Interaction and thermal studies on graphene oxide in NC/DEGDN/GO nanocomposites

Before considering the uses of graphene oxide (GO) in nitrate ester-based materials for performance and safety improvement, its interaction, compatibility and dispersion with the host matrices need to be well understood. This work addresses the interaction and dispersity of GO with nitrocellulose (NC)/diethylene glycol dinitrate (DEGDN)-based nanocomposites. The GO and DEGDN were successfully synthesised and characterised. The NC/DEGDN proved to be a good hosting matrix for the dispersion of GO nanosheets. Analysis of atomic force microscopy (AFM) showed that the thicknesses of dispersed GO were in the range of 1–4 nm suggesting that the GO in the nanocomposite consists of 1–2 layers for a 0.5% w/w GO containing nanocomposite and 2–4 layers for a 0.75% w/w nanocomposite. ATR-FTIR spectroscopy analysis established red-shifting of 744 to 752 cm⁻¹ for the O–NO₂ bond stretching vibrations, indicating bond stabilization by donor electron from the GO. The Raman spectra analysis showed GO peaks blue-shifting and broadening which is attributed to hydrogen bonding interaction between GO sheets and –NO₂ groups. The activation energy of nitrate ester decomposition of NC/DEGDN/GO nanocomposites increases as a function of GO content from 167 kJ mol⁻¹ and reaches a maximum of 214 kJ mol⁻¹ for a 0.5% w/w GO loading. This suggests an improvement of the nitrate ester bond stability. These findings open a new direction to the application of GO in nitrate ester-based materials for increased stability, safety and shelf life.

Before considering the use of graphene oxide (GO) in nitrate ester-based materials for improved safety and performance its interaction, compatibility, and dispersion with the host matrices needs to be well understood.     

Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity

Objective

IL-17A is implicated in periodontitis pathogenesis. The roles of IL-17B–IL-17F and IL-17A/F are unknown. This study aimed to determine clinical associations between IL-17 family cytokines and periodontitis and to investigate the biological roles of IL-17A and IL-17E using in vitro model systems.

Materials and methods

Samples from 97 patients with periodontitis and 77 healthy volunteers were used in the study. Serum, saliva and gingival crevicular fluid (GCF) levels of IL-17 family cytokines were measured by ELISA. Oral keratinocytes were stimulated with a P. gingivalis biofilm, or IL-17A, in the presence and absence of IL-17E and the expression of IL-8 and CXCL5 were investigated by ELISA and real-time-PCR. NF-κB phosphorylation in similar experiments was also measured using a cell-based ELISA.

Results

Serum, saliva and GCF IL-17A levels were higher in periodontitis patients and correlated positively with clinical parameters of attachment loss, pocket depth and bleeding on probing. Serum IL-17E levels were lower in periodontitis patients and the serum IL-17A:IL-17E ratio correlated positively with clinical parameters. In vitro, IL-17E inhibited Porphyromonas gingivalis and IL-17A induced expression of chemokines by reducing phosphorylation of the NF-κB p65 subunit.

Conclusions

Serum IL-17A:IL-17E may be a marker of disease severity. IL-17E may have opposing roles to IL-17A in periodontitis pathogenesis. IL-17E can negatively regulate IL-17A and periodontal pathogen induced expression of chemokines by oral keratinocytes.     

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a common malignant tumor of the digestive system worldwide, especially in China. Due to the lack of effective early detection methods, ESCC patients often present at an advanced stage at the time of diagnosis, which seriously affects the prognosis of patients. At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy. Therefore, there is an unmet need for a noninvasive method to detect ESCC in the early stages. With the emergence of a large class of non-invasive diagnostic tools, serum tumor markers have attracted much attention because of their potential for detection of early tumors. Therefore, the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers, and discusses the origins, clinical applications, and technical challenges of clinical validation of various types of biomarkers.     

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt(TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.     

罂粟科植物罂粟、延胡索和岩黄连镇痛作用的研究进展

疼痛是人类的第五大生命体征,既是机体的一种自我保护,同时也是机体对伤害性刺激的预警。尽管阿片类药物具有显著的不良反应及成瘾性,但目前该类药物仍是治疗严重急慢性疼痛的主要治疗药物。本文整理了具有镇痛功效的罂粟科植物罂粟、延胡索和岩黄连,从古籍记载、主要活性成分、药理作用和临床研究几个方面对其进行综述,以期更科学地发掘具有镇痛强,成瘾性低,毒副作用小的药物。     

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.     

Diagnosis and multi-modality treatment of adult pulmonary plastoma:Analysis of 18 cases and review of literature

The clinical data of 18 patients with PB from April 1989 to April 2013 was analyzed retrospectively,including 11 men and 7 women,aged 45 and 76 years old(mean 53 years).There were 12 eases of PB occurrlng in right lung and other cases in left lung,AraBng them,3 patients had no symptoms,and 15 patients displayed symptoms of cough,chest pain,asthenia or minor hacmoptysis.Overall,11 patients had a preoperative diagnosis of lung cancer,7 patients were preoperatively diagnosed as the other disease,which included lung benign tumor(n=5)and mediastinal mass(n=2).All patients received a radical resection.Six patients received postoperative cisplalinbascd chemothcrapy,and two paticnts received postoperative irradiation with the dose of 55 Gy.Histologically.14 eases of 18 patients had biphasie pulmonary blastema and four cases had well differentiated fetal adenocarcinoma.A total of 12 patients died in a period of 6-36 months after operation,and 1 ease was lost after 2 years of follow up.The median survival time was 19 months,PB is a rare primary lung malignant embryonal neoplasm.Despite its assumed embyonal origin,the tumor has a predileetion for adults.A preoperative correct diagnosis is very difficult in spite of modern diagnostic imaging and biopsy techniques,Surgical resection is the main method for diagnosis and treatment.Postoperative chemotherapy or irradiation can help eliminate tumor remnants.Its prognosis is very poor,especially for the biphasie type.     

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes’ epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redox-dead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO₂-OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO₂-OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO₂-OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.Soluble epoxide hydrolase (sEH) has a conserved cysteine (Cys521) proximal to its catalytic center. This cysteine can undergo Michael addition with electrophilic lipids, which inhibits hydrolysis of the enzyme’s epoxyeicosatrienoic acid (EET) substrates (1). This in turn elevates EET levels, which mediate blood vessel dilation and lowers blood pressure (BP), especially in the setting of hypertension (2, 3). Diverse sEH inhibitors limit injury in a variety of diseases (4), providing broad cardiovascular protection (5) against hypertension (6, 7), ischemia and reperfusion injury (8, 9), hypertrophy, and heart failure (10), as well as inflammation (11, 12). Consistent with the therapeutic potential of hydrolase inhibitors, sEH null mice are protected from pathological interventions (13). Conversely, genetic alterations that promote enhanced hydrolase activity are a risk factor for human heart failure (14).The endogenous lipid electrophile 10-nitrooctadec-9-enoic acid (nitro-oleic acid, NO₂-OA) inhibits sEH in vitro (1). NO₂-OA and other fatty acid nitroalkenes appear to signal via pleiotropic mechanisms including targeting and activating peroxisome proliferator-activated receptor gamma (PPARγ), the Kelch-like erythroid cell-derived protein with CNC homology (EHC)-associated protein-1 (Keap1), and nuclear factor (erythroid-derived)-like-2 (Nrf2)-regulated antioxidant response genes and inhibiting proinflammatory gene expression regulated by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (15, 16). Nitroalkenes are produced by radical addition of nitrogen dioxide (·NO₂) to one or more of the olefinic carbons of an unsaturated fatty acid. Nitrogen dioxide is both a product of oxidative inflammatory reactions involving nitric oxide (NO) and nitrite and the acidification nitrite. When the electron-withdrawing nitro group is bonded to alkenyl groups, this confers an electrophilic reactivity to fatty acids (17, 18). Thus, fatty acid nitroalkenes can modify proteins covalently via reversible Michael addition reactions that overall serves to link cellular metabolic and redox homeostasis with the posttranslational regulation of target protein function.Nitro fatty acids, which have been detected endogenously in plasma and urine of humans, animal models, and plants (19–21), mediate salutary cardiovascular signaling actions (22). For example they relax blood vessels, attenuate platelet activation, and reduce inflammation via cyclic guanosine monophosphate (cGMP)-independent mechanisms (23, 24). Of relevance, the Mediterranean diet is characterized by high consumption of unsaturated fatty acids, especially from olive oil and fish rich in oleic and linoleic acid, together with vegetables rich in nitrite and nitrate (25). The acidic and low-oxygen conditions in the stomach provide an environment for efficient nitration of such unsaturated fatty acids by nitrite (26).NO₂-OA normalizes blood pressure in an angiotensin (Ang) II-induced murine model of hypertension via undefined mechanisms (27). This was notable as pharmacological inhibitors of sEH also lower BP in murine hypertension, including salt- or Ang II-induced models (6, 7). As NO₂-OA inhibits sEH, we hypothesized that this mechanism may account for BP lowering in the setting of hypertension. Furthermore, as the Mediterranean diet both contains nitro fatty acids and can elevate their endogenous generation, this mechanism may contribute to dietary-induced BP decreases that in turn will reduce the risk of adverse cardiovascular event (28).Given the complexity of causally establishing whether nitro fatty acids lower BP by inhibiting sEH, especially in the setting of dietary-induced endogenous fatty acid nitration, we generated a Cys521Ser sEH knockin (KI) mouse. This “redox-inactive” sEH thiol mutant, rendered insensitive to adductive inhibition by lipid electrophiles in vitro, provided a novel model system for testing the impact of lipid nitroalkenes on sEH hydrolysis of vasoactive EET species and downstream physiological responses (1). The data reveal that nitro fatty acids, applied exogenously as a pharmacological agent or generated endogenously as part of the Mediterranean diet, inhibit sEH to elevate plasma EETs, which in turn lower BP.     

Perennial grasslands enhance biodiversity and multiple ecosystem services in bioenergy landscapes

Agriculture is being challenged to provide food, and increasingly fuel, for an expanding global population. Producing bioenergy crops on marginal lands—farmland suboptimal for food crops—could help meet energy goals while minimizing competition with food production. However, the ecological costs and benefits of growing bioenergy feedstocks—primarily annual grain crops—on marginal lands have been questioned. Here we show that perennial bioenergy crops provide an alternative to annual grains that increases biodiversity of multiple taxa and sustain a variety of ecosystem functions, promoting the creation of multifunctional agricultural landscapes. We found that switchgrass and prairie plantings harbored significantly greater plant, methanotrophic bacteria, arthropod, and bird diversity than maize. Although biomass production was greater in maize, all other ecosystem services, including methane consumption, pest suppression, pollination, and conservation of grassland birds, were higher in perennial grasslands. Moreover, we found that the linkage between biodiversity and ecosystem services is dependent not only on the choice of bioenergy crop but also on its location relative to other habitats, with local landscape context as important as crop choice in determining provision of some services. Our study suggests that bioenergy policy that supports coordinated land use can diversify agricultural landscapes and sustain multiple critical ecosystem services.In agricultural landscapes, balancing the provisioning of food and energy with maintenance of biodiversity and ecosystem functions is a global challenge. To avoid impacts on food production, attention is increasingly being focused on the potential for marginal lands to support bioenergy production (1). Marginal lands, those suboptimal for food production, may consist of relatively small areas within generally productive landscapes or larger regions where conditions generally limit crop productivity. However, there is increasing recognition that these lands are already performing a variety of useful functions, and their conversion to bioenergy cropping could reduce these services. For example, in the north central United States, rising commodity prices are predicted to bring marginal croplands—including Conservation Reserve Program lands—into annual crop production with negative impacts on wildlife habitat and water quality (2, 3). With 2013 corn plantings at recent record highs (4) and new reports of grassland and wetland conversion to cropland (5, 6), this may be occurring already.An alternative to annual cropping is conversion of marginal croplands to perennial, cellulosic crops for bioenergy. Although current US biofuel production centers on grain ethanol derived from annual monocultures of maize (Zea mays), this situation could change with full implementation of the 2007 US Energy Independence and Security Act (7), which calls for increased production of cellulosic biofuels. In the Midwest United States, perennial grasses and forbs grown on marginal lands could provide up to 25% of national targets for cellulosic biofuel, with substantial greenhouse gas (GHG) benefits (8). Moreover, increasing the area of perennial cover on the landscape is predicted to positively affect a diverse array of organisms and ecological functions (9–11), leading to important synergies that have not yet informed the ongoing bioenergy debate. Here we provide the most comprehensive empirical evaluation of this hypothesis to date, reporting data that elucidate the impacts of different bioenergy cropping systems on a wide variety of organisms and the ecosystem functions they perform.Previous studies have examined the ability of select bioenergy crops to support specific taxa (12) or individual services such as energy production (13) or GHG mitigation (14), without consideration of the tradeoffs or synergies that can arise when considering entire suites of organisms and ecosystem functions. We report on a unique multidisciplinary study of matched sets of organisms and ecosystem services and show that perennial grass energy crops (switchgrass, Panicum virgatum, and mixed prairie plantings) synergistically enhance diversity of a variety of organisms and levels of the services they provide. We further quantify the importance of landscape context on service provisioning, suggesting that policy supporting intentional design of bioenergy landscapes could increase sustainability of both food and energy production.