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1.
Food Chem ; 367: 130754, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34384983

RESUMO

N-acetylneuraminic acid (Neu5Ac) is widely spread in many biologically significant glycans of mammals, commonly as a terminal α-glycoside. It is of great significance to develop analytical techniques for detection of Neu5Ac. Herein, a high-sensitive fluorescent biosensor for Neu5Ac has been developed based on FRET between CdSe/ZnS quantum dots (QDs) and BHQ2, as well as exonuclease III (Exo III)-assisted recycling amplification strategy. Employing the specially designed three-level FRET systems and fluorescent signal recovery mechanism, together with five-step recycling signal amplification chain reactions, an ultralow detection limit of 24 fM was achieved. Meanwhile, good linear response ranges within 0.2-12.5 pM and 12.5-1000 pM were founded. The assay has excellent performance in real sample detection, and thus offers great potential for detection of sialic acids modified glycans/lipids in the fields of medical diagnosis and food testing.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Compostos de Selênio , Animais , DNA , Exodesoxirribonucleases , Transferência Ressonante de Energia de Fluorescência , Limite de Detecção , Ácidos Siálicos , Sulfetos , Compostos de Zinco
2.
J Org Chem ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34644085

RESUMO

Employing the methyl ß-perfluoroalkylpropionate as the Michael acceptor, an efficient approach for the synthesis of perfluoroalkylated pyrrolidine-fused coumarins has been achieved. A tandem reaction involving [3 + 2] cycloaddition and intramolecular transesterification was proposed for the mechanism. The enhanced electrophilicity resulting from the strong electron-withdrawing ability of the perfluoroalkyl group was crucial for this tandem reaction.

3.
Oncoimmunology ; 10(1): 1976953, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595059

RESUMO

Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, represented by progression-free survival (PFS) and overall survival (OS), of combined chemotherapy and adoptive cellular therapy (ACT) in advanced colon cancer patients. Plasma was collected from colorectal cancer patients (CRC) treated with either chemotherapy alone (oxaliplatin and capecitabine) (XELOX CT alone group, n = 19), or ACT with a mixed dendritic cell/cytokine-induced killer cell product (DC-CIK) + XELOX (ICT group, n = 20). Circulating microbiota analysis was performed by PCR amplification and next-generation sequencing of variable regions V3~V4 of bacterial 16S rRNA genes. The association of the blood microbial diversity with clinical response to the therapy as measured by RECIST1.1 and OS was evaluated. The baseline Chao index of blood microbial diversity predicted prolonged PFS and OS of DC/CIK immunotherapy. More diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified among responders to DC/CIK compared with non-responders. The plasma bacterial DNA copy number is inversely correlated with the CD3-/CD16+/CD56+ NK cells in circulation and decreased following DC-CIK; however, the Chao index of plasma microbiota significantly increased after administration of the DC-CIK product and this subsequent change was correlated with the number of CD3-/CD16+/CD56+ and CD8+/CD28+ cells infused. The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK. Cellular immunotherapy can affect the plasma microbiota's diversity in a manner favorable to clinical responses.


Assuntos
Neoplasias Colorretais , Microbiota , Neoplasias Colorretais/terapia , Células Dendríticas , Humanos , Imunoterapia , Imunoterapia Adotiva , RNA Ribossômico 16S/genética , Linfócitos T
4.
Microbiol Spectr ; : e0135221, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643438

RESUMO

The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.

5.
Eur J Nutr ; 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657185

RESUMO

PURPOSE: To evaluate the effects of the association between first trimester vitamin D (VitD) concentrations and increased prepregnancy body mass index (BMI) on early fetal growth restriction (FGR). METHODS: This retrospective cohort study included 15,651 women with singleton pregnancy who delivered at the International Peace Maternity and Child Health Hospital between January 2015 and November 2016. Women were classified in two groups based on their serum 25(OH)D vitamin levels status: VitD sufficient (SUFF) group and VitD insufficient or deficient (INSUFF/DEF). The cut-off point for vit D concentration was 50.00 nmol/L. Comparisons were made between women with normal prepregnancy body weight (BMI 18.5-23.9 kg/m2) and overweight and obese (OWO) women (BMI > 24.0 kg/m2). Early FGR was defined as first-trimester gestational age-adjusted crown-rump length (CRL) in the lowest 20th centile of the population. Multivariate logistic regression was used to evaluate the association between maternal serum 25(OH)D levels and prepregnancy BMI with first trimester CRL and early FGR. RESULTS: In VitD INSUFF/DEF group, the first trimester CRL was decreased (P = 0.005), and the risk of early FGR was increased by 13% (95% CI 1.04-1.24, P = 0.004) compared to the VitD SUFF group. In OWO group, the first trimester CRL was also significantly decreased (P < 0.0001), and the risk of early FGR was significantly increased by 58% (95% CI 1.40-1.78, P < 0.001) compared with normal weight group. Furthermore, there was a significant combined effect of maternal VitD concentrations and OWO on CRL (P for interaction = 0.02) and the risk of early FGR (P for interaction = 0.07). CONCLUSION: Sufficient first trimester serum 25(OH)D concentration was a protective factor for early fetal growth, especially among OWO mothers. Chinese Clinical Trial Registry (Registration number: ChiCTR1900027447 with date of registration on November 13, 2019-retrospectively registered).

6.
Molecules ; 26(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684689

RESUMO

There is an ever-increasing trend toward bendable and high-energy-density electrochemical storage devices with high strength to fulfil the rapid development of flexible electronics, but they remain a great challenge to be realised by the traditional slurry-casting fabrication processes. To overcome these issues, herein, a facile strategy was proposed to design integrating an electrode with flexible, high capacity, and high tensile strength nanosheets with interconnected copper micro-fibre as a collector, loaded with a novel hierarchical SnO2 nanoarchitecture, which were assembled into core-shell architecture, with a 1D micro-fibre core and 2D nanosheets shell. When applied as anode materials for LIBs, the resultant novel electrode delivers a large reversible specific capacity of 637.2 mAh g-1 at a high rate of 1C. Such superior capacity may benefit from rational design based on structural engineering to boost synergistic effects of the integrated electrode. The outer shell with the ultrathin 2D nanoarchitecture blocks can provide favourable Li+ lateral intercalation lengths and more beneficial transport routes for electrolyte ions, with sufficient void space among the nanosheets to buffer the volume expansion. Furthermore, the interconnected 1D micro-fibre core with outstanding metallic conductivity can offer an efficient electron transport pathway along axial orientation to shorten electron transport. More importantly, the metal's remarkable flexibility and high tensile strength provide the hybrid integrated electrode with strong bending and stretchability relative to sintered carbon or graphene hosts. The presented strategy demonstrates that this rational nanoarchitecture design based on integrated engineering is an effective route to maintain the structural stability of electrodes in flexible LIBs.

7.
Front Oncol ; 11: 705455, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646764

RESUMO

Background: Glioblastoma (GBM) is the most common primary intracranial tumor and originates from the small pool of adult neural stem and progenitor cells (NSPCs). According to the World Health Organization (WHO) classification of brain tumors, gliomas are classified into grades I-IV, and GBM is defined as the highest grade (IV). GBM can be disseminated by cerebrospinal fluid (CSF), but extracranial metastasis is rare. Additionally, the pathway and mechanism involved remain unclear. Case Presentation: We report a rare case of left temporal lobe GBM with multiple bone metastases and soft tissue metastasis. This 49-year-old right-handed man who was diagnosed with GBM underwent surgery on May 9, 2017, followed by radiochemotherapy in June 2017. On August 13, 2019, local relapse was found. Then, the patient received a second surgery but not radiochemotherapy. In November 2019, the patient was reported to be suffering from low back pain for nearly 1 month. On December 6, 2019, magnetic resonance imaging (MRI) of the thoracolumbar vertebrae and abdominal computed tomography (CT) confirmed metastases on the ninth posterior rib on the right, the third anterior rib on the left, and the T7 and T10 vertebrae and their appendages. CT-guided rib space-occupying puncture biopsy was performed, and GBM was identified by pathology. Conclusion: We should pay attention to extracranial metastasis of GBM. Timely detection and early treatment improve overall quality of patients' life. The extracranial metastasis in this patient may have occurred through the spinal nerve root or intercostal nerve. Further clinical observations are required to clarify the pathway and mechanism involved.

8.
BMC Pregnancy Childbirth ; 21(1): 688, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627184

RESUMO

BACKGROUND: Fetal growth velocity standards have yet to be established for the Chinese population. This study aimed to establish such standards suitable for the Chinese population. METHODS: We performed a multicenter, population-based longitudinal cohort study including 9075 low-risk singleton pregnant women. Data were collected from the clinical records of 24 hospitals in 18 provinces of China. Demographic characteristics, reproductive history, fetal ultrasound measurements, and perinatal outcome data were collected. The fetal ultrasound measurements included biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL). We used linear mixed models with cubic splines to model the trajectory of four ultrasound parameters and estimate fetal weight. Fetal growth velocity was determined by calculating the first derivative of fetal size curves. We also used logistic regression to estimate the association between fetal growth velocities in the bottom 10th percentile and adverse perinatal outcomes. RESULTS: Fetal growth velocity was not consistent over time or among individuals. The estimated fetal weight (EFW) steadily increased beginning at 12 gestational weeks and peaked at 35 gestational weeks. The maximum velocity was 211.71 g/week, and there was a steady decrease in velocity from 35 to 40 gestational weeks. The four ultrasound measurements increased in the early second trimester; BPD and HC peaked at 13 gestational weeks, AC at 14 gestational weeks, and FDL at 15 gestational weeks. BPD and HC also increased from 19 to 24 and 19 to 21 gestational weeks, respectively. EFW velocity in the bottom 10th percentile indicated higher risks of neonatal complications (odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.79-2.78) and preterm birth < 37 weeks (OR = 3.68, 95% CI: 2.64-5.14). Sensitivity analyses showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse pregnancy outcomes for appropriate-for-gestational age neonates. CONCLUSIONS: We established fetal growth velocity curves for the Chinese population based on real-world clinical data. Our findings demonstrated that Chinese fetal growth patterns are somewhat different from those of other populations. Fetal growth velocity could provide more information to understand the risk of adverse perinatal outcomes, especially for appropriate-for-gestational age neonates.

10.
China CDC Wkly ; 3(33): 702-705, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34594972

RESUMO

What is already known on this topic?: The norovirus has often caused outbreaks in schools and kindergartens, but minimal research has been performed on environmental contamination during norovirus outbreaks in schools and kindergartens. What is added by this report?: This report conveys the norovirus detection rates and viral loads in different environmental sites in 45 norovirus outbreaks in Beijing Municipality from October to December 2020. What are the implications for public health practice?: The evidence presented here can instruct professionals and the public to sample and disinfect key locations of the environment purposefully when responding to norovirus outbreaks.

11.
Biomed Pharmacother ; 144: 112338, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34678728

RESUMO

Chloroethylnitrosoureas (CENUs) are an important family of chemotherapies in clinical treatment of cancers, which exert antitumor activity by inducing the formation of DNA interstrand crosslinks (dG-dC ICLs). However, the drug resistance mediated by O6-alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability largely decrease the antitumor efficacy of CENUs. In this study, we synthesized an azobenzene-based hypoxia-activated combi-nitrosourea prodrug, AzoBGNU, and evaluated its hypoxic selectivity and antitumor activity. The prodrug was composed of a CENU pharmacophore and an O6-benzylguanine (O6-BG) analog moiety masked by a N,N-dimethyl-4-(phenyldiazenyl)aniline segment as a hypoxia-activated trigger, which was designed to be selectively reduced via azo bond break in hypoxic tumor microenvironment, accompanied with releasing of an O6-BG analog to inhibit AGT and a chloroethylating agent to induce dG-dC ICLs. AzoBGNU exhibited significantly increased cytotoxicity and apoptosis-inducing ability toward DU145 cells under hypoxia compared with normoxia, indicating the hypoxia-responsiveness as expected. Predominant higher cytotoxicity was observed in the cells treated by AzoBGNU than those by traditional CENU chemotherapy ACNU and its combination with O6-BG. The levels of dG-dC ICLs in DU145 cells induced by AzoBGNU was remarkably enhanced under hypoxia, which was approximately 6-fold higher than those in the AzoBGNU-treated groups under normoxia and those in the ACNU-treated groups. The results demonstrated that azobenzene-based combi-nitrosourea prodrug possessed desirable tumor-hypoxia targeting ability and eliminated chemoresistance compared with the conventional CENUs.

12.
Rev. bras. med. esporte ; 27(3): 257-261, July-Sept. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1288584

RESUMO

ABSTRACT Introduction Study the relationship between the metabolic enzyme and the biological image, filtered by an adaptive filtering algorithm. Objective The research aims to In this study, human metabolic enzymes were evaluated by electrocardiogram and electromyogram images, and an adaptive filtering algorithm removed the noises in the images. Methods The electrocardiogram and electromyogram images at different periods were obtained, and the calculation method and application scope of the adaptive filtering algorithm were analysed. Results Adaptive filter was designed by the combination of adaptive filtering algorithm and dynamic information. Therefore, the artefact of the image was removed. Conclusions The adaptive filtering algorithm can effectively remove the noise or artefact in electrocardiogram and electromyogram signals. The optimal image information can be obtained. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Introdução Estudar a relação entre a enzima metabólica e a imagem biológica filtrada por um algoritmo de filtragem adaptativa. Objetivo O objetivo da pesquisa, neste estudo, é avaliar enzimas metabólicas humanas por meio de imagens de eletrocardiograma e eletromiograma, sendo que um algoritmo de filtragem adaptativa eliminou o ruído nas imagens. Métodos Imagens de eletrocardiograma e eletromiograma foram obtidas em diferentes períodos e foram analisados o método de cálculo e o escopo de aplicação do algoritmo de filtragem adaptativa. Resultados a filtragem adaptativa foi projetada combinando um algoritmo de filtragem adaptativa e informações dinâmicas. Portanto, o artefato foi removido da imagem. Conclusões O algoritmo de filtragem adaptativa pode efetivamente eliminar ruído ou artefato em sinais de eletrocardiograma e eletromiograma. Informações de imagem ideais podem ser obtidas. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.


RESUMEN Introducción Estudiar la relación entre la enzima metabólica y la imagen biológica, filtrada por un algoritmo de filtrado adaptativo. Objetivo La investigación tiene como objetivo, en este estudio, evaluar las enzimas metabólicas humanas mediante imágenes de electrocardiograma y electromiograma, y un algoritmo de filtrado adaptativo eliminó los ruidos en las imágenes. Métodos Se obtuvieron las imágenes de electrocardiograma y electromiograma en diferentes períodos y se analizó el método de cálculo y alcance de aplicación del algoritmo de filtrado adaptativo. Resultados El filtrado adaptativo se diseñó mediante la combinación de un algoritmo de filtrado adaptativo e información dinámica. Por lo tanto, se eliminó el artefacto de la imagen. Conclusiones El algoritmo de filtrado adaptativo puede eliminar eficazmente el ruido o artefacto en las señales de electrocardiograma y electromiograma. Se puede obtener la información de imagen óptima. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

13.
Rev. bras. med. esporte ; 27(3): 249-252, July-Sept. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1288588

RESUMO

ABSTRACT Introduction High-intensity rehabilitation training will produce exercise fatigue. Objective A backpropagation (BP) network neural algorithm is proposed to predict sports fatigue based on electromyography (EMG) signal images. Methods The principal component analysis algorithm is used to reduce the dimension of EMG signal features. The knee joint angle is estimated by the regularized over-limit learning machine algorithm and the BP neural network algorithm. Results The RMSE value of the regularized over-limit learning machine algorithm is lower than that of the BP neural network algorithm. At the same time, the ρ value of the regularized over-limit learning machine algorithm is closer to 1, indicating its higher accuracy. Conclusions The model training time of the regularized over-limit learning machine algorithm has been greatly reduced, which improves efficiency. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Introdução O treinamento de reabilitação de alta intensidade produzirá fadiga ao exercício. Objetivo Um algoritmo neural de backpropagation network (BP) é proposto para prever a fadiga esportiva com base em imagens de sinais de eletromiografia (EMG). Métodos O algoritmo de análise de componente principal é usado para reduzir a dimensão das características do sinal EMG. O ângulo da articulação do joelho é estimado usando o algoritmo de aprendizado de máquina de limite regularizado acima e o algoritmo de rede neural BP. Resultados o valor RMSE do algoritmo de aprendizado de máquina acima do limite regularizado é menor que o do algoritmo de rede neural BP. Ao mesmo tempo, o valor de ρ do algoritmo de aprendizado de máquina acima do limite regularizado está próximo de 1, indicando sua maior precisão. Conclusões O tempo de treinamento do modelo de algoritmo de aprendizado de máquina acima do limite regularizado foi bastante reduzido, o que melhora a eficiência. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.


RESUMEN Introducción El entrenamiento de rehabilitación de alta intensidad producirá fatiga por ejercicio. Objetivo Se propone un algoritmo neuronal de red de retropropagación (BP) para predecir la fatiga deportiva basándose en imágenes de señales de electromiografía (EMG). Métodos El algoritmo de análisis de componentes principales se utiliza para reducir la dimensión de las características de la señal EMG. El ángulo de la articulación de la rodilla se estima mediante el algoritmo de la máquina de aprendizaje por encima del límite regularizado y el algoritmo de red neuronal BP. Resultados el valor de RMSE del algoritmo de la máquina de aprendizaje por encima del límite regularizado es menor que el del algoritmo de red neuronal de BP. Al mismo tiempo, el valor ρ del algoritmo de la máquina de aprendizaje por encima del límite regularizado está más cerca de 1, lo que indica su mayor precisión. Conclusiones El tiempo de entrenamiento del modelo del algoritmo de la máquina de aprendizaje por encima del límite regularizado se ha reducido en gran medida, lo que mejora la eficiencia. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

14.
Nanoscale ; 13(35): 15067-15073, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533554

RESUMO

The most efficient approach for cancer identification and monitoring is the detection of cancer-associated protein biomarkers but an accurate diagnosis requires multiple analyses. Glycosylation profiling can provide important biological information since different glycoforms are involved in malignant transformation. Here, a near-infrared (NIR) light activated fluorescence resonance energy transfer (FRET) strategy for the efficient and reliable simultaneous dual imaging of the mucin 1 (MUC1) protein backbone and MUC1-specific sialic acid (Sia) is reported. MUC1, an important tumor biomarker, is overexpressed and under-glycosylated in most tumor cells. Two aptamer-functionalized nanoprobes, Cy5-labeled Sia aptamer-functionalized gold nanostars (Sia-GNSs) and MUC1 aptamer-functionalized quantum dots (MUC1-QDs), were successfully constructed with high specificity and biocompatibility. Upon excitation with NIR light, Sia-GNSs endothermically released the Cy5-labeled Sia aptamer that specifically binds to Sia. The Cy5 fluorescence can be observed due to the FRET effect when the Cy5-labeled Sia aptamer and MUC1-QDs bind to the same MUC1 molecule. Dual imaging and relative quantification of MUC1 and its sialylation were achieved in vitro, in vivo and in clinical tissue samples. This efficient platform allows for the simultaneous detection of protein biomarkers and their glycosylation pattern, with significant potential for clinical cancer diagnostics.


Assuntos
Aptâmeros de Nucleotídeos , Pontos Quânticos , Transferência Ressonante de Energia de Fluorescência , Mucina-1 , Imagem Óptica
15.
Int J Mol Med ; 48(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34498713

RESUMO

Investigating the factors that influence the inflammatory response of microglial cells is crucial for understanding the pathogenesis of cryptococcal meningitis (CM). MicroRNAs (miRNAs/miRs) play an important role in inducing host defenses and activating the immune response during microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis remain poorly defined. In a previous study, the authors assessed the miRNA profiles of THP­1 (human acute monocytic leukemia cells) cells following Cryptococcus neoformans (C. neoformans) infection. In the present study, it was found that miR­4792 expression was downregulated in BV2 cells infected with C. neoformans, whilst that of its target gene, epidermal growth factor receptor (EGFR), was upregulated. Infected cells in which miR­4792 was overexpressed exhibited a decreased EGFR transcript expression, reduced mitogen­activated protein kinase (MAPK) signaling and a decreased secretion of inflammatory cytokines. In addition, following antifungal treatment in patients with cryptococcal meningitis, the levels of miR­4792 in the cerebrospinal fluid significantly increased, whilst the expression of EGFR significantly decreased. In addition, receiver operator characteristic analysis revealed miR­4792 (AUCROC=0.75) and EGFR (AUCROC=0.79) as potential diagnostic markers in patients with cryptococcal meningitis.

16.
PLoS One ; 16(9): e0256304, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495990

RESUMO

Developing countries need a large number of social infrastructure projects (e.g. schools, medical care, nursing homes). But the government's finance to invest in these projects is limited. By using the public-private partnership (PPP) mode to attract social capital to invest in PPP projects, it can relieve the financial pressure and improve the operation efficiency. The cooperation between government and consumer can ensure the sustainable development of the project operation. A system dynamics model of tripartite evolutionary game is developed to analyze the interaction of participant's strategies and simulate the corresponding evolution process. We employ the scenario analysis method to investigate the impact of the key parameters in relation with PPP projects based on realistic scenario assumptions. The results reveal the effect of some policies including reverse effect, blocking effect and over-reliance effect. Specifically, the results show that high penalty can prevent social capital from providing low-quality services, the low cost of government regulation can promote social capital to provide high-quality services, compensation to consumer can increase the enthusiasm of consumer participating in supervision, appropriate difference between price and cost of high-quality service as social capital's profit can encourage social capital to provide high-quality service. These policy suggestions will contribute to the sustainable development of social infrastructures in PPP mode.

17.
Front Microbiol ; 12: 712886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497594

RESUMO

Minimal inhibitory concentration (MIC) is defined as the lowest concentration of an antimicrobial agent that can inhibit the visible growth of a particular microorganism after overnight incubation. Clinically, antibiotic doses for specific infections are determined according to the fraction of MIC. Therefore, credible assessment of MICs will provide a physician valuable information on the choice of therapeutic strategy. Early and precise usage of antibiotics is the key to an infection therapy. Compared with the traditional culture-based method, the approach of whole genome sequencing to identify MICs can shorten the experimental time, thereby improving clinical efficacy. Klebsiella pneumoniae is one of the most significant members of the genus Klebsiella in the Enterobacteriaceae family and also a common non-social pathogen. Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, which can produce antibacterial effects of most Gram-positive and -negative bacteria. In this study, we used single-nucleotide polymorphism (SNP) information and nucleotide k-mers count based on metagenomic data to predict MICs of meropenem against K. pneumoniae. Then, features of 110 sequenced K. pneumoniae genome data were combined and modeled with XGBoost algorithm and deep neural network (DNN) algorithm to predict MICs. We first use the XGBoost classification model and the XGBoost regression model. After five runs, the average accuracy of the test set was calculated. The accuracy of using nucleotide k-mers to predict MICs of the XGBoost classification model and XGBoost regression model was 84.5 and 89.1%. The accuracy of SNP in predicting MIC was 80 and 81.8%, respectively. The results show that XGBoost regression is better than XGBoost classification in both nucleotide k-mers and SNPs to predict MICs. We further selected 40 nucleotide k-mers and 40 SNPs with the highest correlation with MIC values as features to retrain the XGBoost regression model and DNN regression model. After 100 and 1,000 runs, the results show that the accuracy of the two models was improved. The accuracy of the XGBoost regression model for k-mers, SNPs, and k-mers & SNPs was 91.1, 85.2, and 91.3%, respectively. The accuracy of the DNN regression model was 91.9, 87.1, and 91.8%, respectively. Through external verification, some of the selected features were found to be related to drug resistance.

18.
Int J Biol Macromol ; 191: 377-384, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34560149

RESUMO

A strategy by exogenous addition of quorum sensing molecule farnesol to improve the production, antioxidant activity and antitumor activity of extracellular polysaccharide (EPS) of Grifola frondosa by liquid fermentation was proposed in the study. The highest yield of EPS induced by farnesol was 1.25 g/L, which was 150% higher than that of the control. Four polysaccharides including EPS-C-0M, EPS-C-0.2M, EPS-F-0M and EPS-F-0.2M were extracted and purified under the conditions of control and farnesol respectively. The physicochemical properties, antioxidant activities and antitumor activities were studied. Their chemical composition differed in sugar, protein and uronic acid contents, and they were composed of six constituent monosaccharides with different ratios, with the average molecular weights of 1.12 × 103, 1.89 × 103, 1.41 × 103 and 2.02 × 103 kDa, respectively. They presented similar FT-IR spectra, but different surface morphology. Antioxidant experiments showed that they had strong scavenging activities on ABTS+, hydroxyl radical, O2- and DPPH radical. Antitumor experiments showed that they had strong inhibitory effects on human cervical cancer (HeLa) cells and human liver cancer cells (HepG2) cells. Among the four polysaccharides, EPS-F-0.2M showed the highest antioxidant and antitumor activities, indicating that farnesol could regulate the biological activity of EPS by affecting structure and properties. These results demonstrated that appropriate adjustment of culture conditions had potential application in the development of polysaccharides with high antioxidant and antitumor activity. It provided a new strategy to enhance the production and bioactivity of edible and medicinal fungal polysaccharides by using quorum sensing molecules.

19.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166247, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487812

RESUMO

The Sorbin and SH3 domain-containing protein 2 (Sorbs2) is an important component of cardiomyocyte sarcomere. It has been recently reported that loss of Sorbs2 is causally associated with arrhythmogenic cardiomyopathy in human. However, the ionic mechanisms leading to cardiac arrhythmogenesis by Sorbs2 deficiency are unknown. In this study, we hypothesized that Sorbs2 plays an important role in regulating cardiac ion channel expression and function. Using electrophysiological and molecular biological approaches, we found that the Sorbs2 knockout (KO) mice progressively developed cardiac structural and electrical remodeling as early as 1 to 2 months of age and died prematurely at 5 to 7 months of age. Electrocardiographic recordings showed that Sorbs2 KO mice had conduction delays, spontaneous ventricular extrasystoles and polymorphic ventricular tachyarrhythmia. Intracellular recordings revealed abnormal action potentials with depolarized resting potential, reduced upstroke velocity, prolonged repolarization, and effective refractory period in the ventricular preparations of Sorbs2 KO mice. Patch clamp experiments demonstrated that Sorbs2 KO mice displayed distinct abnormalities in the expression and function of cardiac ion channels, including those of the voltage-gated Na+ channels, L-type Ca2+ channels, the voltage-gated K+ channels and the inward-rectifier K+ channels. Moreover, Sorbs2 physically interacted with the RNAs and/or proteins of important cardiac ion channels and directly regulated their expression in vitro. Our results indicate that Sorbs2 plays a pivotal role in the regulation of cardiac channel physiology. Loss of Sorbs2 promotes cardiac ion channelopathies and life-threatening arrhythmias.

20.
J Diabetes Investig ; 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564935

RESUMO

Werner syndrome is a rare autosomal recessive premature progeroid syndrome caused by mutations in the WRN gene. It is characterized by early onset of age-related diseases, such as cataracts, atherosclerosis, diabetes mellitus, osteoporosis, and malignancies, in which diabetes often onset at the 30s-40s. Herein we report a Chinese patient of Werner syndrome with uncommon early-onset diabetes at 18 years old, who had low BMI, insulin resistance, negative antibodies of diabetes, and early onset of cataracts. Genome sequencing and RT-PCR confirm the diagnosis. A novel heterozygous splice-site mutation in the WRN gene (c.1270-2A>T) was identified. This case reminds clinicians that when young diabetic patients are encountered, if she is accompanied by premature aging, attention should be paid to identifying the possibility of Werner syndrome based on diagnostic criteria.

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