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The heterogeneity of extracellular matrix (ECM) topology, stiffness, and architecture is a key factor modulating cellular behavior and osteogenesis. However, the effects of heterogeneous ECM electric potential at the micro- and nanoscale on osteogenesis remain to be elucidated. Here, the heterogeneous distribution of surface potential is established by incorporating ferroelectric BaTiO3 nanofibers (BTNF) into poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix based on phase-field and first-principles simulation. By optimizing the aspect ratios of BTNF fillers, the anisotropic distribution of surface potential on BTNF/P(VDF-TrFE) nanocomposite membranes can be achieved by strong spontaneous electric polarization of BTNF fillers. These results indicate that heterogeneous surface potential distribution leads to a meshwork pattern of fibronectin (FN) aggregation, which increased FN-III7-10 (FN fragment) focal flexibility and anchor points as predicted by molecular dynamics simulation. Furthermore, integrin clustering, focal adhesion formation, cell spreading, and adhesion are enhanced sequentially. Increased traction of actin fibers amplifies mechanotransduction by promoting nuclear translocation of YAP/Runx2, which enhances osteogenesis in vitro and bone regeneration in vivo. The work thus provides fundamental insights into the biological effects of surface potential heterogeneity at the micro- and nanoscale on osteogenesis, and also develops a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.
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Mecanotransdução Celular , Osteogênese , Diferenciação Celular , Regeneração Óssea , Fibronectinas/farmacologiaRESUMO
Cold coagulation and blood stasis (CCBS) syndrome is one of the common traditional Chinese medicine (TCM) syndromes of gynecological diseases. However, the molecular mechanism of CCBS syndrome is still unclear. Thus, there is a need to reveal the occurrence and regulation mechanism of CCBS syndrome, in order to provide a theoretical basis for the treatment of CCBS syndrome in gynecological diseases. The plasma proteins in primary dysmenorrhea (PD) patients with CCBS syndrome, endometriosis (EMS) patients with CCBS syndrome, and healthy women were screened using Label-free quantitative proteomics. Based on the TCM theory of "same TCM syndrome in different diseases," the differentially expressed proteins (DEPs) identified in each group were subjected to intersection mapping to obtain common DEPs in CCBS syndrome. The DEPs of gynecological CCBS syndrome in the intersection part were again cross-mapped with the DEPs of gynecological CCBS syndrome obtained by the research group according to the TCM theory of "different TCM syndromes in same disease" theory in the early stage, so as to obtain the DEPs of gynecological CCBS syndrome that were shared by the two parts. The common DEPs were subjected to bioinformatics analysis, and were verified by enzyme-linked immunosorbent assay (ELISA). A total of 67 common DEPs were identified in CCBS syndrome, of which 33 DEPs were upregulated and 34 DEPs were downregulated. The functional classification of DEPs involved in metabolic process, energy production and conversion, immune system process, antioxidant activity, response to stimulus, and biological adhesion. The subcellular location mainly located in the cytoplasm, nucleus, and extracellular. Gene ontology (GO) enrichment analysis showed that the upregulated DEPs mainly concentrated in lipid transport, cell migration, and inflammatory reaction, and the downregulated DEPs mostly related to cell junction, metabolism, and energy response. Protein domain enrichment analysis and clustering analysis revealed that the DEPs mainly related to cell proliferation and differentiation, cell morphology, metabolism, and immunity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis clustering analysis showed that the upregulated DEPs were involved in inflammation and oxidative damage, while the downregulated DEPs were involved in inflammation, cell adhesion, cell apoptosis, and metabolism. The results of ELISA showed significantly increased levels of Cell surface glycoprotein MUC18 (MCAM) and Apolipoprotein C1 (APOC1), and significantly decreased levels of Vasodilator-stimulated phosphoprotein (VASP), Fatty acid-binding protein 5 (FABP5), and Vinculin (VCL) in patients with CCBS syndrome compared with healthy women. We speculated that cold evil may affect the immune process, inflammatory response, metabolic process, energy production and conversion, oxidative damage, endothelial cell dysfunction, and other differential proteins expression to cause CCBS syndrome in gynecological diseases.
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Estresse Oxidativo , Proteômica , Humanos , Feminino , Apoptose , Adesão Celular , Inflamação , Proteínas de Ligação a Ácido GraxoRESUMO
Polymerase chain reaction (PCR) variants requiring specific primer types are widely used in various PCR experiments, including generic PCR, inverse PCR, anchored PCR, and ARMS PCR. Few tools can be adapted for multiple PCR variants, and many tools select primers by filtration based on the given parameters, which result in frequent design failures. Here we introduce PrimerScore2, a robust high-throughput primer design tool that can design primers in one click for multiple PCR variants. It scores primers using a piecewise logistic model and the highest-scored primers are selected avoiding the issue of design failure and the necessity to loosen parameters to redesign, and it creatively evaluates specificity by predicting the efficiencies of all target/non-target products. To assess the prediction accuracy of the scores and efficiencies, two next generation sequencing (NGS) libraries were constructed-a 12-plex and a 57-plex-and the results showed that 17 out of 19 (89.5%) low-scoring pairs had a poor depth, 18 out of 19 (94.7%) high-scoring pairs had a high depth, and the depth ratios of the products were linearly correlated with the predicted efficiencies with a slope of 1.025 and a coefficient of determination (R2) 0.935. 116-plex and 114-plex anchored PCR panels designed by PrimerScore2 were applied to 26 maternal plasma samples with male fetuses, the results showed that the predicted fetal DNA fractions were concordant with fractions measured in gold standard method (Y fractions). PrimerScore2 was also used to design 77 monoplex Sanger sequencing primers, the sequencing results indicated that all the primers were effective.
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Modelos Logísticos , Masculino , Humanos , Reação em Cadeia da PolimeraseRESUMO
The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of 2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-CoV-2 epidemics in several large cities or provinces of China. However, information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-CoV-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-CoV-2 transmission profiles. Genomic epidemiology revealed multiple SARS-CoV-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size. Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-CoV-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-CoV-2 strains during the early COVID-19 epidemic in China.
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COVID-19 , Epidemias , COVID-19/epidemiologia , China/epidemiologia , Cidades/epidemiologia , Meios de Cultura , Humanos , SARS-CoV-2/genéticaRESUMO
The beta-blocker atenolol (ATE), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are frequently detected in municipal wastewater effluents, but little is known about their ecotoxicological effect on aquatic animals. Herein, ATE and VEN were selected to explore their accumulation and global DNA methylation (GDM) in zebrafish tissues after a 30-day exposure. Molecular dynamics (MD) stimulation was used to investigate the toxic mechanism of ATE and VEN exposure. The results demonstrated that ATE and VEN could reduce the condition factor of zebrafish. The bioaccumulation capacity for ATE and VEN was in the order of liver > gut > gill > brain and liver > gut > brain > gill, respectively. After a 30-day recovery, ATE and VEN could still be detected in zebrafish tissues when exposure concentrations were ≥10 µg/L. Moreover, ATE and VEN induced global DNA hypomethylation in different tissues with a dose-dependent manner and their main target tissues were liver and brain. When the exposure concentrations of ATE and VEN were increased to 100 µg/L, the global DNA hypomethylation of liver and brain were reduced to 27% and 18%, respectively. In the same tissue exposed to the same concentration, DNA hypomethylation induced by VEN was more serious than that of ATE. After a 30-day recovery, the global DNA hypomethylations caused by the two drugs were still persistent, and the recovery of VEN was slower than that of ATE. The MD simulation results showed that both ATE and VEN could reduce the catalytic activity of DNA Methyltransferase 1 (DNMT1), while the effect of VEN on the 3D conformational changes of the DNMT1 domain was more significant, resulting in a lower DNA methylation rate. The current study shed new light on the toxic mechanism and potential adverse impacts of ATE and VEN on zebrafish, providing essential information to the further ecotoxicological risk assessment of these drugs in the aquatic environment.
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Atenolol , Peixe-Zebra , Animais , Bioacumulação , DNA , Metilação de DNA , Cloridrato de Venlafaxina/toxicidadeRESUMO
Mitochondria, as vital energy supplying organelles, play important roles in cellular metabolism, which are closely related with mitochondrial pH (â¼8.0). In this work, a novel multimodal fluorescent probe was employed for ratiometric and colorimetric detection of pH. The probe is designed to work by controlling benzothiazole phenol-hemicyanine system as the interaction site and hemicyanine connected by conjugate bonds as the mitochondrial targeting, which also could make the fluorescence of probe red-shifted. This system results in a perfect ratiometric fluorescent response, whose emission changed from red to blue under pH 2.0-10.0, having a broad linear range (pH = 3.0-10.0). And the marked colour change (light yellow to deep purple via naked eye under pH 2.0-11.0) could be used to construct the test strip colorimetry and smartphone APP detection method, realizing the fast, portable, and accurate detection of pH in vitro and environment. Besides, the probe owns the characteristics of easy loading, high selectivity and staining ability of mitochondria, and low cytotoxicity, thereby allowing imaging of pH values and real-time monitor the subcellular mitochondria pH changes caused by drugs in living cells. It thus could be used to monitor the organ-specific dynamics related to transitions between pathological and physiological states.
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Colorimetria , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Mitocôndrias , Espectrometria de FluorescênciaRESUMO
Comparisons of large igneous provinces (LIPs) and black shales from different cratons can provide important constraints on Precambrian paleogeographic reconstructions and a better understanding of the environmental effects of large-scale volcanic events. A comparison of intraplate mafic events mostly interpreted as LIPs or portions of LIPs (LIP fragments/remnants due to continental breakup or erosion) from the North China Craton (NCC) and North Australian Craton (NAC) shows good correlation in the age range from 1800 Ma to 1300 Ma, and four robust age matches at ca. 1790-1770 Ma, ca. 1730 Ma, ca. 1680-1670 Ma and ca. 1320 Ma have been identified. Most notably, the coeval ca. 1320 Ma Yanliao LIP in the eastern-northern NCC and the Derim Derim-Galiwinku LIP in the NAC are also characterized by similar field occurences and dominantly subalkaline tholeiitic basalts and intraplate geochemical compositions, and are interpreted as portions of the same LIP, separated by continental breakup. Subsequent to 1300 Ma, the NCC and NAC exhibit very different magmatic histories, indicating that separation of these two cratons occurred, likely subsequent to the ca. 1320 Ma LIP event. A comparison of Paleo-Mesoproterozoic black shales from the NCC and NAC provides further evidence for close connections between these regions during this period. Black shales of the Chuanlianggou Formation in the northern NCC and the Cuizhuang Formation in the southern NCC were deposited in the age range ca. 1650-1635 Ma and can be correlated with ca. 1640-1635 Ma black shales in the Barney Creek Formation of the NAC. Deposition of black shales within the Xiamaling Formation in the NCC and the Velkerri and Kyalla formations of the McArthur Basin in the NAC occurred synchronously at ca. 1380-1360 Ma. Our results from matching of LIP ages and black shales combined with paleomagnetic data show that the northern-northeastern margin of the NCC was connected to the northern margin of the NAC from ca. 1800 Ma to 1300 Ma. This long-lived late Paleoproterozoic to mid-Mesoproterozoic connection lasted for at least 500 million years until separation of the NCC from the NAC between ca. 1320 and ca. 1230-1220 Ma.
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Bushen-Tiaojing-Fang (BSTJF) is commonly used to treat infertility. This study investigated the effects of BSTJF on the pregnancy outcomes of patients with repeated controlled ovarian stimulation (COS), on mitochondrial function, and on oxidative stress in ovarian granulosa cells (GCs) and follicular fluid (FF). The samples and clinical data of 97 patients, including 35 in the control group, 29 in the placebo group and 33 in the BSTJF group, were collected for this study. The mitochondrial ultrastructure, ATP content, mitochondrial DNA (mtDNA) number, 8-hydroxy-2-deoxyguanosine (8-OHdG), Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) activity levels, and mRNA expression levels of Mn-SOD, GSH-Px, and nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) were analyzed. The high-grade embryo (P < 0.001), implantation (P = 0.033), and clinical pregnancy (P = 0.031) rates, as well as the ATP content (P = 0.014), mtDNA number (P = 0.035), GSH-Px activity (P = 0.004 in GCs and P = 0.008 in FF) and mRNA expression levels (P = 0.019), were significantly lower in the placebo group than in the control group, whereas the 8-OHdG content was significantly (P = 0.006 in FF) higher in the placebo group than in the control group. Compared with those in the placebo group, the high-grade embryo rate (P = 0.007), antioxidant enzyme activity (P = 0.037 and 0.036 in Mn-SOD; P = 0.047 and 0.030 in GSH-Px) and mRNA level (P < 0.001 in Nrf2, P = 0.039 in Mn-SOD and P = 0.002 in GSH-Px) were significantly higher in the BSTJF group, as were changes in mitochondrial ultrastructure, ATP (P = 0.040) and mtDNA number (P = 0.013). In conclusion, BSTJF can improve oxidative stress in patients with repeated COS and pregnancy outcomes.
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Medicamentos de Ervas Chinesas/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Trifosfato de Adenosina/metabolismo , Adulto , Implantação do Embrião/fisiologia , Feminino , Líquido Folicular/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Infertilidade Feminina/metabolismo , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Gravidez , Resultado da Gravidez , Superóxido Dismutase/metabolismoRESUMO
Cys (Cysteine), Hcy (homocysteine), and GSH (glutathione) are three important kinds of biothiols, playing crucial roles in the variety of pathological and physiological processes. It is greater challenges to simultaneously identify different biothiols due to their similar molecular structures and chemical characteristics. In this work, we employed a multi-emissive fluorescent probe by sulfonyl benzoxadiazole (SBD) with halogen chloride unit as the interaction site based on aromatic substitution-rearrangement strategy to discriminate Cys and Hcy/GSH. The response of probe 1 to Cys would generate FRET and cause a red-shift of fluorescence emission, while Hcy/GSH only lead to different degrees of fluorescence enhancement owing to PET. The probe showed good selectivity, high sensitivity, and low detection limits to three biothiols (Cys: 0.86 µM, Hcy: 0.48 µM and GSH: 0.54 µM). Such capability of the probe could be demonstrated to successfully quantitatively detect the concentrations of Cys/Hcy/GSH in human plasmas. In addition, the probe was also successfully applied for imaging biothiols in lysosomes and real-time monitoring GSH changes in living cells through two-photon fluorescence microscopy.
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Cisteína , Corantes Fluorescentes , Glutationa , Homocisteína , Humanos , Espectrometria de FluorescênciaRESUMO
As a specific biomarker, neuron-specific enolase (NSE) is an essential clinical indicator for diagnosing small cell lung cancer. In this paper, a sandwich-type electrochemical immunosensor was designed for the quantitative detection of NSE. AuPt nanoblock spherical nanoarchitectonics (AuPt NSNs), a bimetallic nanoparticle with a rugged morphology, were utilized as the substrate, which could enhance the electronic conduction and increase the immobilization capacity of the primary antibody (Ab1). Moreover, through a simple hydrothermal method, Au/CuxO@CeO2 was prepared as a spiny core-shell nanocube with cerium dioxide (CeO2) and gold nanoparticles (Au NPs) loading. The combination of Cu2O, CuO, and CeO2 showed favorable catalytic activity toward hydrogen peroxide (H2O2). Furthermore, the deposition of Au NPs on the spiny surface structure enhanced the specific surface area and biocompatibility, thereby rendering it more effective for loading the second antibody (Ab2). As the label material, the Au/CuxO@CeO2 achieved signal amplification and sensitive detection with the immunosensor. Under optimal conditions, the designed immunosensor possessed a broad linear range of 50 fg mL-1 to 100 ng mL-1 and a limit of detection of 31.3 fg mL-1, along with satisfactory performance in sensitivity, selectivity, and stability.
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Técnicas Biossensoriais/métodos , Cério/química , Ouro/química , Limite de Detecção , Nanoestruturas/química , Neurônios/enzimologia , Fosfopiruvato Hidratase/metabolismo , Anticorpos Imobilizados/química , Eletroquímica , Peróxido de Hidrogênio/química , Modelos Lineares , Nanopartículas Metálicas/químicaRESUMO
Minimally invasive surgery, including laparoscopic and thoracoscopic procedures, benefits patients in terms of improved postoperative outcomes and short recovery time. The challenges in hand-eye coordination and manipulation dexterity during the aforementioned procedures have inspired an enormous wave of developments on surgical robotic systems to assist keyhole and endoscopic procedures in the past decades. This paper presents a systematic review of the state-of-the-art systems, picturing a detailed landscape of the system configurations, actuation schemes, and control approaches of the existing surgical robotic systems for keyhole and endoscopic procedures. The development challenges and future perspectives are discussed in depth to point out the need for new enabling technologies and inspire future researches.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Portal vein tumor thrombus (PVTT) promotes distant metastasis of hepatocellular carcinoma (HCC), which increases the mortality of patients with HCC and PVTT. The aim of the present study was to develop an early risk warning system for distant metastasis of hepatitis B virus (HBV)-associated primary HCC (HBV-HCC) with PVTT. Data from 346 patients (263 and 83 in the modeling and validation cohorts, respectively) who had received primary diagnoses of HBV-HCC and PVTT between January 2012 and June 2015 at Beijing Ditan Hospital (Beijing, China) were retrospectively examined. In the modeling cohort, univariate and multivariate logistic regression analyses were conducted to determine the factors that were significantly associated with distant metastasis. Furthermore, an early risk warning model for distant metastasis was proposed and validated through receiver operating characteristic curve analysis in the validation cohort. The results revealed that neutrophil to lymphocyte ratios of ≥2.31, red blood cell counts of ≥4.07×1012 cells/l, C-reactive protein levels of ≥7.02 mg/l, aspartate aminotransferase levels of ≥118.5 U/l and tumor thrombus site (at branch) were significantly positively associated with distant metastasis of HBV-HCC with PVTT (P<0.05; odds ratio >1.000). A formula for predicting distant metastasis was obtained with an accuracy of ~70%. The results of the present study may allow for the early prediction of distant metastasis and facilitate the administration of appropriate treatment to improve the outcomes and prognosis of patients with intermediate to advanced HCC.
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In this work, a label-free electrochemical immunosensor was developed for the detection of procalcitonin (PCT), using toluidine blue functionalized NiFe Prussian-blue analog nanocubes (NiFe PBA nanocubes@TB) as a signal amplifier. NiFe PBA nanocubes was synthesized by a simple and efficient self-templating method in this work. NiFe PBA nanocubes with open-framework construction not only provides a larger specific area to load a mass of antibodies but produces an excellent signal without adding extra reaction reagent. Besides, the electrochemical performance of NiFe PBA nanocubes can be enhanced after functionalized with TB. The developed immunosensor exhibited favorable performance for PCT detection with a linear range from 0.001 to 25â¯ngâ¯mL-1 and a detection limit of 3â¯×â¯10-4â¯ngâ¯mL-1. Moreover, the immunosensor with acceptable reproducibility, selectivity, and stability may provide a new strategy in the clinical detection of PCT.
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Ferrocianetos/química , Imunoensaio , Ferro/química , Nanocompostos/química , Níquel/química , Pró-Calcitonina/análise , Cloreto de Tolônio/química , Técnicas Biossensoriais , Técnicas Eletroquímicas , Humanos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
BACKGROUND: Haptic devices with active translation and orientation outputs are highly preferred in surgical teleoperation. However, commercial products are expensive, while state-of-the-art research prototypes are difficult to reproduce outside the original laboratories. METHODS: This paper presents the design and experimental characterizations of two styluses for the CombX, a haptic device with both force and torque outputs constructed from two TouchX haptic devices, which have only force outputs at their styluses. The arrangement was optimized to improve the specifications. Additional functions for surgical teleoperation were also integrated. RESULTS: The CombX has a translation workspace larger than 160 × 160 × 160 mm3 . After calibration, it can provide force outputs of up to 16.32 N and torque outputs of up to 316 mNm. The CombX has also been successfully used to teleoperate a continuum surgical manipulator for two surgical tasks. CONCLUSION: The results show that the CombX is a viable option for surgical teleoperation.
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Desenho de Equipamento , Procedimentos Cirúrgicos Robóticos/instrumentação , Telemedicina/instrumentação , Calibragem , Humanos , Instrumentos Cirúrgicos , TorqueRESUMO
The study evaluated the effects of branched-chain volatile fatty acids (BCVFA) and fibrolytic enzyme (FE) on rumen development in calves. Forty Holstein male calves at the same ages (15 ± 2.5 days of age) and weights (45 ± 3.3 kg of body weight [BW]) were assigned randomly to four groups with a 2 × 2 factorial arrangement of treatments. Supplemental BCVFA (0 g/d or 18 g/d) and FE (0 g/d or 1.83 g/d) were fed to calves. Data were analyzed as a 2 × 2 factorial arrangement random design by the mixed procedure of SAS. The BCVFA × FE interaction was observed for ruminal propionate, blood growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and GH receptor (GHR) and IGF-1 receptor (IGF-1R) expression in the rumen mucosa. Dry matter intake was higher for BCVFA addition. The higher average daily gain and ruminal volatile fatty acids were observed for BCVFA or FE addition. Stomach weight and the length and width of rumen papillae were higher for BCVFA addition. The higher expression of GHR, IGF-1R and 3-hydroxy-3-methylglutaryl-CoA synthase 1 in rumen mucosa, and blood GH and IGF-1 were observed with BCVFA or FE addition. Blood ß-hydroxybutyrate and acetoacetate were higher for BCVFA addition. The results indicated that rumen development was promoted by BCVFA, but was not affected with FE addition in calves.
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Ração Animal , Celulase , Ácidos Graxos Voláteis/farmacologia , Rúmen , Animais , Bovinos , Endo-1,4-beta-Xilanases , Distribuição Aleatória , Rúmen/efeitos dos fármacos , Rúmen/crescimento & desenvolvimento , Rúmen/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Effective detection of cancer biomarkers plays a crucial role in the prevention of early cancer. Here, a sandwich-type electrochemical immunosensor was successfully constructed for sensitive detection of carcinoembryonic antigen (CEA) using MoS2/CuS-Au as sensing platform and mulberry-like Au@PtPd porous nanorods (Au@PtPd MPs) as signal amplifiers. The large surface area and good biocompatibility of MoS2/CuS-Au increased the loading of primary antibody. And the good conductivity of MoS2/CuS-Au accelerated the electron transport rate of the electrode surface. Au@PtPd MPs with large specific surface area and a large number of catalytically active sites showed excellent electrocatalytic performance for hydrogen peroxide reduction. The sandwich-type immunosensor prepared by the signal amplification strategy exhibited a wide linear detection range (50â¯fg/mL to 100â¯ng/mL) and a low detection limit of 16.7â¯fg/mL (S/Nâ¯=â¯3), featuring good selectivity, stability and reproducibility. Moreover, the satisfactory results in analysis of human serum samples indicated that it possessed a potential application promising in early clinical diagnoses.
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Técnicas Biossensoriais , Antígeno Carcinoembrionário/isolamento & purificação , Neoplasias/diagnóstico , Antígeno Carcinoembrionário/química , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/isolamento & purificação , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Nanopartículas Metálicas/química , Nanotubos/químicaRESUMO
BACKGROUND: Post-operative recurrence rates are high for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to explore the factors associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter). METHODS: This was a retrospective study of 203 (training cohort) and 64 (validation cohort) patients newly diagnosed with HBV-related HCC who had a single small primary tumor. The first year of post-operative follow-up was examined. Factors potentially associated with HCC recurrence were identified using Cox regression analyses. A model was constructed based on the factors identified and the prognostic value of the model was evaluated using receiver operating characteristic (ROC) curve analysis and calculation of the area under the ROC curve (AUC). RESULTS: A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase (GGT) were independently associated with 1-year recurrence rate after surgery. A predictive model based on these four factors had an AUC of 0.711 (95% confidence interval, 0.643-0.772) in the training cohort and 0.727 (95% confidence interval, 0.601-0.831) in the validation cohort. The 1-year recurrence rate was significantly lower in the low-risk group than in the high-risk group in both the training cohort (17.0% vs. 49.5%, P < 0.001) and the validation cohort (43.2% vs. 74.1%, P = 0.031). CONCLUSION: A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase were independently associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter).
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BACKGROUND: Considering the insufficient ruminal synthesis of folic acid (FA), the higher degradability of FA, and the reduction of sodium selenite (SS) by ruminal microbes into non-absorbable elemental Se, this study evaluated the effects of rumen-protected FA (RPFA) and rumen-protected SS (RPSS) on lactation performance, nutrient digestion and blood metabolites in dairy cows. RESULTS: Dry matter (DM) intake and milk composition were unaltered, milk and milk fat yields were higher for both supplements, and milk protein yield was higher for RPFA addition. Digestibility of DM, neutral detergent fibre and acid detergent fibre was higher for both supplements, whereas that of organic matter and crude protein was higher for RPFA addition. Ruminal pH and ammonia N were lower, and concentration of total volatile fatty acids was higher for both supplements. Activity of cellobiase and xylanase was higher for RPFA addition, whereas that of pectinase and protease was higher for both supplements. The populations of total ruminal fungi, protozoa, Ruminococcus flavefaciens and Butyrivibrio fibrisolvens were higher for both supplements. The RPFA × RPSS interaction was significant for α-amylase activity, total ruminal bacteria and R. albus populations; these three variables were increased by RPSS but the increase was greater when cows were also fed RPFA. CONCLUSION: The results indicated that addition of RPFA or RPSS improved lactation performance, nutrient digestibility and ruminal fermentation in dairy cows by stimulating ruminal microbial growth and enzyme activity. © 2019 Society of Chemical Industry.
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Bovinos/fisiologia , Suplementos Nutricionais/análise , Ácido Fólico/administração & dosagem , Rúmen/metabolismo , Selenito de Sódio/administração & dosagem , Amônia/metabolismo , Animais , Bovinos/microbiologia , Digestão , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Ácido Fólico/metabolismo , Microbioma Gastrointestinal , Lactação , Leite/química , Leite/metabolismo , Rúmen/microbiologia , Selenito de Sódio/metabolismoRESUMO
A sandwich-type electrochemical immunosensor was fabricated for the quantitation of alpha fetoprotein (AFP). To this end, the Au@Pt dendritic nanorods loaded with amino functionalized molybdenum selenide nanosheets (Au@Pt 41 DNRs/NH2-MoSe2 NSs) with enhanced peroxidase-like properties were selected as the secondary antibody label (Ab2) to achieve signal amplification. The as-obtained Au@Pt DNRs/NH2-MoSe2 NSs exhibited better catalytic activity toward hydrogen peroxide reduction and offered rich anchors for bioconjugation. Meanwhile, gold nanoparticles anchored on an amino functionalized graphene (Au NPs/NH2-GS) composite with admirable conductivity and biocompatibility was used as the matrix material to improve sensitivity. Under optimal conditions, amperometric current responses had a good linear relationship with the logarithm values of AFP concentration in the range 10â¯fgâ¯mL-1 to 200â¯ngâ¯mL-1 with a detection limit of 3.3â¯fgâ¯mL-1 (S/Nâ¯=â¯3). Additionally, the immunosensor had excellent reproducibility, selectivity, and stability, which indicated superior performance for AFP detection compared with previous reports. The satisfactory results of human serum samples analysis showed that the designed immunosensor has potential applicability for the sensitive detection of other tumor markers.
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Anticorpos Imobilizados/química , Técnicas Biossensoriais , Técnicas Eletroquímicas/instrumentação , Ouro/química , Nanopartículas Metálicas/química , Molibdênio/química , Nanocompostos/química , Platina/química , Compostos de Selênio/química , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/análise , Grafite/química , Peróxido de Hidrogênio/química , Limite de Detecção , Microscopia Eletrônica de Transmissão , Oxirredução , Reprodutibilidade dos TestesRESUMO
A sandwich-type electrochemical immunosensor for detecting amyloid-beta protein was fabricated based on Au NP-functionalized reduced graphene oxide (Au@rGO) as an effective sensing platform and AuCu xO-embedded mesoporous CeO2 (AuCu xO@m-CeO2) nanocomposites as the catalytic matrix. The AuCu xO@m-CeO2 composites were obtained by adjusting the amount of m-CeO2 in the reaction to expose enormous active sites. Also, AuCu xO@m-CeO2 was applied as a matrix to immobilize antibodies by forming bridged bonds between m-CeO2 and carboxyl functional groups of antibodies without additional agents. Furthermore, AuCu xO with prominent catalytic activities dramatically improved the performance of the fabricated immunosensor. Also, the morphology, structure, and electronic state of the surface were characterized by SEM, XRD, TEM, and XPS. In addition, the immunosensor demonstrated a wide linear range of 100 fg mL-1 to 10 ng mL-1. This study may provide a way for sensitively detecting various biomarkers.