Dietary intervention reprograms bone marrow cellular signaling in obese mice

ObjectivesThe current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity.MethodsMice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt).ResultsWeight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-β-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group.ConclusionsOur findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual

Abnormal bile acid metabolism is an important feature of gut microbiota and fecal metabolites in patients with slow transit constipation

Destructions in the intestinal ecosystem are implicated with changes in slow transit constipation (STC), which is a kind of intractable constipation characterized by colonic motility disorder. In order to deepen the understanding of the structure of the STC gut microbiota and the relationship between the gut microbiota and fecal metabolites, we first used 16S rRNA amplicon sequencing to evaluate the gut microbiota in 30 STC patients and 30 healthy subjects. The α-diversity of the STC group was changed to a certain degree, and the β-diversity was significantly different, which indicated that the composition of the gut microbiota of STC patients was inconsistent with healthy subjects. Among them, Bacteroides, Parabacteroides, Desulfovibrionaceae, and Ruminiclostridium were significantly upregulated, while Subdoligranulum was significantly downregulated. The metabolomics showed that different metabolites between the STC and the control group were involved in the process of bile acids and lipid metabolism, including taurocholate, taurochenodeoxycholate, taurine, deoxycholic acid, cyclohexylsulfamate, cholic acid, chenodeoxycholate, arachidonic acid, and 4-pyridoxic acid. We found that the colon histomorphology of STC patients was significantly disrupted, and TGR5 and FXR were significantly downregulated. The differences in metabolites were related to changes in the abundance of specific bacteria and patients’ intestinal dysfunction. Analysis of the fecal genomics and metabolomics enabled separation of the STC from controls based on random forest model prediction [STC vs. control (14 gut microbiota and metabolite biomarkers)—Sensitivity: 1, Specificity: 0.877]. This study provided a perspective for the diagnosis and intervention of STC related with abnormal bile acid metabolism

RF Spatial Modulation Using Antenna Arrays

A new method of spatial linear modulation is presented for the RF signal modulation. The constant envelope and phase modulated signals are transmitted to an antenna array and then combined in space; the linear modulation is realized at the same time. The concentric antenna pairs are applied to eliminate the mismatch of phase delay among the modulated signals from different antenna pairs. The measurement results of an RF signal around 2.45 GHz modulated by a 3.84 Mbps QPSK signal are presented. The proposed spatial modulator is able to simplify RF transmitter design and achieve highly efficient power transmission

Generalized bivariate mixture model of directional wind speed in mixed wind climates

Probabilistic modeling of the directional wind speed has been an important topic in the fields of wind energy assessment as well as structural wind-resistant design. The mixture model is required for the probabilistic modeling on the directional wind speed as the wind climates often show the mixture nature. For accuracy and robustness concerns in engineering applications, a generalized bivariate mixture (GBM) model of the directional wind speed is developed by using the copula-based bivariate distribution function. In this model, the marginal distributions and connection function for each sub-model can be flexibly defined. In parametrizing the model, the data-driven parametric estimation including a data preprocess and an automatic unsupervised fitting process is presented. The performance of GBM model is verified using two data sets and compared with the offset elliptical normal mixture (OENM) model. The robustness of GBM model is found for its good performance in fitting to the targets with or without smoothing process, and in tackling directional wind speed with the extremely complex probability characteristic

Radial forces of waterjet propulsion mixed-flow pump

Fluctuations of fluid pressure in hydraulic machinery can cause resonance and fatigue da-mage of blades. In order to study fluid-induced forces, which are caused by impeller-diffuser interaction, unsteady radial forces due such an effect was conducted in a mixed-flow pump with a vaned diffuser by using CFD computation and model experiment. A closed-loop test rig was built for the pump and a co-rotating dynamometer was installed between the impeller and the pump shaft to measure the instantaneous forces and moments on the impeller. The dynamic behavior of the experimental rotor-shaft system was determined by carrying out extensive calibrations. The measured forces at the blade passing frequency showed an unexpected dependency on flow rate. Another important observation was that the blade excitation forces cause the impeller to whirl in the direction opposite to shaft rotation. The computed global characteristics and the magnitude of blade interaction forces showed good agreement with measurements, respectively. The measured results were compared with the unsteady ones estimated by using CFD code-Fluent. Over a large range of flow rates, the trend of force variation agrees well with the measurements. The reasons for deviation of prediction from experiment were explained

Flow pattern and hydraulic performance of tubular pump

In order to establish a relationship between flow pattern and hydraulic performance of a tubular pump, the flow pattern and hydraulic performance at a low flow rate, best efficiency point and a high flow rate were investigated by means of flow simulation, performance test and PIV measurement in a tubular pump. The steady flow field in the pump was obtained through solving the time-averaged N-S equations in the multiple reference frames (MRF) with the help of the SIMPLEC algorithm and the RNG k-ε turbulence model. The flow patterns in the pump were analyzed at different operating points. There was a large recirculation zone before the blades inlet when the pump operated at the low flow rate. The flow patterns were fine and there was no any reverse flow regions in the pump when it worked at the BEP (Best Efficiency Point) and the high flow rate. The results indicated the hydraulic loss in the suction pipe is similar to that in a normal pipe, but the hydraulic loss in the discharge pipe depended on operating points. A minimum hydraulic loss in the discharge appeared at the BEP. The estimated performance was in agreement with the test data, both the predicted flow patterns and the PIV measurements showed that there was remarked reverse flow region in front of blades near the tip and there existed a large separated flow zone near the hub downstream of blades at the low flow rate. Thus, attention should be paid on the flow pattern in impeller and guide vanes at a low flow rate in the optimal design of such a tubular pump

DataSheet_1_Dietary intervention reprograms bone marrow cellular signaling in obese mice.docx

ObjectivesThe current study aimed to investigate the pathogenesis of obesity-induced impaired bone mass accrual and the impact of dietary intervention on bone density in the mouse model of obesity.MethodsMice were fed with chow diet (CD) for 10 months, high-fat-diet (HFD) for 10 months, or HFD for 6 months then transferred to chow diet for 4 months (HFDt).ResultsWeight loss and decreased intrahepatic lipid accumulation were observed in mice following dietary intervention. Additionally, HFD feeding induced bone mass accrual, while diet intervention restrained trabecular bone density. These changes were further reflected by increased osteogenesis and decreased adipogenesis in HFDt mice compared to HFD mice. Furthermore, HFD feeding decreased the activity of the Wingless-related integration site (Wnt)-β-Catenin signaling pathway, while the Wnt signaling was augmented by diet intervention in the HFDt group.ConclusionsOur findings suggest that a HFD inhibits bone formation and that dietary intervention reverses this inhibition. Furthermore, the dietary intervention was able to compensate for the suppressed increase in bone mass to a level comparable to that in the CD group. Our study suggests that targeting the Wnt signaling pathway may be a potential approach to treat obesity-induced impaired bone mass accrual.</p

Decreased levels of active SMAD2 correlate with poor prognosis in gastric cancer.

BACKGROUND: TGF-β plays a dual role in the progression of human cancer. During the early stages of carcinogenesis, TGF-β functions as a tumor suppressor. During the late stages of tumor development, however, TGF-β can promote tumor growth and metastasis. A shift in Smad2/3 phosphorylation from the carboxy terminus to linker sites is a key event determining biological function of TGF-β in colorectal and hepatocellular carcinoma. In the present study, we investigated the potential role of differential Smad2/3 phosphorylation in gastric adenocarcinoma. METHODOLOGY: Immunohistochemical staining with anti-P-Smad2/3C and P-Smad2/3L antibodies was performed on 130 paraffin-embedded gastric adenocarcinoma specimens. The relationship between P-Smad2/3C and P-Smad2/3L immunohistochemical score and clinicopathologic characteristics of patients was analyzed. Real time PCR was used to measure mRNA expression of Smad2 and Smad3 in cancer and surrounding non-tumor tissue. PRINCIPAL FINDINGS: No significant P-Smad2L and/or P-Smad3L positive staining was detected in the majority of specimens (positive staining in 18/130 samples). Positive P-Smad2/3L staining was not associated with a decrease in carboxyterminal phosphorylation staining. Loss of P-Smad2C remarkably correlated with depth of tumor infiltration and poor differentiation of cancer cells in patients with gastric cancer. No correlation was detectable between P-Smad3C and clinicopathologic characteristics of gastric adenocarcinoma. However, co-staining analysis revealed that P-Smad3C co-localised with α-SMA and collagen I in gastric cancer cells, indicating a potential link between P-Smad3C and epithelial-to-mesenchymal transition of cancer. Real time PCR demonstrated reduced mRNA expression of Smad2 in gastric cancer when compared with surrounding non-tumor tissue in 15/16 patients. CONCLUSIONS: Loss of P-Smad2C tightly correlated with cancer invasion and poor differentiation in gastric cancer. Contrary to colorectal and hepatocellular carcinoma, canonical carboxy-terminal phosphorylation, but not linker phosphorylation, of Smad2 is critical for gastric cancer

Figure 5

<p>Real-time PCR was performed to determine mRNA expression of Smad2 (<b>A</b>) and Smad3 (<b>B</b>) in 16 gastric cancer tissues and surrounding non-tumor tissues (No. 1–5: middle differentiated cancer; No. 6–13: poorly differentiated cancer and No. 14–16: signet-ring cell cancer).</p

Correlation between P-Smad2C change (cancer cells versus normal tissues) and differentiation of gastric cancer (G) (n = 130).

<p>Kendall-tau rank correlation coefficient.</p