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130 result(s) for "Cai, Weibin"
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Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice
Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy. The current challenges for diabetic cardiomyopathy (DCM) are unclear mechanisms and no effective therapy in clinics. Here, the authors found that the decrease of cardiac retinol dehydrogenase 10 in type 2 diabetes leads to retinol metabolism disorder, cardiac lipid toxicity and cardiomyopathy development, suggesting that correcting the imbalance of cardiac retinol metabolism may be an effective strategy for the treatment of DCM.
IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr−/−) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD). To observe the role of IL-25 in lipid metabolism, model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo , whereas bone marrow-derived macrophages, the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro . IL-25 was decreased in NAFLD patients and obese mice. In addition, IL-25 reduced body weight gain and lipid accumulation, enhanced lipid uptake by macrophages and increased the expression of lipolysis and β-oxidation enzymes via alternatively activating macrophages. IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages. Furthermore, IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD + /NADH and ATP. In conclusion, IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity, highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.
Distinct cardiac energy metabolism and oxidative stress adaptations between obese and non-obese type 2 diabetes mellitus
: Little is known about the pathophysiological diversity of myocardial injury in type 2 diabetes mellitus (T2DM), but analyzing these differences is important for the accurate diagnosis and precise treatment of diabetic cardiomyopathy. This study aimed to elucidate the key cardiac pathophysiological differences in myocardial injury between obese and non-obese T2DM from mice to humans. : Obese and non-obese T2DM mouse models were successfully constructed and observed until systolic dysfunction occurred. Changes in cardiac structure, function, energy metabolism and oxidative stress were assessed by biochemical and pathological tests, echocardiography, free fatty acids (FFAs) uptake fluorescence imaging, transmission electron microscopy, . Key molecule changes were screened and verified by RNA sequencing, quantitative real-time polymerase chain reaction and western blotting. Further, 28 human heart samples of healthy population and T2DM patients were collected to observe the cardiac remodeling, energy metabolism and oxidative stress adaptations as measured by pathological and immunohistochemistry tests. : Obese T2DM mice exhibited more severe cardiac structure remodeling and earlier systolic dysfunction than non-obese mice. Moreover, obese T2DM mice exhibited severe and persistent myocardial lipotoxicity, mainly manifested by increased FFAs uptake, accumulation of lipid droplets and glycogen, accompanied by continuous activation of the peroxisome proliferator activated receptor alpha (PPARα) pathway and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β), and sustained inhibition of glucose transport protein 4 (GLUT4) and adipose triglyceride lipase (ATGL), whereas non-obese mice showed no myocardial lipotoxicity characteristics at systolic dysfunction stage, accompanied by the restored PPARα pathway and GLUT4, sustained inhibition of p-GSK-3β and activation of ATGL. Additionally, both obese and non-obese T2DM mice showed significant accumulation of reactive oxygen species (ROS) when systolic dysfunction occurred, but the NF-E2-related factor 2 (Nrf2) pathway was significantly activated in obese mice, while was significantly inhibited in non-obese mice. Furthermore, the key differences found in animals were reliably verified in human samples. : Myocardial injury in obese and non-obese T2DM may represent two different types of complications. Obese T2DM individuals, compared to non-obese individuals, are more prone to develop cardiac systolic dysfunction due to severe and persistent myocardial lipotoxicity. Additionally, anti-oxidative dysfunction may be a key factor leading to myocardial injury in non-obese T2DM.
Separation of Chloride and Sulfate Ions from Desulfurization Wastewater Using Monovalent Anions Selective Electrodialysis
The high concentration of chloride ions in desulphurization wastewater is the primary limiting factor for its reusability. Monovalent anion selective electrodialysis (S-ED) enables the selective removal of chloride ions, thereby facilitating the reuse of desulfurization wastewater. In this study, different concentrations of NaCl and Na2SO4 were used to simulate different softened desulfurization wastewater. The effects of current density and NaCl and Na2SO4 concentration on ion flux, permselectivity (PSO42−Cl−) and specific energy consumption were studied. The results show that Selemion ASA membrane exhibits excellent permselectivity for Cl− and SO42−, with a significantly lower flux observed for SO42− compared to Cl−. Current density exerts a significant influence on ion flux; as the current density increases, the flux of SO42− also increases but at a lower rate than that of Cl−, resulting in an increase in permselectivity. When the current density reaches 25 mA/cm2, the permselectivity reaches a maximum of 50.4. The increase in NaCl concentration leads to a decrease in the SO42− flux; however, the permselectivity is reduced due to the elevated Cl−/SO42− ratio. The SO42− flux increases with the increase in Na2SO4 concentration, while the permselectivity increases with the decrease in Cl−/SO42− ratio.
The Sandwich-Structured PVA/PA/PVA Tri-Layer Nanofiltration Membrane with High Performance for Desalination and Pollutant Removal
Nanofiltration (NF) has become a widely used technology in water treatment due to its environmental friendliness, energy efficiency, cost-effectiveness, and operational simplicity. However, polyamide (PA) NF membranes still face challenges, including low permeate flux, limited resistance to organic pollutants, and inadequate resilience to residual chlorine. To address these issues, this study developed a thin-film composite (TFC) NF membrane featuring a separation layer of sandwich structure. Initially, a single separation layer of polyvinyl alcohol (PVA) NF membrane was prepared, followed by the fabrication of a PA layer on its surface, and ultimately, a second PVA layer was constructed on the PA layer. The experimental results show that the PVA/PA/PVA sandwich structure TFC exhibits high permeability to pure water and robust resistance to both pollution and residual chlorine. The PVA-0.20/PA/PVA-0.20 TFC, prepared with a 0.20%w/v PVA solution, achieved a pure water flux of up to 22.05 L m−2 h−1 bar−1 (LMH/bar), which was 2.92 times higher than that of the control TFC membrane. Additionally, it demonstrated a salt rejection rate exceeding 96% for Na2SO4 and over 99% for Congo Red (CR) and Victoria Blue B (VB). In comparison with the control TFC membrane, the PVA-0.20/PA/PVA-0.20 membrane exhibited significantly enhanced resistance to pollution. Following immersion in a 1000 ppm NaClO solution for 4 h, the rejection rate of the control TFC membrane decreased markedly and that of the PVA-0.20/PA/PVA-0.20 membrane decreased marginally, indicating excellent resistance to residual chlorine. Due to the robust overall performance of the PVA/PA/PVA membrane, it holds potential advantages for application in treating reclaimed water or slightly polluted water.
Oncomirs miRNA-221/222 and Tumor Suppressors miRNA-199a/195 Are Crucial miRNAs in Liver Cancer: A Systematic Analysis
Background The high mortality rate of hepatocellular carcinoma (HCC) is partly due to a lack of good diagnostic markers and treatment strategies. Recently, several microRNA (miRNA) profiling studies were conducted with HCC; however, their inconsistency means that their diagnostic or therapeutic value is debatable. Aims This study aims to systematically evaluate the consistency of miRNAs from multiple independent studies. Methods A systematic analysis of miRNAs from eligible publications was conducted, followed by real-time PCRs. The targets of highly consistent miRNAs were collected using online programs, followed by enrichment analyses for gene ontology terms and Kyoto encyclopedia of genes and genomes pathways. Results In total, 241 differentially expressed miRNAs were reported in 13 HCC profiling studies, of which 137 were upregulated and 104 downregulated. Among consistently upregulated miRNAs (cutoff > fourfold), miRNA-222, miRNA-21, miRNA-221, miRNA-210, and miRNA-224 were found increased in 8, 6, 6, 5, and 5 different studies, respectively. Among 137 downregulated miRNAs, miRNA-195, miRNA-199a, miRNA-125b, and miRNA-99a were reported in 8, 8, 5, and 5 studies, respectively. These results were confirmed by real-time PCR. Enrichment analyses demonstrated that programmed cell death and proliferation play important roles during the interplay of miRNA with HCC. Conclusions miRNAs most consistently related to HCC are oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195.
Investigation of Surface Defects in Optical Components Based on Reflection Mueller Matrix Spectroscopy
Nanoscale defects on the surface of ultra-precision optical elements seriously affect the beam quality in optical systems. In response to the challenge of detecting nanoscale defects on optical component surfaces, we propose a method for the detection and classification of various types of defects on optical component surfaces via reflection Mueller matrix spectroscopy (RMMS). Firstly, an electromagnetic scattering theoretical model for various types of defects on the surface of optical elements and the incident and scattered fields were established by combining the bidirectional reflection distribution function (BRDF) and the Rayleigh–Rice vector scattering theory. Then, the optimal conditions for RMMS measurements were determined by numerically simulating the BRDF. On this basis, the surface roughness and pockmarks of the optical test plate were simulated and analyzed via RMMS, and the results were verified experimentally; then, dirty particles and pockmarks above the surface of the optical element and subsurface bubble defects (SSBD) were simulated and analyzed via RMMS. The results showed that some elements of the Mueller matrix could significantly distinguish defects on the surface of the optical element with dimensions smaller than the visible wavelength, and the dimensions of various types of defects of the element could be inverted using the values of the Mueller matrix elements. This method provides a theoretical basis and reference for the detection and classification of various types of defects in precision optical components.
Combination of pigment epithelium-derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis
Nasopharyngeal carcinoma (NPC), which has the highest incidence in South China, is mainly treated by radiotherapy. However, the survival rate remains low. Angiogenesis is closely correlated with progress of NPC. Thus, the combination of anti‐angiogenesis with radiation is an attractive strategy for NPC treatment. A heterogenic xenografted human NPC nude mice model was established to investigate the effect of pigment epithelium‐derived factor (PEDF), a potent anti‐angiogenic factor, and the combined effect of PEDF and radiotherapy on nasopharyngeal carcinoma. Pigment epithelium‐derived factor remarkably suppressed the growth of NPC by 43.52% and decreased the tumor microvessel density (MVD). Pigment epithelium‐derived factor had no effects on the proliferation and apoptosis of NPC cell lines by MTT and flow cytometry assay. However, PEDF decreased vascular endothelial growth factor (VEGF) in NPC cell lines by downregulation of hypoxia‐inducible factor 1α, a crucial transcriptional factor for VEGF expression, as demonstrated by western blotting and immunofluorescent staining assay. Interestingly, irradiation alone could also effectively downregulate VEGF and MVD of xenografted tumor, which indicates that irradiation suppresses NPC not only by killing tumor cells but also through anti‐angiogenesis. Furthermore, combined treatment of PEDF with irradiation enhanced the antitumor efficacy. The MVD and VEGF in the combined therapy were much less than in the treatment with PEDF or radiotherapy alone. Our observation demonstrated that the combination of PEDF with radiotherapy enhances the efficacy of the antitumor effect on NPC by the coordinated inhibition on angiogenesis, which implies the potential role of PEDF as an adjuvant agent for NPC treatment. (Cancer Sci 2011; 102: 1789–1798)
n-Octyltrichlorosilane Modified SAPO-34/PDMS Mixed Matrix Membranes for Propane/Nitrogen Mixture Separation
In this study, zeolite molecular sieve SAPO-34/polydimethylsiloxane (PDMS) mixed matrix membranes (MMMs) were prepared to recover propane. n-Octyltrichlorosilane (OTCS) was introduced to improve compatibility between SAPO-34 and PDMS, and enhance the separation performance of the MMMs. Physicochemical properties of the MMMs were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and water contact angle (WCA). Results showed that, after modification, alkyl chains were successfully grafted onto SAPO-34 without changing its crystal structure, particles in the MMMs were evenly distributed in the base film, and the hydrophobicity of the MMMs was enhanced. Moreover, the effects of SAPO-34 filling content, operating pressure, and feed gas concentration on the separation performance was explored. This indicated that the modification with OTCS effectively enhanced the separation performance of SAPO-34/PDMS MMMs. When the filling content of modified SAPO-34 was 15%, the maximal separation factor of 22.1 was achieved, and the corresponding propane permeation rate was 101 GPU.
The Influence of Water-Level Fluctuation on the Instability and Seepage Failure of Dump-Fill Cofferdam
Due to the double disturbance effect of dredging and filling, there will be a problem with weir slope stability after the formation of a fill type saturated clay weir. In order to study the influence of water-level fluctuation on the instability and seepage failure of the dump-fill cofferdam, the saturated-unsaturated seepage theory and strength reduction method are embedded into the finite element system such that the fluid-solid coupling stability of the dump-fill cofferdam is analyzed. The results show that the influence of water-level fluctuation on the instability and seepage failure of the dump-fill cofferdam can be revealed by the coupling analysis excellently. The variation of the saturation line of the cofferdam is consistent with the variation of water-level rising, but the change response of the saturation line of the cofferdam has a lag property during the water-level decline process in that the water level changes faster. The maximum displacement of the cofferdam can be approximated as two stages, namely, the stable growth stage and the accelerated growth stage (slip initiation), in which the influence of the water-level fluctuation on the displacement of stable growth stage is more obvious. Based on the fluid-solid coupling analysis, the most dangerous sliding surface of the cofferdam is located at the position of the horse path, with a critical strength reduction coefficient of approximately 1.475. The possibility of seepage failure of the cofferdam will be increased if the water level exceeds the height of the impermeable wall.