=1.815, 95% confidence interval ( CI): 1.357-2.429 and OR=1.364, 95% CI: 1.001-1.854, respectively] in comparison to those with normal sleep duration. Among the male older people, no connection was identified between sleep duration and risks for depressive symptoms ( P>0.05). Residing in rural areas, suffering from chronic diseases and having limited ability for Instrumental Activities of Daily Living (IADL) were risk factors for developing depressive symptoms ( P<0.05). The sleep duration for 2015 and that for 2018 were found to be statistically different in the depressive older people ( P<0.001), but no no statistically significant difference was found between the sleep duration for 2015 and that for 2018 among the non-depressive older people. Findings for chronic diseases and IADL for 2015 and those for 2018 were statistically different in the depressive older population ( P<0.001). In the non-depressive older population, findings for chronic diseases, IADL and tobacco smoking status for 2015 and those for 2018 showed statistical difference ( P<0.05). Further sensitivity analysis showed that in the female older population, short sleep duration increased the risks for depressive symptoms ( OR=1.819, 95% CI: 1.356-2.440, P<0.001), while long sleep duration did not affect the risks for depressive symptoms. In the male older population, short or long sleep duration were not associated with the risks for depressive symptoms. CONCLUSION: The association between sleep duration and the risks for depressive symptoms was different for men and women. For the female older population, the possibility of depressive symptoms should be considered for those with short or long sleep duration. For the male older population, short or long sleep duration had little impact on the risks for depressive symptoms.


Asunto(s)
Actividades Cotidianas , Depresión , Anciano , China/epidemiología , Estudios de Cohortes , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Sueño
15.
Glycobiology ; 31(9): 1230-1238, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34132764

RESUMEN

Glycosylation is important for biological functions of proteins and greatly affected by diseases. Exploring the glycosylation profile of the protein-specific glycosylation and/or the site-specific glycosylation may help understand disease etiology, differentiate diseases and ultimately develop therapeutics. Patients with multiple sclerosis (MS) and patients with neuromyelitis optica spectrum disorder (NMOSD) are sometimes difficult to differentiate due to the similarity in their clinical symptoms. The disease-related glycosylation profiles of MS and NMOSD have not yet been well studied. Here, we analyzed site-specific glycan profiles of serum proteins of these patients by using a recently developed mass spectrometry technique. A total of 286 glycopeptides from 49 serum glycoproteins were quantified and compared between healthy controls (n = 6), remitting MS (n = 45) and remitting NMOSD (n = 23) patients. Significant differences in the levels of site-specific N-glycans on inflammation-associated components [IgM, IgG1, IgG2, complement components 8b (CO8B) and attractin], central nerve system-damage-related serum proteins [apolipoprotein D (APOD), alpha-1-antitrypsin, plasma kallikrein and ADAMTS-like protein 3] were observed among three study groups. We furthered demonstrated that site-specific N-glycans on APOD on site 98, CO8B on sites 243 and 553 are potential markers to differentiate MS from NMOSD with an area under receiver operating curve value > 0.75. All these observations indicate that remitting MS or NMOSD patients possess a unique disease-associated glyco-signature in their serum proteins. We conclude that monitoring one's serum protein glycan profile using this high-throughput analysis may provide an additional diagnostic criterion for differentiating diseases, monitoring disease status and estimating response-to-treatment effect.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Biomarcadores , Humanos , Inmunoglobulina G , Esclerosis Múltiple/diagnóstico , Neuromielitis Óptica/diagnóstico , Proyectos Piloto
16.
J Org Chem ; 86(4): 3648-3655, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33372518

RESUMEN

Three-substituted 4H-quinolizin-4-ones were obtained via a facile method with good selectivity and high efficiency. On the basis of alkyne substrate control, the mild and cost-efficient reaction has a broad substrate scope (20 examples, up to 93% yield) and is also easy to scale up. Active sites on the products allow for further modifications. The alkyne substrate control strategy could be further extended to achieve more complex three-substituted 4H-quinolizin-4-one skeletons.


Asunto(s)
Alquinos , Estructura Molecular
17.
J Mol Cell Cardiol ; 144: 119-126, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32470469

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) severity greatly varies among patients even with the same HCM gene mutations. This variation is largely regulated by modifier gene(s), which, however, remain largely unknown. The current study is aimed to identify modifier genes using BXD strains, a large murine genetic reference population (GRP) derived from crosses between C57BL/6 J (B6) and D2 DBA/2 J (D2) mice. D2 mice natualy carrythe genetic basis and phenotypes of HCM. METHODS: Myocardial hypertrophy, the major phenotype of HCM, was determined by cardiomyocyte size on cardiac sections in 30 BXD strains, and their parental B6 and D2 strains and morphometric analysis was performed. Quantitative Trait Locus (QTL) mapping for cardiomyocyte sizes was conducted with WebQTL in GeneNetwork. Correlation of cardiomyocyte size and cardiac gene expression in BXDs accessed from GeneNetwork were evaluated. QTL candidate genes associated with cardiomyocyte sizes were prioritized based on the score system. RESULTS: Cardiomyocyte size varied significantly among BXD strains. Interval mapping on cardiomyocyte size data showed a significant QTL on chromosome (Chr) 2 at 66- 73.5 Mb and a suggestive QTL on Chr 5 at 20.9-39.7 Mb. Further score system revealed a high QTL score for Xirp2 in Chr 2. Xirp2 encodes xin actin-binding repeat containing 2, which is highly expressed in cardiac tissue and associate with cardiomyopathy and heart failure. In Chr5 QTL, Nos3, encoding nitric oxide synthase 3, received the highest score, which is significantly correlated with cardiomyocyte size. CONCLUSION: These results indicate that Xirp2 and Nos3 serve as novel candidate modifier genes for myocardial hypertrophy in HCM. These candidate genes will be validated in our future studies.


Asunto(s)
Cardiomiopatía Hipertrófica/etiología , Genes Modificadores , Predisposición Genética a la Enfermedad , Animales , Biomarcadores , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/metabolismo , Mapeo Cromosómico , Biología Computacional/métodos , Bases de Datos Genéticas , Ecocardiografía , Regulación de la Expresión Génica , Estudios de Asociación Genética , Patrón de Herencia , Ratones , Miocitos Cardíacos/metabolismo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo
18.
Artículo en Inglés | MEDLINE | ID: mdl-31778997

RESUMEN

BACKGROUND: Interleukin-33 (IL-33) is reported to be involved in Th2-skewed eosinophilic inflammation. A recent study also found that IL-33 exerted opposite effects on Th17 response in different diseases. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (NPs) was not explored. OBJECTIVES: The purpose of this study was to investigate the expression and function of IL-33 in chronic rhinosinusitis with NPs. MATERIALS AND METHODS: NP tissues from 60 NP patients and normal tissues of the inferior turbinate from 20 controls were sampled in operation. Immunochemistry was performed to identify eosinophilic or non-eosinophilic NPs. The expressions of IL-33 and Th1/2/17 cytokines were compared between different subtypes of NPs. The effect of IL-33 on Th response was detected in dispersed nasal polyp cells (DNPCs), and the signaling pathways involved in the process were detected using Western blot. RESULTS: The concentration of IL-33 was significantly elevated in both eosinophilic and non-eosinophilic NPs compared with controls. By in vitro study, we found that IL-33 can induce IL-4 and IL-5 production from eosinophilic DNPCs through the PI3K/AKT pathway, whereas IL-33 can induce IL-17 production from non-eosinophilic DNPCs through the ERK1/2 pathway. CONCLUSION: IL-33 is involved in Th2/Th17 response in NPs. Our study suggests that different types of NPs need a different treatment target.


Asunto(s)
Eosinofilia , Interleucina-33 , Pólipos Nasales , Células Th17 , Células Th2 , Citocinas/metabolismo , Humanos , Inflamación , Pólipos Nasales/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Rinitis/metabolismo , Transducción de Señal , Sinusitis/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo
19.
Int J Mol Sci ; 21(5)2020 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-32131445

RESUMEN

The progress of wound regeneration relies on inflammation management, while neovascular angiogenesis is a critical aspect of wound healing. In this study, the bioactive core and corona synergism of quantized gold (QG) were developed to simultaneously address these complicated issues, combining the abilities to eliminate endotoxins and provide oxygen. The QG was constructed from ultrasmall nanogold and a loosely packed amine-based corona via a simple process, but it could nonetheless eliminate endotoxins (a vital factor in inflammation also called lipopolysaccharides) and provide oxygen in situ for the remodeling of wound sites. Even while capturing endotoxins through electrostatic interactions, the catalytic active sites inside the nanogold could maintain its surface accessibility to automatically transform the overexpressed hydrogen peroxide in hypoxic wound regions into oxygen. Since the inflammatory stage is an essential stage of wound healing, the provision of endotoxin clearance by the outer organic corona of the QG could slow inflammation in a way that subsequently promoted two other important stages of wound bed healing, namely proliferation and remodeling. Relatedly, the efficacy of two forms of the QG, a liquid form and a dressing form, was demonstrated at wound sites in this study, with both forms promoting the development of granulation, including angiogenesis and collagen deposition. Thus, the simply fabricated dual function nanocomposite presented herein not only offers reduced batch-to-batch variation but also increased options for homecare treatments.


Asunto(s)
Antiinflamatorios/farmacología , Depuradores de Radicales Libres/farmacología , Oro/química , Nanofibras/química , Cicatrización de Heridas , Aminas/química , Animales , Antiinflamatorios/química , Vendajes , Hipoxia de la Célula , Células Cultivadas , Endotoxinas/toxicidad , Fibroblastos/efectos de los fármacos , Depuradores de Radicales Libres/química , Humanos , Peróxido de Hidrógeno/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Oxígeno/metabolismo
20.
Molecules ; 25(20)2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33053784

RESUMEN

This study explores the amounts of common chemical ultraviolet (UV) filters (i.e., avobenzone, bemotrizinol, ethylhexyl triazone, octocrylene, and octyl methoxycinnamate) in cosmetics and the human stratum corneum. An ultrasound-vortex-assisted dispersive liquid-liquid microextraction (US-VA-DLLME) method with a high-performance liquid chromatography-diode array detector was used to analyze UV filters. A bio-derived solvent (i.e., anisole) was used as the extractant in the US-VA-DLLME procedure, along with methanol as the dispersant, a vortexing time of 4 min, and ultrasonication for 3 min. The mass-transfer rate of the extraction process was enhanced due to vortex-ultrasound combination. Various C18 end-capped columns were used to investigate the separation characteristics of the UV filters, with XBridge BEH or CORTECS selected as the separation column. Calibration curves were constructed in the 0.05-5 µg/mL (all filters except octocrylene) and 0.1-10 µg/mL (octocrylene) ranges, and excellent analytical linearities with coefficients of determination (r2) above 0.998. The developed method was successfully used to analyze sunscreen. Moreover, experiments were designed to simulate the sunscreen-usage habits of consumers, and the cup method was used to extract UV filters from the human stratum corneum. The results suggest that a makeup remover should be employed to remove water-in-oil sunscreens from skin.


Asunto(s)
Cosméticos , Epidermis/química , Microextracción en Fase Líquida/métodos , Ondas Ultrasónicas , Cromatografía Líquida de Alta Presión , Humanos , Solventes
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