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Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.
ABSTRACT IMPACT: Novel adipokines like tetranectin help explain why some people progress from obesity to diseases like diabetes, atherosclerosis, and dislipidemia OBJECTIVES/GOALS: Obesity has an established association with diabetes, dyslipidemia, and atherosclerosis. Preventing progression from obesity to insulin resistance requires understanding of the regulatory mechanisms involved in the loss of insulin sensitivity. Adipose tissue is well known to function as an endocrine organ that produces many kinds of adipokines. METHODS/STUDY POPULATION: Blood sample analysis from human patients and mice was used to determine associations between tetranectin and obesity. Samples were tested with a monoclonal anti-tetranectin antibody for detection with western blot. A tetranectin mutant knock out mouse line was compared to wild type littermates on high fat diet for 4 months. Insulin tolerance tests and glucose tolerance were used to determine progression to insulin resistance and glucose intolerance. Histological analysis of metabolic tissue was used to demonstrate adipocyte hypertrophy and liver steatosis. RESULTS/ANTICIPATED RESULTS: In the current study, we report the identification and initial characterization of a novel adipokine tetranectin. Tetranectin, which is coded by the C-type lectin domain family 3 member B (CLEC3B) gene, is ubiquitously expressed in various mouse tissues, whereas it is highly enriched in white adipose tissue. We found that the serum level of tetranectin was much higher in both obese and diabetic patients. Knocking out the tetranectin gene in mice protected against glucose intolerance in males but reduced insulin and glucose tolerance in females, without effects on food intake and body weight for either sex. Mechanistically, tetranectin targets liver tissues and its deficiency increases lipid accumulation in hepatocytes in females. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have identified a novel adipokine which mediates a different metabolic crosstalk among tissues to maintain systemic glucose and lipid metabolism in different genders. Further investigation of tetranectin’s function could yield a new target for precise therapeutic treatment for obesity and its associated metabolic diseases in different genders
We report the first shock-tube experiments on dual-mode Richtmyer–Meshkov instability (RMI). An extended soap-film technique is adopted to generate a dual-mode gaseous interface such that its initial wavenumber (
) and phase of the fundamental waves are well controlled. By extracting interfacial contours from the distinct schlieren images, a Fourier analysis is performed from linear to weakly nonlinear stages and the growth of each basic wave is obtained. A noticeable difference between the growth of each basic mode and the corresponding single-mode RMI is observed, which suggests evident mode coupling effects in the dual-mode RMI. For dual-mode interfaces with in-phase
waves, the mode coupling suppresses (promotes) the growth of the
) mode, while for interfaces with anti-phase
modes, the growth of the
) mode is weakly influenced (evidently inhibited). However, for the combination of
waves, the mode coupling has a negligible influence on the growth of each basic wave. The modal theory of Haan (Phys. Fluids B, vol. 3, 1991, pp. 2349–2355), originally for multi-mode Rayleigh–Taylor instability, is reformulated for the dual-mode RMI, and it is found that this model overestimates the present experimental results for ignoring the nonlinear saturation. This model is then modified by accounting for both the mode coupling and nonlinear saturation, which well predicts the experimental results not only for the growth of the basic waves but also for the growth of second harmonics.
Richtmyer–Meshkov instability of the SF6 gas layer surrounded by air is experimentally investigated. Using the soap film technique, five kinds of gas layer with two sharp interfaces are generated such that the development of each individual interface is highlighted. The flow patterns are determined by the amplitudes and phases of two corrugated interfaces. For a layer with both interfaces planar, the interface velocity shows that the reflected rarefaction waves from the second interface accelerate the first interface motion. For a layer with the second interface corrugated but the first interface planar, the reflected rarefaction waves make the first interface develop with the same phase as the second interface. For a layer with the first interface corrugated but the second interface planar, the rippled shock seeded from the first interface makes the second interface develop with the same phase as the first interface and the layer evolves into an ‘upstream mushroom’ shape. For two interfaces corrugated with opposite (the same) phase but a larger amplitude for the first interface, the layer evolves into ‘sinuous’ shape (‘bow and arrow’ shape, which has never been observed previously). For the interface amplitude growth in the linear stage, the waves’ effects are considered in the model to give a better prediction. In the nonlinear stage, the effect of the rarefaction waves on the first interface evolution is quantitatively evaluated, and the nonlinear growth is well predicted. It is the first time in experiments to quantify the interfacial instability induced by the rarefaction waves inside the heavy gas layer.
Mangrove species have developed nutrient conservation mechanisms to adapt to oligotrophic intertidal environments. However, nutrient enrichment occurs worldwide, particularly in estuarine and coastal regions. Mangrove species may change their adaptive strategies if nutrient availability increases substantially. To understand how nutrient resorption (a major nutrient conservation strategy) responds to nutrient enrichment, a common mangrove species in China, Aegiceras corniculatum (black mangrove), was selected, and saplings were cultivated in nutrient-enriched soils. After one year, neither N nor P resorption efficiency showed significant variations with nutrient availability and there was no difference between N and P resorption efficiency. Overall, nutrient resorption efficiency of A. corniculatum remained at ∼40%, lower than the global average levels of evergreen plants (∼50%), indicating incomplete resorption of nutrients. Incomplete resorption was also evidenced by the nutrient concentrations, resorption proficiency and N: P ratio of plant leaves. Collectively, these results indicate that black mangrove can maintain constant nutrient resorption efficiency under eutrophic conditions.
In recent years, there has been an increasing interest in detecting disease-related rare variants in sequencing studies. Numerous studies have shown that common variants can only explain a small proportion of the phenotypic variance for complex diseases. More and more evidence suggests that some of this missing heritability can be explained by rare variants. Considering the importance of rare variants, researchers have proposed a considerable number of methods for identifying the rare variants associated with complex diseases. Extensive research has been carried out on testing the association between rare variants and dichotomous, continuous or ordinal traits. So far, however, there has been little discussion about the case in which both genotypes and phenotypes are ordinal variables. This paper introduces a method based on the γ-statistic, called OV-RV, for examining disease-related rare variants when both genotypes and phenotypes are ordinal. At present, little is known about the asymptotic distribution of the γ-statistic when conducting association analyses for rare variants. One advantage of OV-RV is that it provides a robust estimation of the distribution of the γ-statistic by employing the permutation approach proposed by Fisher. We also perform extensive simulations to investigate the numerical performance of OV-RV under various model settings. The simulation results reveal that OV-RV is valid and efficient; namely, it controls the type I error approximately at the pre-specified significance level and achieves greater power at the same significance level. We also apply OV-RV for rare variant association studies of diastolic blood pressure.
Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.
The excessive use of plastic, especially polystyrene (PS), has caused serious environmental pollution. The efficient utilization of plastics and the conversion of plastics into value-added carbon materials are the concerns of researchers. Herein, we propose novel “pyrolysis–deposition” method to convert one popular plastic substance, PS, into ordered mesoporous carbons (OMCs). During the synthesis process, PS is pyrolyzed into small organic gases under high temperature, which is then adsorbed through capillary adsorption into the mesoporous of SBA-15 in the presence of catalyst. The obtained OMCs have high specific surface area, uniform pore size, and ordered pore structure. The OMCs exhibit specific capacitance of 118 F/g at a current density of 0.2 A/g and electrochemical stability of 87.2% at a current density of 2 A/g after 5000 cycles. The pyrolysis–deposition strategy provides a new idea to convert waste plastics into high-performance carbon materials for electrochemical applications.
High-fidelity experiments of Richtmyer–Meshkov instability on a single-mode air/
interface are carried out at weak shock conditions. The soap-film technique is extended to create single-mode gaseous interfaces which are free of small-wavelength perturbations, diffusion layers and three-dimensionality. The interfacial morphologies captured show that the instability evolution evidently involves the smallest experimental uncertainty among all existing results. The performances of the impulsive model and other nonlinear models are thoroughly examined through temporal variations of the perturbation amplitude. The individual growth of bubbles or spikes demonstrates that all nonlinear models can provide a reliable forecast of bubble development, but only the model of Zhang & Guo (J. Fluid Mech., vol. 786, 2016, pp. 47–61) can reasonably predict spike development. The distinct images of the interface morphology obtained also provide a rare opportunity to extract interface contours such that a spectral analysis of the interfacial contours can be performed, which realizes the first direct validation of the high-order nonlinear models of Zhang & Sohn (Phys. Fluids, vol. 9, 1997, pp. 1106–1124) and Vandenboomgaerde et al. (Phys. Fluids, vol. 14 (3), 2002, pp. 1111–1122) in terms of the fundamental mode and high-order harmonics. It is found that both models show a very good and almost identical accuracy in predicting the first two modes. However, the model of Zhang & Sohn (1997) becomes much more accurate in modelling the third-order harmonics due to the fewer simplifications used.
A novel luminogen-functionalized SBA-15, denoted as SNT, was developed by incorporating tris(4-bromophenyl)amine (TBPA) into SBA-15 via a “fixation-induced emission” strategy. The emission of TBPA on the matrix of SBA-15 was greatly enhanced, making the SNT possible as a fluorescence sensor. Cefalexin, a typical antibiotic, was chosen as the model analyte to be assayed and sensitive detection performance was achieved. This is the first time for cefalexin to be detected by a fluorescent method. Moreover, the SNT can be recycled by simply washing with proper solvents then used for next detection. This work provides a strategy to greatly improve the emission characteristics of fluorophores, even if a mediocre small fluorophore. It can be extended to design practical fluorescent sensors with high performance and recyclability by this strategy.
There is an urgent need to understand lived experiences of climate change in the context of African cities, where even small climate shocks can have significant implications for the livelihoods of the urban poor. This article examines narratives of climate and livelihood changes within Jinja Municipality, Uganda, emphasizing how Jinja's residents make sense of climate change through their own narrative frames rather than through the lens of global climate change discourses. We demonstrate how the onset of climate change in Jinja is widely attributed to perceived moral and environmental failings on the part of a present generation that is viewed as both more destructive than previous generations and unable to preserve land, trees and other resources for future generations. A focus on local ontologies of climate change highlights how the multiple, intersecting vulnerabilities of contemporary urban life in Jinja serve to obfuscate not only the conditions of possibility of an immediate future, but the longer-term horizons for future generations, as changing weather patterns exacerbate existing challenges people face in adapting to wider socio-economic changes and rising livelihood vulnerability. This form of analysis situates changing climate and environments within the context of everyday urban struggles and emphasizes the need for civic participation in developing climate change strategies that avoid the pitfalls of climate reductionism. The article draws on more than 150 qualitative interviews, generational dialogue groups, and creative methods based on research-led community theatre.
Diabetic nephropathy (DN) is a major cause of chronic kidney disease. We aimed to investigate the effect of the low-protein diets (LPD) supplemented with ketoacids (LPD+KA) in KKAy mice, an early type 2 DN model. KKAy mice were treated with normal protein diet (NPD), LPD or LPD+KA from 12 to 24 weeks of age. A period of 12-week treatment with LPD significantly reduced albuminuria as compared with that observed after NPD treatment. Treatment with LPD+KA further reduced albuminuria as compared with that observed with LPD treatment alone. Moreover, LPD treatment reduced mesangial expansion, thickness of glomerular basement membrane and the severity of the podocyte foot process effacement in KKAy mice; these effects were more pronounced in KKAy mice treated with LPD+KA. Both LPD and LPD+KA treatments slightly reduced total body weight, but had no significant effect on kidney weight and blood glucose concentrations when compared with NPD-treated KKAy mice. LPD treatment slightly attenuated oxidative stress in kidneys as compared with that observed in NPD-treated KKAy mice; however, LPD+KA treatment remarkably ameliorated oxidative stress in diabetic kidneys as shown by decreased malondialdehyde concentrations, protein carbonylation, nitrotyrosine expression and increased superoxide dismutase expression. Nutritional therapy using LPD+KA confers additional renal benefits as compared with those of LPD treatment alone in early type 2 DN through inhibition of oxidative stress.
The granitic rocks of the Tarim large igneous province (LIP) are temporally and spatially related to mafic intrusions. However, their tectonic setting and genetic relationship are debated. Here, we report geochemical, and zircon U–Pb–Hf isotopic results for three alkali feldspar granitic plutons in the Halajun area, western margin of the Tarim Block. Zircon U–Pb ages suggest these plutons were emplaced at 268–275 Ma, coeval with the neighbouring mafic–ultramafic complexes and syenitic rocks. These granitic rocks have high contents of SiO2, alkalis, Rb, Th, Zr and REE (except Eu), and high ratios of FeO*/MgO and Ga/Al, and show strong depletions in Ba, Sr, Eu, which are commonly observed in the A1-type granites. Zircon Hf isotopes reveal a limited range of εHf(t) values from −1.0 to +3.5 for different samples from three granitic plutons, obviously higher than those (mostly <0) of the mafic rocks. This distinct difference, along with a Daly gap and small volume of mafic rocks, argues against extreme fractionation of mafic magma as the main origin of the A1-type granites. Instead the A1-type granites were most likely derived from partial melting of newly underplated rocks triggered by the upwelling asthenosphere, followed by extensive fractionation. These A1-type granites were emplaced within an anorogenic setting during the late stage of the Tarim LIP, which possibly lasts for more than 30 Ma. The Piqiang mafic–ultramafic complex directly stemmed from asthenospheric mantle and Halajun A1-type granites represent two manners of vertical crustal growth.
Nutritional status of 380 hospitalised children aged from 1 month to 5 years with liver disease was evaluated in a single paediatric centre. The total prevalence of stunting (height-for-age Z (HAZ) < −2), underweight (weight-for-age Z (WAZ) < −2) and wasting (weight-for-height Z < −2) was 9·8, 9·0 and 7·9 %, respectively. The overall nutritional risk (−2 ≤ Z < −1) of stunting, underweight and wasting was 11·8, 12·9 and 12·6 %. The prevalence of undernutrition was significantly higher in children with cholestasis than children without cholestasis (stunting, 17·5 %/4·4 %, P < 0·001, and underweight, 14·9 %/4·9 %, P < 0·001). HAZ and WAZ scores were significantly higher in children without cholestasis than children with cholestasis (0·58 (sd 1·59)/−0·68 (sd 1·99), P < 0·001, and 0·37 (sd 1·35)/−0·47 (sd 1·75), P < 0·001). Further multivariate logistic regression analysis strengthened the evidence that cholestasis was significantly associated with undernutrition of stunting (OR = 4·18, P = 0·002) and underweight (OR = 3·26, P = 0·008), and suggested that the prevalence of stunting caused by infection was lower than other aetiologies in hospitalised children with liver disease (OR = 0·10, P = 0·002). We concluded that a high prevalence of malnutrition and risk of undernutrition presents in hospitalised young children with liver disease, especially in children with cholestasis. Nutrition assessment is recommended for hospitalised children with liver disease.
A congruent melting compound LiNaV2O6 has been synthesized by high-temperature solution reaction and it has been grown with sizes up to 11 × 6 × 2 mm3 by the top-seeded growth method for the first time. LiNaV2O6 crystallizes in the monoclinic system with space group C2/c, with a = 10.184(2) Å, b = 9.067(2) Å, c = 5.8324(11) Å, β = 108.965(14)°. UV–Vis–NIR diffuse reflectance spectrum of LiNaV2O6 shows that it has a wide transmittance range from 385 to 2500 nm. The ab initio calculations show that the birefringence of LiNaV2O6 is 0.136 at 589.3 nm. Therefore, LiNaV2O6 may be a new birefringent material. Based on the analysis of the relationship between crystal structure and linear optical properties, it is found that the large birefringence is attributed to the particular arrangement of V–O anionic groups.
To examine changes in periconceptional folic acid supplementation behaviour among Chinese women of reproductive age after the implementation of a folic acid supplementation programme.
Two cross-sectional surveys were conducted.
One survey was before (2002–2004) and the other was after (2011–2012) implementation of the programme, both were conducted in two areas of China with different prevalence of neural tube defects. Information on supplementation behaviours was collected in face-to-face interviews with women early in their pregnancy.
A total of 1257 and 1736 pregnant women participated before and after the programme, respectively.
The rate of periconceptional folic acid supplementation increased from 15 % to 85 % in the high-prevalence population and from 66 % to 92 % in the low-prevalence population. However, more than half of the women began taking the supplement after learning they were pregnant. The proportion of women who began taking folic acid before their last menstrual period decreased after the programme in rural areas with both a high and low prevalence of neural tube defects.
Although periconceptional folic acid supplementation among Chinese women increased substantially after the programme, supplementation was often initiated too late to be effective in preventing neural tube defects. Educational and promotional campaigns should focus on how to increase the rate of folic acid supplementation before pregnancy.
The Chinese judicial system has long been influenced by a populist legal ideology that prioritizes public accountability and political legitimacy over professional autonomy. In recent years, however, the Chinese legal profession has begun to mobilize collectively, albeit episodically, to challenge this populism. Drawing on legal documents, interviews, media reports, and online discussions, this paper provides a scholarly analysis of the Li Zhuang case in 2009−11, in which the fate of an individual criminal defence lawyer was linked with the main ideological conflict in China’s legal system and the highest-level political struggles in the Chinese state. It demonstrates that, although populism remains an intimidating force in China’s judicial practice, lawyers, scholars, and other legal professionals may be laying a foundation for collective solidarity to pursue professionalism through their mobilization against populism.
Children treated for medulloblastoma (MB) exhibit long-term impairments in declarative memory, but the pathophysiology underlying this is unclear. Previous studies report declines in global white matter volume, but have failed to link this to declines in memory performance. We examined the effects of treatment on measures of global brain structure (i.e., total white and gray matter volume) and specific memory structures (i.e., hippocampus and uncinate fasciculus). We used volumetric MRI and diffusion tensor imaging in pediatric survivors of MB and one survivor of astrocytoma treated with cranial-spinal radiation (n = 20), and healthy controls (n = 13). Compared to controls, the survivor group exhibited reduced white matter volume, damage to the uncinate fasciculus, and a smaller right hippocampus. Critically, reduced hippocampal volume was not related to differences in brain volume, suggesting that the hippocampus may be especially vulnerable to treatment effects. A subset of the survivors (n = 10) also underwent memory testing using the Children's Memory Scale (CMS). Performance on the general index of the CMS was significantly correlated with measures of hippocampal volume and uncinate fasciculus. The examination of treatment effects on specific brain regions provides a better understanding of long-term cognitive outcome in children with brain tumors, particularly medulloblastoma. (JINS, 2014, 1, 1–13)
Approximately 50 % of patients with inflammatory bowel disease (IBD) suffer from anaemia, with Fe deficiency being the most common cause. CD52 monoclonal antibody (mAb) targets the cell surface CD52 and is effective in depleting lymphocytes through cytolytic effects in vivo. The aim of the present study was to investigate the therapeutic effect of anti-mouse CD52 mAb on Fe-deficient anaemia in IBD. IL-10 knockout mice (IL-10− / −) of 12 weeks with established colitis were treated with anti-mouse CD52 mAb once per week for 2 weeks. Severity of colitis, blood T lymphocytes, blood Hb, haematocrit, plasma erythropoietin (EPO), serum Fe concentration, transferrin saturation, splenic Fe stores, expression of liver hepcidin mRNA, Western blotting of the phosphorylated form of Smad1/5/8 and total Smad1 were measured at the end of the experiment. IL-10− / − mice treated with CD52 mAb showed a reduction in the percentage of CD4+ and CD4+CD45+ T cells in blood and weight loss typically associated with colonic inflammation, serum levels of EPO, the expression of liver hepcidin mRNA and total Smad1 protein, while they showed an increase in Hb concentrations, haematocrit, levels of serum Fe, transferrin saturation and splenic Fe stores. The present results indicated that anti-CD52 therapy may ameliorate Fe-deficient anaemia by reducing colonic inflammation. These findings may open novel horizons in the treatment of patients with IBD by resetting of immunological homeostasis in the gut by depleting the activated T cells in the gut mucosa.
Red meat and dairy products contain high sialic acid (Sia) levels, but the metabolic fate and health impact in children remain unknown. The aims of the present study were to quantify the levels of urinary Sia N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc) and ketodeoxynonulosonic acid (KDN) and to determine their relationship with dietary Sia intake. Spot urine samples were collected from 386 healthy children aged 3 (n 108), 4 (n 144) and 5 (n 134) years at 06.30–07.00, 11.30–12.00 and 16.30–17.00 hours. Food intake levels were recorded on the day of urine sample collection. Sia levels were quantified using LC–MS/MS with [13C3]Sia as an internal standard. We found that (1) total urinary Sia levels in healthy pre-school children ranged from 40 to 79 mmol Sia/mol creatinine; (2) urinary Sia levels were independent of age and consisted of conjugated Neu5Ac (approximately 70·8 %), free Neu5Ac (approximately 21·3 %), conjugated KDN (approximately 4·2 %) and free KDN (approximately 3·7 %); Neu5Gc was detected in the urine of only one 4-year-old girl; (3) total urinary Sia levels were highest in the morning and declined over time in 4- and 5-year-old children (P< 0·05), but not in 3-year-old children; (4) Sia intake levels at breakfast and lunch were approximately 2·5 and 0·16 mg Sia/kg body weight; and (5) there was no significant correlation between dietary Sia intake levels and urinary Sia levels. Urinary Sia levels varied with age and time of day, but did not correlate with Sia intake in 3- to 5-year-old children. The difference in urinary Sia levels in children of different age groups suggests that the metabolism and utilisation rates of dietary Sia are age dependent.