Cerebrovascular risk factors impact brain phenotypes and cognitive function in healthy population

Cognitive decline is a major characteristic of ageing. Studies show that cardiovascular risk factors (CVR) are associated with cognitive declines and brain phenotypes, but the causality between CVR and cognitive function needs further understanding. In this study, we seek to investigate the causalities between CVR, brain phenotypes and cognitive function. We first generate a general factor (gCVR) representing common CVR and a score representing the polygenic risk (PRS). We then identify phenotypes of brain and cognitive functions associated with gCVR and PRS. Moreover, we conduct causal mediation analysis to evaluate the indirect effect of PRS through CVR, which infers the causality of gCVR on brain phenotypes and cognition. Further, we test the mediation effect of gCVR on the total effect of brain phenotypes on cognitive function. Finally, the causality between CVR and brain phenotypes is cross validated using Mendelian randomization (MR) with genetic instruments. The results show that CVR mediates the effect of PRS on brain phenotypes and cognitive function, and CVR also mediates the effect of brain phenotypes on cognitive changes. Additionally, we validate that the variation in a few brain phenotypes., e.g., volume of grey matter, are caused by CVR

Cerebrovascular risk factors impact brain phenotypes and cognitive function in healthy population

Cognitive decline is a major characteristic of ageing. Studies show that cardiovascular risk factors (CVR) are associated with cognitive declines and brain phenotypes, but the causality between CVR and cognitive function needs further understanding. In this study, we seek to investigate the causalities between CVR, brain phenotypes and cognitive function. We first generate a general factor (gCVR) representing common CVR and a score representing the polygenic risk (PRS). We then identify phenotypes of brain and cognitive functions associated with gCVR and PRS. Moreover, we conduct causal mediation analysis to evaluate the indirect effect of PRS through CVR, which infers the causality of gCVR on brain phenotypes and cognition. Further, we test the mediation effect of gCVR on the total effect of brain phenotypes on cognitive function. Finally, the causality between CVR and brain phenotypes is cross validated using Mendelian randomization (MR) with genetic instruments. The results show that CVR mediates the effect of PRS on brain phenotypes and cognitive function, and CVR also mediates the effect of brain phenotypes on cognitive changes. Additionally, we validate that the variation in a few brain phenotypes., e.g., volume of grey matter, are caused by CVR

Comparison of a solvent mixture assisted dilute acid and alkali pretreatment in sugar production from hybrid Pennisetum

Abstract(#br)The effects of an acetone-butanol-ethanol (ABE) mixture on dilute H 2 SO 4 and NaOH pretreatment for enzymatic saccharification of hybrid Pennisetum (HP) were investigated. The results showed that ABE assisted the removal of xylan and lignin during H 2 SO 4 and NaOH pretreatment, respectively. The glucose yield of HP increased from 33.6% to 52.9% with the assistance of a relatively higher concentration of ABE mixture (ABE4) during H 2 SO 4 pretreatment, and during NaOH pretreatment, a lower concentration of ABE (ABE2) increased the glucose yield from 64.6% to 80.2%. The hydrolysis yield increases were related to the compositional change and surface characteristics of the pretreated materials. As observed by X-ray photoelectron spectroscopy, ABE4 resulted in a greater lignin content on the surface of materials than that produced by ABE2 during NaOH pretreatment, which possibly increased the non-productive adsorption of cellulase, thus decreasing the hydrolysis yield. The results suggested that an ABE mixture could be used as an auxiliary agent for further increasing of the digestibility of acid- and alkali-pretreated lignocellulosic materials. However, the digestibility was different depending on the concentrations of ABE during acid and alkali pretreatments

SP13786 Inhibits the Migration and Invasion of Lung Adenocarcinoma Cell A549 by Supressing Stat3-EMT via CAFs Exosomes

Background and objective Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs. Methods CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods. Results α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05). Conclusion As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells

Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas

Insulin-like growth factor binding protein 2 (IGFBP-2) is a malignancy-associated protein measurable in tumors and blood. Increased IGFBP-2 is associated with shortened survival of advanced glioma patients. Thus, we examined plasma IGFBP-2 levels in glioma patients and healthy controls to evaluate its value as a plasma bio-marker for glioma. Plasma IGFBP-2 levels in 196 patients with newly diagnosed glioma and 55 healthy controls were analyzed using an IGFBP-2 ELISA kit. Blood was collected before surgery, after two-cycle adjuvant chemotherapy, and at recurrence. Plasma IGFBP-2 levels were correlated with disease-free survival (DFS) using Cox regression analyses. We found that preoperative plasma IGFBP-2 levels were significantly higher in high-grade glioma patients (n = 43 for grade III glioma; n = 72 for glioblastoma multiforme [GBM]) than in healthy controls (n = 55; p < 0.001) and low-grade (grade II) glioma patients (n = 81; p < 0.001). No significant differences in preoperative plasma IGFBP-2 levels were observed between grade III glioma and GBM patients or between grade II glioma patients and healthy controls. After recurrence, plasma IGFBP-2 levels were significantly increased in GBM patients (n = 26; p < 0.001). Preoperative plasma IGFBP-2 levels were significantly correlated with DFS in GBM patients (hazard ratio, 1.404; 95% confidence interval, 1.078–1.828; p = 0.012). We conclude that preoperative plasma IGFBP-2 levels are significantly higher in high-grade glioma patients than in low-grade glioma patients and healthy subjects, and are significantly correlated with recurrence and DFS in patients with GBM. Longitudinal studies with a larger study population are needed to confirm these findings

Morphological Control of Supported ZnO Nanosheet Arrays and Their Application in Photodegradation of Organic Pollutants

Supported nanostructured photocatalysis is considered to be a sustainable and promising method for water pollution photodegradation applications due to its fascinating features, including a high surface area, stability against aggregation, and easy handling and recovery. However, the preparation and morphological control of the supported nanostructured photocatalyst remains a challenge. Herein, a one-step hydrothermal method is proposed to fabricate the supported vertically aligned ZnO nanosheet arrays based on aluminum foil. The morphologically controlled growth of the supported ZnO nanosheet arrays on a large scale was achieved, and the effects of hydrothermal temperature on morphologic, structural, optical, and photocatalytic properties were observed. The results reveal that the surface area and thickness of the nanosheet increase simultaneously with the increase in the hydrothermal temperature. The increase in the surface area enhances the photocatalytic activity by providing more active sites, while the increase in the thickness reduces the charge transfer and thus decreases the photocatalytic activity. The influence competition between the area increasing and thickness increasing of the ZnO nanosheet results in the nonlinear dependence between photocatalytic activity and hydrothermal temperature. By optimizing the hydrothermal growth temperature, as fabricated and supported ZnO nanosheet arrays grown at 110 &deg;C have struck a balance between the increase in surface area and thickness, it exhibits efficient photodegradation, facile fabrication, high recyclability, and improved durability. The RhB photodegradation efficiency of optimized and grown ZnO nanosheet arrays increased by more than four times that of the unoptimized structure. With 10 cm2 of as-fabricated ZnO nanosheet arrays, the degradation ratio of 10 mg/L MO, MB, OFL, and NOR was 85%, 51%, 58%, and 71% under UV irradiation (365 nm, 20 mW/cm2) for 60 min. All the target pollutant solutions were almost completely degraded under UV irradiation for 180 min. This work offers a facile way for the fabrication and morphological control of the supported nanostructured photocatalyst with excellent photodegradation properties and has significant implications in the practical application of the supported nanostructured photocatalyst for water pollution photodegradation

Morphological Control of Supported ZnO Nanosheet Arrays and Their Application in Photodegradation of Organic Pollutants

Supported nanostructured photocatalysis is considered to be a sustainable and promising method for water pollution photodegradation applications due to its fascinating features, including a high surface area, stability against aggregation, and easy handling and recovery. However, the preparation and morphological control of the supported nanostructured photocatalyst remains a challenge. Herein, a one-step hydrothermal method is proposed to fabricate the supported vertically aligned ZnO nanosheet arrays based on aluminum foil. The morphologically controlled growth of the supported ZnO nanosheet arrays on a large scale was achieved, and the effects of hydrothermal temperature on morphologic, structural, optical, and photocatalytic properties were observed. The results reveal that the surface area and thickness of the nanosheet increase simultaneously with the increase in the hydrothermal temperature. The increase in the surface area enhances the photocatalytic activity by providing more active sites, while the increase in the thickness reduces the charge transfer and thus decreases the photocatalytic activity. The influence competition between the area increasing and thickness increasing of the ZnO nanosheet results in the nonlinear dependence between photocatalytic activity and hydrothermal temperature. By optimizing the hydrothermal growth temperature, as fabricated and supported ZnO nanosheet arrays grown at 110 °C have struck a balance between the increase in surface area and thickness, it exhibits efficient photodegradation, facile fabrication, high recyclability, and improved durability. The RhB photodegradation efficiency of optimized and grown ZnO nanosheet arrays increased by more than four times that of the unoptimized structure. With 10 cm2 of as-fabricated ZnO nanosheet arrays, the degradation ratio of 10 mg/L MO, MB, OFL, and NOR was 85%, 51%, 58%, and 71% under UV irradiation (365 nm, 20 mW/cm2) for 60 min. All the target pollutant solutions were almost completely degraded under UV irradiation for 180 min. This work offers a facile way for the fabrication and morphological control of the supported nanostructured photocatalyst with excellent photodegradation properties and has significant implications in the practical application of the supported nanostructured photocatalyst for water pollution photodegradation

Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model

Abstract Background This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model. Methods T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2, caspase 3, and osteoblast marker genes were detected by RT-qPCR. Results The biomechanical properties of bones from DIO-FENO group were significantly lower than those in the control and DIO-PBS groups. Besides, the trabecular number was lower than those of the other groups, though the cortical porosity was decreased compared with that of DIO-PBS group because of the increase of apoptotic cells. The expression of osteocalcin and collagen I were decreased after treatment with fenofibrate in T2DM mice. Moreover, the cell viability was decreased after treated with different concentrations of fenofibrate, and the expression of Runx2 decreased after treated with high dose of fenofibrate. Conclusion Fenofibrate decreases the bone quality of T2DM mice through decreasing the expression of collagen I and osteocalcin, which may be resulted from the down regulation of Runx2 expression

Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

Abstract A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis