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1.
GM Crops Food ; 12(1): 36-46, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32835603

RESUMO

Consumer preference for the mandatory labeling of genetically modified (GM) foods promotes public support for the implementation of GM food policies. This study analyzes consumers' preference for the traceability of GM soybean oil. Survey data were collected through a self-administered survey covering 804 randomly sampled urban residents in the eastern, central and western regions of China. Using a logit model, this analysis examines the impacts of influential factors on consumers' preference for traceability. The results show that about 56.5% of the respondents have a positive preference for the traceability of GM soybean oil. Factors increasing the preference for traceability include a better perception of the attributes of nutrition benefit and potential health risk, perceived inadequacy of simple mandatory labels, more attention paid to food labels, and distrust in the agencies overseeing GM food safety. Enhancing consumers' perceptions of GM-related attributes and awareness of food labels will help improve the mandatory labeling management of GM foods.


Assuntos
Alimentos Geneticamente Modificados , Óleo de Soja , China , Comportamento do Consumidor , Rotulagem de Alimentos , Inquéritos e Questionários
2.
Sci Rep ; 10(1): 16245, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004865

RESUMO

With considerable accumulation of RNA-Seq transcriptome data, we have extended our understanding about protein-coding gene transcript compositions. However, alternatively compounded patterns of human protein-coding gene transcripts would complicate gene expression data processing and interpretation. It is essential to exhaustively interrogate complex mRNA isoforms of protein-coding genes with an unified data resource. In order to investigate representative mRNA transcript isoforms to be utilized as transcriptome analysis references, we utilized GTEx data to establish a top-ranked transcript isoform expression data resource for human protein-coding genes. Distinctive tissue specific expression profiles and modulations could be observed for individual top-ranked transcripts of protein-coding genes. Protein-coding transcripts or genes do occupy much higher expression fraction in transcriptome data. In addition, top-ranked transcripts are the dominantly expressed ones in various normal tissues. Intriguingly, some of the top-ranked transcripts are noncoding splicing isoforms, which imply diverse gene regulation mechanisms. Comprehensive investigation on the tissue expression patterns of top-ranked transcript isoforms is crucial. Thus, we established a web tool to examine top-ranked transcript isoforms in various human normal tissue types, which provides concise transcript information and easy-to-use graphical user interfaces. Investigation of top-ranked transcript isoforms would contribute understanding on the functional significance of distinctive alternatively spliced transcript isoforms.

3.
Med Oncol ; 37(11): 99, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040185

RESUMO

Angiogenesis is a prerequisite for multiple myeloma development. Tumor cells can stimulate angiogenesis by secreting vascular endothelial growth factor A (VEGFA), but we previously reported that tumor angiogenesis was not significantly reduced when VEGFA expression was inhibited in myeloma cells. Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment and have been reported to be involved in the regulation of angiogenesis. In this study, we performed in vitro macrophage coculture studies and studies with RPMI 8226 and TAMs cell-conditioned media to explore their effects on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Our results showed that M2 macrophages and RPMI 8226 cells could synergistically promote HUVEC proliferation, migration, and tube formation, and that VEGFA depletion in both cell types suppressed HUVEC tube formation ability. Conversely, M1 macrophages inhibited the tube formation in HUVECs. Mechanistically, M2 macrophage secretion of VEGFA may affect vascular endothelial growth factor receptor 1 signaling to regulate angiogenesis. In summary, our results suggest that macrophage clearance or inducing of transformation of M2 macrophages into M1 macrophages are potential treatment strategies for multiple myeloma.

4.
J Proteome Res ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058664

RESUMO

Rapid identification of methicillin-sensitive Staphylococcus aureus (MSSA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-intermediate S. aureus (VISA) is important for accurate treatment, timely intervention, and prevention of outbreaks. Here, 90 S. aureus isolates were analyzed for protein biomarker discovery, including MSSA, vancomycin-susceptible S. aureus (VSSA), hVISA, and VISA strains. Label-free data-independent acquisition proteomics was used to identify protein biomarkers that allow for discrimination among MSSA, hVISA, and VISA strains. There were 8786 nonredundant peptides identified, corresponding to 418 different annotated nonredundant proteins. Two VISA protein biomarkers, two hVISA protein biomarkers, and one MSSA protein biomarker with high sensitivities and specificities were discovered and verified. Data are available via MassIVE with identifier MSV000085776.

5.
Genet Test Mol Biomarkers ; 24(10): 632-640, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33064010

RESUMO

Background: Recent discoveries indicate that the enzyme fatty acid 2-hydroxylase (FA2H) is associated with biological behavior and can be used for outcome prediction in several types of cancers. Such relevancy, however, between FA2H and ovarian cancer is not clear. Therefore, we carried out this study to compare the expression of FA2H with the clinicopathological features of ovarian cancer. Methods: Using the Oncomine database, we examined the expression levels of the FA2H gene in ovarian cancer tissues and their adjacent noncancerous tissues that had been evaluated by quantitative reverse-transcription polymerase chain reaction (PCR) analyses. We performed Kaplan-Meier curve analyses for overall survival and progression-free survival. In addition, relationships between the FA2H expression levels and clinicopathological features of ovarian cancer were analyzed. Finally, FA2H small interfering RNAs (siRNAs) or negative control siRNAs were separately transfected into OVCAR-3 and SKOV-3 cells to explore the downstream effects. From these results, Gli1 expression was tested by real-time PCR, and the effects of FA2H expression levels on the sensitivity of ovarian cancer cells to cisplatin chemotherapy was evaluated using sulforhodamine B assays. Results: Compared with the adjacent tissues, FA2H was expressed at lower levels in the ovarian cancer tissues. In survival analyses, decreased FA2H was significantly associated with poorer survival outcome in multiple subtypes of ovarian cancer. In addition, FA2H expression was significantly associated with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage, differentiation, lymph node involvement, tumor size, ascites, CA125 levels, and pelvic involvement. Knockdown of FA2H expression by siRNAs in the OVCAR-3 and SKOV-3 cell lines reduced their sensitivity to cisplatin, via modulation of GLI Family Zinc Finger 1 (Gli1) gene expression. Conclusion: Our results demonstrate that FA2H is a biomarker for ovarian cancer and it may serve as a useful prognostic factor.

6.
Medicine (Baltimore) ; 99(40): e22186, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019393

RESUMO

This study aimed to verify the relationship between the number of fusion level and the risk of screw loosening by using cortical bone trajectory (CBT) screws in patients with lumbar degenerative disease.We retrospectively reviewed the serial plain radiograph images of lumbar degenerative disease patients who had undergone posterior fixation and fusion surgery with CBT from 2014. All included patients should have been followed-up with computed tomography scan or plain radiograph for at least 6 months after operation. We individually evaluated the prevalence of screw loosening according to each vertebral level. We also determined whether the number of screw fixation affected the prevalence of screw loosening and whether S1 fixation increased the risk of screw loosening.The screw-loosening rates were high at the S1 level. Moreover, although fixation involved to S1, the loosening rates evidently increased (Fisher exact test, P = .002). The screw-loosening rate was 6.56% in 2 level fusion. However, it increased with the number of fusion levels (3 level: 25.00%, 4 level: 51.16%, and 5 level: 62.50%). To investigate if the number of fusion level affected the S1 screw loosening, we classified the cohort of patients into either involving S1 (S1+ group) or not (S1- group) according to different fusion levels (). The screw loosening between 2 group in 2 (5.56% vs 6.98%) and 3 fusion level (26.32% vs 22.73%) did not exhibit any significant difference. Interestingly, significantly high screw loosening was found in 4 fusion level (60.00% vs 15.38%), indicating that the higher fusion level (4 level) can directly increase the risk of S1 screw loosening.Our data confirmed that the screw-loosening rate increases rate when long segment CBT fixation involves to S1. Therefore, in case of long-segment fixation by using CBT screw, surgeons should be aware of the fusion level of S1.


Assuntos
Parafusos Ósseos , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Fusão Vertebral/instrumentação , Osso Cortical/diagnóstico por imagem , Análise de Falha de Equipamento/métodos , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
PLoS One ; 15(10): e0240372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031429

RESUMO

This study presents a multi-stage random regret minimization (RRM) model as an emergency rescue decision support system to determine the emergency resource pre-allocation schedule for the freeway network. The proposed methodology consists of three steps: (1) improved accident frequency approach to identify the black spots on the freeway network, (2) stochastic programming (SP) model to determine the initial allocation plan sets, and (3) regret-based model in the logarithmical specification to select the most minimal regret one considering the factors of the response time, total cost and demand. The model is applied to the case study of 2014-2016 freeway network in Shandong, China. The results show that the random regret minimization (RRM) model can improve the full-compensation of SP model to a certain degree. RRM in logarithmical specification performs lightly better than random utility maximization (RUM) and RRM in the linear-additive specification in this case. This approach emerges as a valuable tool to help decision makers to allocate resources before traffic accident occurs, with the aim of minimizing the total regret of their decisions.

8.
Braz J Phys Ther ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33077345

RESUMO

BACKGROUND: The timing and coordination of infant kicking may allow for activities that facilitate learning and cognitive development. OBJECTIVE: This study examined spontaneous kicking and associations with changes in kicking during a learning paradigm in typically developing infants. METHODS: Ten healthy full-term infants participated in two experiments at 3 months of age: spontaneous kicking and the mobile paradigm. The inter-limb, intra-limb, and spatiotemporal parameters during spontaneous kicking were collected by 3D motion capture. Learning was measured in the mobile paradigm where an infant's leg was tethered to an overhead mobile. The mobile offered visual and auditory reinforcement when the infant kicked. Changes in kicking rate indicate learning. Friedman tests were used to determine the dominant inter-/intra-limb kicking patterns. Spearman's rank correlation coefficients were used to assess the correlations between spontaneous kicking and performance in the mobile paradigm. RESULTS: A significant negative correlation (r = -0.72, p = 0.03) was observed between the percentages of unilateral kicking and normalized kicking rate during the extinction phase of the paradigm. There was a trend of positive correlation (r = 0.58, p < 0.10) between dissociated hip-ankle joint coupling and the last three-minute of the acquisition phase of the paradigm. CONCLUSION: Exploratory kicking behaviors elicited by visual and auditory feedback may be related to lower extremity movement control. Enhancing movement experience through appropriate external feedback may be critical in treatment programs to support infant development. Future studies to assess how exploratory motor behaviors contribute to development in motor and other domains are warranted.

9.
Hum Reprod ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33067638

RESUMO

STUDY QUESTION: Do decidua-derived factors stimulate the conversion of circulating neutrophils to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in early human pregnancy? SUMMARY ANSWER: Circulating neutrophils can acquire PMN-MDSC-like phenotypes and function via phosphorylated signal transducer and activator of transcription 5/programmed death ligand 2 (pSTAT5/PD-L2) signalling after stimulation with decidua-derived granulocyte macrophage colony-stimulating factor (GM-CSF). WHAT IS KNOWN ALREADY: PMN-MDSCs are an important immunoregulatory cell type in early pregnancy. Neutrophils are of high heterogeneity and plasticity and can polarize to immunosuppressive PMN-MDSCs upon stimulation. STUDY DESIGN, SIZE, DURATION: For analysis of myeloid-derived suppressor cell (MDSC) subset proportions, 12 endometrium tissues and 12 peripheral blood samples were collected from non-pregnant women, and 40 decidua tissues and 16 peripheral blood samples were obtained from women with normal early pregnancy undergoing elective surgical pregnancy termination for nonmedical reasons with gestation age of 6-10 weeks. Twenty-nine decidua tissues were collected for isolation of CD15+ PMN-MDSCs. Twenty endometrium tissues and 30 decidua tissues were collected for cytokine analysis, immunohistochemistry or neutrophil stimulation. Peripheral blood samples were obtained from 36 healthy donors for isolation of CD3+ T cells and CD15+ neutrophils. PARTICIPANTS/MATERIALS, SETTING, METHODS: The proportion of MDSC subsets in the decidua and peripheral blood of normal early pregnancy, endometrium and peripheral blood of non-pregnant women was analysed by flow cytometry. The phenotypes and function of decidual PMN-MDSCs and circulating neutrophils were compared by flow cytometry. Circulating neutrophils were stimulated with decidual explant supernatant (DES) and the phenotypes were measured by flow cytometry and immunofluorescence. The suppressive capacity of decidual PMN-MDSCs and DES-conditioned neutrophils was analysed by flow cytometry with or without anti-programmed cell death-1 (PD-1) antibody. Cytokines from DES and endometrial explant supernatant (EES) were detected by a Luminex assay. GM-CSF expression was determined by ELISA and immunohistochemistry. Neutrophils were stimulated with DES, EES, DES with anti-GM-CSF antibody or EES with GM-CSF. CD11b, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), PD-L2 and pSTAT5 expression were measured by flow cytometry. MAIN RESULTS AND THE ROLE OF CHANCE: The frequency of PMN-MDSCs was significantly increased in the decidua of early pregnancy compared with peripheral blood of non-pregnant women, the endometrium of non-pregnant women or peripheral blood during early pregnancy. Decidual PMN-MDSCs suppressed T-cell proliferation and cytokine production. Phenotypes of decidual PMN-MDSCs were similar to mature activated neutrophils. DES-induced CD11b, LOX-1, PD-L2 expression and STAT5 phosphorylation in neutrophils. The PD-L2 expression in neutrophils was dependent on STAT5 phosphorylation. Both decidual PMN-MDSCs and DES-conditioned neutrophils suppressed T-cell proliferation via PD-1 signalling. GM-CSF was up-regulated in the decidua and induced CD11b, LOX-1 and PD-L2 expression on neutrophils. DES significantly induced CD11b, LOX-1, PD-L2 expression and STAT5 phosphorylation. Anti-GM-CSF antibody remarkably blocked such stimulation in neutrophils. EES did not induce CD11b, LOX-1, PD-L2 expression or STAT5 phosphorylation, while GM-CSF treatment sufficiently stimulated CD11b, LOX-1, PD-L2 expression and STAT5 phosphorylation in neutrophils. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The study was based on in vitro experiments and we were not able to evaluate neutrophils differentiation to PMN-MDSCs in other sites before entering the maternal-foetal interface due to the limited availability of human samples. This needs to be explored using murine models. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study demonstrating that decidual PMN-MDSCs are a group of immunoregulatory cells with mature status, and that neutrophils can be induced to a PMN-MDSC-like phenotype with decidua-derived GM-CSF via pSTAT5/PD-L2 signalling. This study indicates that GM-CSF can facilitate immune tolerance of early pregnancy through regulating PMN-MDSCs and further provides a potential role of GM-CSF in prevention and treatment for pregnancy complications. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81671481) and National Natural Science Foundation of China (81871179). All authors have no competing interests to declare.

10.
Sensors (Basel) ; 20(19)2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33020430

RESUMO

Robotic harvesting shows a promising aspect in future development of agricultural industry. However, there are many challenges which are still presented in the development of a fully functional robotic harvesting system. Vision is one of the most important keys among these challenges. Traditional vision methods always suffer from defects in accuracy, robustness, and efficiency in real implementation environments. In this work, a fully deep learning-based vision method for autonomous apple harvesting is developed and evaluated. The developed method includes a light-weight one-stage detection and segmentation network for fruit recognition and a PointNet to process the point clouds and estimate a proper approach pose for each fruit before grasping. Fruit recognition network takes raw inputs from RGB-D camera and performs fruit detection and instance segmentation on RGB images. The PointNet grasping network combines depth information and results from the fruit recognition as input and outputs the approach pose of each fruit for robotic arm execution. The developed vision method is evaluated on RGB-D image data which are collected from both laboratory and orchard environments. Robotic harvesting experiments in both indoor and outdoor conditions are also included to validate the performance of the developed harvesting system. Experimental results show that the developed vision method can perform highly efficient and accurate to guide robotic harvesting. Overall, the developed robotic harvesting system achieves 0.8 on harvesting success rate and cycle time is 6.5 seconds.

11.
Aging Cell ; : e13236, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029941

RESUMO

Blood-brain barrier (BBB) disruption contributes to neurodegenerative diseases. Loss of tight junction (TJ) proteins in cerebral endothelial cells (ECs) is a leading cause of BBB breakdown. We recently reported that miR-195 provides vasoprotection, which urges us to explore the role of miR-195 in BBB integrity. Here, we found cerebral miR-195 levels decreased with age, and BBB leakage was significantly increased in miR-195 knockout mice. Furthermore, exosomes from miR-195-enriched astrocytes increased endothelial TJ proteins and improved BBB integrity. To decipher how miR-195 promoted BBB integrity, we first demonstrated that TJ proteins were metabolized via autophagic-lysosomal pathway and the autophagic adaptor p62 was necessary to promote TJ protein degradation in cerebral ECs. Next, proteomic analysis of exosomes revealed miR-195-suppressed thrombospondin-1 (TSP1) as a major contributor to BBB disruption. Moreover, TSP1 was demonstrated to activate selective autophagy of TJ proteins by increasing the formation of claudin-5-p62 and ZO1-p62 complexes in cerebral ECs while TSP1 impaired general autophagy. Delivering TSP1 antibody into the circulation showed dose-dependent reduction of BBB leakage by 20%-40% in 25-month-old mice. Intravenous or intracerebroventricular injection of miR-195 rescued TSP1-induced BBB leakage. Dementia patients with BBB damage had higher levels of serum TSP1 compared to those without BBB damage (p = 0.0015), while the normal subjects had the lowest TSP1 (p < 0.0001). Taken together, the study implies that TSP1-regulated selective autophagy facilitates the degradation of TJ proteins and weakens BBB integrity. An adequate level of miR-195 can suppress the autophagy-lysosome pathway via a reduction of TSP1, which may be important for maintaining BBB function.

12.
J Surg Oncol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33084068

RESUMO

BACKGROUND AND OBJECTIVES: A recent study proposed simple classifications of microscopic vascular invasion (MVI): microscopic portal vein invasion (MPVI) and microvessel invasion (MI). We aim to validate these classifications of MVI. METHODS: This retrospective study consecutively enrolled 514 Barcelona Clinic Liver Cancer stage 0, A, and B naïve hepatocellular carcinoma patients who underwent liver resection in our institution from 2011 to 2017. RESULTS: Among these 514 patients, 240 patients were classified as having no MVI at all (designated as no vascular invasion, NVI), 157 patients were classified as having MI only, and 117 patients were classified as having MPVI. The 5-year overall survival (OS) rate in the MI-only group was 83.3%, which was not significantly different from that of the NVI group (87.2%), p = .20. Using NVI as a reference, multivariate analysis showed that MI-only is not an independent variable associated with OS. The 5-year OS in the MPVI group was 59.2%, which was significantly lower than those for MI-only (p < .001) and NVI groups (p < .001). Using NVI as a reference, multivariate analysis showed that MPVI is an independent variable associated with OS (HR, 3.12; 95% CI, 1.80-5.40; p < .001). CONCLUSIONS: The results of this study validate the simple MVI classifications to be clinically useful.

13.
J Med Econ ; : 1, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084446

RESUMO

OBJECTIVES: Extreme prematurity exerts a substantial economic burden on families and societies worldwide, especially in developing countries with limited healthcare resources. This study aimed to estimate initial hospitalization charges after extremely preterm birth in China over previous decade. METHODS: A retrospective study was conducted in the largest tertiary neonatal intensive care unit in Shanghai, China, including 441 extremely preterm infants (gestational age <28 weeks) discharged between 2010 and 2019. Hospitalization data and medical charges were obtained from electronic inpatient medical records. Subgroup analysis was conducted to examine how the charges and length of stay varied by gestational age, discharge year, survival status, and major morbidities. RESULTS: The median total hospitalization charge was $20 770.70 with a median length of stay of 70.0 days. Total and daily charges declined as gestational age increased. A rising trend was found over time for overall and daily medical charges. Compared with decedents, survivors had longer length of stay and higher total hospitalization charges, but their charge per day was lower. Total hospitalization charges were significantly higher in infants with necrotizing enterocolitis (Stage II-III), bronchopulmonary dysplasia, and sepsis when compared with neonates of the same gestational age without these co-morbidities. Charges for treatments accounted for the highest proportion (31.3%). LIMITATIONS: Local statistics collected retrospectively might limit generalizability to other regions. Long-term medical charges were not reported. CONCLUSION: Economic burden of the initial hospitalization for extremely preterm infants was substantial in China. Such economic factors should be fully taken into account for perinatal consultations, medical insurance policy-making, and clinical decisions.

14.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 451-454, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018025

RESUMO

Inspired by the application of recurrent neural networks (RNNs) to image recognition, in this paper, we propose a heartbeat detection framework based on the Gated Recurrent Unit (GRU) network. In this contribution, the heartbeat detection task from ballistocardiogram (BCG) signals was modeled as a classification problem where the segments of BCG signals were formulated as images fed into the GRU network for feature extraction. The proposed framework has advantages in fusion of multi-channel BCG signals and effective extraction of the temporal and waveform characteristics of the heartbeat signal, thereby enhancing heart rate estimation accuracy. In laboratory collected BCG data, the proposed method achieved the best heart rate estimation results compared to previous algorithms.


Assuntos
Balistocardiografia , Algoritmos , Coleta de Dados , Frequência Cardíaca , Redes Neurais de Computação
15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3273-3276, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018703

RESUMO

Contingent learning is an agent for infants to explore the environment, which enhances the maturation of different developmental domains. This paper presents one of the first to investigate neural activities related to contingent learning of infants by analyzing their motor response that could elicit an audio-visual feedback. Three different kinds of motor response of infants were investigated, including unilateral kicks, synchronized kicks, and alternate kicks. Electroencephalographic (EEG) signals of infants were recorded before the motor experiments. Higher theta band power and lower upper beta power at the right temporal lobe of infants predicted a higher ratio of total unilateral kicks and a lower ratio of synchronized kicks at the later acquisition stage of the experiment. As contingent learning could be reflected by specific motor response in relation to the audio-visual stimuli, the results suggested that right temporal oscillations could predict different levels of contingent learning of infants.


Assuntos
Eletroencefalografia , Aprendizagem , Retroalimentação Sensorial , Humanos , Lactente , Modalidades de Fisioterapia
16.
Metabolism ; 113: 154403, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33065162

RESUMO

BACKGROUND: Retinol-binding protein 4 (RBP4) is elevated and associated with inflammation in metabolic diseases. Disruption of the retinol cascade and O-GlcNAcylation of the RBP4 receptor (STRA6) are found in diabetic kidneys. OBJECTIVES: We investigated whether the disruption of the retinol cascade induces RBP4 overproduction and if O-linked GlcNAc modification targets RBPR2 and contributes to the disruption of retinol cascades in diabetic livers. METHODS: Western blot or immunohistochemistry for RBPR2, CRBP1, LRAT, RALDH, RARα, RARγ, RXRα, RBP4, GFAT, OGT, OGA and inflammatory markers, as well as ELISA for RBP4, were performed in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. Immunoprecipitation and dual fluorescence staining were used to explore O-GlcNAc-modified RBPR2 and RBP4 binding activity on RBPR2. Transfection of the CRBP1 gene was done to verify whether a disrupted retinol cascade induces RBP4 overproduction. OGT silencing was done to investigate the association of O-GlcNAcylation with the disruption of retinol cascade. RESULTS: Disruption of retinol cascade, RBP4 overproduction, O-GlcNAcylation of RBPR2, decreased RBP4 binding activity on RBPR2 and inflammation were found in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. CRBP1 gene transfection reversed the suppression of the cellular retinol cascade and simultaneously attenuated the RBP4 overproduction and inflammation in high glucose-treated hepatocytes. The silencing of OGT reversed the disruption of the cellular retinol cascade, RBP4 overproduction and inflammation induced by high glucose in hepatocytes. CONCLUSIONS: This study indicates that the disruption of cellular retinol cascade is strongly associated with RBP4 overproduction and inflammation in diabetic livers. RBPR2 is one target for high glucose-mediated O-linked GlcNAc modification, which causes liver retinol dyshomeostasis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33086433

RESUMO

The association of albuminuria, as measured by urine albumin-to-creatinine ratio (UACR) concentration, with subclinical cardiac dysfunction in hypertensive patients is unclear. Our study aimed to examine its relationship in hypertensive patients compared with that in normotensive patients. The study participants were recruited from Danyang, a city of Jiangsu Province from 2017 to 2019. Categorical and continuous analyses were performed with sex-specific UACR tertiles and natural logarithmically transformed UACR, respectively. Comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking was performed using Philips CX50 device. The 2857 participants (mean age = 52.7 ± 11.8 years) included 1673 (58.6%) women, 1125 (39.4%) hypertensive patients, 546 (19.1%) patients with microalbuminuria, and 38 (1.3%) patients with macroalbuminuria. Comorbidities were increasingly prevalent across the tertiles of UACR. Increased left ventricular (LV) mass index, decreased global longitudinal strain (GLS) and LV ejection fraction, lower E/A ratio and e' velocity, and higher E/e' ratio were significantly associated with higher UACR on unadjusted analyses (p ≤ .01). After adjustment for covariates, UACR was only independently associated with lower GLS (tertile 3 = 20.7% vs. tertile 1 = 20.9%; p = .04). The results of hypertensive patients (p ≤ .04) but not normotensive patients (p ≥ .16) were similar to those of the total cohort. Subgroup analyses revealed similar results in patients without coronary artery disease, or without LV hypertrophy, or without diabetes. In conclusion, increased UACR is associated with worse subclinical systolic function in Chinese hypertensive patients but not in normotensive participants.

18.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097546

RESUMO

Many important proteins undergo pH-dependent conformational changes resulting in "on-off" switches for protein function, which are essential for regulation of life processes and have wide application potential. Here, we report a pair of cellulosomal assembly modules, comprising a cohesin and a dockerin from Clostridium acetobutylicum, which interact together following a unique pH-dependent switch between two functional sites rather than on-off states. The two cohesin-binding sites on the dockerin are switched from one to the other at pH 4.8 and 7.5 with a 180° rotation of the bound dockerin. Combined analysis by nuclear magnetic resonance spectroscopy, crystal structure determination, mutagenesis, and isothermal titration calorimetry elucidates the chemical and structural mechanism of the pH-dependent switching of the binding sites. The pH-dependent dual-binding-site switch not only represents an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials beyond an on-off switch for biotechnological applications.

19.
Sci Rep ; 10(1): 18154, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097755

RESUMO

This study compared effects of plasma-activated medium (PAM) with effects of conventional clinical thermal therapy on both lung cancer cells and benign cells for management of malignant pleural effusion (MPE). For MPE treatment, chemotherapy, photodynamic therapy, and thermal therapy are used but caused systemic side effects, patient photosensitivity, and edema, respectively. Recent studies show that plasma induces apoptosis in cancer cells with minor effects on normal cells and is cost-effective. However, the effects of plasma on MPE have not been investigated previously. This study applied a nonthermal atmospheric-pressure plasma jet to treat RPMI medium to produce PAM, carefully controlled the long-life reactive oxygen and nitrogen species concentration in PAM, and treated the cells. The influence of PAM treatment on the microenvironment of cells was also checked. The results indicated that PAM selectively inhibited CL1-5 and A549 cells, exerting minor effects on benign mesothelial and fibroblast cells. In contrast to selective lethal effects of PAM, thermal therapy inhibited both CL1-5 and benign mesothelial cells. This study also found that fibroblast growth factor 1 is not the factor explaining why PAM can selectively inhibit CL1-5 cells. These results indicate that PAM is potentially a less-harmful and cost-effective adjuvant therapy for MPE.

20.
Sci Rep ; 10(1): 18159, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097822

RESUMO

As urbanization has expanded dramatically, the impacts of urban noise on wildlife have drawn increasing attention. However, previous studies have focused primarily on diurnal songbirds and much less on nocturnal nonpasserines such as nightjars. The savanna nightjar has recently successfully colonized urban areas in Taiwan. Using 1925 calls recorded from 67 individuals, we first investigated the individual differences of the acoustic structures; and, for those acoustic variables with significant individual differences, we examined the correlation between the acoustic structures and the ambient noise levels. We then compared the transmission efficacy of vocal individuality among three sets of acoustic variables: all acoustic variables, noise-related variables, and noise-unrelated variables. Using seven artificial frequency-shifted calls to represent seven different individuals in playback-recording experiments, we also investigated the transmission efficacy of vocal individuality and variable accuracy in three different urban noise levels (high, medium, low). We found that all 30 acoustic variables derived from the acoustic structures demonstrated significant individual differences, and 14 frequency-based variables were negatively correlated with ambient noise levels. Although transmission efficacy was significantly affected by urban noise, individuality information was still transmitted with high accuracy. Furthermore, the noise-unrelated structures (which included the maximum frequency, the maximum amplitude frequency, and the mean frequency of the call) had a significantly higher transmission efficacy of vocal individuality than the noise-related variables (which included the minimum frequency, the frequency at the start and the end of the call) in both field observation and playback-recording experiments. We conclude that these noise-unrelated acoustic features may be one of the key preadaptations for this nocturnal nonpasserine to thrive so successfully in its newly adopted urban environment.

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