Running wheel activity prevents hyperphagia and obesity in Otsuka long-evans Tokushima Fatty rats: role of hypothalamic signaling

Otsuka Long-Evans Tokushima fatty (OLETF) rats lacking cholecystokinin-A receptors are hyperphagic, obese, and diabetic. Although exercise attenuates OLETF rats' obesity, the mechanisms underlying the effects of exercise are unclear. In this study, we determined the effects of running wheel activity on patterns of body weight gain, food intake, and hypothalamic gene expression. We demonstrate that voluntary running activity beginning at 8 wk of age normalized meal patterns, food intake, body weight, and plasma levels of glucose and leptin in OLETF rats. During the initial exercise period, corticotropin-releasing factor (CRF) mRNA expression was significantly elevated in the dorsomedial hypothalamus (DMH) but not in the paraventricular nucleus in both OLETF and control Long-Evans Tokushima rats. In response to long-term exercise, arcuate nucleus (Arc) neuropeptide Y (NPY), and proopiomelanocortin as well as DMH NPY and CRF mRNA expression were increased in Long-Evans Tokushima rats. In contrast, whereas exercising OLETF rats had increased Arc NPY and DMH CRF expression, Arc proopiomelanocortin and DMH NPY mRNA levels were not elevated. Finally, we demonstrate that the effects of exercise on body weight in OLETF rats were long lasting. Although food intake and body weight were increased in OLETF rats when running wheels were locked, weights did not return to those of sedentary OLETF rats. Together, these data suggest that the elevation of DMH CRF expression may mediate the short-term feeding inhibitory effects of exercise and that exercise limits the elevation of DMH NPY expression to account for the overall prevention of OLETF rats' obesity.     

Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice

Peroxisome proliferator-activated receptor (PPAR)-gamma is required for adipogenesis but is also found in the cardiovascular system, where it has been proposed to oppose inflammatory pathways and act as a growth suppressor. PPAR-gamma agonists, thiazolidinediones (TZDs), inhibit cardiomyocyte growth in vitro and in pressure overload models. Paradoxically, TZDs also induce cardiac hypertrophy in animal models. To directly determine the role of cardiomyocyte PPAR-gamma, we have developed a cardiomyocyte-specific PPAR-gamma-knockout (CM-PGKO) mouse model. CM-PGKO mice developed cardiac hypertrophy with preserved systolic cardiac function. Treatment with a TZD, rosiglitazone, induced cardiac hypertrophy in both littermate control mice and CM-PGKO mice and activated distinctly different hypertrophic pathways from CM-PGKO. CM-PGKO mice were found to have increased expression of cardiac embryonic genes (atrial natriuretic peptide and beta-myosin heavy chain) and elevated nuclear factor kappaB activity in the heart, effects not found by rosiglitazone treatment. Rosiglitazone increased cardiac phosphorylation of p38 mitogen-activated protein kinase independent of PPAR-gamma, whereas rosiglitazone induced phosphorylation of extracellular signal-related kinase 1/2 in the heart dependent of PPAR-gamma. Phosphorylation of c-Jun N-terminal kinases was not affected by rosiglitazone or CM-PGKO. Surprisingly, despite hypertrophy, Akt phosphorylation was suppressed in CM-PGKO mouse heart. These data show that cardiomyocyte PPAR-gamma suppresses cardiac growth and embryonic gene expression and inhibits nuclear factor kappaB activity in vivo. Further, rosiglitazone causes cardiac hypertrophy at least partially independent of PPAR-gamma in cardiomyocytes and through different mechanisms from CM-PGKO.     

Amplicon Resequencing Identified Parental Mosaicism for Approximately 10% of “de novo” SCN1A Mutations in Children with Dravet Syndrome

The majority of children with Dravet syndrome (DS) are caused by de novo SCN1A mutations. To investigate the origin of the mutations, we developed and applied a new method that combined deep amplicon resequencing with a Bayesian model to detect and quantify allelic fractions with improved sensitivity. Of 174 SCN1A mutations in DS probands which were considered “de novo” by Sanger sequencing, we identified 15 cases (8.6%) of parental mosaicism. We identified another five cases of parental mosaicism that were also detectable by Sanger sequencing. Fraction of mutant alleles in the 20 cases of parental mosaicism ranged from 1.1% to 32.6%. Thirteen (65% of 20) mutations originated paternally and seven (35% of 20) maternally. Twelve (60% of 20) mosaic parents did not have any epileptic symptoms. Their mutant allelic fractions were significantly lower than those in mosaic parents with epileptic symptoms (P = 0.016). We identified mosaicism with varied allelic fractions in blood, saliva, urine, hair follicle, oral epithelium, and semen, demonstrating that postzygotic mutations could affect multiple somatic cells as well as germ cells. Our results suggest that more sensitive tools for detecting low‐level mosaicism in parents of families with seemingly “de novo” mutations will allow for better informed genetic counseling.     

Mesopore-dominant nitrogen-doped carbon with a large defect degree and high conductivity via inherent hydroxyapatite-induced self-activation for lithium-ion batteries

In this study, N-doped mesopore-dominant carbon (NMC) materials were prepared using bio-waste tortoise shells as a carbon source via a one-step self-activation process. With intrinsic hydroxyapatites (HAPs) as natural templates to fulfill the synchronous carbonization and activation of the precursor, this highly efficient and time-saving method provides N-doped carbon materials that represent a large mesopore volume proportion of 74.59%, a high conductivity of 4382 m S⁻¹, as well as larger defects, as demonstrated by Raman and XRD studies. These features make the NMC exhibit a high reversible lithium-storage capacity of 970 mA h g⁻¹ at 0.1 A g⁻¹, a strong rate capability of 818 mA h g⁻¹ at 2 A g⁻¹, and a good capacity of 831 mA h g⁻¹ after 500 cycles at 1 A g⁻¹. This study provides a highly efficient and feasible method to prepare renewable biomass-derived carbons as advanced electrode materials for the application of energy storage.

A hydroxyapatite-induced self-activation method has been used to prepare nitrogen-doped mesopore-dominant carbon. The carbon has abundant macro/mesopores, high conductivity, and favorable defects and exhibited high-performance in LIBs.     

Effects of multiwalled carbon nanotubes on CH4 hydrate in the presence of tetra-n-butyl ammonium bromide

Hydrate formation is an important technology for gas storage and transportation. In this work, the effect of multiwalled carbon nanotubes (MWCNTs) on CH₄ hydrate formation was examined by determining the phase equilibrium conditions and kinetics characteristics of a mixed system of CH₄, tetra-n-butyl ammonium bromide (TBAB), and MWCNTs. The phase equilibrium was examined in the temperature range of 286.13–293.04 K and the pressure range of 0.55–6.56 MPa for various mass fractions of MWCNTs (0.004, 0.1, 0.5, and 1.0 wt%). In the CH₄ + TBAB system, the presence of MWCNTs was found to shift the phase equilibrium conditions to a lower temperature by about 1 K compared with those in the absence of MWCNTs. However, the concentration of MWCNTs had little effect on the phase equilibrium conditions. When the concentration of MWCNTs was 1.0 wt%, the addition of MWCNTs reduced the induction time of hydrate formation by 79.5%. When the concentration of MWCNTs was 0.1 wt%, the addition of MWCNTs enhanced the hydrate growth rate by 61.5%. Powder X-ray diffraction patterns revealed that hydrates with orthorhombic structures (corresponding to TBAB·38H₂O with 3D cages) were formed in the systems with and without MWCNTs. Moreover, peaks corresponding to MWCNTs were not observed in the patterns of the hydrates and the addition of MWCNTs had no influence on the structure and type of hydrate. Thus, MWCNTs were not incorporated into the hydrate cages.

Hydrate formation is an important technology for gas storage and transportation.     

Conducting polymer-coated MIL-101/S composite with scale-like shell structure for improving Li–S batteries

Lithium–sulfur batteries are regarded as a promising energy storage system. However, they are plagued by rapid capacity decay, low coulombic efficiency, a severe shuttle effect and low sulfur loading in cathodes. To address these problems, effective carriers are highly demanded to encapsulate sulfur in order to extend the cycle life. Herein, we introduced a doped-PEDOT:PSS-coated MIL-101/S multi-core–shell structured composite. The unique structure of MIL-101, large specific area and conductive shell ensure high dispersion of sulfur in the composite and minimize the loss of polysulfides to the electrolyte. The doped-PEDOT:PSS-coated sulfur electrodes exhibited an increase in initial capacity and an improvement in rate characteristics. After 192 cycles at the current density of 0.1C, a doped-PEDOT:PSS-coated MIL-101/S electrode maintained a capacity of 606.62 mA h g⁻¹, while the MIL-101/S@PEDOT:PSS electrode delivered a capacity of 456.69 mA h g⁻¹. The EIS measurement revealed that the surface modification with the conducting polymer provided a lower resistance to the sulfur electrode, which resulted in better electrochemical behaviors in Li–S battery applications. Test results indicate that the MIL-101/S@doped-PEDOT:PSS is a promising host material for the sulfur cathode in the lithium–sulfur battery applications.

Lithium–sulfur batteries are regarded as a promising energy storage system.     

女性脑卒中尿失禁患者盆底肌训练的循证实践

目的促进女性脑卒中尿失禁患者盆底肌训练最佳证据的应用,提高临床护理质量。方法采用澳大利亚乔安娜·布里格斯研究中心临床证据实践应用系统,基于现有的最佳证据,制订了5条审查标准,应用于复旦大学附属华山医院2个神经内科病房开展质量审查,包括证据应用前的基线审查、证据应用和证据应用后的再审查。结果证据应用后,5条审查标准的执行率从0. 00%~7. 50%上升至92.30%~100. 00%。护士的平均知识得分由38. 18分上升至93. 42分,患者的平均知识得分由3. 33分上升至7. 64分。进行盆底肌训练的12例女性脑卒中尿失禁患者,其出院后1个月尿失禁评分较入院时下降(P 0. 05)。结论女性脑卒中尿失禁患者盆底肌训练最佳证据的应用,能规范护士在尿失禁护理实践中的行为,提高护士对尿失禁患者评估和管理能力。     

早期胃癌检出情况及其内镜下特征分析（附43例报道）*

目的调查分析浙江省余姚地区早期胃癌(EGC)的检出情况,探讨EGC内镜下特点及病理学特征。方法回顾性收集2016年度宁波大学医学院附属阳明医院消化内镜中心行胃镜检查患者的病例资料,筛选统计出EGC(检查时发现并经病理确诊)的检出率,并对发现的43例EGC患者(47处病灶)的临床资料进行回顾性总结,对比分析其普通白光内镜下特征、窄带成像(NBI)放大内镜下特征及病理学特征。结果 EGC的总体检出率为0.23%(43/18 534),占胃癌总检出例数的24.71%(43/174)。本研究发现EGC以发生在胃窦部最常见(36.17%,17/47),病灶大小以1.0 cm为主(68.09%,32/47),内镜下形态以0-Ⅱc型病灶为主,占55.32%(26/47)。白光内镜下表现为黏膜发红35处(74.47%,35/47)、边界清晰43处(91.49%,43/47)、表面不规则42处(89.36%,42/47)、黏膜萎缩和(或)肠上皮化生39处(82.98%,39/47)、边缘毛刺状17处(36.17%,17/47)、白色不透明物质(WOS)8处(17.02%,8/47)、表面溃疡13处(27.66%,13/47),自发性出血21处(44.68%,21/47)。30处病灶行NBI放大内镜检查,病灶边界线清晰占86.67%(26/30),病灶黏膜下微血管不规则或消失占96.67%(29/30),病灶上皮微细结构和腺管开口不规则或消失占90.00%(27/30)。病理分型以分化型为主(89.36%,42/47)。结论 EGC多见于胃窦部,形态以0-Ⅱc型为主,在白光内镜下注意观察胃黏膜局部色调的改变及特征,以及NBI放大内镜下病灶边界、黏膜下微血管及上皮微细结构和腺管开口的变化,有助于提高EGC的诊断率。     

Nanodiamond-based layer-by-layer nanohybrids mediate targeted delivery of miR-34a for triple negative breast cancer therapy

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and significantly associated with poor prognosis and high risk of recurrence. miR-34a has been identified as a potent tumor suppressor whose expression is dramatically downregulated in TNBC. Currently, rectification of miRNA abnormality serves as a novel tumor therapeutic strategy. miR-34a is thus used as powerful antitumor agent for miRNA-based therapy against TNBC. However, miRNA-based antitumor therapy is challenged by effective targeted delivery of miRNA. In the present study, nanodiamond (ND), protamine (PS) and folic acid (FA) were used to construct ND-based layer-by-layer nanohybrids through a self-assembly approach for targeted miR-34a delivery in TNBC cells and xenograft TNBC tumors. We found that the targeted delivery of miR-34a remarkably suppressed cell proliferation, migration and induced the apoptosis of TNBC cells in vitro and inhibited tumor growth in vivo via down-regulating Fra-1 expression. The data suggest a great potential of ND-based nanohybrids for targeted intratumoral delivery of miR-34a for TNBC therapy.

The construction of nanodiamond-based layer-by-layer nanohybrids.