Cardiovascular disease (CVD) is the greatest cause of death, accounting for nearly one-third of all deaths worldwide. The increase in obesity rates over 3 decades is widespread and threatens the ...public health in both developed and developing countries. Obesity, the excessive accumulation of visceral fat, causes the clustering of metabolic disorders, such as type 2 diabetes, dyslipidemia, and hypertension, culminating in the development of CVD. Adipose tissue is not only an energy storage organ, but an active endocrine tissue producing various biologically active proteins known as adipokines. Since leptin, a central regulator of food intake and energy expenditure, was demonstrated to be an adipose-specific adipokine, attention has focused on the identification and characterization of unknown adipokines to clarify the mechanisms underlying obesity-related disorders. Numerous adipokines have been identified in the past 2 decades; most adipokines are upregulated in the obese state. Adipokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and resistin are pro-inflammatory, and exacerbate various metabolic and cardiovascular diseases. However, a small number of adipokines, including adiponectin, are decreased by obesity, and generally exhibit antiinflammatory properties and protective functions against obesity-related diseases. Collectively, an imbalance in the production of pro- and antiinflammatory adipokines in the obese condition results in multiple complications. In this review, we focus on the pathophysiologic roles of adipokines with cardiovascular protective properties.
Nitrous oxide (N2O) is a greenhouse gas that also plays the primary role in stratospheric ozone depletion. The use of nitrogen fertilizers is known as the major reason for atmospheric N2O increase. ...Empirical bottom‐up models therefore estimate agricultural N2O inventories using N loading as the sole predictor, disregarding the regional heterogeneities in soil inherent response to external N loading. Several environmental factors have been found to influence the response in soil N2O emission to N fertilization, but their interdependence and relative importance have not been addressed properly. Here, we show that soil pH is the chief factor explaining regional disparities in N2O emission, using a global meta‐analysis of 1,104 field measurements. The emission factor (EF) of N2O increases significantly (p < .001) with soil pH decrease. The default EF value of 1.0%, according to IPCC (Intergovernmental Panel on Climate Change) for agricultural soils, occurs at soil pH 6.76. Moreover, changes in EF with N fertilization (i.e. ΔEF) is also negatively correlated (p < .001) with soil pH. This indicates that N2O emission in acidic soils is more sensitive to changing N fertilization than that in alkaline soils. Incorporating our findings into bottom‐up models has significant consequences for regional and global N2O emission inventories and reconciling them with those from top‐down models. Moreover, our results allow region‐specific development of tailor‐made N2O mitigation measures in agriculture.
We identified soil pH as the chief factor modifying regional response in N2O emission to N fertilization, based on an updated global meta‐analysis of 1,104 field measurements. Both N2O emission factor (i.e. EF) and nonlinearity coefficient (i.e. ΔEF) were found to negatively correlated with soil pH. Incorporating our findings into bottom‐up models could help to construct sound global N2O inventories, to reconcile the discrepancies between top‐down and bottom‐up N2O estimates, and to develop optimized region‐specific measures for N2O mitigation from agriculture.
In humans, oxidative stress and antioxidant defenses are the sum of a complicated network of enzymatic and non‐enzymatic processes. Depending on the stage and severity of diseases, a patient's ...antioxidant armamentarium may increase as an appropriate response to an oxidant challenge, whereas others may decrease as an indication of unbalanced consumption. In some cases, the formation of reactive oxygen species is a requisite and healthy event. In fact, free radicals can affect intracellular signal transduction and gene regulation, resulting in cytokine production essential to the inflammatory process. In many other cases, especially liver diseases, excessive oxidative stress undoubtedly contributes to the progression and pathological findings of disease and serves as a prognostic indicator. Reactive oxygen species are highly reactive molecules that are naturally generated in small amounts through metabolism and could damage cellular molecules such as lipids, proteins or DNA. Oxidative stress plays a major role in many liver diseases. In this review, we summarize the biological character of free radicals and some antioxidants, and the related methods of analysis. Then, we discusses the association of oxidative stress to many types of liver diseases.
Wound dressings with high flexibility, mechanical strength, and porosity have received increasing attention. Herein, nanocomposite sponges of sodium alginate/graphene oxide (GO)/polyvinyl alcohol ...were prepared by a freeze-thawing cyclic process and freeze-dried molding. The properties of the sponges were investigated including morphology, mechanical properties, swelling, water vapor permeability, in vitro norfloxacin (NFX) release, antibacterial property, and biocompatibility as well as in vivo wound healing in a mouse model. A GO concentration of 1 wt% resulted in the sponges with a homogeneously porous and interconnected network structure, which exhibited suitable water absorption, breathability, and mechanical properties. Hemolysis tests indicated that the prepared sponges were non-hemolytic material. The CCK-8 assay demonstrated that the presence of an appropriate amount of GO could promote the cell proliferation. The sponges displayed excellent bioavailability of NFX, with a sustained release behavior and a strong inhibitory effect against both Escherichia coli and Staphylococcus aureus. The in vivo evaluations demonstrated that the sponges enhanced wound healing. Therefore, these novel nanocomposite sponges are promising candidates for wound healing applications.
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•The sponges (SPG) were prepared by a freeze-thawing method and freeze-dried technology.•The SPG exhibited uniform pore structure and excellent flexibility.•Graphene oxide improved biocompatibility of the SPG.•The SPG could be used as an excellent wound dressing for biomedical field.
The NLRP3 inflammasome is a multiprotein complex that protects hosts against a variety of pathogens. However, the molecular mechanisms of modulating NLRP3 inflammasome activation, especially at the ...priming step, are still poorly understood. This study was designed to elucidate the negative regulation of nuclear factor E2-related factor-2 (Nrf2) on the activation of NLRP3 inflammasome.
We reported that Nrf2 activation inhibited NLRP3 expression, caspase-1 cleavage, and subsequent IL-1β generation. Compared with normal cells, Nrf2-deficient cells showed upregulated cleaved caspase-1, which were attributed to the increased transcription of NLRP3 caused by excess reactive oxygen species (ROS). Furthermore, priming of the NLRP3 inflammasome was sensitive to the exogenous ROS levels induced by H
O
or rotenone. Combined with adenosine triphosphate, rotenone triggered higher activity of the NLRP3 inflammasome compared with lipopolysaccharide, suggesting that ROS promoted the priming step. In addition, Nrf2-induced NQO1 was involved in the inhibition of the NLRP3 inflammasome. In an in vivo alum-induced peritonitis mouse model, Nrf2 activation suppressed typical IL-1 signaling-dependent inflammation, whereas Nrf2
mice exhibited a significant increase in the recruitment of immune cell and the generation of IL-1β compared with wild-type mice.
We elucidated the effects and possible mechanisms of Nrf2 activation-induced NQO1 expression on NLRP3 inflammasome inactivation and established a novel regulatory role of the Nrf2 pathway in ROS-induced NLRP3 priming.
We demonstrated Nrf2 negatively regulating NLRP3 inflammasome activity by inhibiting the priming step and suggested that Nrf2 could be a potential target for some uncontrolled inflammasome activation-associated diseases. Antioxid. Redox Signal. 26, 28-43.
Placoderms, as the earliest branching jawed vertebrates, are crucial to understanding how the characters of crown gnathostomes comprising Chondrichthyes and Osteichthyes evolved from their stem ...relatives. Despite the growing knowledge of the anatomy and diversity of placoderms over the past decade, the dermal scales of placoderms are predominantly known from isolated material, either morphologically or histologically, resulting in their squamation being poorly understood. Here we provide a comprehensive description of the squamation and scale morphology of a primitive taxon of Antiarcha (a clade at the root of jawed vertebrates),
, based on the virtual restoration of an articulated specimen by using X-ray computed tomography. Thirteen morphotypes of scales are classified to exhibit how the morphology changes with their position on the body in primitive antiarchs, based on which nine areas of the post-thoracic body are distinguished to show their scale variations in the dorsal, flank, ventral, and caudal lobe regions. In this study, the histological structure of yunnanolepidoid scales is described for the first time based on disarticulated scales from the type locality and horizon of
. The results demonstrate that yunnanolepidoid scales are remarkably different from their dermal plates as well as euantiarch scales in lack of a well-developed middle layer. Together, our study reveals that the high regionalization of squamation and the bipartite histological structure of scales might be plesiomorphic for antiarchs, and jawed vertebrates in general.
Diabetes mellitus exacerbates myocardial ischemia/reperfusion (MI/R) injury by incompletely understood mechanisms. Adipocyte dysfunction contributes to remote organ injury. However, the molecular ...mechanisms linking dysfunctional adipocytes to increased MI/R injury remain unidentified. The current study attempted to clarify whether and how small extracellular vesicles (sEV) may mediate pathological communication between diabetic adipocytes and cardiomyocytes, exacerbating MI/R injury.
Adult male mice were fed a normal or a high-fat diet for 12 weeks. sEV (from diabetic serum, diabetic adipocytes, or high glucose/high lipid-challenged nondiabetic adipocytes) were injected intramyocardially distal of coronary ligation. Animals were subjected to MI/R 48 hours after injection.
Intramyocardial injection of diabetic serum sEV in the nondiabetic heart significantly exacerbated MI/R injury, as evidenced by poorer cardiac function recovery, larger infarct size, and greater cardiomyocyte apoptosis. Similarly, intramyocardial or systemic administration of diabetic adipocyte sEV or high glucose/high lipid-challenged nondiabetic adipocyte sEV significantly exacerbated MI/R injury. Diabetic epididymal fat transplantation significantly increased MI/R injury in nondiabetic mice, whereas administration of a sEV biogenesis inhibitor significantly mitigated MI/R injury in diabetic mice. A mechanistic investigation identified that miR-130b-3p is a common molecule significantly increased in diabetic serum sEV, diabetic adipocyte sEV, and high glucose/high lipid-challenged nondiabetic adipocyte sEV. Mature (but not primary) miR-130b-3p was significantly increased in the diabetic and nondiabetic heart subjected to diabetic sEV injection. Whereas intramyocardial injection of a miR-130b-3p mimic significantly exacerbated MI/R injury in nondiabetic mice, miR-130b-3p inhibitors significantly attenuated MI/R injury in diabetic mice. Molecular studies identified AMPKα1/α2, Birc6, and Ucp3 as direct downstream targets of miR-130b-3p. Overexpression of these molecules (particularly AMPKα2) reversed miR-130b-3p induced proapoptotic/cardiac harmful effect. Finally, miR-130b-3p levels were significantly increased in plasma sEV from patients with type 2 diabetes mellitus. Incubation of cardiomyocytes with diabetic patient sEV significantly exacerbated ischemic injury, an effect blocked by miR-130b-3p inhibitor.
We demonstrate for the first time that miR-130b-3p enrichment in dysfunctional adipocyte-derived sEV, and its suppression of multiple antiapoptotic/cardioprotective molecules in cardiomyocytes, is a novel mechanism exacerbating MI/R injury in the diabetic heart. Targeting miR-130b-3p mediated pathological communication between dysfunctional adipocytes and cardiomyocytes may be a novel strategy attenuating diabetic exacerbation of MI/R injury.
Systemic immune-inflammation index (SII), calculated by immunoinflammatory cell counts of peripheral blood, is considered a predictor of survival outcome in several solid tumors, including gastric ...cancer (GC). However, there is no study focusing on the prognostic value of SII in the early stage of GC. This study aims to compare prognostic prediction capabilities of several inflammatory indices, nutritional indices, and tumor markers to further verify the superior prognostic value of SII in stage I-II GC patients after surgery.
In this study, 548 patients (358 in the training group and 190 in the validation group) with stage I-II GC after radical surgery were retrospectively analyzed. The peripheral blood indices of interest were SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), advanced lung cancer inflammation index (ALI), systemic inflammation score (SIS), prognostic nutritional index (PNI), body mass index (BMI), albumin, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate-associated antigen 19-9 (CA19-9), and alpha-fetoprotein (AFP). The time-dependent receiver operating characteristic (t-ROC) curves and the area under the curve (AUC) were used to determine the optimal cutoff value and prognostic ability of each parameter. Kaplan-Meier curves and multivariable Cox regression models were used to evaluate independent prognostic factors. The nomogram was constructed based on the result of bidirectional stepwise regression model.
The optimal cutoff value of SII was 508.3. The 5-year overall survival rate of the low SII (SII-L) group was significantly higher than that of the high SII (SII-H) group (92% vs. 80%, P < 0.001), especially in the elderly and stage II patients (91% vs. 73%, P = 0.001; 86% vs. 67%, P = 0.003, respectively). The significant prognostic values of SII were consistent in most subgroups. In multivariate analysis, SII and CA19-9 were the only two independent prognostic hematology indices. The AUC value of SII (0.624) was greater than that of CA19-9 (0.528) and other prognostic parameters. Adding SII to the conventional model improved the predictive ability of 5-year overall survival as shown by the significantly increased net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (P = 0.033, P = 0.053, respectively) and modestly improved consistency index (C-index) (increased by 1.6%). External validation of SII-based nomogram demonstrated favorable predictive performance and discrimination. In addition, interactive web dynamic nomogram was published to facilitate clinical use.
SII is a simple but powerful index with a high predictive value to predict survival outcome in patients with stage I-II GC after radical operation. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.
Soil-probe contact resistance and finite radius and heat capacity of the heat pulse (HP) probe produce significant errors in thermal property estimates. In this study, we demonstrated that estimating ...soil thermal properties from late-time data of the temperature change-by-time (ΔT(t)) curve reduces these errors effectively. The weighted nonlinear curve fitting method was applied to estimate soil thermal properties following the pulsed infinite line source (PILS) theory using ΔT(t) data from the complete (PILS-Complete), peak-time (PILS-Peak), and late-time (PILS-Late) ranges. Three experiments on specific heat of soil solids (cs), soil thermal properties, and soil water content (θHP) were conducted to examine the performance of these approaches. The results showed that the PILS-Complete and PILS-Peak methods overestimated cs by 16.6% and 13.0% respectively, and the error from the PILS-Late method reduced to 3.2%. Soil thermal conductivity measurements from the PILS-Late method agreed well with those from the identical-cylindrical-perfect-conductors theory and with the estimates from the heat flux plate data. The PILS-Late method also effectively reduced the overestimation of soil heat capacity and underestimation of soil thermal diffusivity. In comparing to the PILS-Complete method, the PILS-Late method reduced the root mean square error (RMSE) of θHP from 0.039 to 0.021 m3 m-3 on a sand soil, and from 0.032 to 0.018 m3 m-3 on a clay loam soil. Thus, using late-time data improved the accuracy of HP method for measuring soil thermal properties.
The diversity in positions of nasal capsules has been well documented in various subgroups of placoderms or jawed stem gnathostomes. However, the condition in primitive antiarchs (i.e., the ...Yunnanolepidoidei) remains unclear, and the positional shift of nasal capsules in the Antiarcha has never been mentioned. Here we re-describe the headshield of Parayunnanolepis xitunensis, a yunnanolepidoid antiarch from the Lower Devonian of China, using X-ray computed tomography scanning. The study provides new anatomical details of the headshield including the sclerotic capsules, the visceral side of the rostral and pineal plates, and the dorsal profile of the endocranium. Parayunnanolepis xitunensis bears a pair of nasal capsules underlying the rostral plate between the eyes, resembling Romundina but differing from most euantiarchs, whose nasal capsules are encased in the preorbital recess in front of the eyes. A phylogenetic analysis based on a modified matrix indicates a stepwise forward migration of nasal capsules within antiarchs, accompanied by the innovation of the preorbital recess and the loss of the preorbital depression.
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