Hepatic Glucose Metabolism Disorder Induced by Adipose Tissue-Derived miR-548ag via DPP4 Upregulation.

The present study aimed to explore the molecular mechanism underlying the regulation of glucose metabolism by miR-548ag. For the first time, we found that miR-548ag expression was elevated in the abdominal adipose tissue and serum of subjects with obesity and type 2 diabetes mellitus (T2DM). The conditional knockout of adipose tissue Dicer notably reduced the expression and content of miR-548ag in mouse adipose tissue, serum, and liver tissue. The combined use of RNAseq, an miRNA target gene prediction software, and the dual luciferase reporter assay confirmed that miR-548ag exerts a targeted regulatory effect on DNMT3B and DPP4. miR-548ag and DPP4 expression was increased in the adipose tissue, serum, and liver tissue of diet-induced obese mice, while DNMT3B expression was decreased. It was subsequently confirmed both in vitro and in vivo that adipose tissue-derived miR-548ag impaired glucose tolerance and insulin sensitivity by inhibiting DNMT3B and upregulating DPP4. Moreover, miR-548ag inhibitors significantly improved the adverse metabolic phenotype in both obese mice and db/db mice. These results revealed that the expression of the adipose tissue-derived miR-548ag increased in obese subjects, and that this could upregulate the expression of DPP4 by targeting DNMT3B, ultimately leading to glucose metabolism disorder. Therefore, miR-548ag could be utilized as a potential target in the treatment of T2DM.

miR-548ag functions as an oncogene by suppressing MOB1B in the development of obesity-related endometrial cancer.

Obesity is a high-risk factor in the development of endometrial cancer (EC). Our previous study observed that miR-548ag was significantly overexpressed in the sera of obese individuals. Here, we report the function of miR-548ag and its mechanism in promoting the obesity-related progression of EC. The content of miR-548ag was increased in the serum of obese EC individuals. Bioinformatics analysis indicated that the survival rate of EC patients with a higher expression of miR-548ag was significantly reduced. The Mps One Binder Kinase Activator 1B (MOB1B, the core member of the Hippo signaling pathway) is a direct target gene of miR-548ag, which is inversely correlated with the expression of miR-548ag. The overexpression of miR-548ag enhances the proliferation, invasion, and migration, and inhibits apoptosis by downregulating the expression of MOB1B, leading to the deactivation of the Hippo pathway in EC cell lines and contributing to tumor progression in vivo. Our study has established that miR-548ag functions as an oncogene by suppressing MOB1B in the development of obesity-related EC.

Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway.

OBJECTIVE: Our previous results have shown that obesity-induced excessive palmitic acid (PA) can promote the expression of KLF7, which plays a vital role in regulation of inflammation, glucose metabolism. But the exact mechanism of PA up-regulating the expression of KLF7 is not clear yet. This study is intend to explore whether PA promoting KLF7 expression through GPRs/NF-κB signaling pathway, causing inflammation and glucose metabolism disorders. METHODS: Cells were blocked GPRs/NF-κB under PA stimulation in vitro to demonstrate the molecular mechanism of PA up-regulates KLF7 expression. The regulatory effect of p65 on KLF7 was detected by luciferase reporter gene assay. Blocking GPRs/NF-κB in diet-induced obesity mice to detect the expression of KLF7, inflammatory cytokines and glucose metabolism related factors, clarifying the effects of GPRs/NF-κB on KLF7 in vivo. RESULTS: In 3T3-L1 adipocytes and HepG2 cells, PA could up-regulate the expression of KLF7 by promoting the GPR40/120-NF-κB signaling pathway, leading to inflammation and reduced glucose consumption (p < 0.05 for both). Luciferase reporter gene assay and ChIP assay showed that p65 could transcriptionally up-regulates the expression of KLF7. In high-fat diet (HFD) mice, after intraperitoneal injection of GPR40 or GPR120 blocker, the levels of p-p65 and KLF7 in epididymal white adipose tissue and liver were significantly decreased (p < 0.05 for both). Pharmacological inhibition of p-p65 significantly attenuated KLF7 expression and improved glucose tolerant and insulin sensitive (p < 0.05 for both). CONCLUSIONS: Our results indicate that obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 signaling pathway.

miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.

AIM/INTRODUCTION: Obesity is considered an important risk factor for many metabolic disorders, especially type 2 diabetes mellitus, and microRNAs (miRNAs) play a vital role in the development of type 2 diabetes mellitus. Therefore, we conducted this study to investigate the role of miR-4431 in the obesity-associated pathobiology of type 2 diabetes mellitus. MATERIALS AND METHODS: Subjects were divided into normal control (n = 36), obese (n = 36), and type 2 diabetes mellitus (n = 12) groups, and serum miR-4431 levels were analyzed. Adenovirus-vectored miR-4431 mimic or sponge was intraperitoneally injected into the normal diet group and the high-fat diet group (HFD) mice to investigate glucose tolerance, insulin sensitivity, and lipid levels. The downstream target genes of miR-4431 were predicted using bioinformatics, and they were verified in vitro. RESULTS: Serum miR-4431 levels were significantly high in obese and type 2 diabetes mellitus individuals, and positively correlated with the body mass index and fasting plasma glucose levels. In HFD mice, miR-4431 levels in the serum, white adipose tissue, and liver were significantly increased. Moreover, miR-4431 impaired glucose tolerance, insulin sensitivity, and lipid metabolism in mice. Bioinformatic prediction suggested that TRIP10 and PRKD1 could be the downstream target genes of miR-4431. The HFD mice showed a remarkable reduction in the mRNA levels of TRIP10 and PRKD1 in the liver, which were countered by blocking miR-4431. In HepG2 and L02 cells, miR-4431 could downregulate TRIP10 and PRKD1 while blocking glucose uptake. The luciferase reporter assay showed that miR-4431 could bind TRIP10 and PRKD1 3'-UTR. CONCLUSION: miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.

PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.

BACKGROUND: Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. METHODS: Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. RESULTS: KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 µM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 µM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn't contribute to PA or OA-induced KLF15 reduction. CONCLUSIONS: Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.

Influence of Welding Speed on Microstructure and Mechanical Properties of 5251 Aluminum Alloy Joints Fabricated by Self-Reacting Friction Stir Welding.

In the present study, 8 mm-thick 5251 aluminum alloy was self-reacting friction stir welded (SRFSW) employing an optimized friction stir tool to analyze the effect of welding speed from 150 to 450 mm/min on the microstructure and mechanical properties at a constant rotation speed of 400 rpm. The results indicated that high-quality surface finish and defect-free joints were successfully obtained under suitable process parameters. The microhardness distribution profiles on the transverse section of joint exhibited a typical "W" pattern. The lowest hardness values located at the heat-affected zone (HAZ) and the width of the softened region decreased with increasing welding speed. The tensile strength significantly decreased due to the void defect, which showed mixed fracture characteristics induced by the decreasing welding speed. The average tensile strength and elongation achieved by the SRFSW process were 242.61 MPa and 8.3% with optimal welding conditions, and the fracture surface exhibited a typical toughness fracture mode.

Potential biomarker in serum for predicting susceptibility to type 2 diabetes mellitus: Free fatty acid 22:6.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is closely linked to increased levels of free fatty acids (FFAs) in obese individuals, although which FFA is most associated with type 2 diabetes mellitus is unclear. This study aimed to identify the specific FFAs that best predict the occurrence of type 2 diabetes mellitus in obese individuals, and assess their potential application value. MATERIALS AND METHODS: Participants were divided into three groups: a normal weight group (n = 20), an obese group (n = 10) and a type 2 diabetes mellitus group (n = 10). FFAs in serum samples were determined by ultra-high-pressure liquid chromatography-mass spectrometry, and orthogonal partial least squares discriminant analysis models were used to study the FFA profile among the three groups. RESULTS: Compared with the normal weight group, 14 FFAs (C8:0/10:0/14:0/16:1/18:1/20:2/ 20:3 /20:4/ 20:5/ 22:6/7:0/9:0/11:0 and C13:0) were significantly increased in the obese group, and nine FFAs (C14:0, C18:1, C20:1, C 18:2, C20:2, C20:3, C18:3, C20:5 and C22:6) were significantly increased in the type 2 diabetes mellitus group. Subsequently, the Venn diagram results showed that six FFAs (C14:0, C18:1, C20:2, C20:3, C20:5 and C22:6) were significantly increased in both the obese and type 2 diabetes mellitus groups. Among these six, C22:6 was finally identified as an independent risk factor for type 2 diabetes mellitus, and had a great potential to predict the susceptibility to type 2 diabetes mellitus (area under the curve 0.803). CONCLUSIONS: C22:6 can be an independent risk factor for type 2 diabetes mellitus, and it has a great potential to predict the susceptibility to type 2 diabetes mellitus.

Assessing the occurrence and status of wheat in late Neolithic central China: the importance of direct AMS radiocarbon dates from Xiazhai.

The introduction of wheat into central China is thought to have been one of the significant contributions of interactions between China and Central Asia which began in the 3rd millennium bc. However, only a limited number of Neolithic wheat grains have been found in central China and even fewer have been directly radiocarbon dated, making the date when wheat was adopted in the region and its role in subsistence farming uncertain. Based on systematic archaeobotanical data and direct dating of wheat remains from the Xiazhai site in central China, as well as a critical review of all reported discoveries of Neolithic and Bronze Age wheat from this region, we conclude that many wheat finds are intrusive in Neolithic contexts. We argue that the role of wheat in the subsistence of the late Neolithic and early Bronze Age of central China was minimal, and that wheat only began to increase in its subsistence role in the later Bronze Age during the Zhou dynasty after ca. 1000 bc.

Perfluoroalkyl acids (PFAAs) with isomer analysis in the commercial PFOS and PFOA products in China.

Perfluoroalkyl acids (PFAAs) have been widely used in consumer and industrial products for decades and are widely detected in the environment and humans all over the world. The information on the isomeric profiles of commercial products is important to identify the manufacturing origins of PFAAs in the environment. For the first time, the PFAA compositions and isomeric profiles of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) were reported in three PFOS and five PFOA commercial products manufactured in China. The purity of the three PFOS products was 76.7-80.6%. The major impurity in the PFOS products is PFOA, which contributes more than 10%. Other impurities include perfluorohexanesulfonate (PFHxS), perfluorohexanoate (PFHxA) and perfluoroheptanoate acids (PFHpA). The percentage of linear PFOS (n-PFOS) in the three products was 66.2-71.9%, similar to that in the product manufactured by 3M (70.3%). The purity of the five PFOA products was relatively high (94.0-95.8%), and the major impurity was PFOS (2.06-3.09%). The percentage of n-PFOA in the five PFOA products was 76.4-77.9%, which was similar to that in the 3M PFOA (78%). Although it is widely accepted that telomerization is currently the predominant manufacturing method for PFOA, yielding an isomerically pure and linear product, the results in the present study suggest that electrochemical fluorination is still used by some manufacturers in China.

Highly active magnetic bismuth tungstate/magnetite composite under visible light irradiation in the presence of hydrogen peroxide.

Bi2WO6/Fe3O4 composites were synthesized using hydrothermal method and their photocatalytic activity to degrade rhodamine B (RhB) under visible light irradiation assisted with H2O2 and underlying mechanisms were investigated. The composites were 3D flower-like microspheres constructed by 2D Bi2WO6 nanosheets loaded with spherical Fe3O4 nanoparticles. The composited photocatalysts could be easily harvested from the reaction solution by an external magnetic field. In the presence of H2O2, a large amount of hydroxyl radicals (·OHs) were produced by H2O2 reacting with photogenerated electrons. Fe3O4 not only promoted the separation of hole-electron pairs but also acted as a Fenton-like reagent, expediting the production of ·OH. Thus, the composites in the presence of H2O2 displayed much higher photocatalytic efficiency to degrade RhB than pure Bi2WO6. 98% of RhB (initial concentration 10 mg/L) was degraded in 2 h visible irradiation and 60% of total organic carbon (TOC) was removed in 3 h by 0.5 g/L Bi2WO6/Fe3O4 (5:1). The composite displayed high photodegradation efficiency at pH 3-9. Our study suggests that a visible light driven and highly active magnetic photocatalyst-Fenton coupling oxidation system may have potential application in water treatment and environmental cleaning.

Novel mesoporous graphite carbon nitride/BiOI heterojunction for enhancing photocatalytic performance under visible-light irradiation.

A novel organic-inorganic three-dimensional (3D) mesoporous graphite carbon nitride/BiOI (MCN/BiOI) heterojunction photocatalyst with excellent visible-light-driven photocatalytic performance was synthesized by a facile solvothermal method and used for degradation of bisphenol A (BPA) in water. After hybridization with MCN, a heterojunction was formed and the photogenerated carriers could be effectively separated by the internal electric field built at the heterojunction interface. The photocatalytic and photoelectrochemical performance of BiOI were improved and much higher than pure BiOI and MCN. The best photocatalytic performance was achieved with MCN proportion of 10%, and the kobs was approximately 1.6 times of pure BiOI and 3.4 times of MCN under simulated solar light irradiation, respectively. The photocurrent intensity generated by 10%-MCN/BiOI electrode was about 1.5 and 2.0 times of those induced by BiOI and MCN under visible-light irradiation, respectively. The superoxide radical species were predominant in the reaction system.

Enhanced photocatalytic performance of boron doped Bi2WO6 nanosheets under simulated solar light irradiation.

Bi2WO6 doped with different amounts of boron atoms (0.1, 0.5, 1.0, 5.0 and 10% B) were synthesized using hydrothermal method and their photocatalytic activities to degrade rhodamine B (RhB) under simulated solar light was investigated. The successful incorporation of B atoms in Bi2WO6 was proved by FT-IR, Raman spectra and XPS. Doping with B could affect the pore structure and volume. 0.5% B/Bi2WO6 displayed more mesopores with higher total pore volume than pure Bi2W6; while the pores of 10% B/Bi2WO6 mainly distributed in microporous range with much less total pore volume. As a result, 0.5% B/Bi2WO6 displayed stronger adsorption capacity to RhB, favoring the photodegradation. In addition, the doped B atoms could act as electron traps and facilitate the separation of photogenerated electron-hole pairs due to its electron deficient and oxytropic characteristics. 0.5% B/Bi2WO6 displayed the highest photocatalytic activity under simulated solar light with rate constant (kobs) 8.8 times of that using pure Bi2WO6. Its photoactivity was affected by solution pH and the optimum was achieved at pH 7. At this condition, around 100% of RhB (10(-5)mol/L) was degraded in 180 min. The photogenerated holes were the main active species responsible for the photodegradation of RhB by B/Bi2WO6.