bluuebunny/crossref_metadata_2025 huggingface dataset:
HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)
Authors: Sharifzad Farzaneh , Mardpour Soura , Mardpour Saeid , Fakharian Esmaeil , Taghikhani Adeleh , Sharifzad Amirhosein , Kiani Sahar , Heydarian Yasaman , Los Marek J , Azizi Zahra , Ghavami Saeid , Hamidieh Amir Ali , Ebrahimi Marzieh
Published: February 2020

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.
Dimensionally Scaled Experiments and the Theories on the Water-Drive Process
Authors: Croes G.A. , Schwarz N.
Published: February 2020

Published in Petroleum Transactions, AIME, Volume 204, 1955, pages 35–42.

This paper reports the results of a series of model displacement experiments carried out for measuring the efficiency of the water-drive process. This series forms a continuation and extension of that described by Engelberts and Klinkenberg. Detailed information has been obtained on the influence of the oil/water viscosity ratio. The results are represented in the form of a diagram from which both the oil recovery and the water/oil ratio can be easily read off as a function of the total production (oil plus water) for all values of the viscosity ratio M between 1 and 500.

These results are viewed in the light of the two existing theories on water flooding, viz. that of Buckley and Leverett and that of Dietz.

It is shown that if the Buckley-Leverett theory applies, the relation between the relative permeability ratio and saturation, which plays a major role in this theory, can be calculated with a high degree of accuracy from the results of the model experiments.

Dietz's theory is found to be in agreement with the experimental results in a certain range of circumstances. A discussion of the physical background of the BuckleyLeverett and Dietz theories makes it clear why the latter fails to agree with some of the experimental results.

Introduction

For an economical exploitation of oil fields both a rational control of natural (primary) recovery processes and a proper application of artificial (secondary) recovery methods are essential. These require detailed information upon the dependence of the relevant flow processes on the variables by which they are governed.

Three methods are available for obtaining this information:(statistical) analysis of actual field data;appropriately scaled model experiments; andmathematical analysis of the physical problem.

If sufficient data were available, the first method would, in principle, be the most reliable one, although it has the drawback that the basic relationships between the variables involved are to a large extent obscured by the natural inhomogeneities of most reservoirs.
Wettability Versus Displacement in Water Flooding in Unconsolidated Sand Columns
Authors: Newcombe Jack , McGhee John , Rzasa M.J.
Published: February 2020

Published in Petroleum Transactions, AIME, Volume 204, 1955, pages 227–232.

A series of water floods was made on laboratory prepared unconsolidated sand columns to study the effects on oil recovery of the solid-water-oil contact angle, the oil-water interfacial tension, flood rate, and oil viscosity.

A procedure was developed for treating silica sand with silicone polymer to produce surfaces of varying degrees of wettability as evaluated by measuring the contact angle on a flat silica plate that had been simultaneously treated with the sand. Fluid interfacial tensions were changed by the use of surface active agents in the flood water. Water-wet, oil-wet, and intermediate wettability systems were studied at high and at low values of interfacial tension, at several flood rates, and with oils of different viscosities.

For both oil-wet and water-wet systems and a low viscosity oil, recoveries were functions of the oil-water interfacial tension; also, increase in flood rate resulted in increased oil recoveries. High interfacial tension floods were more efficient than low interfacial tension floods on water-wet systems, while low interfacial tension floods were more efficient on oil-wet systems. Intermediate or neutral wettability systems were less sensitive to rate of flood advance and interfacial tension than either oil-wet or water-wet systems.

The effects of surface forces on oil recovery for high viscosity oils were not so well defined as for low viscosity oils.

Introduction

Reservoir rock surfaces vary in their wettability, some being water-wet while others are apparently oil-wet. The factor of wettability enters into reservoir performance in both primary and secondary recovery, and into laboratory measurements of capillary pressure, connate water saturation, and relative permeabilities. In theory, the degree of wettability is measured by the contact angle for the system solid-water-oil. A water-wet system is defined as one in which the advancing water contact angle is less than 90°. An oil-wet system is one in which the advancing water contact angle is greater than 90°.
Neuromuscular shoulder activity during exercises with different combinations of stable and unstable weight mass.
Authors: Baritello Omar , Khajooei Mina , Engel Tilman , Kopinski Stephan , Quarmby Andrew , Mueller Steffen , Mayer Frank
Published: February 2020

Background: Recent shoulder injury prevention programs have utilized resistance exercises combined with different forms of instability, with the goal of eliciting functional adaptations and thereby reducing the risk of injury. However, it is still unknown how an unstable weight mass (UWM) affects the muscular activity of the shoulder stabilizers. Aim of the study was to assess neuromuscular activity of dynamic shoulder stabilizers under four conditions of stable and UWM during three shoulder exercises. It was hypothesized that a combined condition of weight with UWM would elicit greater activation due to the increased stabilization demand. Methods: Sixteen participants (7 m/9 f) were included in this cross-sectional study and prepared with an EMG-setup for the: Mm. upper/lower trapezius (U.TA/L.TA), lateral deltoid (DE), latissimus dorsi (LD), serratus anterior (SA) and pectoralis major (PE). A maximal voluntary isometric contraction test (MVIC; 5 sec.) was performed on an isokinetic dynamometer. Next, internal/external rotation (In/Ex), abduction/adduction (Ab/Ad) and diagonal flexion/extension (F/E) exercises (5 reps.) were performed with four custom-made-pipes representing different exercise conditions. First, the empty-pipe (P; 0.5 kg) and then, randomly ordered, water-filled-pipe (PW; 1 kg), weight-pipe (PG; 4.5 kg) and weight + water-filled-pipe (PWG; 4.5 kg), while EMG was recorded. Raw root-mean-square values (RMS) were normalized to MVIC (%MVIC). Differences between conditions for RMS%MVIC, scapular stabilizer (SR: U.TA/L.TA; U.TA/SA) and contraction (CR: concentric/eccentric) ratios were analyzed (paired t-test; p ≤ 0.05; Bonferroni adjusted α = 0.008). Results: PWG showed significantly greater muscle activity for all exercises and all muscles except for PE compared to P and PW. Condition PG elicited muscular activity comparable to PWG (p > 0.008) with significantly lower activation of L.TA and SA in the In/Ex rotation. The SR ratio was significantly higher in PWG compared to P and PW. No significant differences were found for the CR ratio in all exercises and for all muscles. Conclusion: Higher weight generated greater muscle activation whereas an UWM raised the neuromuscular activity, increasing the stabilization demands. Especially in the In/Ex rotation, an UWM increased the RMS%MVIC and SR ratio. This might improve training effects in shoulder prevention and rehabilitation programs.Trial Registration: not applicable
The Roles of Lumbar load thresholds in lifetime cumulative lifting exposure to predict disk protrusion in an Asian Population
Authors: Hung Isabella Yu-Ju , Shih Tiffany Ting-Fang , Chen Bang-Bin , Ho Ing-Kang , Liou Saou-Hsing , Guo Yue Leon
Published: February 2020

Background: The purpose of this study was to determine whether a specific threshold per lifting movement, the accumulation above which best predicts lumbar disk protrusion, exists or the total lifting load should be considered.
Methods: This was a retrospective study. Subjects with various lifting exposures were recruited. Disk protrusion was assessed by magnetic resonance imaging. The cumulative lifting load was defined as the sum of the time-weighed lumbar load for each job and was calculated using a biomechanical software system. The effectiveness of accumulation above different thresholds in predicting disk protrusion were compared using four statistical methods.
Results: A total of 252 men and 301 women were included in the final analysis. For the men, 3000 Newtons for each lifting task was the optimal threshold for predicting L4-S1 disk protrusion, whereas for the women, 2800 Newtons was optimal.
Conclusions Our findings suggested that for cumulative lifting exposure, including the total lifting load without defining a minimal exposure limit might not be the optimal method for predicting disk protrusion. The NIOSH 3400 Newton recommended limits do not appear to be the optimal thresholds for preventing disk protrusion. Different lifting thresholds might be needed for men and women in the workplace for their safety.

Keywords: Cumulative, Lifting load, Cross-sectional study, Threshold,
Disk protrusion
Skin transcriptome reveals the periodic changes in genes underlying cashmere (ground hair) follicle transition in Cashmere goats
Authors: Yang Feng , Liu Zhihong , Zhao Meng , Mu Qing , Che Tianyu , Xie Yuchun , Ma Lina , Mi Lu , Zhao hong Yan , Li Jinquan
Published: February 2020

Background: Cashmere goats make an outstanding contribution to the livestock textile industry and their cashmere is famous for its slenderness and softness and has been extensively studied. However, there are few reports on the molecular regulatory mechanisms of the secondary hair follicle growth cycle in cashmere goats. In order to explore the regular transition through the follicle cycle and the role of key genes in this cycle, we used a transcriptome sequencing technique to sequence the skin of Inner Mongolian cashmere goats during different months. We analyzed the variation and difference in genes throughout the whole hair follicle cycle. We then verified the regulatory mechanism of the cashmere goat secondary hair follicle growth cycle using fluorescence quantitative PCR. Results: The growth cycle of cashmere hair could be divided into three distinct periods: a growth period (March–September), a regression period (September–December), and a resting period (December–March). The results of differential gene analyses showed that March was the most significant month. Cluster analysis of gene expression throughout the whole growth cycle further supported the key nodes of the three periods of cashmere growth, and the differential gene expression of keratin corresponding to the ground haircashmere growth cycle further supported the results from tissue slices. Quantitative fluorescence analysis showed that KAP3-1, KRTAP 8-1, and KRTAP 24-1 genes had close positive correlation with the cashmere growth cycle, and their regulation was consistent with the growth cycle of cashmere. Conclusion: The growth cycle of cashmere cashmere could be divided into three distinct periods: a growth period (March–September), a regression period (September–December) and a resting period (December–March). March was considered to be the beginning of the cycle. KAP and KRTAP showed close positive correlation with the growth cycle of secondary hair follicle cashmere growth, and their regulation was consistent with the cashmere growth cycle. But hair follicle development-related genes are expressed earlier than cashmere growth, indicating that cycle regulation could alter the temporal growth of cashmere. This study laid a theoretical foundation for the study of the cashmere development cycle and provided evidence for key genes during transition through the cashmere cycle. Our study provides a theoretical basis for cashmere goat breeding.
Functional Outcomes and Complications of Intramedullary Fixation Devices for Midshaft Clavicle Fractures: A Systematic Review and Meta-Analysis.
Authors: Hoogervorst Paul , Dam Tess van , Verdonschot Nico , Hannink Gerjon
Published: February 2020

Background:An alternative to the current gold standard in operative treatment of displaced midshaft clavicle fractures using plate osteosynthesis, is internal fixation by means of an intramedullary fixation device. These devices differ considerably in their specifications and characteristics and an adequate evaluation of their clinical results is warranted.Methods:A systematic review was conducted to identify all papers reporting functional outcomes, union rates and/or complications using an intramedullary fixation device for the management of midshaft clavicle fractures. Multiple databases and trial registries were searched from inception until February 2020. Meta-analysis was conducted based on functional outcomes and type of complication per type of intramedullary fixation device. Pooled estimates of functional outcomes scores and incidence of complications were calculated using a random effects model. Risk of bias and quality was assessed using the Cochrane risk of bias and ROBINS-I tools. The confidence in estimates were rated and described according to the recommendations of the GRADE working group.Results:Sixty-seven studies were included in this systematic review. The majority of studies report on the use of Titanium Elastic Nails (TEN). At 12 months follow up the Titanium Elastic Nail and Sonoma CRx report an average Constant-Murley score of 94.4 (95%CI 93-95) and 94.0 (95%CI 92-95) respectively. The most common reported complications after intramedullary fixation are implant-related and implant-specific. For the TEN, hardware irritation and protrusion, telescoping or migration, with a reported pooled incidence 20% (95%CI 14-26) and 12% (95%CI 8-18), are major contributors to the total complication rate. For the Rockwood/Hagie Pin, hardware irritation is identified as the most common complication with 22% (95%CI 13-35). The most common complication for the Sonoma CRx was cosmetic dissatisfaction in 6% (95%CI 2-17) of cases.Conclusion:Although most studies were of low quality, in general, good functional results and union rates irrespective of the type of device are found in the reviewed literature. However, there are clear device-related and device-specific complications for each. The results of this systematic review and meta-analysis can help guide surgeons in choosing the appropriate operative strategy, implant and informing their patient.Level of EvidenceIV
Elevated glycosylated hemoglobin levels and their interactive effects on hypertension risk in nondiabetic Chinese population: a cross-sectional survey
Authors: song jian , wei nana , zhao yingying , jiang yuhong , wu xuesen , gao huaiquan
Published: February 2020

Background: Abnormal glucose metabolism has been suggested to be involved in the development of hypertension. This study investigated the effect of the association and potential interaction of glycosylated hemoglobin (HbA1c) and other factors on the risk of hypertension among Chinese nondiabetic adults. Methods : As a cross-sectional survey, the current work deployed a questionnaire survey, anthropometric tests, and biochemical measures for each of the eligible participants. The HbA1c levels were quantified and grouped by quartiles. Correlations between HbA1c and hypertension, isolated systolic hypertension (ISH), and isolated diastolic hypertension (IDH) risk in nondiabetics were investigated by univariate and multivariate logistic analyses. For evaluating the interactive effects, the parameters of relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were calculated, respectively. Results : In the current study, 1,462 nondiabetic subjects were enrolled. In total, the prevalence rates of hypertension, ISH and IDH were 22.4%, 9.6% and 4.5%, respectively. When HbA1c levels were grouped by quartile, it was revealed that the prevalence rates of hypertension and ISH were substantially elevated across groups (Pfor trend<0.001). In the multivariable logistic regression analyses, in comparison with the first quartile of HbA1c, the normalized OR for hypertension risk was 1.90 (95% CI: 1.28-2.80) for the highest quartile. Also, the risk of ISH was significantly increased with HbA1c level in the highest quartile relative to in the bottom quartile (OR: 2.23,95% CI:1.47-3.71). However, no significant relationship between the HbA1c level and IDH risk was observed (OR: 1.78, 95% CI: 0.82-3.84). Eventually, it was demonstrated from the interactive effect analysis that HbA1c significantly interacted with abdominal obesity(RERI: 1.48, 95% CI: 0.38-2.58; AP: 0.37, 95% CI: 0.14-0.60 and SI: 1.96, 95% CI: 1.06-3.62) and family history of hypertension(AP: 0.37, 95% CI: 0.05-0.70) in influencing the risk of hypertension in nondiabetic participants.Conclusion: Higher HbA1c levels were associated with an increased risk of hypertension and ISH, but not IDH among Chinese nondiabetic adults. Moreover, the risk of hypertension was also aggravated by the upregulated HbA1c in a synergistic manner alongside abdominal obesity and family history of hypertension.
The CD4 cell count at which to initiate HIV-associated cryptococcal antigen (CrAg) screening and pre-emptive antifungal treatment among CrAg positive persons may need to be raised to 200 cells/μL. Evidence based on a meta-analysis
Authors: Li Yao , Huang Xiaojie , Chen Hui , Qin Yuanyuan , Hou Jianhua , Li Aixin , Wu Hao , Yan Xiaofeng , Chen Yaokai
Published: February 2020

Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4<100 cells/μL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent Cryptococcal meningitis related deaths. The strategy may also be considered for those persons with a CD4 count of<200 cells/uL according the WHO guidelines. However, there remains little evidence for doing so in those HIV-infected persons with this CD4 cell count. Objective: We aimed to assess the necessity of CrAg screening and the efficacy of pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL. Methods: We conducted a meta-analysis using data obtained from randomized controlled studies (RCTs) and cohort studies found in Pubmed, Web of Science, Cochrane Library and EMBASE/MEDLINE. Results: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4<200 cells/µL was 5% (95%CI: 3-6). The incidence of CM in CrAg+ persons was 7- fold (7%, 95%CI: 4-10) that of CrAg negative (CrAg-) persons (1%, 95%CI: 0-1). Among CrAg+ persons who did not receive any treatment or only received placebo, the incidence of CM was 9% (95%CI: 5-13), whereas the incidence of CM among those who received antifungal therapy was 2% (95%CI: 0-3), a highly statistically significant reduction of 78% (RR: 6.03, 95%CI: 2.74-13.24, p<0.00001). Conclusions: In our meta-analysis, the incidence of CM in CrAg+ persons were significantly higher than in CrAg- persons with CD4<200 cells/µL. Furthermore, the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ persons with CD4<200 cells/µL.
Phenolics and related in vitro functional activities of different varieties of fresh waxy corn: a whole grain
Authors: Chen Lirong , Guo Yuqiu , Li Xiaoyue , Gong Kuijie , Liu Kaichang
Published: February 2020

The polyphenol distribution in fresh waxy corns of different color varieties and their functional activities, which may be useful for treating various chronic diseases, were investigated. The in vitro antioxidant activity, and hypoglycemic and hypocholesterolemic effects of the free and bound corn phenolics were determined to evaluate the edible value of fresh waxy corn. The colored varieties contained more phenols than the common varieties (white and/or yellow). The total free phenolic acid content of the six varieties was 6637.73 μg/g DW (dry weight), which was slightly higher (P >0.05) than that of the total bound form (6276.65 μg/g DW). The total free flavonoid content was 5850.09 μg/g DW, which was higher (P < 0.05) than that of the total bound form (4874.51μg/g DW). No bound anthocyanin was detected in the methanol extracts of the tested varieties. For all the varieties, free polyphenols contributed 86-100% and 70-78% of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging abilities, respectively, and 100% of the ferric reducing capacity. The free phenolics in fresh waxy corn showed significantly better (P < 0.05) hypoglycemic effect than the bound form in terms of inhibition of α-amylase activity, whereas the bound phenolics of most varieties showed higher α-glucosidase inhibitory activity than the free forms. The free phenolics showed significantly better (P < 0.05) glycocholesterol binding than the bound form for all varieties. The bound polyphenols showed better sodium cholate and taurocholate binding than the free form for most varieties. In conclusion, the difference between free and bound polyphenol content and functional activities indicates that fresh waxy corn can be potentially used for the development of functional food.Keywords: fresh waxy corn; polyphenol; antioxidant activity; hypoglycemic; hypocholesterol
Luteal blood flow as a predictive factor for methotrexate treatment outcomes in women with unruptured tubal pregnancy
Authors: Wang Li , Pei Meili , Yang Ting , Zhao Juan , Yang Xiaofeng
Published: February 2020

Background: Blood flow in the corpus luteum is associated with luteal function. However, the impact of luteal blood flow on methotrexate (MTX) treatment in women with unruptured tubal pregnancy has not been reported. The aim of the present study was to observe the impact of luteal blood flow on the therapeutic effect of MTX in women with unruptured tubal pregnancy. Methods: A prospective observational study recruited 129 women with unruptured tubal pregnancy in the First Affiliated Hospital of Xi’an Jiaotong University from September 2016 to June 2018. One hundred and fifteen women were treated successfully with MTX, and women were divided into 2 groups according to luteal blood flow: the poor luteal blood flow group and the abundant luteal blood flow group. The therapeutic effects were compared between the two groups. Results: Women in the abundant luteal blood flow group had a significantly higher serum β-human chorionic gonadotropin (β-hCG) level 4 days, 1 week and 2 weeks after MTX treatment compared with women in the poor luteal blood flow group ( P <0.05). The average diameter of the ectopic mass 1 week, 2 weeks and 3 weeks after MTX treatment in women with abundant luteal blood flow was significantly larger ( P <0.05), and the time of serum β-hCG clearance and ectopic mass disappearance were significantly longer compared with those in women in the poor luteal blood flow group ( P <0.05). Conclusions: Luteal blood flow might be a predictive factor for MTX treatment outcomes in women with unruptured tubal pregnancy, and those with abundant luteal blood flow need a longer recovery time.
Impact of Spring Freshet Flooding and Summer Rainfall Flooding on the Water Quality of an Alpine Barrier Lake
Authors: LI Chun-hua , Ye Chun , LI Ji-xuan , WEI Wei-wei , ZHENG Ye , KONG Ming , WANG Hao
Published: February 2020

Background: Barrier lakes, formed by river interception, are particularly influenced by the upstream river. As such, spring freshet flooding and summer rainfall flooding due to wet precipitation (e.g. snow and rainfall) may sharply increase the concentrations of nitrogen, phosphorous and carbon compounds in barrier lakes. Too much nutrients will lead to lake eutrophication. In this study, we used Lake Jingpo, the world’s second largest alpine barrier lake, to examine the impact of spring freshet flooding and summer rainfall flooding on its water quality by building a hydrodynamic water-quality model with MIKE 21. Results:The MIKE 21 HD hydrodynamic model and MIKE 21 AD convection and diffusion module were calibrated using meteorological data, hydrological data, and water quality data collected in 2018. All errors were in the acceptable range. According to model simulation results, the flow velocity in Lake Jingpo is generally weak (mostly lower than 0.015 m/s), but it increases to 0.045 m/s and above during spring freshet flooding (April–May) and summer rainfall flooding (August–September), which is much higher than in other months. The flow volume of its largest inflowing river reaches 4.81×108 m3, 29.77×108 m3, and 58.4×108 m3 during spring freshet flooding, summer rainfall flooding, and 30-year frequency rainfall flooding period, respectively. The longest diffusion distances from the lake mouth to the downstream way are 16.3 km, 33.1 km, and 43.6 km during the spring freshet flooding, summer rainfall flooding, and 30-year frequency rainfall flooding period, respectively. A larger amount of precipitation leads to longer diffusion distances and increased concentrations of total nitrogen (TN), total phosphorous (TP), chemical oxygen demand (CODMn), and ammonia-nitrogen (NH4-N) in the lake. Conclusions: The sudden increase in water volume during spring flooding and summer rainfall flooding led to the rapid spread of nutrients and pollutants carried by the water into the barrier lake, resulting in a deterioration of lake water quality. In addition to pollution source control measures, ecological restoration and the construction of a buffer system in the catchment are very important measures to effectively improve the buffer capacity of barrier lakes in light of spring freshet flooding and summer rainfall flooding.
Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice
Authors: Arai Chikako , Suyama Aki , Arai Shigeyuki , Arai Norie , Yoshizane Chiyo , Koya-Miyata Satomi , Mizote Akiko , Endo Shin , Ariyasu Toshio , Mitsuzumi Hitoshi , Ushio Shimpei
Published: February 2020

Background: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. Methods: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. Results: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cellsin vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce adipocyte hypertrophy. Conclusions: The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.
Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor
Authors: Zhang Deling , Liu Hua , Zhang Yemin , Li Junfeng , Fu Yalin , Zheng Yuyang , Wu Jie , Ma Mingke , Wen Zhongyuan , Wang Changhua
Published: February 2020

Adiponectin, an adipokine produced and secreted by adipocytes, is involved in regulating the development and progression of insulin resistance, diabetes, and diabetic complications. Heat shock protein 60 (HSP60) is a molecular chaperone, most commonly presenting in mitochondria and participating in the maintenance of protein homeostasis. Accumulating studies have demonstrated that the elevated circulating HSP60 and the decreased intracellular HSP60 are closely associated with diabetic complications such as diabetic cardiomyopathy. However, the underlying mechanism remains poorly understood. In the present study, we reported that HSP60 interacted directly with adiponectin receptors. Its abundance was positively associated with adiponectin action. Furthermore, HSP60 depletion markedly mitigated the protective impacts of adiponectin on high glucose-induced oxidative stress and cell apoptosis in rat cardiac H9c2 cells. In addition, HSP60 knockdown significantly enhanced proteasome activity leading to the degradation of adiponectin receptor 1. Taken together, we showed for the first time that HSP60 interacted with adiponectin receptors and mediated adiponectin signaling through stabilizing adiponectin receptor. This in vitro study also provides an alternative explanation for mechanism by which adiponectin exerts its action.
Analysis of the Effect of Rural Residents Serious Illness Medical Insurance on Relieving the Economic Burden of Rural Residents in China:A Case Study in Jinzhai County
Authors: Li Yang , Duan Guangfeng , Xiong Linping
Published: February 2020

Background

In 2003, China established a New Rural Cooperative Medical System(NRCMS) for rural residents, which had alleviated the burden of medical expenses of rural residents, but the reimbursement for high medical was insufficient. Therefore, China had gradually established a Serious Illness Insurance System (SIMIS) on the basis of NRCMS. After the payment of NRCMS, patients who met the requirements of SIMIS policy would be given a second payment to further alleviate the economic burden of patients with high medical expenses in rural areas. The purpose of this study is to analyze the effect of the implementation of SIMIS on alleviating the economic burden of rural residents in Jinzhai County.

Methods

Based on the inpatient reimbursement data of NRCMS in Jinzhai County, Anhui Province from 2013 to 2016. We adopt descriptive and regression discontinuity (RD) method to analyze the payment effect of SIMIS. The RD analysis object (n = 7353) was the patients whose annual serious illness expenses were between CNY 10,000 and CNY 30,000, and the descriptive analysis object (n = 2720) was the patients compensated by SIMIS.

Results

The results of RD showed that the actual medical insurance payment proportion (AMIPP) increased by about 2.5% (lwald = 0.025, P < 0.01), inside medical insurance self-payment proportion (IMSPP) increased by about 2% (lwald = 0.020, P < 0.10), outside medical insurance self-payment proportion (OMISPP) decreased by about 1.6% (lwald = -0.016, P < 0.05). The descriptive results showed that the serious illness patients mostly chose to go to hospital outside the county. The annual average number of hospitalizations was 3.64. The reimbursement mainly came from the NRCMS. The payment amount of SIMIS was relatively small, and the out of pocket medical expenses were still high.

Conclusion

The medical technology level of Jinzhai County could not meet the needs of seriously illness patients, the number of beneficiaries of SIMIS was small, and the ability to relieve the burden of medical expenses of rural residents was insufficient. The high out of pocket expenses increased the possibility that people with good economic conditions could enjoy the reimbursement of SIMIS, resulting in inequity.
Transcriptomic and anatomic profiling reveal germination process of different wheat varieties in response to waterlogging stress
Authors: Shen Changwei , Yuan Jingping , Qiao Hong , Wang Zijuan , Liu Yuanhai , Ren Xiujuan , Wang Fei , Liu Xing , Zhang Ying , Chen Xiling , Ou Xingqi
Published: February 2020

Background Waterlogging is one of the most serious abiotic stresses affecting wheat-growing regions in China. There are considerable differences in waterlogging tolerance among different wheat varieties, and the mechanisms governing the waterlogging tolerance of wheat seeds during germination have not been elucidated. Methods To reveal the adaptability of wheat to waterlogging stress during germination, we analysed the germination rate and anatomical structure of three wheat seeds, ‘Zhoumai 22’(ZM22), ‘Bainong 207’(BN207) and ‘Bainong 607’(BN607). At the same time, Illumina sequencing technology was used to determine the transcriptome of these three wheat varieties during germination. Results The results showed that there was no significant difference between the germination rate of BN607 after 3 days of waterlogging treatment and that of the control seeds. However, under waterlogging stress, the degree of emulsification and degradation of endosperm cells was higher than that of the control treatment, and amyloplasts in endosperm were significantly reduced. Transcriptomic data were obtained from seed samples (a total of 18 samples) of three wheat varieties under the waterlogging and control treatments. A total of 2775 differentially expressed genes (DEGs) were identified by comprehensive analysis. In addition, by analysing the correlation between the expression levels of DEGs and seed germination rates in three wheat varieties under waterlogging stress, it was found that the relative expression levels of 563 and 398 genes were positively and negatively correlated with the germination rate of wheat seeds, respectively. The GO and KEGG analyses found that the difference in waterlogging tolerance of the three wheat varieties was related to the abundance of key genes involved in the glycolysis pathway, the starch and sucrose metabolism pathway, and the lactose metabolism pathway. The alcohol dehydrogenase (ADH) gene in the endosperm of BN607 was immediately induced after short-term waterlogging, and the energy provided by the glycolysis pathway enabled the seeds of BN607 to germinate as early as possible, while the expression of the AP2/ERF transcription factor was upregulated to further enhance its waterlogging tolerance. Conclusions Taken together, the results of this study help to elucidate the mechanisms by which different wheat varieties respond to waterlogging stress during germination.
Telemedical care improves quality of life in patients with schizophrenia and bipolar disorder. Results of a randomized controlled trial
Authors: Stentzel Ulrike , Berg Neeltje van den , Strobel Lara N. , Schulte Josephine , Langosch Jens M. , Hoffmann Wolfgang , Grabe Hans J.
Published: February 2020

Background Schizophrenia and bipolar disorder are serious psychiatric disorders with a high disease burden, a high number of years of life lived with disability and a high risk for relapses and re-hospitalizations. Besides, both diseases are often accompanied with a reduced quality of life. A low level of quality of life is one predictor for relapses. This study examines whether a telemedical care program can improve quality of life. Methods Post stationary t elem e di c a l c a re of patients with severe psychiatric disorders” (Tecla) is a prospective controlled randomized intervention trial to implement and evaluate a telemedical care concept for patients with schizophrenia and bipolar disorder. Participants were randomized to an intervention or a control group. The intervention group received telemedical care including regular, individualized telephone calls and SMS-messages. The quality of life was measured with the German version of the WHOQOL-BREF. Effects of telemedicine on quality of life after 6 months were analyzed using t-tests to compare the intervention with the control group. Participants also evaluated the telemedical care program based on a short standardized interview. Results 118 participants were recruited, thereof 57.6% men (n = 68). Participants were on average 43 years old (SD) 13). The IG showed higher QoL scores as the control group (CG) 6 months after baseline for the WHOQOL total sum score (t-test (CI) 93.1 (92.4-93.8) vs 89.7 (88.8-90.6), p < 0.0001) and for 4 of 5 domains: Global 62.0 (60.9-63.0) vs. 56.8 (55.6-58.1), p < 0.0001; Physical health 63.8 (63.0-64.7) vs. 59.6 (58.5-60.6), p < 0.0001; Psychological 60.9 (60.0-61.9) vs. 56.4 (55.1-57.6), p < 0.0001; Environment 70.8 (70.1-71.6) vs. 67.5 (66.7-68.3), p < 0.0001. Conclusion The Tecla telemedical care concept has improved the quality of life in patients with severe psychiatric disorders. It provides for a low-threshold and well suitable component in psychiatric treatment.
Neuronal Lipoprotein Lipase Deficiency alters Neuronal Function and Hepatic Metabolism
Authors: Bruce Kimberley , Wang Hong , Dobrinskikh Evgenia , Rudenko Ivan A , Gao Hong , Libby Andrew E , Gorkhali Sachi , Yu Tian , Zsombok Andrea , Eckel Robert H
Published: February 2020

Background: The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL may be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Methods: Measures of glucose homeostasis in mice homozygous (NEXLPL-/-) and heterozygous (NEXLPL+/-) for neuronal LPL deficiency were compared to that of WT mice. A detailed analysis of hepatic glucose and lipid metabolism was also determined in NEXLPL+/- at 6-18 mo. To determine the effect of neuronal LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. In addition, we used Fluorescence Lifetime Imaging Microscopy (FLIM) as a novel method to visualize changes in neuronal metabolism following LPL-depletion directly in the PVN. Results: Here we show that despite obesity, mice with reduced neuronal LPL also show improved glucose tolerance and reduced hepatic lipid accumulation with aging, concomitant with reduced hepatic lipogenic gene expression (e.g. SCD1 and FADS2). Retroviral tracing and patch clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons lacking LPL. Quantification of the free versus bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD), revealed that LPL loss resulted in altered substrate utilization characterized by increased glucose utilization and TCA cycle flux. These findings were recapitulated by analysis of global metabolites from hypothalamic cell lines either deficient in, or over-expressing, LPL. Conclusions: Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to alter neuronal metabolism and function, leading to changes in systemic glucose metabolism including improved hepatic function with age.
Night sleep duration and risk of each lipid profile abnormality in a Chinese population: a prospective cohort study
Authors: Song Qiaofeng , Liu Xiaoxue , Zhou Wenhua , Wu Shouling , wang xizhu
Published: February 2020

Background To explore the associations between sleep duration and abnormalities in each serum lipid level in a Chinese population. Methods A prospective study was conducted with 33,817 participants from the general Chinese population. Sleep duration was categorized as ≤5, 6, 7, 8 or ≥9 h. Each lipid profile abnormality was defined according to the Chinese Guidelines for the Prevention and Treatment of Dyslipidemia in Adults. The Cox proportional hazards model was used to assess these associations. Results Compared with a seven-hour sleep duration, longer sleep duration was significantly associated with high low-density lipoprotein cholesterol (LDL-C) (HR: 1.18; 95% CI: 1.10–1.17) in fully adjusted models. And a longer sleep duration was significantly associated with low high-density lipoprotein cholesterol (HDL-C) levels (HR: 1.22; 95% CI: 1.19–1.35). In subgroup analyses, the positive association between long sleep duration and high LDL-C and low HDL-C levels in men and in the different age groups were more pronounced than the association in women. No significant interactions were observed in the association between sleep duration and each abnormal serum lipid level by sex/age in the study population(p- interaction>0.05). Conclusions These findings suggest that longer sleep duration is associated with high LDL-C and low HDL-C levels among the Chinese population.
Genetic evidence for imported malaria and local transmission in Richard Toll, Senegal
Authors: Daniels Rachel F. , Schaffner Stephen F. , Dieye Yakou , Dieng Gnagna , Hainsworth Michael , Fall Fatou B. , Diouf Coumba Ndoffene , Ndiop Medoune , Cissé Moustapha , Gueye Alioune Badara , Sarr Oumar , Guinot Philippe , Deme Awa B. , Bei Amy K. , Sy Mouhamad , Thwing Julie , MacInnis Bronwyn , Earle Duncan , Guinovart Caterina , Sene Doudou , Hartl Daniel L. , Ndiaye Daouda , Steketee Richard W. , Wirth Dyann F. , Volkman Sarah K.
Published: February 2020

Background: Malaria elimination efforts can be undermined by imported malaria infections. Imported infections are classified based on travel history.Methods: We applied a genetic strategy to better understand the contribution of imported infections and to test for local transmission in the very low prevalence region of Richard Toll, Senegal.Results: Genetic relatedness analysis, based upon molecular barcode genotyping data derived from diagnostic material, provided evidence for both imported infections and ongoing local transmission in Richard Toll. Evidence for imported malaria included finding that a large proportion of Richard Toll parasites were genetically related to parasites from Thiès, Senegal, a region of moderate transmission with extensive available genotyping data. Evidence for ongoing local transmission included finding parasites of identical genotype that persisted across multiple transmission seasons as well as enrichment of highly related infections within the households of non-travelers compared to travelers.Conclusions: These data indicate that, while a large number of infections may have been imported, there remains ongoing local malaria transmission in Richard Toll. These proof-of-concept findings underscore the value of genetic data to identify parasite relatedness and patterns of transmission to inform optimal intervention selection and placement. This work was supported by the Bill & Melinda Gates Foundation, Grant Number OPP1156051
Epac ameliorates tubulointerstitial inflammation in diabetic nephropathy via C/EBPβ/SOCS3/STAT3 pathway
Authors: Yang Wenxia , Zhang Shumin , Wang Huafen , Liu Yifei , Liu Jialu , Sun Lin , Xiao Li
Published: February 2020

Background: Tubulointerstitial inflammation plays a pivotal role in the progression of diabetic nephrology (DN), and tubular cells act as the driving force in the inflammation cascade. The aim of the study is to investigate whether activation of Epac alleviates tubulointerstitial inflammation through SOCS3/JAK/STAT3 pathway under DN. Methods: The kidney morphological changes and the level of oxidative stress were observed in db/db mice treated with Epac agonist (8-pCPT-2’-O-Me-cAMP). The expression of inflammatory cytokines, fibrosis markers, C/EBPβ, SOCS3 and p-STAT3 in renal tissues were assessed. In in vitro study, the changes of above genes and proteins were also detected in human proximal tubular cell line (HK-2) incubated with high glucose (HG) with and without Epac agonist. Overexpression of SOCS3 plasmid, SOCS3 siRNA and C/EBP-β siRNA were employed and the translocation of C/EBP-β and p-STAT3 were observed by immunofluorescence. Macrophage migration assay were detected in Transwell system. Results: In db/db mice, we observed that the expression of MCP-1 was up-regulated in renal tubular cells, which concurrent with increased influx of macrophages, cytokines production (MCP-1, TNF-α, and IL-6), and tubulointerstitial fibrosis. Moreover, we also found that these changes were accompanied by reduced C/EBP-β expression and increased SOCS3 and phosphorylated STAT3 (p-STAT3) expression. However, after treated db/db mice with 8-O-cAMP, an Epac activator, the expression of SOCS3 further up-regulated while other protein expression profile was partially reversed. In vitro , high glucose (30mM, HG) treatment down-regulated C/EBP-β expression while increased SOCS3, p-STAT3 and MCP-1 expression in HK-2 cells; Activation of Epac by 8-O-cAMP further increased the gene and protein expression of SOCS3 while reversed the changes of the other proteins. Mechanistically, under HG ambience, knockdown of C/EBP-β or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on MCP-1 expression. Furthermore, 8-O-cAMP treatment enhanced the nuclear-translocation of C/EBP-β and further increased the transcription of SOCS3 gene, which decreased MCP-1 expression through inhibiting the phosphorylation of STAT3 in HK-2 cells. Conclusions: These data indicate that Epac ameliorates tubulointerstitial inflammation in DN at least partially through C/EBPβ/SOCS3/STAT3 pathway. Therefore, Activation of Epac by 8-O-cAMP may be a novel therapeutic strategy for DN.