A novel temperate phage vB_KpnP_ZX1 was isolated from hospital sewage samples using the clinically derived K57-type Klebsiella pneumoniae as a host. Phage vB_KpnP_ZX1, encoding three lysogen genes, ...the repressor, anti-repressor, and integrase, is the fourth phage of the genus Uetakevirus, family Podoviridae, ever discovered. Phage vB_KpnP_ZX1 did not show ideal bactericidal effect on K. pneumoniae 111-2, but TEM showed that the depolymerase Dep_ZX1 encoded on the short tail fiber protein has efficient capsule degradation activity. In vitro antibacterial results show that purified recombinant Dep_ZX1 can significantly prevent the formation of biofilm, degrade the formed biofilm, and improve the sensitivity of the bacteria in the biofilm to the antibiotics kanamycin, gentamicin, and streptomycin. Furthermore, the results of animal experiments show that 50 µg Dep_ZX1 can protect all K. pneumoniae 111-2-infected mice from death, whereas the control mice infected with the same dose of K. pneumoniae 111-2 all died. The degradation activity of Dep_ZX1 on capsular polysaccharide makes the bacteria weaken their resistance to immune cells, such as complement-mediated serum killing and phagocytosis, which are the key factors for its therapeutic action. In conclusion, Dep_ZX1 is a promising anti-virulence agent for the K57-type K. pneumoniae infection or biofilm diseases.
Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few ...prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.
We investigated associations of major circulating SFAs palmitic acid (16:0) and stearic acid (18:0) and MUFA oleic acid (18:1n-9) in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7) and estimated dietary SFAs and MUFAs.
In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.
At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.
In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.
The paper is devoted to study the uniqueness of solutions for a differential system with coupled integral boundary conditions under a Lipschitz condition. Our approach is based on the Banach's ...contraction principle. The interesting point is that the Lipschitz constant is related to the spectral radius corresponding to the related linear operators.
As the main reservoir of oil and gas resources, the physical and mechanical properties of the rock are complicated. The strong heterogeneity of rock and the flow in porous media further influences ...the nature of stress propagation. Therefore, considering the heterogeneous particle model and fluid-structure coupling, it is very important to study the variation law of rock mechanical properties under a stress state, which lays a foundation for formation fracturing and mining. In this paper, the mechanical properties of the rock are studied by the ideal, heterogeneous, and flow models in porous media. The results show that the stress of the contact surface between particles of the same size is large. Still, the stress of the contact surface between different particles is larger, which is more likely to become the weak mechanical link of failure. When the displacement of the z-axis is the same, the x and y-axis increase the axial stress of the z-axis. The peak stress is high and more sensitive when the particle size difference is small. When water is in the pores, the rock strength obtained under consolidated undrained is greater than that under consolidated drained.
Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood.
The aim of this study was to assess ...the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases.
We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone–binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses’ Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors.
Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (−8.7%), IGFBP-3 (−2.2%), estrone (−6.4%), total estradiol (−5.7%), free estradiol (−8.1%), leptin (−6.4%), CRP (−16.6%), IL-6 (−8.1%), and sTNFR-2 (−5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee.
Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.
Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating levels of free fatty acids in mice. This study is performed to ...evaluate the association between serum and aqueous humor myonectin concentrations with diabetic retinopathy (DR). This study was performed in a population of 228 patients with type 2 diabetes (T2DM) and 72 control subjects. Diabetic patients were then divided into T2DM patients without DR, non-proliferative diabetic retinopathy (NPDR) patients, and proliferative diabetic retinopathy (PDR) patients. Serum and aqueous humor myonectin concentrations were significantly lower in the case group than in the control group. PDR patients showed significantly decreased serum and aqueous humor myonectin concentrations than in the other two T2DM patients. In addition, NPDR patients showed significantly lower serum and aqueous humor myonectin concentrations than T2DM patients without DR. Logistic regression analysis demonstrated that serum and aqueous humor myonectin was correlated with a decreased risk of T2DM and DR. Simple linear regression analysis showed that serum myonectin was negatively correlated with duration of disease, body mass index (BMI), and HbA1c. Duration of disease and BMI were still correlated with the serum myonectin after a multiple linear regression analysis. Aqueous humor myonectin was negatively correlated with duration of disease, systolic blood pressure (SBP), and diastolic blood pressure. Duration of disease and SBP was still correlated with the aqueous humor myonectin after a multiple linear regression analysis. Our investigation indicates an inverse association of serum and aqueous humor myonectin with DR.
Growing data suggest that antibiotic exposure is associated with a long-lasting alteration in gut microbiota, and may be related to subsequent cardiovascular disease (CVD). We investigated ...associations of life-stage and duration of antibiotic exposure during adulthood with subsequent CVD events.
This study included 36 429 women initially free of CVD and cancer from the Nurses' Health Study. We estimated hazard ratios (HRs) for CVD (a composite endpoint of coronary heart disease or stroke) according to duration of antibiotic use in young (age 20-39), middle (age 40-59), and late (age 60 and older) adulthood. During an average of 7.6 years of follow-up, 1056 participants developed CVD. Women with long-term use of antibiotics (for ≥2 months) in late adulthood had a significantly increased risk of CVD (HR 1.32, 95% confidence interval 1.03-1.70) after adjustment for covariates (such as demographic factors, diet and lifestyle, reasons for antibiotic use, overweight or obesity, disease status, and other medication use), as compared to women who did not use antibiotics in this life-stage. Longer duration of antibiotic use in middle adulthood was also related to higher risk of CVD (P trend = 0.003) after controlling for these covariates. There was no significant relationship between the use in young adulthood and the risk of CVD.
In this study which examined the antibiotic use in different life-stages, longer duration of exposure to antibiotics in the middle and older adulthood was related to an increased risk of future CVD events among elderly women at usual risk.
A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to ...abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.
In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models.
We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut microbiome composition, particularly Clostridiales, and their potential for carbohydrate utilization via polysaccharide degradation. This was particularly true for fruit fiber sources (i.e., pectin). Most striking, fiber intake was associated with significantly greater CRP reduction in individuals without substantial Prevotella copri carriage in the gut, whereas those with P. copri carriage maintained stable CRP levels regardless of fiber intake.
Our findings offer human evidence supporting a fiber-gut microbiota interaction, as well as a potential specific mechanism by which gut-mediated systemic inflammation may be mitigated.
Medical image segmentation has the significance of research in digital image processing. It can locate and identify the organ cells, which is essential for clinical analysis, diagnosis, and ...treatment. Since the high heterogeneity of pathological tissues and the inconspicuous resolution in multimodal magnetic resonance images, we propose a multimodal brain tumor image segmentation method based on ACU-Net network. In the beginning, we preprocess brain images to ensure the balanced number of categories. We adopt deep separable convolutional layers to replace the ordinary architecture in the U-Net to distinguish the spatial correlation and appearance correlation of the mapped convolutional channel. We introduce residual skip connection into the ACU-Net to heighten the propagation capacity of features and quicken the convergence speed of the network, to realize the capture of deep abnormal regions. We use the active contour model to against the image noise and edge cracks, come true the tracking of tumor deformation and solve the problem of edge blur in edema area, so as to divide the tumor core and enhanced necrotic parenchymal area exactly in the abnormal area. In this paper,17926 MRI images of 335 patients in the BraTS 2015, BraTS 2018, and BraTS 2019 datasets are used for training and verifying. Our experiments demonstrate that ACU-Net network has better performance than the other segmentation algorithms in subjective vision and objective indicators when applied to brain tumor image segmentation.
The auxiliary power module (APM) in the electrical vehicle converts the high voltage of battery pack to the low voltage to supply the electric power for the internal loads, including electric power ...steering, electric turbo, headed windshield and cooling pumps. The increasing demands on charging time and mileage have made the battery packs with even higher voltage (e.g. 800 V) a promising option. However, it brings a new challenge for the APM, and either the 1.2‐kV silicon carbide (SiC) device or the three‐level (TL) topology are used conventionally. This work proposes a cost‐effective hybrid SiC/Si‐based T‐type TL LLC$ LLC$ resonant converter for the vehicular APM application with a high step‐down ratio. The 1.2‐kV SiC and 650‐V Si devices are used as the main and auxiliary switches, respectively. It fully utilizes the voltage rating of device, and also improves the efficiency compared with conventional TL topology. To improve the gain range and electromagnetic interference performance, a variable frequency and adjustable phase‐shift modulation scheme is adopted. At the same time, the steady‐state time‐domain model is established to elaborate the operation principles, topology features, and boundary conditions for soft‐switching. Furthermore, the precise solutions for switching frequency and phase‐shift angle are figured out. Finally, the effectiveness of model is verified by the simulation as well as the experiment. A 1‐kW prototype for the application in the APM is demonstrated with the input voltage of 640–840 V and a constant output of 48 V/ 21 A.
PDF
