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Herein, NiCoP nanoparticles decorated on reduced graphene oxide (rGO) were synthesized through a two-step hydrothermal-phosphorization route as enhanced microwave absorbers. Microstructure investigations indicate that NiCoP nanoparticles are uniformly anchored on the surface of rGO. Compared with the bare NiCoP, NiCoP/rGO nanocomposites reveal clearly improved microwave absorbing performance. The strongest reflection loss (RL) values of NiCoP/rGO hybrid absorber can reach −20.61 dB at 6.43 GHz with a matching thickness of 4.4 mm, and a broad effective absorption bandwidth (RL < −10 dB) of 4.13 GHz (13.87–18 GHz) can be obtained at only 2.0 mm, while the RL values of the pure NiCoP cannot reach −10 dB in the entire measurement frequency range. This improvement of microwave absorption is ascribed to the polarization, interface interaction and synergistic effect between NiCoP and rGO nanosheets. NiCoP/rGO nanocomposites are expected to be novel microwave absorption materials with high microwave absorption properties. Benefiting from the dipoles polarization, interfacial polarization, conductivity loss and multiple reflection and scattering, the NiCoP/rGO nanocomposites have a broader qualified bandwidth (QB, RL ≤ −10 dB). Image 1 • NiCoP nanoparticles were in-situ decorated on rGO without using bridging agent. • The effective bandwidth of NiCoP/rGO (RL < −10 dB) covers 13.87–18 GHz at only 2.0 mm. • NiCoP/rGO is novel bifunctional magnetic/dielectric material for absorbing microwave. [ABSTRACT FROM AUTHOR]

Goethite is ubiquitous in the environment and plays key role in preserving dissolved organic matter (DOM) and deactivating potentially toxic elements (PTEs) by adsorbing DOM and PTEs. Various non-Fe metals are usually incorporated into natural goethite, substituting Fe in the goethite structure, which dramatically influence the physico-chemical properties and adsorption behavior of the goethite. In the present study, adsorption of DOM and Pb(II) on Mn-substituted goethite samples was investigated. The results displayed that the specific surface area (SSA) of mineral samples increased by 67.6% as the incorporation of Mn for Fe, from 25.71 m2 g−1 for pure goethite to 43.09 m2 g−1for Mn-goethite. Besides, the Mn substitution caused more hydroxyl groups and relatively fewer positive charges on mineral surface, and Mn in the Mn-goethite samples was predominantly present as Mn(III). The amount of DOM adsorbed to per unit mass of goethite was increased as Mn content increased, which was attributed to Mn incorporation increasing the SSA of mineral samples. However, the SSA-normalized absorption capacity for goethite to DOM was decreased by Mn because Mn substitution decreased the number of positive charges of mineral samples, which weakened the electrostatic attraction between DOM and the minerals. The amount of Pb(II) adsorbed to per unit mass of goethite was increased by Mn substitution, and the amount of Pb(II) adsorbed to per unit SSA of goethite increased as the amount of Mn substitution increased, indicating that the increased capacity for adsorbing Pb was not only caused by the SSA increasing but also by there were more surface hydroxyl groups on the Mn-goethite than pure goethite and Pb(II) preferentially adsorbed to Mn sites on the Mn-goethite. The present study results showed that Mn-goethite could be used to sequester DOM and remediate soil contaminated with PTEs because Mn-goethite has a high adsorption capacity and is environmentally benign. [Display omitted] • The enhancement of Mn-substitution for the DOM and Pb adsorption capacity of mineral. • PH plays an important role in the adsorption of DOM and Pb on mineral samples. • Ionic strength does not significantly affect Pb (II) adsorption to Mn-goethite. • Electrostatic interaction has important effect on the adsorption Mn-goethite to DOM. • Surface complexation is main mechanism involved in Pb (II) adsorption at low pH level. [ABSTRACT FROM AUTHOR]

The self-sacrificing template zeolitic imidazolate framework-67 (ZIF-67) was pyrolyzed to generate Co nanoparticles embedded in nanoporous carbon (Co-NC), and iron oxyhydroxide (FeOOH) was wrapped on the Co-NC surface via electrodeposition to shape the Co-NC@FeOOH composites for improving the OER kinetics. [Display omitted] • FeOOH nanosheets coated on Co species embedded in nanoporous carbon to form novel electrocatalyst. • Co-NC@FeOOH supports strongly accelerated electron transfer, thereby improving the OER kinetics. • Co-NC@FeOOH hybrids will hold promise in development of electrode materials. There is still a tremendous challenge in designing environmentally friendly oxygen evolution reaction (OER) catalysts that are inexpensive and high-performing for practical applications. Herein, the self-sacrificing template zeolitic imidazolate framework-67 (ZIF-67) was pyrolyzed under N 2 atmosphere to generate Co species embedded in nanoporous carbon (Co-NC). Then, iron oxyhydroxide (FeOOH) was wrapped onto the Co-NC surface via electrodeposition to shape the Co-NC@FeOOH composites. Benefiting from the core–shell structure, high conductivity, and distributed active sites, Co-NC@FeOOH presents distinguished OER performance with a low overpotential (336 mV) at 10 mA cm−2 and small Tafel slope (49.46 mV dec-1). This work furnishes a rosy passage for receiving cost-effective electrocatalysts with high efficiency for OER. [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsA) is a non-enzymatic antioxidant abundant in kiwifruit. However, physical injuries and long-term storage can decrease the AsA content and shorten shelf-life of fresh-cut kiwifruit. This study confirmed that treatment with 1 mg/L ozone for 10min was an effective fresh-keeping strategy, as indicated in alleviating AsA loss, promoting antioxidant capacity and inhibiting bacterial growth, thereby prolonging the shelf-life of fresh-cut kiwifruit. The results revealed that ozonized kiwifruits exhibited higher AsA content by increasing glutathione (GSH) content and promoting activities of key enzymes included in the AsA-GSH cycle. Particularly, the related enzymes regulating AsA content were changed after day 6. Meanwhile, ozone increased the total flavonoid content (TFC) and the total phenolic content (TPC) since AsA content was significantly correlated to TPC and TFC, as revealed by correlation analysis. In conclusion, the application of ozone can be used to maintain the commercial and consumptive value of fresh-cut fruits over an extended time. • Ozone treatment (1 mg/L) for 10 min increased the shelf-life of fresh-cut kiwifruit by up to 12 days. • Ozone treatment regulated the phenolic and flavonoid contents of fresh-cut kiwifruit. • Phenolic antioxidants protect ascorbic acid from decomposition under ozone treatment. • Enzymes regulating ascorbic acid metabolism changed after day 6. • Ozone treatment promoted the antioxidant capacity of fresh-cut kiwifruit. [ABSTRACT FROM AUTHOR]

Inflammasome NLRP3 plays a crucial role in the process of colitis and colitis­-associated colon cancer. Even though much is known regarding the NLRP3 inflammasome that regulates pro-inflammatory cytokine release in innate immune cells, the role of NLRP3 in non-immune cells is still unclear. In this study, we showed that NLRP3 was highly expressed in mesenchymal-like colon cancer cells (SW620), and was upregulated by tumor necrosis factors-α (TNF-α) and transforming growth factor-β1 (TGF-β1) respectively, during EMT in colon cancer epithelial cells HCT116 and HT29. Knockdown of NLRP3 retained epithelial spindle-like morphology of HCT116 and HT29 cells and reversed the mesenchymal characteristic of SW620 cells, indicated by the decreased expression of vimentin and MMP9 and increased expression of E-cadherin. In addition, knockdown of NLRP3 in colorectal carcinoma cells displayed diminished cell migration and invasion. Interestingly, during the EMT process induced by TNF-α or TGF-β1, the cleaved caspase-1 and ASC speck were not detected, indicating that NLRP3 functions in an inflammasome-independent way. Further studies demonstrated that NLRP3 protein expression was regulated by NF-κB signaling in TNF-α or TGF-β1-induced EMT, as verified by the NF-κB inhibitor Bay 11-7082. Moreover, NLRP3 knockdown reduced the expression of Snail1, indicating that NLRP3 may promote EMT through regulating Snail1. In summary, our results showed that the NLRP3 expression, not the inflammasome activation, was required for EMT in colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into epithelial lineage, but the precise mechanisms controlling this process are unclear. Our aim is to explore the roles of Wnt/β-catenin in the epithelial differentiation of MSCs. Using indirect co-culture of rat MSCs with rat airway epithelial cells (RTE), MSCs expressed several airway epithelial markers (cytokeratin 18, tight junction protein occudin, cystic fibrosis transmembrance regulator). The protein levels of some important members in Wnt/β-catenin signaling were determined, suggested down-regulation of Wnt/β-catenin with epithelial differentiation of MSCs. Furthermore, Wnt3α can inhibit the epithelial differentiation of MSCs. A loss of β-catenin induced by Dickkopf-1 can enhance MSCs differentiation into epithelial cells. Lithium chloride transiently activated β-catenin expression and subsequently decreased β-catenin level and at last inhibited MSCs to differentiate into airway epithelium. Taken together, our study indicated that RTE cells can trigger epithelial differentiation of MSCs. Blocking Wnt/β-catenin signaling may promote MSCs to differentiate towards airway epithelial cells. [Copyright &y& Elsevier]

Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury. • Long-term fluoride exposure blocks the development of chondrocytes. • Excessive fluoride could induce chondrocytes apoptosis. • Long-term excessive fluoride triggered autophagy. • Fluoride-induced chondrocytes apoptosis is associated with CytC/Bcl-2/P53 pathways. [ABSTRACT FROM AUTHOR]

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury. [Display omitted] [ABSTRACT FROM AUTHOR]

The present study has examined the virulence potential of Escherichia coli isolates harboring at least one virulence gene (associated with ExPEC or InPEC pathotype and belonging to different phylogenetic groups: A, B1, B2 or D), isolated from free ranging Tibetan yak feces. The E. coli isolates (n = 87) were characterized for different serogroups and a mouse model of subcutaneous–infection was used to envisage the virulence within these E. coli strains. Of the 87 E. coli isolates examined, 23% of the E. coli isolates caused lethal infections in a mouse model of subcutaneous infection and were classified as killer. Moreover, the majority of the killer strains belonged to phylogroup A (65%) and serogroup O 60 or O 101 (35%). Phylogroup B1, serogroups O 60 and O 101 were statistically associated with the killer status ( P < 0.05). However, positive associations (OR >1) were observed between the killer status isolates and all other bacterial virulence traits. This study comprises the first report on the virulence potential of E. coli strains isolated from free-ranging Tibetan yaks feces. Our findings suggest that pathogenic E. coli of free ranging yaks is highly worrisome, as these feces are used as manures by farmers and therewith pose a health risk to humans upon exposure. [ABSTRACT FROM AUTHOR]

Applying biochar to soil has been recognized as a promising practice of climate-smart agriculture, with considerable potential in enhancing soil organic carbon (SOC) sequestration. Previous studies showed that biochar-induced increases in SOC stock varied substantially among experiments, while the explanatory factors responsible for such variability are still not well assessed. Here, we conducted an integrative meta-analysis of the magnitude and efficiency of biochar-induced change in SOC stock, using a database including 476 field measurements at 101 sites across the globe. Biochar amendment increased SOC stock by 6.13 ± 1.62 (95% confidence interval, CI) and 7.01 ± 1.11 (95% CI) Mg C ha−1, respectively, compared to their unfertilized (R 0) and mineral nitrogen (N) fertilized (R n) references. Of which approx. 52% (R 0) and 50% (R n) were contributed directly by biochar-C input. Corresponding biochar carbon efficiencies in R 0 and R n datasets were estimated as 58.20 ± 10.37% and 65.58 ± 9.26% (95% CI), respectively. The change magnitude of SOC stock increased significantly (p < 0.01) with the increasing amount of biochar-C input, while carbon efficiency of biochar showed an opposite trend. Biochar amendment sequestered larger amounts of SOC with higher efficiency in acidic and loamy soils than in alkaline and sandy soils. Biochar amendments with higher C/N ratio caused higher SOC increase than those with lower C/N ratio. Random forest (RF) algorithm showed that accumulative biochar-C input, soil pH, and biochar C/N ratio were the three most-important factors regulating the SOC stock responses. Overall, these results suggest that applying high C/N ratio biochar in acidic soils is a recommendable agricultural practice from the perspective of enhancing organic carbon. [Display omitted] • Biochar increased SOC by 6.1 and 7.0 Mg C ha−1 in non- and fertilized cases, respectively. • Corresponding average efficiency of biochar-C was 58.2% and 65.6%, respectively. • Direct and indirect way contributed basically equally to the biochar-induced SOC accrual. • Biochar-C input, soil pH, and biochar C/N ratio were the most important factors. • Biochar amendment sequestered more SOC in acidic soils than in alkaline soils. [ABSTRACT FROM AUTHOR]

• CO 2 is directly converted to lower olefins by a carbon-confined MgH 2 nano-lamellae. • Carbon confines MgH 2 in nanoscale to improve the reactivity for CO 2 hydrogenation. • Carbon-confined MgH 2 nano-lamellae offers solid hydrogen for CO 2 hydrogenation. • Solid hydrogen for CO 2 hydrogenation increases the efficiency of hydrogen utilization. The direct production of lower olefins from CO 2 hydrogenation has attracted enormous attention for its significant roles in mitigating CO 2 emissions and developing green chemistry. For the first time, we report carbon-confined MgH 2 nano-lamellae storing solid hydrogen for hydrogenation of CO 2 to lower olefins. The carbon-confined MgH 2 nano-lamellae achieve high selectivity to C 2 = - C 4 = species under low H 2 /CO 2 ratios, which can significantly increase the efficiency of H 2 utilization comparing with traditional methods. DFT calculations show that the lattice H− of MgH 2 can combine to the C site of CO 2 molecule to form Mg formate, while the aromatic H+ of carbon can combine to the O site of CO 2 molecule to form H 2 O, which both promote the CO 2 hydrogenation. The high selectivity of lower olefins is ascribed to the low concentration of solid hydrogen under low H 2 /CO 2 ratios, by which the Mg formate can be further hydrogenated to lower olefins before fully hydrogenated to saturated hydrocarbons. This novel conversion method for CO 2 -to-olefins by carbon-confined MgH 2 nano-lamellae can inspire the catalysts design for CO 2 to value-added chemicals. [ABSTRACT FROM AUTHOR]

Graphical abstract Using acetone and antimony acetate as the starting materials, 2D porous hybrid nanosheets with ultrathin antimony nanoplates (∼0.5 nm thick) being anchored on graphene-like carbon porous nanosheets were facily constructed with outstanding electrochemical performances as anode materials for sodium-ion batteries. Abstract Rational design and facile synthesis of two-dimensional (2D) materials still remain a great challenge. Herein, a facile process was proposed to construct 2D porous hybrid nanosheets, with ultrathin antimony nanoplates (with a thickness of ca. 0.5 nm) being anchored on acetone-derived graphene-like carbon porous nanosheets, by an aldol reaction and subsequent carbothermal reduction method using acetone and antimony acetate as the starting raw materials. The novel structural and compositional characteristics afford the 2D porous hybrid nanosheets with impressive boosting electrochemical sodium storage properties in terms of excellent cycling stability, high reversible specific capacity, and superior rate performance. The present work would provide significant value for the development of both synthetic methodology of 2D materials and their application as electrode active materials for energy storage and conversion. [ABSTRACT FROM AUTHOR]

The increase of vascular wall tension can lead to endothelial injury during hypertension, but its potential mechanism remains to be studied. Our results of previous study showed that HUVECs could induce changes in HMGB1/RAGE to resist abnormal mechanical environments in pathological mechanical stretching. In this study, we applied two different kinds of mechanical tension to endothelial cells using the in vitro mechanical loading system FlexCell-5000T and focused on exploring the expression of miR-107 related pathways in HUVECs with excessive mechanical tension. The results showed that miR-107 negatively regulated the expression of the HMGB1/RAGE axis under excessive mechanical tension. Excessive mechanical stretching reduced the expression of miR-107 in HUVECs, and increased the expression of the HMGB1/RAGE axis. When miR-107 analog was transfected into HUVECs with lipo3000 reagent, the overexpression of miR-107 slowed down the increase of the HMGB1/RAGE axis caused by excessive mechanical stretching. At the same time, the overexpression of miR-107 inhibited the proliferation and migration of HUVECs to a certain extent. On the contrary, when miR-107 was silent, the proliferation and migration of HUVECs showed an upward trend. In addition, the study also showed that under excessive mechanical tension, miR-107 could regulate the expression of FGF-2 by HMGB1. In conclusion, these findings suggest that pathological mechanical stretching promote resistance to abnormal mechanical stimulation on HUVECs through miR-107/HMGB1/RAGE/FGF-2 pathway, thus promote vascular repair after endothelial injury. The suggest that miR-107 is a potential therapeutic target for hypertension. Schematic illustration of the role of the miR-107/HMGB1/RAGE/FGF-2 axis after hypertensive-induced excessive mechanical stretching leads to cellular injury. [Display omitted] • Excessive mechanical stretching of blood vessels during hypertension causes endothelial damage. • The miR-107/HMGB1/RAGE axis promotes endothelial repair by promoting FGF-2 expression. • The protein interaction between HMGB1 and FGF-2 was confirmed by immunoprecipitation. • GO enrichment showed that HMGB1/RAGE/FGF-2 actively responded to extracellular stimuli. [ABSTRACT FROM AUTHOR]

Ehrlichiosis is an emerging infectious disease of domestic animals which is transmitted by ticks. This disease has been reported earlier in most parts of China in dogs, cattle and humans, but there is no published data regarding this disease in goats. The present study provided the evidence of Ehrlichia infection in goats in Wuhan, China on the basis of clinical signs, gross lesions, serum-biochemical, histopathological and PCR. Twenty four goats were presented to the veterinary hospital of Huazhong Agricultural University during July, 2016. The goats were diagnosed for Ehrlichia in monocytic and granulocytic forms by blood smear examination. Further confirmation was done by PCR examination, while histopathological examination revealed degeneration and inflammation in different tissues. The biochemical criterion and blood samples analysis showed significant (P < 0.05) changes. The present study reported that goats are naturally exposed to Ehrlichia infection. To the best of our knowledge, this is the first clinical report of Ehrlichia infection in goats infested with infected ticks. [ABSTRACT FROM AUTHOR]

Fasciolosis is an important plant borne trematode zoonosis in ruminants caused by the Fasciola hepatica and Fasciola gigentica , It is classified as a neglected tropical disease and found in more than 50 countries especially where sheep and cattle are reared. Fasciolosis is a serious animal health problems in many rural and urban areas of world, causing significant financial losses due to decrease in production and viscera condemnation in animals. Accurate diagnosis of fasciolosis is always remained a challenging task for the field practitioners. There is no comprehensive summary on the occurrence and distribution of the infection at international level. Therefore, we intended to provide a complete overview on the prevalence and epidemiology of fasciolosis in farm animals from a global prospective. It includes to map the global distribution of fasciolosis in different areas of the world to identify the endemic regions which may be a source of potential disease outbreak. The financial liability related to fasciolosis on the livestock production has also been addressed. For this purpose, the published data during 2000–2015 (15 years) on fasciolosis was reviewed and collected by electronic literature search of four databases including Google, PubMed, Science Direct, and Web of Science. Data presented are contemplated to enhance our current understanding of the parasite's geographical distribution, host range, and economic losses. Information provided would be useful for the application of more effective control strategies against fasciolosis in different geo-economics regions of the world. [ABSTRACT FROM AUTHOR]

The paper focused on the effects of l -Arginine ( l -Arg) on the water holding capacity (WHC) and texture of salt-soluble meat proteins (SSMP) gel and the thermal gelling mechanism were investigated. The addition of 0–0.25 g l -Arg/100 g increased the WHC, hardness, springiness cohesiveness and chewiness of SSMP gel. Rheology indicated the addition of l -Arg increased storage modulus (G′), but decreased phase angle (tan δ ). Differential scanning calorimeter (DSC) disclosed that l -Arg-treatment caused the disappearance of the first and third transition peaks, but the increase of the enthalpy of the second denaturation (ΔH 2 ). Low field nuclear magnetic resonance (LF-NMR) showed l -Arg at 0.25 g/100 g increased the fraction of spin–spin relaxation times distribution for immobile water ( T 21 ). Scanning electron microscopy (SEM) revealed that l -Arg promoted to form a dense, uniform SSMP gel. The results suggested that the thermal stability and gelation of SSMP were affected by l -Arg, which changed the microstructure of SSMP gel, and ultimately improving the corresponding WHC and texture, as well as changing the distribution of T 2 . [ABSTRACT FROM AUTHOR]

Abstract: Deficiency of adiponectin (APN), an adipocyte-derived vascular protective molecule, contributes to diabetic vascular injury. The current study determined whether obesity/hyperlipidemia may alter the vascular response to APN, and investigated the involved mechanisms and pathologic significance. Adult male Sprague–Dawley rats were fed a regular or high-fat diet (HF) for 4–16weeks. Circulating APN levels, aortic pAMPK/AMPK, peNOS/eNOS, and APN receptor expression levels were determined. Compared to time-matched animals fed control diet, plasma APN levels in HF-diet animals were significantly increased at 8weeks, and rapidly declined thereafter. Despite unchanged or elevated circulating APN levels, phosphorylated AMPK and eNOS in vascular tissue were significantly reduced at all observed time points. Recombinant full-length APN (rAPN)-induced AMPK/eNOS phosphorylation and vasodilatation were significantly reduced in 16-week obese/hyperlipidemic aortic segments. Vascular APN receptor 1 (AdipoR1) and receptor 2 (AdipoR2) expression were significantly reduced 16weeks after HF-diet. Pre-incubation of rAPN with obese/hyperlipidemic plasma, but not with normal plasma, significantly reduced its AMPK and eNOS activation effect, and blunted its protective effect against TNFα-induced HUVEC apoptosis. This study demonstrated for the first time that obesity/hyperlipidemia reduces vascular responsiveness to APN. Modification/inactivation of APN by unidentified factors present in obese/hyperlipidemic plasma, decreased vascular AdipoR1/R2 expression, and reduced circulating APN levels contribute to reduced vascular responsiveness to APN at different stages of the obese condition. Reduced APN bioactivity allows unmitigated TNFα pro-apoptotic and pro-inflammatory actions, contributing to vascular injury in obesity/hyperlipidemia. [ABSTRACT FROM AUTHOR]

Abstract: Endothelial dysfunction is the earliest pathologic alteration in diabetic vascular injury and plays a critical role in the development of atherosclerosis. Plasma levels of adiponectin (APN), a novel vasculoprotective adipocytokine, are significantly reduced in diabetic patients, but its relationship with endothelial dysfunction remains unclear. The present study aims to determine whether APN deficiency may cause endothelial dysfunction and to investigate the involved mechanisms. Vascular rings were made from the aortic vessels of wild type (WT) or APN knockout (APN−/−) mice. Endothelial function, total NO production, eNOS expression/phosphorylation, superoxide production, and peroxynitrite formation were determined. ACh and acidified NaNO2 (endothelial dependent and independent vasodilators, respectively) caused similar concentration-dependent vasorelaxation in WT vascular rings. APN−/− rings had a normal response to acidified NaNO2, but a markedly reduced response to ACh (>50% reduction vs. WT, P <0.01). Both superoxide and peroxynitrite production were increased in APN−/− vessels (P <0.01 vs. WT). Pretreatment with superoxide scavenger Tiron significantly, but incompletely restored vascular vasodilatory response to ACh. In APN−/− vessels, eNOS expression was normal, but NO production and eNOS phosphorylation was significantly reduced (P <0.01 vs. WT). Treatment of APN−/− mice in vivo with the globular domain of adiponectin reduced aortic superoxide production, increased eNOS phosphorylation, and normalized vasodilatory response to ACh. Increased NO inactivation combined with decreased basal NO production contributes to endothelial dysfunction development when there is a paucity of APN production. Interventions directed towards increasing plasma APN levels may improve endothelial function, and reduce cardiovascular complications suffered by diabetic patients. [Copyright &y& Elsevier]