Search

The mode-1 semidiurnal internal tides that emanate from multiple sources in the Sulu-Sulawesi Seas are investigated using multi-satellite altimeter data from 1993–2020. A practical plane-wave analysis method is used to separately extract multiple coherent internal tides, with the nontidal noise in the internal tide field further removed by a two-dimensional (2-D) spatial band-pass filter. The complex radiation pathways and interference patterns of the internal tides are revealed, showing a spatial contrast between the Sulu Sea and the Sulawesi Sea. The mode-1 semidiurnal internal tides in the Sulawesi Sea are effectively generated from both the Sulu and Sangihe Island chains, forming a spatially inhomogeneous interference pattern in the deep basin. A cylindrical internal tidal wave pattern from the Sibutu passage is confirmed for the first time, which modulates the interference pattern. The interference field can be reproduced by a line source model. A weak reflected internal tidal beam off the Sulawesi slope is revealed. In contrast, the Sulu Island chain is the sole energetic internal tide source in the Sulu Sea, thus featuring a relatively consistent wave and energy flux field in the basin. These energetic semidiurnal internal tidal beams contribute to the frequent occurrence of internal solitary waves (ISWs) in the study area. On the basis of the 28-year consistent satellite measurements, the northward semidiurnal tidal energy flux from the Sulu Island chain is 0.46 GW, about 25% of the southward energy flux. For M2, the altimetric estimated energy fluxes from the Sulu Island chain are about 80% of those from numerical simulations. The total semidiurnal tidal energy flux from the Sulu and Sangihe Island chains into the Sulawesi Sea is about 2.7 GW.

Three main classes are considered of significant influence factors when predicting the energy consumption rate of electric vehicles (EV): environment, driver behaviour, and vehicle. These classes take into account constant or variable parameters which influences the energy consumption of the EV. In this paper, we develop a new model taking into account the three classes as well as the interaction between them in order to improve the quality of EV energy consumption. The model depends on a new approach based on machine learning and especially k-NN algorithm in order to estimate the EV energy consumption. Following a lazy learning paradigm, this approach allows better estimation performance. The advantage of our proposal, in regards to mathematical approach, is taking into account the real situation of the ecosystem on the basis of historical data. In fact, the behavior of the driver (driving style, heating usage, air conditioner usage, battery state, etc.) impacts directly the EV energy consumption. The obtained results show that we can reach up to 96.5% of accuracy about the estimated of energy-consumption. The proposed method is used in order to find the optimal path between two points (departure-destination) in terms of energy consumption.

Short-chain fatty acids (SCFAs), particularly acetate, propionate and butyrate, are mainly produced by anaerobic fermentation of gut microbes. SCFAs play an important role in regulating energy metabolism and energy supply, as well as maintaining the homeostasis of the intestinal environment. In recent years, many studies have shown that SCFAs demonstrate physiologically beneficial effects, and the signalling pathways related to SCFA production, absorption, metabolism, and intestinal effects have been discovered. Two major signalling pathways concerning SCFAs, G-protein-coupled receptors (GPRCs) and histone deacetylases (HDACs), are well recognized. In this review, we summarize the recent advances concerning the biological properties of SCFAs and the signalling pathways in inflammation and glucose and lipid metabolism.

Objectives Anthocyanins derived from different plant sources have been found to possess a variety of health-promoting effects, including antiinflammatory properties and protection from oxidative stress. The aim of this study was to investigate the dose-response relationship between anthocyanins and metabolic risk factors as well as inflammatory and oxidative biomarkers in healthy adult volunteers. Methods We conducted a randomized, double-blind, placebo-controlled trial, which included an increasing dosing schedule of 20, 40, 80, 160, and 320 mg of purified anthocyanins or placebo. Participants (n = 111) were administered either agent for 14 consecutive days. Results No significant differences in either baseline characteristics or daily intake of dietary nutrients were detected between the experimental and control groups. After anthocyanin supplementation, there was a significant difference in adjusted fasting plasma glucose levels. The group receiving 80 mg/d of anthocyanin had the lowest baseline-adjusted fasting plasma glucose when compared with placebo (F = 3.556, P = 0.007). Logarithmically adjusted plasma interleukin-10 levels were negatively correlated with increasing anthocyanin dose (F = 2.738, P = 0.025). Similarly, 8-iso-prostaglandin F2α levels decreased with increasing anthocyanins dose (F = 3.513, P = 0.009). Conclusions Taken together, our results suggest that anthocyanin supplementation at a dose greater than 80 mg/d is an effective antioxidant and antiinflammatory agent in healthy young adults.

Corpse-removal behavior of the red imported fire ant (RIFA) and the effects of lethal substances on RIFA signal communication were investigated in this study. The RIFA corpses, obtained through freezing, ether, 0.25 mg/L thiamethoxam, and starvation to death treatments, and naturally dead red fire ants were subjected to gas chromatography–mass spectrometry to identify the cuticular hydrocarbon profiles that had an effect on the corpse-removal behavior. The results showed that lethal toxic substances altered the epidermal compounds of RIFA and affected their corpse-removal behavior. Lethal toxic substances increased the number of worker touches with corpses and identification time of corpses. In addition, the content of piperidine (1,1′-(1,2-ethanediyl)bis-) on the surface of the corpse was different following the various treatments. Contamination with toxic substances resulted in the increased secretion of piperidine and led to increased identification time of corpses, number of touch with corpses, and total time for removal of corpses. Piperidine content was higher under conditions of natural death (4.67 ± 0.55%) and with thiamethoxam (10.43 ± 0.78%), freezing (0.83 ± 0.25%), and ether treatment (12.50 ± 0.70%) than under starvation treatment (0). The higher content of piperidine led to a longer number of touches with corpses and identification time. Piperidine compounds may be an element in warning information, which could affect the occurrence of different corpse-removal behaviors.

Coenzyme Q10 (CoQ10) is a well-known anti-adipogenic factor that possesses the capability to regulate non-alcoholic fatty liver disease (NAFLD). However, the mechanism by which CoQ10 acts on NAFLD is still unclear. In this study, the role of CoQ10 in the prevention of NAFLD was investigated in vivo and in vitro. C57BL/6J mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with CoQ10 (1800 mg kg-1 HFD) for 24 weeks. HepG2 cells were treated with sodium palmitate for investigating the mechanism of action of CoQ10 on NAFLD. The results showed that CoQ10 alleviated HFD-induced weight gain and NAFLD, accompanied by an anti-hyperlipidaemia effect, by reducing the serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Importantly, CoQ10 could downregulate the expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), which are related to lipid synthesis, and upregulate the expression of peroxisome proliferator-activated receptors α (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) associated with fatty acid oxidation. Similar to the results from mice, treatment with CoQ10 alleviated sodium palmitate-induced hepatocyte steatosis via the inhibition of lipogenesis and promotion of fatty acid oxidation. However, Compound C, as an AMPK inhibitor, could significantly block the benefits derived from CoQ10 treatment. In conclusion, CoQ10 could serve as an AMPK activator and regulate the hepatic lipid metabolism to inhibit the abnormal accumulation of hepatic lipids and prevent NAFLD progression.

A comparison of the different types of resting state reveals some interesting characteristics of spontaneous brain activity that cannot be found in a single condition. Differences in the amplitude of low-frequency fluctuation (ALFF) between the eyes open (EO) and the eyes closed (EC) almost have a spatially distinct pattern with traditional EO-EC activation within sensory systems, suggesting the divergent functional roles of ALFF and activation. However, the underlying mechanism is far from clear. Since the thalamus plays an essential role in sensory processing, one critical step toward understanding the divergences is to depict the relationships between the thalamus and the ALFF modulation in sensory regions. In this preliminary study, we examined the association between the changes of ALFF and the changes of thalamic functional connectivity (FC) between EO and EC. We focused on two visual thalamic nuclei, the lateral geniculate nucleus (LGN) and the pulvinar (Pu). FC results showed that LGN had stronger synchronization with regions in lateral but not in medial visual networks, while Pu had a weaker synchronization with auditory and sensorimotor areas during EO compared with EC. Moreover, the patterns of FC modulation exhibited considerable overlaps with the ALFF modulation, and there were significant correlations between them across subjects. Our findings support the crucial role of the thalamus in amplitude modulation of low-frequency spontaneous activity in sensory systems, and may pave the way to elucidate the mechanisms governing distinction between evoked activation and modulation of low-frequency spontaneous brain activity.

Azadirachtin, as the most promising and effective botanical insecticide, exhibits significant growth inhibition activity against agricultural and forestry pests. However, its biochemical effects at the metabolic level compared with those of other insect growth regulators have not been studied. Therefore, in this study, a GC-MS based untargeted metabolomics approach was applied to compare azadirachtin with pyriproxyfen (a juvenile hormone analog) and tebufenozide (a molting hormone analog) in terms of their metabolic effects on Bactrocera dorsalis larvae. The bioactivity of azadirachtin against B. dorsalis larvae was significantly different than those of pyriproxyfen and tebufenozide. A total of 693 mass features were recognized, and 112 metabolites were identified in this study. The results showed that a total of 16, 13 and 10 differentially regulated metabolites corresponding to 12, 5 and 8 pathways occur in Aza versus CK, Pyr versus CK and Teb versus CK group, respectively. Further analysis showed that 6 differentially regulated metabolites corresponding to 5 key pathways could be the primary differential metabolic response of B. dorsalis larvae to the three insect growth regulators. The pathways were myo-inositol corresponding to ascorbate and aldarate metabolism as the specific response of B. dorsalis larvae to azadirachtin; xylitol, xylulose and 3-aminopropionitrile corresponding to pentose and glucuronate interconversions, and cyanoamino acid metabolism as the common responses to azadirachtin and pyriproxyfen; and 3-hydroxypropionic acid and beta-alanine corresponding to propanoate metabolism and beta-alanine metabolism as the specific responses to tebufenozide. The results showed that the metabolic response of B. dorsalis larvae to azadirachitin is closer to that of pyriproxyfen than tebufenozide. The differentially regulated metabolites and pathways responsible for this difference are discussed.

Skeletal muscle is an important and complex organ with a variety of functions in humans and animals. Skeletal myogenesis is a multistep and complex process, and increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play critical roles in skeletal myogenesis. In this study the expression of miR-351-5p is dynamically regulated during skeletal myogenesis in vitro and in vivo. Cell-counting kit-8, qRT-PCR, and EdU immunofluorescence analysis showed that miR-351-5p overexpression promoted the proliferation and inhibited the differentiation of C2C12 myoblast, whereas inhibition of miR-351-5p had the opposite effect. In addition, miR-351-5p mediated the regulation of muscle fiber type transition in vivo. In vitro, loss of miR-351-5p in muscle tissues promoted muscle hypertrophy and increased slow-twitch fibers in the gastrocnemius muscles of mice. Luciferase reporter assay and functional analyses demonstrated that lactamase β ( LACTB) is a direct target of miR-351-5p involved in the regulation of skeletal myogenesis. Expression levels of a myogenesis-associated lncRNA ( lnc-mg) correlated negatively with miR-351-5p and positively with LACTB during C2C12 myoblast proliferation and differentiation. Further analyses showed that lnc-mg acted as a molecular sponge for miR-351-5p, demonstrating its involvement in the negative regulation of LACTB by miR-351-5p during skeletal myogenesis. These findings indicate that miRNA-351-5p functions in skeletal myogenesis by targeting LACTB and is regulated by lnc-mg, supporting the role of the competing endogenous RNA network in skeletal myogenesis.-Du, J., Zhang, P., Zhao, X., He, J., Xu, Y., Zou, Q., Luo, J., Shen, L., Gu, H., Tang, Q., Li, M., Jiang, Y., Tang, G., Bai, L., Li, X., Wang, J., Zhang, S., Zhu, L. MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase β and is regulated by lnc-mg.

Recent BOLD-fMRI studies have revealed spatial distinction between variability- and mean-based between-condition differences, suggesting that BOLD variability could offer complementary and even orthogonal views of brain function with traditional activation. However, these findings were mainly observed in block-designed fMRI studies. As block design may not be appreciate for characterizing the low-frequency dynamics of BOLD signal, the evidences suggesting the distinction between BOLD variability and mean are less convincing. Based on the high reproducibility of signal variability modulation between continuous eyes-open (EO) and eyes-closed (EC) states, here we employed EO/EC paradigm and BOLD-fMRI to compare variability- and mean-based EO/EC differences while the subjects were in light. The comparisons were made both on block-designed and continuous EO/EC data. Our results demonstrated that the spatial patterns of variability- and mean-based EO/EC differences were largely distinct with each other, both for block-designed and continuous data. For continuous data, increases of BOLD variability were found in secondary visual cortex and decreases were mainly in primary auditory cortex, primary sensorimotor cortex and medial nuclei of thalamus, whereas no significant mean-based differences were observed. For the block-designed data, the pattern of increased variability resembled that of continuous data and the negative regions were restricted to medial thalamus and a few clusters in auditory and sensorimotor networks, whereas activation regions were mainly located in primary visual cortex and lateral nuclei of thalamus. Furthermore, with the expanding window analyses we found variability results of continuous data exhibited a rather slower dynamical process than typically considered for task activation, suggesting block design is less optimal than continuous design in characterizing BOLD variability. In sum, we provided more solid evidences that variability-based modulation could represent orthogonal views of brain function with traditional mean-based activation.

Intramuscular fat (IMF) content and composition are considered crucial indicators of porcine meat quality. However, the molecular mechanism of porcine IMF development is still mostly unclear. Recently, new evidence suggested that microRNA (miRNAs) play important roles in porcine intramuscular adipogenesis. Previously, microRNA-125a-5p (miR-125a-5p) was identified as an important regulator of adipogenesis. In the present study, we found that the expression of miR-125a-5p is dynamically regulated during porcine intramuscular preadipocytes differentiation and that its expression levels in different porcine muscle tissues were negatively involved with IMF content. To investigate the potential function role of miR-125a-5p in IMF development, porcine intramuscular preadipocytes were collected and transfected with miR-125a-5p mimics, inhibitors, or a negative control (NC), respectively. The results showed that overexpression of miR-125a-5p promoted proliferation and inhibited differentiation of porcine intramuscular preadipocytes while inhibition of miR-125a-5p had the opposite effects. Furthermore, a luciferase reporter assay demonstrated that porcine kruppel like factor 3 (KLF13) is a target gene of miR-125a-5p during porcine intramuscular preadipocytes differentiation. Interestingly, porcine ELOVL fatty acid elongase 6 (ELOVL6), a regulator of fatty acid composition, was also identified as a target gene of miR-125a-5p during porcine intramuscular adipogenesis. Further studies show that miR-125a-5p overexpression reduced total saturated fatty acids (SFA) content and monounsaturated fatty acids (MUFA)/SFA ratios while having no significant impact on polyunsaturated fatty acids (PUFA)/SFA and n-6/n-3 ratios. Taken together, our results identified that miR-125a-5p may be a novel regulator of porcine intramuscular adipogenesis and the fatty acid composition of porcine IMF.

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional levels. In this study, we showed that miR-125a-5p was expressed at lower levels in the adipose tissues of high-fat diet (HFD)-fed mice than the normal chow (NCW)-fed mice. MiR-125a-5p expression were strongly up-regulated by nearly five-fold, when 3T3-L1 preadipocyte were induced and differentiated into mature adipocytes. Functional analysis indicated that overexpression of miR-125a-5p promoted 3T3-L1 preadipocyte proliferation and inhibited its differentiation. By contrast, inhibition of miR-125a-5p repressed 3T3-L1 preadipocyte proliferation and accelerated its differentiation. Furthermore, a dual-luciferase reporter assay demonstrated that signal transducer and activator of transcription 3 (STAT3) is a direct target gene of miR-125a-5p during 3T3-L1 preadipocyte differentiation. Further analysis confirmed that the process of miR-125a-5p inhibiting 3T3-L1 preadipocyte differentiation might be associated with the regulation of fatty acid metabolism related genes. Taken together, our results indicated that miR-125a-5p might promote 3T3-L1 preadipocyte proliferation, whereas inhibiting 3T3-L1 preadipocyte differentiation by negatively regulating STAT3.

The dynamic response of circular sandwich panels with aluminium honeycomb and corrugated cores under projectile impact was investigated experimentally and numerically. Impulse loaded on the panel was controlled by projectile launching velocity and the deformation process of sandwich panels was recorded by a high-speed camera in the experiments. Typical deformation/failure modes of face-sheets and cores were obtained and analysed. The back face-sheet deflections and strain histories of face-sheets were measured and discussed. A parametric study was conducted by LS-DYNA 3D to analyse the effect of geometrical configuration on energy absorption mechanism and back face-sheet permanent deflection of circular sandwich panels. The results indicated that the impact resistance of the structure was sensitive to geometrical configuration. Increasing face-sheet thickness and core relative density significantly improved sandwich structure impact resistance. Increasing foil thickness improved the panel impact resistance more efficiently than decreasing wall side length. The results have important reference value to guide engineering application of the sandwich structure subjected to impact loading.

Aims We previously found that miR-10b inhibits cholesterol efflux from thioglycollate-elicited mouse peritoneal macrophages through repressing ATP binding cassette transporter (ABCA1). Herein, we deciphered the mechanism underlying macrophage miR-10b expression and the role of miR-10b in atherosclerosis. Methods and results MiR-10b expression was increased in the arteries with advanced but not early atherosclerotic plaques of ApoE-/- mice. Free cholesterol-induced macrophage apoptotic cells (FC-AM) promoted miR-10b expression in mouse resident peritoneal macrophages (RPM) by up-regulation of Twist1/2 in a Mer receptor tyrosine kinase dependent manner. Surprisingly, antagomiR-10b de-repressed ABCA1 in RPM engulfing FC-AM but not in RPM alone or RPM-derived foam cells; systemic delivery of antagomiR-10b enhanced reverse cholesterol transport from RPM engulfing FC-AM but not from RPM or the foam cells in ApoE-/- mice. Mechanistically, RPM engulfing FC-AM possessed sufficient miR-10b functionally repressing ABCA1 expression, whereas RPM and foam cells had little miR-10b incompetently repressing ABCA1 expression. Notably, antagomiR-10b administration reduced advanced plaque size and also enhanced plaque stability in ApoE-/-mice, which were associated with increased plaque macrophage ABCA1 expression and reduced plaque apoptosis and inflammation. However, antagomiR-10b administration did not affect early atherosclerotic plaque formation in ApoE-/- mice. Conclusion These data suggest that apoptotic cell induction of miR-10b in macrophages is important in advanced atherosclerosis progression.

Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance.

The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown benefit. However, the effect of CoQ10 as a primary preventive agent against cardiovascular diseases (CVDs) has not been well studied.The objective of this study was to investigate the effect of CoQ10 on CVD risk factors in dyslipidemic patients.In this randomized, double-blinded, placebo-controlled trial, 101 dyslipidemic subjects without taking any hypoglycemic or hypolipidemic drugs were administrated to 120 mg CoQ10 or placebo daily for 24 weeks. Anthropometric parameters, lipid and glycemic profile, biomarkers of inflammation, and antioxidant capacity were evaluated before and after 12 and 24 weeks of intervention.All 101 subjects were included in the analysis. On the 12th week, compared to placebo, CoQ10 supplementation decreased systolic (P = .010) and diastolic pressure (P = .001) and increased serum total antioxidant capacity (TAC; P = .003). On the 24th week, compared to placebo, CoQ10 supplementation further lowered blood pressure and TAC, reduced triglyceride (P = .020) and low-density lipoprotein cholesterol (P = .016), and increased ApoA-I (P .001) while decreasing homeostasis model assessment of insulin resistance index (P = .009). Adjustment for change of physical activity and energy intake did not alter the effect of CoQ10 on the aforementioned parameters but led to significant decrease of non-high-density lipoprotein cholesterol in CoQ10 group compared to placebo (P = .031).Twenty-four-week treatment of CoQ10 ameliorates multiple CVD risk factors. The versatility and safety of CoQ10 makes it a potential candidate for the primary prevention of CVD.

The dynamic crushing behavior of the open-cell aluminum foam with negative Poisson’s ratio (NPR) was investigated using the finite-element (FE) method. The plateau stress, the specific energy absorption, and the deformation modes are determined using the FE models. The results indicate that the plateau stress and specific energy absorption (SEA) of NPR open-cell foam under impact loading are less than the conventional foam with the same relative density, and the deformation pattern of NPR open-cell foam material is completely different from the conventional foam material. The NPR open-cell foam material is not suitable for energy absorption under low-velocity impact, but the negative Poisson’s ratio effect on deformation modes becomes smaller with the impact velocity increasing. The length-to-height ratio which is defined for a cell having certain geometric characteristics is a key parameter to design the NPR foams materials.

Dietary therapy is the mainstay of treatment for diabetes. This study examined the effect of a low glycemic index (GI) multi-nutrient supplement, consumed in place of breakfast, on glycemic control in patients with type 2 diabetes mellitus (T2DM). A total of 71 participants were randomized at a 2:1 ratio into either a breakfast replacement group or a normal breakfast group for a 12-week interventional study. The primary outcome measure was change in hemoglobin A1c (HbA1c). Nutrition status and somatometry were studied as secondary outcomes. The breakfast replacement group displayed a −0.2% absolute reduction in HbA1c (95% CI (confidence interval), −0.38% to −0.07%, p = 0.004), while the HbA1c of the control group increased 0.3% (95% CI, 0.1% to 0.5%, p = 0.005). The baseline Mini Nutritional Assessment score for both groups was 26.0 and no significant changes occurred following intervention. However, there was a statistically significant difference in body mass index between the treatment and control groups (p = 0.032) due to the weight gain in the control group (increased 0.5 kg, 95% CI was 0.2 to 0.9, p = 0.007). These data suggest that breakfast replacement with a low GI multi-nutrient supplement can improve glycemic and weight control in T2DM.

This paper presents a blast experiment to investigate the blast-resistance of square sandwich panels with hexagon aluminum honeycomb cores. Different heights and cell side length s for honeycomb core were considered in the experiment. The impulse loading on the panel was calculated by using the displacement history of ballistic pendulum. The interaction between the shockwave and panel, as well as the deformation/failure modes of face sheet and core, were discussed. Finite-element simulation was also conducted to investigate the dynamic response of the sandwich panel. The simulation captured most of the details of the deformation patterns. The velocity, displacement, strain history and energy absorption of the sandwich panel was analyzed.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (People's Republic) Acute myeloid leukaemia (AML) is an aggressive hematologic neoplasm with distinct molecular and genetic features which is characterized by differentiation blockade and uncontrolled proliferation of malignant clones of immature myeloid cells. The growth arrest and DNA-damage induced 45 (GADD45) family protein GADD45g, has been shown to mediate DNA repair, cell cycle, senescence and apoptosis in response to various physiological and environmental stressors. Altered expression of GADD45g has been observed in multiple types of solid tumors, the function of GADD45g in hematopoietic malignancies remains almost completely unknown. Here, we found that GADD45g expression was preferentially silenced in AML, especially in AML with MLL rearrangements and FLT3-ITD mutations, and reduced expression of GADD45g correlates with poor prognosis in AML patients. Ectopic expression of GADD45g suppresses leukemic growth, induced apoptosis, senescence and differentiation of AML cells in vitro and in vivo. What's more, GADD45g caused downregulation of DNA repair proteins, resulting in inhibition of DNA double-strand break repair pathways and leading to DNA damage accumulation in AML cells. Moreover, GADD45g is epigenetically silenced in AML by both promoter DNA methylation and histone deacetylation, while the HDACi is more powerful. Exogenous expression of FLT3-ITD and MLL-AF9 repress GADD45G expression in AML, and the expression of GADD45G could be significantly induced by the small-molecule inhibitors FLT3 TKI or BRD4i target FLT3 or MLL respectively. Furthermore, the combination of HDACi and FLT3 TKI or BRD4i exerted a synergistic effect against FLT3-ITD+ or MLL-rearranged AML, respectively. These findings suggest that GADD45G may act as a tumor suppressor in AML and provide a novel and promising therapeutic target for AML.

This study determined the long-term influence of prenatal nicotine exposure (PN) on blood pressure and vascular functions in the aged offspring rats. PN did not affect body weight and plasma adrenocorticotropic hormone level; however, it significantly reduced plasma angiotensin I and angiotensin II in both sexes. Systolic pressure in the male aged PN offspring was significantly higher. Angiotensin II-increased mean arterial pressure was higher in the aged PN offspring than that in the control regardless of sex. AT1 receptor blocker losartan, not AT2 receptor antagonist PD123319, reduced blood pressure in the aged PN rats more than that in the control. In the aged PN offspring, angiotensin II-increased vessel contraction and intracellular calcium level were higher in small mesenteric arteries. Acetylcholine-mediated vascular relaxation was weaker, and nitric oxide-related endothelial functions were damaged in aortic rings of PN offspring. Thickness of the wall of mesenteric arteries was increased in the male aged PN offspring. Ratio of AT1/AT2 receptors was significantly increased in the vessel of the PN group regardless of sex. These data provide new information on the very long term influence of PN on vascular structures and functions in the aged offspring, demonstrate that the aged PN female rats were not free of vascular risks after menopause, and suggest that multiple pathways may be involved in the detrimental alterations of the cardiovascular system of the PN rats.

Biological soil crusts (BSCs) are important sources of carbon input to ecosystems in arid and semiarid regions, where vascular plants are restricted by the rigorous environment and limited soil water. Sand dune stabilization by revegetation can enhance colonization and development of BSCs on sandy soil surfaces, and convert BSCs from the early successional stage dominated by cyanobacteria and algae to the later stage dominated by lichens and mosses. This study estimated the carbon fixation by two successional stages of BSCs based on four years of field observations. Carbon fixation by two BSCs has been compared via estimating daily carbon fixation using measuring net photosynthesis with ten sampling plots per crust stage in situ, combining with calculating the wet daytime of crustal cryptogam thallus. However, diurnal carbon fixation of both BSCs was largely determined by crustal water content rather than photosynthesis photon flux and temperature. The range of optimal gravimetric water content for early BSCs was 1–3.5%, and 1–5% for the later BSCs. The annual carbon fixation was 11.36 g C m − 2 yr − 1 for cyanobacteria–algae dominated crusts and 26.75 g C m − 2 yr − 1 for lichen–moss dominated crusts. The latter had a higher carbon input due to a higher water-holding capacity, prolonging wet daytime and higher chlorophyll content, as well as higher light capture. These findings indicate the recovery of BSCs is expected to significantly increase carbon input into sandy desert ecosystems.

Insufficient gastric mucosa drug concentration and short contact time were the main reason for the lack of eradication efficacy of Helicobacter pylori for peptic ulcer patients. Novel multi-core chitosan microspheres were prepared for stomach-specific delivery of hydrophilic antibiotics for the treatment of peptic ulcer. Chitosan microspheres with multiple Eudragit L100 cores were easily prepared by a new emulsification/coagulation encapsulating method. Swelling behaviors, surface amino groups and mucin absorption ability were investigated and the formulation that showed best mucoadhesive potential was adopted. The multi-core chitosan microspheres exhibited good mucoadhesiveness as well as controlled release manner for incorporated antibiotics in acidic environment. The release rate could be easily modulated with accumulative release ranging from 47.3 to 79.3% in 6 h. Accordingly, the multi-core chitosan microspheres could serve as a satisfactory vehicle for stomach-specific delivery of hydrophilic antibiotics.

Biological soil crusts are important cover in arid desert landscapes, yet their importance as habitats to secondary producers such as ants is relatively unknown. This study was conducted to determine if the presence and development of biological soil crusts on dune surfaces stabilized by revegetation facilitates ant establishment and survival. We measured topsoil properties and crustal features during different successional stages, which were characterized by cyanobacteria and algae, lichens, and mosses, respectively. The species richness and abundance (nest density) of ants were closely associated with silt content, soil organic matter, nitrogen and soil moisture, as well as topsoil temperature. However, ant nest distribution was largely dependent on the biomass and thickness of crusts and topsoil. These findings provide evidence that the recovery or development of biological soil crusts on dune surfaces in the Tengger Desert could favor and maintain higher ant species diversity. Therefore, the disturbance of crusts would result in a reduction of ant species richness and abundance in desert systems.

In this paper, the silicon nanocrystals (Si NCs)/SiO2 hybrid films designed for nonvolatile memory applications are prepared by electron-beam co-evaporation of Si and SiO2. Transmission electron microscopy images and Raman spectra verify the formation of Si NCs. Metal-oxide-semiconductor capacitor structure with Si NCs embedded in the gate oxide is fabricated to characterize the memory behaviors. High-frequency capacitance–voltage and capacitance–time measurements further demonstrate the memory effect of the structure resulting from the charging or discharging behaviors of Si NCs. It is found that the memory window can be changed by adjusting the Si/SiO2 wt. ratio in source material. The memory devices with Si NCs/SiO2 hybrid film as floating gate yield good retention characteristics with small charge loss.

MicroRNAs are a class of 18–22-nucleotide noncoding RNAs that posttranscriptionally regulate gene expression and have been shown to play an important role during myoblast differentiation. In this study, we found that the expression of miR-145a-5p was gradually increased during C2C12 myoblast differentiation, and miR-145a-5p inhibitors or mimics significantly suppressed or promoted the relative expression of specific myogenesis related marker genes. Moreover, overexpression or inhibition of miR-145a-5p enhanced or repressed the expression of some special genes involved in the endogenous Wnt signaling pathway during C2C12 myoblast differentiation, includingWnt5a,LRP5,Axin2, andβ-catenin. These results indicated that miR-145a-5p might be considered as a new myogenic differentiation-associated microRNA that can promote C2C12 myoblast differentiation by enhancing genes related to myoblasts differentiation.

Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin-loaded dodecylamine-graft-γ-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitro evaluation, Caco-2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%.

and extended hospital stays. Non-serious complications included formation of a hematoma, discoloration, oozing, swelling, or bleeding at the entry site. P values < 0.05 were considered significant. Results: An independent T-test indicated a significant (p < .001) increase in the mean percentage in the number of reused SUDs at BBH. There was no difference in the number of complications that developed after surgery between the hospitals, despite the significant difference in the number of SUDs per procedure. When analyzing length of stay, the results showed significant (p < .001) increase in the average mean stay for patients in BBH which may be attributed to the initial health status of patients. No significant differences were found between hospitals in the severity of complications was analyzed (serious vs. non-serious). Conclusion: There was no significant correlation between the reuse of single use medical devices and adverse outcomes for PTCA at either of the two hospitals in which the study took place. Funding: No funding listed. Abstract #: 02NCD005

In accordance with the characteristics of passenger aircraft market demand analysis, this paper constructs a demand analysis model which, at first, establishes ‘typical route’ through route market segmentation, and then determines the market plan of passenger aircraft based on the ‘typical route’ transportation capacity configuration model. Furthermore, by using .net frame and MATLAB, this paper develops a demand analysis system for civil aviation aircraft. The system is efficient, stable, and easy to operate, reduces the complexity of passenger aircraft market analysis, and thus promotes the analyzing efficiency. KeywordsAir transportation; civil airplane market demand;.NET technology; MATLAB

patients seen since 2010 were included in this study. The burden of disease, measured as the ratio of unique diagnoses per total patient encounters, was determined. Prevalence of intestinal helminthiasis, representing the greatest burden to the total patient population, was compared between 25 communities using bivariate and multivariate analysis. Results (Scientific Abstract)/Collaborative Partners (Programmatic Abstract): FD patient records over the past 2 years indicate that intestinal helminthiasis represents the greatest perceived health burden in all 21 Ngobe communities visited, with 32% (95% CI, 5.99) of patients seeking treatment for worms, while non-indigenous patients present with worms in only 10% (95% CI, 4.53) of 421 consultations. Integrating the data from each community into geographic information systems (GIS) has allowed for meaningful graphic data presentation. Summary/Conclusion: The overwhelming burden of helminthiasis is well known to FD clinicians and quantifying this burden in each community has provided both FD and the local Ministry of Health with an improved understanding of 1) geographic distribution of helminth burden, 2) the effectiveness of individual anthelmintic programs, and 3) regions that may require novel anthelmintic approaches. As a consequence of this research and the partnership between Floating Doctors, US medical schools, and local Ministry of Health, a group of first-year medical students from Stony Brook University will be conducting a fecal sample study in the indigenous town of Norteno this summer. In addition to identifying the types of helminths burdening the community they will coordinate with the school’s principal, teachers, and Peace Corps volunteer to implement a helminth education curriculum. This winter MD and MPH students will also be applying for a grant to install a Pan-American Health Organization (PAHO) chlorine filtration system for Norteno’s largest aqueduct.

Apoptosis is an early event of steatohepatitis in non-alcoholic fatty liver disease (NAFLD), and an increase in oxidative stress induced by hyperglycemia has been linked to an acceleration of apoptosis in hepatocytes. Cyanidin-3-O-β-glucoside (C3G), a classic anthocyanin, has been reported to reduce oxidative stress and attenuate non-alcoholic steatohepatitis in mice. In this study, we evaluated the toxicity of high glucose in primary hepatocytes of mice fed with a high fat diet and amelioration of this toxicity by C3G. Incubation of hepatocytes with 35mM glucose for 12h resulted in a significant decrease in cell viability and increase in apoptotic cell death. Furthermore, hyperglycemia-induced mitochondrial depolarization was accompanied by the release of cytochrome c and altered expression of Bax and Bcl-2, suggesting a mitochondria-mediated apoptotic mode of cell death. Pre-incubation with 50μM C3G induced changes associated with better cell survival and function, including a reduction in reactive species generation, improvement of mitochondrial membrane potential, inactivation of caspase-3 and -9, and down-regulation of the pro-apoptotic Bax protein. We further investigated the role of the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways with respect to the anti-apoptotic action of C3G, and our results showed that C3G could activate Akt. Additionally, C3G inactivated c-Jun N-terminal protein kinase (JNK), but not extracellular signal-regulated kinase or p38 MAPK, in glucose-stressed cells. Interestingly, JNK inhibitor enhanced the protective effect of C3G on cell survival. Our results suggest that anthocyanin C3G may exhibit hepatoprotective potential against NAFLD by promoting functional integrity and survival of hepatocytes.

Sufficient mucosal permeability is the bottleneck problem in developing an efficient intestinal delivery system of insulin. Cell-penetrating peptide-based nanocomplexes for the enhanced mucosal permeation of insulin were developed in this study. Penetratin, a cell-penetrating peptide was site-specifically modified with a bis-β-cyclodextrin group. Insulin-loaded nanocomplexes were prepared by self-assembly using penetratin or its bis-β-cyclodextrin modified derivative (P-bis-CD). A stronger intermolecular interaction and higher complex stability were observed for P-bis-CD nanocomplexes than the penetratin nanocomplexes. P-bis-CD nanocomplexes were significantly more efficient for the permeation of insulin as compared to the penetratin nanocomplexes both in vitro and in situ. Interestingly, different cellular internalization mechanisms were observed for the two nanocomplexes. In diabetic rats, intestinal administration of P-bis-CD nanocomplexes resulted in a prominent hypoglycemic effect which lasted for 6 h with maximum inhibitory rate at 60%. The relative pharmacological availability and bioavailability of P-bis-CD nanocomplexes were 10.6% and 7.1%, which were 3.0-fold and 2.3-fold higher than that of penetratin nanocomplexes, respectively. In addition, no sign of toxicity was observed after 7 consecutive days of administration of P-bis-CD nanocomplexes with endotoxin. These results demonstrated that P-bis-CD was a promising epithelium permeation enhancer for insulin and suggested that the chemical modification of cell penetration peptides was a feasible strategy to enhance their potential.

Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin-angiotensin system (RAS) that may mediate cardiac cell death.Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells.Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway.

To investigate whether folic acid would have toxic effects on fetal cardiac, hepatic, and renal functions, this was the first in utero fetal study testing acute effects of folic acid at the last third of gestation. Folic acid (5 mg/day) or 0.9% saline as the control was intragastricly administrated into pregnant ewes. Both maternal and fetal blood were analyzed for pH, PO(2), PCO(2), SO(2)%, hemoglobin, hematocrit, glucose, lactic acid, osmolality, Na(+), and K(+) concentrations. Maternal and fetal cardiovascular functions were assessed by examining cardiac enzymes and cardiovascular responses in vivo. Fetal hepatic and renal functions were examined by analysis of biochemistry index and renal excretion. Folic acid did not alter the blood values in both ewes and fetuses. Cardiac enzyme activities remained unchanged, and no alteration in cardiovascular responses was observed. Folic acid did not affect fetal urine volume, urine electrolytes, and osmolality. Enzyme activities related to hepatic and renal functions were not changed. In addition, maternal application of folic acid had no effect on maternal and fetal lipid profile. The results showed that folic acid used (5 mg/day) during the last third of gestation did not cause biochemical changes related to cardiac, hepatic, and renal functions in both maternal and fetal sheep, providing new information for use of folic acid during late pregnancy.

Police officers' overall evaluation of China's social conditions in 2008 remained much the same as for 2007, with a high evaluation of China's current social conditions and high expectations for the future situation. The outsized income differential and the polarisation of rich and poor, employment and unemployment and embezzlement and corruption were considered the three issues which most influence social stability. Food safety also ranked highly in popular evaluations of their sense of safety, and in hidden dangers to public safety. The degree of popular satisfaction and sense of safety are important means of estimating the level of social order. The quantity of cases reported to public security bodies allows an assessment of two issues, namely social order conditions, and the workload placed on the public security bodies. Keywords: China; employment; food safety; police officers; public security; unemployment