Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration.

Neonatal immunity is functionally immature and skewed towards a T 2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury. However, the role of an imbalanced immune repertoire observed in neonates on tissue regeneration is poorly understood; specifically, whether IL-4 and IL-13 actively modulate neonatal immunity during cardiac injury. Neonatal mice lacking IL-4 and IL-13 (DKOs) examined at 2 days after birth exhibited reduced anti-inflammatory immune populations with basal cardiac immune populations like adult mice. Examination of neonates lacking IL-4 and IL-13 at 2 days post cardiac ischemic injury, induced on the second day after birth, showed impaired cardiac function compared to their control counterparts. Treatment with either IL-4 or IL-13 cytokine during injury restored both cardiac function and immune population profiles in knockout mice. Examination of IL-4/IL-13 downstream pathways revealed the role of STAT6 in mediating the regenerative response in neonatal hearts. As IL-4/IL-13 drives polarization of alternatively activated macrophages, we also examined the role of IL-4/IL-13 signaling within the myeloid compartment during neonatal cardiac regeneration. Injury of IL-4Rα myeloid specific knockout neonates 2 days after birth revealed that loss of IL-4/IL-13 signaling in macrophages alone was sufficient to impair cardiac regeneration. Our results confirm that the T 2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a T 2 profile, are necessary for maintaining and mediating an anti-inflammatory response in the neonatal heart, in part through the activation of alternatively activated macrophages, thereby permitting a niche conducive for regeneration. [Abstract copyright: © The author(s).

Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration

Aims: Neonatal immunity is functionally immature and skewed towards a TH2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury. However, the role of an imbalanced immune repertoire observed in neonates on tissue regeneration is poorly understood; specifically, whether IL-4 and IL-13 actively modulate neonatal immunity during cardiac injury. Methods and results: Neonatal mice lacking IL-4 and IL-13 (DKOs) examined at 2 days after birth exhibited reduced anti-inflammatory immune populations with basal cardiac immune populations like adult mice. Examination of neonates lacking IL-4 and IL-13 at 2 days post cardiac ischemic injury, induced on the second day after birth, showed impaired cardiac function compared to their control counterparts. Treatment with either IL-4 or IL-13 cytokine during injury restored both cardiac function and immune population profiles in knockout mice. Examination of IL-4/IL-13 downstream pathways revealed the role of STAT6 in mediating the regenerative response in neonatal hearts. As IL-4/IL-13 drives polarization of alternatively activated macrophages, we also examined the role of IL-4/IL-13 signaling within the myeloid compartment during neonatal cardiac regeneration. Injury of IL-4Rα myeloid specific knockout neonates 2 days after birth revealed that loss of IL-4/IL-13 signaling in macrophages alone was sufficient to impair cardiac regeneration. Conclusions: Our results confirm that the TH2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a TH2 profile, are necessary for maintaining and mediating an anti-inflammatory response in the neonatal heart, in part through the activation of alternatively activated macrophages, thereby permitting a niche conducive for regeneration

Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels

Effects of pruning and mulching measures on annual soil moisture, yield, and water use efficiency in jujube (Ziziphus jujube Mill.) plantations

Soil desiccation and water shortage are major challenges of rain-fed crop production in the semi-arid areas of the Loess Plateau of China. Mulching and pruning were considered effective strategies to improve harvest by reducing soil water evaporation and plant transpiration rates. In the present study, the possible synergistic effects of the combination of mulching and pruning on soil water status, growth, yield, and water use efficiency were explored in the jujube plant. Field experiments were conducted in a typical hilly semi-arid region over three growing seasons and two dormancy seasons in 2015–2017. The three treatments applied to mountain jujube plantations throughout the year were grassland (CK), regular pruning (PR), and pruning and mulching (PM). Soil water storage (0–200 cm) was higher in the PM than the PR treatment but lower than that of the CK in all three growing seasons. Relative to PR and CK, PM significantly decreased soil water loss during the dormancy season. The soil moisture infiltration depths were 300 cm, 160 cm, and 420 cm in 2016 and 420 cm, 280 cm, and 460 cm in 2017 for PM, PR, and CK, respectively. Soil desiccation was substantially reduced under the PM treatment in the deep soil layer but was less effectively mitigated under the PR treatment. In the CK treatment, soil desiccation appeared at 0–200 cm but was alleviated by heavy rainfall. Fresh fruit yield ranged from 6643–11,056 kg ha−1 for the PM treatment in 2015–2017. This range was 1221–2628 kg ha−1 higher than that for the PR treatment. Water use efficiency was 2.28 kg m−3, 2.05 kg m−3, and 2.22 kg m−3 under the PM treatment in 2015, 2016, and 2017, respectively. These rates were 1.27 × , 1.26 × , and 1.39 × higher, respectively, than those for the PR treatment. These results suggest that the combination of mulching and pruning is an alternative strategy for mitigating soil desiccation in the hilly regions of the Loess Plateau of China. This alternative land management system may be critical for the sustainable cultivation of economically important forest trees in the Loess Plateau region and elsewhere. Keywords: Soil desiccation, Soil water storage, Pruning, Crop yield, Water use efficienc

Exerkines and cardiometabolic benefits of exercise: from bench to clinic

Abstract Regular exercise has both immediate and long-lasting benefits on cardiometabolic health, and has been recommended as a cornerstone of treatment in the management of diabetes and cardiovascular conditions. Exerkines, which are defined as humoral factors responsive to acute or chronic exercise, have emerged as important players conferring some of the multiple cardiometabolic benefits of exercise. Over the past decades, hundreds of exerkines released from skeletal muscle, heart, liver, adipose tissue, brain, and gut have been identified, and several exerkines (such as FGF21, IL-6, and adiponectin) have been exploited therapeutically as exercise mimetics for the treatment of various metabolic and cardiovascular diseases. Recent advances in metagenomics have led to the identification of gut microbiota, a so-called “hidden” metabolic organ, as an additional class of exerkines determining the efficacy of exercise in diabetes prevention, cardiac protection, and exercise performance. Furthermore, multiomics-based studies have shown the feasibility of using baseline exerkine signatures to predict individual responses to exercise with respect to metabolic and cardiorespiratory health. This review aims to explore the molecular pathways whereby exerkine networks mediate the cardiometabolic adaptations to exercise by fine-tuning inter-organ crosstalk, and discuss the roadmaps for translating exerkine-based discovery into the therapeutic application and personalized medicine in the management of the cardiometabolic disease

Experimental Study on the Acoustic Emission Characteristics of Fractured Granite after Repeated High Temperature-Water Cooling

Using the MTS816 rock mechanics servo tester, an acoustic emission monitoring system and high-speed digital photographic equipment, uniaxial compression tests were conducted on granite specimens containing single fracture slabs after repeated treatment (treatment times 1, 5, 10, 15 and 20) with three types of high temperature (250, 350 and 450 °C) water cooling, respectively, to analyze the basic mechanical parameters, acoustic emission change characteristics and fracture evolution of the specimens during the uniaxial compression process. It is shown that the heating temperature and the number of treatments not only have a deteriorating effect on the basic mechanical parameters of the specimens but also have an important effect on the changes in the basic parameters of acoustic emission at different compression stages. At 250 °C, the acoustic emission characteristics of the specimens at the initial tightening stage tended to decrease (N = 1 and 5 times) then, increase (N = 10 and 15 times) and then decrease (N = 20 times) as the number of treatments increased. At the same set temperature, the percentage of the bottom amplitude value of the acoustic emission of the specimen gradually decreases, and the percentage of the high amplitude value gradually increases as the number of treatments increases. After the specimen undergoes one and five treatments at 250 °C, the maximum acoustic emission energy value changes less, the maximum acoustic emission energy value decreases with the increase of treatment times in an approximately exponential function, the specimen is transformed from the brittle damage mode to the plastic damage mode and the effect of the prefabricated fracture on the damage of the specimen gradually disappears

Circulating complement-C1q TNF-related protein 1 levels are increased in patients with type 2 diabetes and are associated with insulin sensitivity in Chinese subjects.

BACKGROUND: Complement-C1q TNF-related protein 1 (CTRP1), a member of the CTRP superfamily, possesses anti-inflammatory and anti-diabetic effects in mice. However, the clinical relevance of CTRP1 has been seldom explored. The current study aimed to investigate the association of circulating CTRP1 and type 2 diabetes mellitus (T2DM) in a Chinese population. DESIGN AND METHODS: Serum CTRP1 and adiponectin levels of 96 T2DM patients and 85 healthy subjects were determined by ELISA, and their associations with adiposity, glucose and lipid profiles were studied. In a subgroup of this study, the 75-g oral glucose tolerance test (OGTT) was performed in 20 healthy and 20 T2DM subjects to evaluate the relationship among serum levels of CTRP1 and adiponectin, insulin secretion and insulin sensitivity. RESULTS: Serum CTRP1 levels were significantly increased in patients with T2DM, compared with healthy controls (p<0.001). Similar to adiponectin, serum levels of CTRP1 were significantly correlated to several parameters involved in glucose metabolism and insulin resistance, and independently associated with fasting glucose levels (p<0.05) after BMI and gender adjustments. Furthermore, CTRP1 levels were positively correlated to insulin secretion, while negatively to insulin sensitivity, as measured by OGTT. CONCLUSION: CTRP1 is a novel adipokine associated with T2DM in humans. The paradoxical increase of serum CTRP1 levels in T2DM subjects may be due to a compensatory response to the adverse glucose and lipid metabolism, which warrants further investigation

Serum CXCL16 as a novel marker of renal injury in type 2 diabetes mellitus.

BACKGROUND: Soluble C-X-C chemokine ligand 16 (CXCL16), a scavenger receptor for oxidized low density lipoprotein, has been shown to promote atherogenic effects in vivo and to predict long-term mortality in acute coronary syndrome. The aim of this study was to explore the association of circulating CXCL16 levels with diabetic subjects with and without renal disease. METHODOLOGY/PRINCIPAL FINDINGS: One hundred twenty Chinese subjects, which included patients with type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and CKD, as well as healthy controls, were enrolled in this study. Serum CXCL16 levels were examined by immunoassay and other clinical biochemical parameters were tested based on standard methods. Our results indicated that, HDL and LDL cholesterol levels are significantly different in DN but not in T2D patients in comparison with healthy subjects. On the other hand, Serum CXCL16 levels were significantly increased in DN subjects compared with age and gender matched healthy and T2DM subjects (p<0.05 respectively). However, no significant changes in serum CXCL16 levels were found between T2DM and healthy subjects. Furthermore, serum CXCL16 concentration negatively correlated with estimated glomerular filtrate rate, creatinine clearance rate and blood albumin, and positively with 24 h proteinuria, blood urea nitrogen (BUN), creatinine, and uric acid after adjusting for age, gender and BMI in subjects with DN. Multiple stepwise regression analyses indicated that serum CXCL16 levels were independently associated with serum 24 h proteinuria, and BUN (p<0.05 respectively). CONCLUSION: Serum CXCL16 may be an indicator of renal injury in subjects with T2DM. Understanding the exact mechanism of elevated CXCL16 in subjects with DN requires further study

Correlation of CTRP1 with fasting glucose (A), HBA1c (B), HOMA-ir (C) and IAI (D) after gender- and BMI-adjustment in 96 T2DM subjects.

<p>Correlation of CTRP1 with fasting glucose (A), HBA1c (B), HOMA-ir (C) and IAI (D) after gender- and BMI-adjustment in 96 T2DM subjects.</p