bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycophenolate mofetil reduces epidural fibrosis by regulating TGF-β1/Smad2/3 axis to repress the proliferation, migration and differentiation of fibroblasts
Authors: Zhu Dongming , Zhang Jie , Zhang Xiaobo , Liu Yun , Yan Lianqi , Sun Yu
Published: May 2020

Background

Excessive fibroblasts proliferation is believed as a major reason in the process of epidural fibrosis, which is known as a troublesome complication of lumbar laminectomy clinically. Mycophenolate mofetil (MMF) is a kind of immunosuppressant, previous studies had shown that it has the function of preventing fibrosis, but the role and mechanism are still unclear. In this study, we determined the repressed effect of MMF on fibroblasts proliferation, migration and differentiation in surgical-induced epidural fibrosis and the underlying mechanism.
Methods

In vitro, the impacts of MMF on cell viability were measured by cell counting kit-8 (CCK-8) assay and the fibroblasts proliferation rates were determined by using EdU incorporation, cell cycle assays and western blot. Additionally, the impacts of MMF on fibroblasts migration and differentiation were analyzed by cell wound scratch assay, transwell assay, immunofluorescence analysis and western blot. In vivo, we built epidural fibrosis models in rats and locally applied MMF. Histological and immunohistochemical staining were used to determine the effect of MMF on reducing epidural fibrosis and fibroblasts functions.
Results

CCK-8 assay demonstrated that MMF repressed fibroblasts proliferation in a time- and a dose-dependent manner. EdU incorporation assay and cell cycle analysis proved the inhibition effect of MMF on the proliferation of fibroblasts. Cell wound scratch assay, transwell assay and immunofluorescence proved the inhibition effect of MMF on the migration and differentiation of fibroblasts. Western blotting analysis proved that MMF inhibited the expression of TGF-β1, p-Smad2 and p-Smad3. The expression of proliferation proteins, migration proteins and differentiation proteins were downregulated. In addition, histological and immunohistochemical stain showed that MMF reduces epidural fibrosis by repressing the proliferation, migration and differentiation of fibroblasts.
Conclusion

MMF could inhibit the proliferation, migration and differentiation of fibroblasts, it reduced surgical-induced epidural fibrosis as well. TGF-β1/Smad2/3 axis may be the latent mechanism in MMF reduced epidural fibrosis. It might provide a new notion for mitigating surgery-induced epidural fibrosis.
Incorporating operational research in programmes funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria in four sub-Saharan African countries
Authors: Camacho Salvador , Maher Dermot , Kamau Edward Mberu , Saric Jasmina , Segura Luis , Zachariah Rony , Wyss Kaspar
Published: May 2020

Background
The current study builds upon a previous situation analysis of the extent to which grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) are being utilized to support operational research and implementation research (OR/IR) activities in recipient countries. The objective of this follow-up study was to identify approaches and pathways to implement an OR component into grants to the Global Fund, in four sub-Saharan African countries. Special focus was given to the Structured Operational Research and Training IniTiative (SORT IT).
Methods
The conceptual framework was based on an analysis to identify elements supporting and blocking the integration of OR, called force field analysis, and a behavioural change assessment covering aspects such as opportunity, motivation, capability and triggers to do the integration. Data were collected through online surveys and stakeholder interviews both via telephone/online conference tools and in person in four countries with a high burden of malaria and tuberculosis. This countries were Ghana, Sierra Leone, the United Republic of Tanzania and Zimbabwe. The stakeholders included programme managers, implementation partners, representatives from international organisations, academic and governmental research institutions and other individuals involved in the countries’ needs assessment and National Strategic Plan development.
Results
We identified opportunities to integrate OR into the countries’ programmes during the funding process, the country’s needs assessment being the most important one, including the need of OR-related capacity. Both the force field analysis and the behavioural change assessment showed that the necessary elements to integrate OR were present in the countries. Motivation, capability and efficiency were found to be a managerial value omnipresent across stakeholders. However, those elements were influenced by the tendency to favour tangible assets over any abstract ones, such as increasing organisational capacity in OR.
Conclusions
In each of the countries assessed, there is potential to integrating OR into the programmes supported by the Global Fund. However, given the relative lack of OR-related capacity and skills encountered, a capacity strengthening tool, such as SORT IT, would be of benefit helping to identify and carry forward OR activities sustainably.
Understanding the spatial unevenness of regional renewable energy deployment: insights for policy design
Authors: Laurentis Carla De , Pearson Peter JG
Published: May 2020

Background

This paper suggests that renewable energy (RE) deployment processes and their spatial unevenness can be explained by analysing the socio-material dimensions of RE. It explains how particular regional RE paths come to be favoured or hampered, and identifies factors that have contributed to these different outcomes. The paper shows the merit of investigating regional agency in energy research.
Methods

Using a novel analytical framework, the research performs a comparative case study analysis of selected regions in Italy and the UK, drawing on data obtained via documentary analysis and extensive in-depth interviews.
Results

The factors that explain regional variation in RE deployment are highlighted, providing evidence of how the distinctive features of RE deployment in five different regions arose and could be identified. The paper shows that understanding the socio-material dimensions of RE offers opportunities to understand the spatial unevenness of RE deployment at the regional levels and how to address it. While some regions have managed to successfully align their strategies and governance in order to maximise their RE potential, others have been less effective. The key features that influence the pace and direction of RE deployment at the regional level are i) the ways in which targets and resource availability are seen as drivers for RE deployment, ii) the degree of political autonomy in planning and the capacity to facilitate consenting processes at sub-regional levels, iii) the political will for RE expansion, elite consensus and the presence of relevant industry actors, and iv) the participation and involvement of regional government, even in the absence of formal regulatory powers, in shaping essential energy infrastructure investment.
Conclusion

While institutional capacity, planning and governance, the variety of actors and interests, compelling visions and credible expectations are all necessary prerequisites for coherent policy outcomes, the effects and degree of success can vary. This variance is influenced by the peculiarities and specificities of the regional contexts in which RE projects emerge. By identifying which aspects tend to constrain or enable RE deployment at the regional level, the paper helps to reveal the policy challenges that emerge and how they might be addressed.
Changing Medical Education Scenario: A wakeup call for reforms in Anatomy Act
Authors: Lalwani Rekha , Kotgirwar Sheetal , Athavale Sunita A.
Published: May 2020

Background Anatomy Act provides legal ambit to medical educationist for the procurement of cadavers. The changing medical education scenario and socio-demographic change has necessitated an urgent review of the concerned legal framework. Suitable amendments addressing the current disparities and deficiencies are long overdue.Methods Anatomy Act in India is a state act and which ensures provision of unclaimed /donated bodies for Medical Education and research. The methodology included three components namely:· Comparison of various Anatomy Acts clause by clause.· Feedback from anatomists.· Formulation of comprehensive model Anatomy Act. Results Various acts studied showed discrepancies in purpose of the act, roles and duties of stake holders, regulation for body donation, procedure to handle unclaimed bodies, disposal of dissected bodies etc. None of the acts defines a donor and neither addresses the issue of transport of anatomical material. Only ten states have a clause for body donation. Acts of only six states have been amended over last 50 years. Three states denied having an act. The whole exercise of review of acts, extensive feedback received from end-users and taking into account global good practices, culminated in drafting of a comprehensive model Anatomy act.Conclusion India, with the largest number of medical colleges is not only at forefront but also a hub of medical education in Southeast Asia region. A legal reform can be a torch bearer to promote ethical and transparent practices for obtaining cadavers for other countries of the region with similar socio-demography and shall also motivate anatomic fraternity across the globe for critical analysis of their respective anatomy acts.
Impact of Temperature Variability on Childhood Allergic Rhinitis in a Subtropical City of China
Authors: Wang Xu , Cheng Jian , Ling Li , Su Hong , Zhao Desheng , Ni Hong
Published: May 2020

Background: Many studies have shown an association of childhood respiratory diseases with short-term temperature variability such as diurnal temperature range (DTR) and temperature change between two neighboring days (TCN). However, the impact of temperature variability on allergic rhinitis (AR) has not been investigated so far. This study sought to evaluate the short-term effect of temperature variability (i.e., TCN and DTR) on AR, as well as to identify vulnerable subpopulations.Method: We collected daily data on emergency room visits and outpatients for AR and weather variables in Hefei, China during 2014–2016. A distributed lag non-linear model that controlled for long-term trend and seasonality, mean temperature, relative humidity, day of week was used to fit the associations of AR with DTR and TCN. Stratified analyses by age, gender and occupation were also performed.Results: During the study period, there were a total of 53538 cases and the average values of DTR and TCN were 8.4 °C (range: 1.0 °C to 21.2 °C) and 0 °C (range: -12.2 °C to 5.9 °C), respectively. While we did not observe an adverse effect of DTR on AR, TCN was significantly associated with increased risk of AR. Specifically, a large temperature drop between two adjacent days (3.8 °C, 5th percentile of TCN) has a delayed and short-lasting effect on AR, with the estimated relative risk of 1.02 (95% confidence interval: 1.01 to 1.04) at lag 12. Moreover, boys and children older than 15 years seemed to be more vulnerable to the effect of TCN.Conclusions: This study provided evidence of an adverse effect of large temperature drops between two adjacent days on childhood AR. Attention paid to boys and older children may help prevent AR attacks.
Effects on development and microbial community of shrimp Litopenaeus vannamei larvae with probiotics treatment
Authors: Wang Ruixuan , Guo Zihan , Tang Yapeng , Kuang Jiawei , Duan Yafei , Lin Heizhao , Jiang Shigui , Shu Hu , Huang Jianhua
Published: May 2020

Shrimp production is the second ranked of the most-traded production in these decades and the whiteleg shrimp Litopenaeus vannamei is the sixth most cultured species. Probiotics are alternative strategy for the promotion of growth and prevention of diseases in aquaculture. To confirmed the effects of the probiotics on development and microbial community of L. vannamei larvae during different development stages, five kinds of probiotics (108~109 CFU/g ) were added into the shrimp larvae rearing environment, and the effects of probiotics on bacterial community and water quality, larval growth and immune index were determined from nauplius larval stage to post larval stage. Results suggested that probiotics treated groups showed larger survival rate than the control groups from Z1 stage to P5 stage. Lactobacillus could improve the larvae’s survival ability, especially in the larval stages M2, M3, P1, P5 stage. It was confirmed that probiotics could promote the growth and development of shrimp larvae and prevent the incomplete molting in their growing process, particularly for EM-treated group. Results suggested that all the probiotics-treated groups had shown significant decreasing trend in the quantity of vibrios, except for the SA-treated group.And different probiotics could inhibite vibrios in different life periods. Amount these probiotics, LA, EM and PB had shown the best effects, including improving survival rate of the larvae, promoting the larval metamorphosis, reducing the quantity of vibrios and NH4-N and NO2-N levels, and increasing bacterial diversity.
Effects of dietary phytogenic supplementation on performance, semen quality and serum biochemical of rabbits
Authors: Abdel-Wareth Ahmed A.A. , Metwally Abdallah E.
Published: May 2020

The authors have requested that this preprint be removed from Research Square.
Effects of different stocking densities on the trachea barrier function and its plasma metabolic profile of finishing broilers
Authors: Wang Yuanyuan , Wang Dianchun , Wang Jiangshui , Li Kaixuan , Heng Chianning , Jiang Lei , Cai Chenhao , Zhan Xiuan
Published: May 2020

Background The experiment was conducted to evaluate the effects of different stocking densities on the trachea barrier and its plasma metabolic profile of finishing broilers.Methods One thousand four hundred and forty 22-day-old Lingnan Yellow feathered broilers were randomly allotted to five different stocking density groups (8, 10, 12, 14, and 16 birds per m2). Each group consisted of three replicates.Results A markedly increased in IL-1β and IL-10 concentrations were observed in 16 birds per m2 treatment group than the groups of 8 and 10 birds per m2 (P < 0.05), but there was no significant difference in IL-4 content among five treatments (P > 0.05). 16 birds per m2 (high stocking density group, HSD) treatment group significantly increased the trachea mucosa thickness than 10 birds per m2 (control group, CSD). HSD group exhibited lower expression of claudin1 and higher muc2 and caspase3 than those in the CSD group. In addition, a total of 10 metabolites were identified at higher (P < 0.05) concentrations, while 7 metabolites were identified at lower (P < 0.05) concentrations in the HSD treatment as compared with the CSD group. Most of these potentially diagnostic biomarkers were involved in substance synthesis and energy metabolism. Further metabolic pathway analysis revealed that pentose and glucuronate interconversions along with pentose phosphate pathway were the most relevant and critical pathway identified from these two groups. The activated pathway may partially interpret the metabolic level to alleviate the adverse effects of stress which caused by high-stocking density in broilers.Conclusions In summary, this study can improve our understanding of the harmful effects of high-stocking density on the trachea barrier and identify two metabolic pathways that may be associated with high-stocking density-induced metabolic disorders in broilers.
Uneven Integration: The Case of Angola
Authors: Haddad Eduardo Amaral , Perobelli Fernando , Araújo Inácio Fernandes , Dentinho Tomas L C
Published: May 2020

Angola’s prospects for reconstruction and development of its poor connectivity infrastructure are heavily dependent upon the export performance of its oil sector. Using an interregional input-output table for Angola, we estimate comprehensive measures of trade in value added revealing different hierarchies of interregional and international trade integration, with implications for regional inequality in the country. By encompassing the subnational perspective in the case study of an African country that shows a strong regional divide, we bring new insights to the existing literature on regional integration in the continent. The different hierarchies of interregional and international trade structures reveal a pattern of uneven integration of Angolan provinces, dominated by strong foreign linkages and weak domestic linkages. It also shows the primacy of Luanda in interregional trade, as this province is associated with the main trade flows involving provinces in the extended economic core of the country. The results shed light to a policy discussion about the role played by a wider and broader integration of the country including the interconnection with its neighboring countries as a way to development of the provinces in the borders, but also stimulating the potential of more central provinces, such as Huambo, Bié and Huíla.
Induction of autophagy mitigates TDP-43 pathology and translational repression of neurofilament mRNAs in mouse models of ALS/FTD
Authors: Kumar Sunny , Phaneuf Daniel , Cordeau Pierre , Boutej Hejer , Kriz Jasna , Julien Jean-Pierre
Published: May 2020

Background:
TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile remains unknown.
Methods:
Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used a Ribotag approach combined with microarray and proteomic analyses to investigate the neuronal translational profiles in mouse model of ALS/FTD.
Results:
Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-ĸB) essential modulator (NEMO), induces autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive impairment, reduced gliosis in the brain of ALS/FTD mouse models. With the Ribotrap method, we investigated the impact of TDP-43 proteinopathy and IMS-088 treatment on the translation profile of neurons of one-year old hTDP-43A315T mice. TDP-43 proteinopathy caused translational dysregulation of specific mRNAs including translational suppression of neurofilament mRNAs resulting in 3 to 4-fold decrease in levels type IV neurofilament proteins. Oral administration of IMS-088 rescued the translational defects associated with TDP-43 proteinopathy and restored the synthesis of neurofilament proteins, which are essential for axon integrity and synaptic function.
Conclusions:
Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies.
ZSCAN25 and CYP2E1 polymorphisms is risk factors for ischemic stroke in a Chinese Han population: a case control study
Authors: Yuan Haozheng , Fan Pei , Yao Li , Lv Yuying , Wei Haidong , Zheng Juan , Han Xinsheng
Published: May 2020

Background

We aimed to explore the relationship between ZSCAN25 and CYP2E1 polymorphisms and Ischemic stroke (IS) susceptibility among a Chinese Han population.
Methods

We enrolled 477 patients with IS and 480 age- and sex- matched health controls. Genotyping of the ZSCAN25 rs10242455, CYP2E1 rs2070672 and rs2515641 were performed by Agena MassARRAY platform. Odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis.
Results

Rs10242455 (OR = 0.56, 95% CI: 0.34–0.93, p = 0.024) was associated with a reduced IS susceptibility, while rs2070672 (OR = 1.40, 95% CI: 1.12–1.75, p = 0.003) and rs2515641 (OR = 1.29, 95% CI: 1.01–1.64, p = 0.041) with an increased IS occurrence. Rs2070672 was observed to correlate with IS risk (OR = 4.06, p = 0.038) at age > 64 years, and rs10242455 (OR = 0.45, p = 0.021) and rs2070672 (OR = 3.28, p = 0.024) affected IS risk in males. In addition, rs10242455 (OR = 1.72, p = 0.014) was significantly associated with hypertension in IS patients.
Conclusion

Our study firstly found that rs10242455 in ZSCAN25, rs2070672 and rs2515641 in CYP2E1 were associated with the occurrence of IS in a Chinese Han population.
Polysaccharide from angelica sinensis attenuates SNP-Induced Apoptosis in osteoarthritis Chondrocytes by Inducing Autophagy via ERK1/2 Pathway
Authors: Xu Chao , Ni Su , Zhuang Chao , Li Chenkai , Zhao Gongyin , Jiang Shijie , Wang Liangliang , Zhu Ruixia , Wijnen Andre J. van , Wang Yuji
Published: May 2020

Objective Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. Method Human primary chondrocytes isolated from articular cartilage of OA patients were treated with SNP alone or in combination with different dose of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3)-II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localisation and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile,activation of ERK 1/2 pathway was determined by western blot. The autophagy inhibitors 3-Methyladenine (3-MA), chloroquine (CQ) and a specific inhibitor of ERK1/2, SCH772984, were used respectively to confirm the autophagic effect of ASP. Results The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocytes proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of ERK1/2 pathway.Conclusion ASP markedly rescued SNP-induced chondrocyte apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP a potential therapeutic supplementation for OA treatment.
Study of a robotic system to detect water leakage and fuel debris -System proposal and feasibility study of visual odometry providing intuitive bird's eye view
Authors: Wang Zhenyu , Endo Gen , Takahashi Masashi , Nabae Hiroyuki , Suzumori Koichi , Nobuyoshi Tsuzuki , Takahashi Hideharu , Kimoto Kazushi , Ihara Tomonori , Kikura Hiroshige
Published: May 2020

To obtain the necessary information of the fuel debris and water leakages in the decommissioning task of Fukushima Daiichi nuclear power plants, an ultrasonic-based investigating method had been proposed towards the future internal investigation of the Primary Containment Vessel (PCV). In this article, we studied the assisting mechanisms and methods for the investigating method, as the rotatable winch mechanism and visual localization method. We used the rotatable winch mechanism to adjust the height and orientation of the ultrasonic sensor and localized the robot with cameras to localize the sensor, as assisting information for data combination. We studied the feasibility of the conventional visual odometry method of applying to the situation and performed localizing accuracy evaluating experiments with a mobile robotic platform prototype. Results showed that the visual odometry method could generate intuitive maps from bird’s eye view, and provided the average error rate of 35mm/1500mm, which met the required error rate for grating movement. The adjustable parameter ranges that could provide the required accuracy were also conducted.
Mechanical Buckling Analysis of Functionally Graded Plates Using an Accurate Shear Deformation Theory
Authors: MADJID BERRABAH HAMZA , BACHIR BOUDERBA
Published: May 2020

In this present study, we are interested in the use of a precise theory of shear deformation for the buckling analysis of plates with functional gradation simply supported such as the refined theory of plates with four variables, several parameters of comparison have been used, dimensional and non-dimensional, the displacement field is compatible with this study, the non-use of shear correction factors is satisfied, the choice of material is very precise in such a way are variable according to the thickness of the plate and on the other hand to make comparison with other researcher and confirms that this study gives precise results and converges, the transverse shear stresses vary through the thickness, the results found is also studied and discussed.
Development and validation of an individualized immune-related gene pairs prognostic signature in papillary renal cell carcinoma
Authors: Zhou Xianghong , Qiu Shi , Jin Di , Jin Kun , Zheng Xiaonan , Yang Lu , Wei Qiang
Published: May 2020

Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p<0.001). Combined with multiple clinical pathological factors, the results of multivariate analyses confirmed that this signature was an independent predictor of OS (HR, 3.548; 95%CI, 2.096−6.006; p<0.001). The results of immune infiltration analysis demonstrated that the abundance of multiple tumor-infiltration lymphocytes such as CD8+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.
The Effect of Crocin Supplementation on Glycemic Control, Insulin Resistance and Active AMPK Levels in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Behrouz Vahideh , Dastkhosh Ali , Hedayati Mehdi , Sedaghat Meghdad , Sharafkhah Maryam , Sohrab Golbon
Published: May 2020

Background Crocin as a carotenoid exerts anti-oxidant, anti-inflammatory, anti-cancer, neuroprotective and cardioprotective effects. Besides, the increasing prevalence of diabetes mellitus and its allied complications, and also patients' desire to use natural products for treating their diseases, led to the design of this study to evaluate the efficacy of crocin on glycemic control, insulin resistance and active adenosine monophosphate-activated protein kinase (AMPK) levels in patients with type-2 diabetes (T2D). Methods In this clinical trial with a parallel-group design, 50 patients with T2D received either 15-mg crocin or placebo, twice daily, for 12 weeks. Anthropometric measurements, dietary intake, physical activity, blood pressure, glucose homeostasis parameters, active form of AMPK were assessed at the beginning and at the end of the study.Results Compared with the placebo group, crocin improved fasting glucose level (P=0.015), hemoglobin A1c (P=0.045), plasma insulin level (P=0.046), insulin resistance (P=0.001), and insulin sensitivity (P=0.001). Based on the within group analysis, crocin led to significant improvement in plasma levels of glucose, insulin, hemoglobin A1c, systolic blood pressure, insulin resistance and insulin sensitivity. The active form of AMPK did not change within and between groups after intervention. Conclusions The findings indicate that crocin supplementation can improve glycemic control and insulin resistance in patients with T2D. Further studies are needed to confirm these findings. Trial Registration This study has been registered at Clinicaltrial.gov with registration number NCT04163757.
Incidence, Risk Factors and Clinical Outcomes of Acute Kidney Injury after Heart Transplantation: A Retrospective Single Center Study.
Authors: Jiang Yiyao , Kong Xiangrong
Published: May 2020

Objectives
This study aimed to identify the incidence rate of Acute kidney injury (AKI) in our center, assess risk factors for one-year mortality, and predict short- and long-term survival after heart transplantation (HTx).
Methods
This single-center, retrospective study from October 2009 to Jan 2020 analyzed the pre-, intra-, and postoperative characteristics of 87 patients who underwent HTx. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk factors were analyzed by multivariable logistic regression models. The log-rank test was used to compare long-term survival.
Results
Twenty-six (36.1%) patients developed AKI. The one-year mortality rates in HTx patients with and without AKI were 26.92% and 10.87%, respectively (P > 0.05). Recipients who required renal replacement therapy (RRT) had a one-year mortality rate of 53.85% compared to 10.87% in those without AKI or RRT (P = 0.003). A long cardiopulmonary bypass (CPB) time (OR: 1.622, 95% CI: 1.014 to 2.595, P = 0.044) was positively related to the occurrence of AKI. A high intraoperative urine volume (OR: 0.566, 95% CI: 0.344 to 0.930, P = 0.025) was negatively correlated with AKI. AKI requiring RRT (HR, 6.402; 95% CI, 2.014–20.355, P = 0.002) was a risk factor for death. Overall survival in patients without AKI at 1, 3, and 5 years was higher than that in patients with AKI (P > 0.05).
Conclusions
AKI is common after HTx and adversely impacts early mortality. A long CPB time and low intraoperative urine volume maybe associated with the occurrence of AKI. AKI requiring RRT could contribute powerful prognostic information to predict short-term survival.
Inhibition of Jiawei Foshou San on invasion and metastasis through MMP/TIMP signaling in endometriosis
Authors: Zhang Ying , Wei Jiahui , Tan Yi , Zhang Chengling , Xu Pingli , Chen Yi
Published: May 2020

Background: The new formula Jiawei Foshou San (JFS) is consisted of ligustrazine, ferulic acid and tetrahydropalmatine designed from Foshou San . Previously JFS inhibited the growth of rat autograft endometriosis with unclear mechanism. To uncover the effect of JFS on invasion and metastasis in endometrial cells and xenograft endometriosis. Methods: In vitro , cell viability assay was performed for IC50 measurement in hEM15A and HEC1-B cells after treating JFS. Effects of JFS on invasion and metastasis were analyzed in scratch wound and transwell assay. In vivo , effect of JFS was evaluated in xenogeneic transplantation of endometriosis model. The gene and protein expression of MMP/TIMP signaling were inspected in vitro and in vivo . Results: Inhibitory effects of JFS were investigated with dose-dependent manner in hEM15A and HEC1-B cells. JFS significantly inhibited the invasion and metastasis in dose- and time-dependent manner. In xenograft endometriosis, JFS reduced the volume of ectopic endometrium. In-depth study, inactive MMP/TIMP signaling expressed the lower MMP-2/9, higher TIMP-1 by JFS in vitro and in vivo . Conclusions: JFS prevent invasion and metastasis via inactivation of MMP/TIMP signaling in endometrial cells and xenograft endometriosis. It reveals the potential mechanism of JFS on endometriosis and the benefit for further application.
Land Use Land Cover (LULC) Change Detection Using Geospatial Technique in Anbessa Forest, Benishangul-Gumuz Region, Ethiopia
Authors: Guyu Daie Ferede , Aduwa Tunkala Anjulo
Published: May 2020

Background

LULC analysis using satellite images for detecting the changes across a given landscape is a very crucial tool for understanding the nexus between forest ecosystems and human activities. LULC pattern of Anbessa forest had undergone fast changes over the last 30 years, but no research measured the level of the changes. The present study was aimed at detecting the LULC change pattern of Anbessa forest using data from satellite images between 1989 and 2019.
Methods

We examined the LULC changes of Anbessa forest using satellite image data over the period of 1989–2019 using geospatial technique.
Results

The results show a 29% and 18% decrease in land area under dense and open forests respectively over a period of 30 years. Conversely there is 32% and 25.6% increase in the land under agricultural land and settlement areas respectively. A relatively small average decrease of 8% in shrub land was found although there was a decrease from 1989 to 2004 and an increase from 2004 to 2019.
Conclusion

The fact that there is a decrease in natural and open forests and an increase in agricultural and settlement areas implies there had been fast degradation of natural forests of Anbessa forest due to human activities. Thus, there should be an intervention project that ensures the sustainability of the forest.
Predictive Factors of Outcome Following Non-Fermenting Gram-Negative Bacilli Peritonitis in Peritoneal Dialysis
Authors: Santos Ana Claudia Moro Lima dos , Hernandes Rodrigo Travanelli , Montelli Augusto Cezar , Monteiro Aydir Cecília Marinho , Barbosa Thais Alves , Camargo Carlos Henrique , Ferreira Adriano Martison , Mondelli Alessandro Lia , Cunha Maria de Lourdes Ribeiro de Souza da , BARRETTI PASQUAL
Published: May 2020

Background Peritonitis due to Gram-negative bacilli (GNB), particularly the non-fermenting GNB (NF-GNB) is a serious complication of peritoneal dialysis (PD) with a low-resolution rate. Beyond the patient’s conditions, microbiological properties as antimicrobial resistance, biofilm and other virulence factors production could explain the bad outcomes. This study aimed to evaluate the influence of the patient’s conditions, microbiological characteristics, including biofilm production, and treatment of peritonitis on the peritonitis resolution. Methods We reviewed the records of 68 peritonitis episodes that occurred between 1997 and 2015 at a single university center. The influence of microbiological and clinical factors on resolution chance was analyzed by logistic regression. Results The etiologies were species of Pseudomonas (51.5%), Acinetobacter (30.9%), and others (18.6%). There was a high (75%) proportion of biofilm producers’ lineages. The in vitro susceptibility rate of Pseudomonas spp. to amikacin, ciprofloxacin, and ceftazidime was significantly greater than that of Acinetobacter spp. and other species; however, there was a similar low-resolution rate (<40%) among the episodes due to these etiologies. Concomitant ESI and resistance to amikacin were independently associated with non-resolution. No other factor, including biofilm production were associated with the outcome Conclusions Peritonitis due to NF-GNB in PD are severe infections with reduced resolution rate; bacterial resistance and concomitant ESI negatively influence the chance of resolution. Even though biofilm production has not had influence the outcome, the found of higher in vitro susceptibility of Pseudomonas than other NF-GNB, with similar resolution rate, suggest bacterial virulence factors as biofilm or others can act in concert, worsening the outcome.
A cross-sectional study on metabolic similarities and differences between inpatients with schizophrenia and those with mood disorders
Authors: Uju Yoriyasu , Kanzaki Tetsuto , Yamasaki Yuki , Kondo Tadayuki , Nanasawa Hideki , Takeuchi Yu , Yanagisawa Yuta , Kusanishi Shun , Nakano Chieko , Enomoto Tetsuro , Sako Akahito , Yanai Hidekazu , Mishima Shunichi , Mimori Seisuke , Igarashi Kazuei , Takizawa Tsuyoshi , Hayakawa Tatsuro
Published: May 2020

Background
One of the main causes of death in psychiatric patients is cardiovascular diseases which are closely related with lifestyle-related diseases. Psychiatric disorders include schizophrenia and mood disorders, whose symptoms and treatment medicines are different, suggesting that they might have different metabolic disorders. Thus, we studied the differences of lifestyle-related diseases between schizophrenia and mood disorders in Japan.
Methods
This cross-sectional study was performed from 2015 to 2017. Study participants were 189 hospitalized patients (144 schizophrenia group, 45 mood disorders group) in the department of psychiatry at Kohnodai hospital. We examined physical disorders, metabolic status of glucose and lipid, estimated glomerular filtration rate (eGFR) and brain magnetic resonance imaging. We compared these data between inpatients with schizophrenia or mood disorders group and the standard. We quoted ‘The National Health and Nutrition Survey in Japan 2015’ by Ministry of Health, Labor and Welfare as the standard. In comparisons between schizophrenia and mood disorders groups, we used analysis of covariance or logistic regression analysis.
Results
The ratio of silent brain infarction (SBI) and cerebral infarction were significantly high in both groups compared with the standard. Schizophrenia group showed significantly higher prevalence of diabetes, low high-density lipoprotein (HDL) cholesterolemia, metabolic syndrome and smoking than the standard. Mood disorders group had significantly high prevalence of low HDL-cholesterolemia compared with the standard. Fasting blood glucose and HbA1c were significantly higher in schizophrenia group and female mood disorders group than the standard. Female mood disorders group had significantly decreased eGFR with increased ratio of eGFR < 60 ml/min than the standard. In comparison between both groups, eGFR and prevalence of smoking in mood disorders group were significantly lower than those in schizophrenia group by adjustment for age.
Conclusions
Participants of both groups had increased ratio of SBI and cerebral infarction, accompanied with glucose and lipid disorders. Distinct from schizophrenia group, mood disorders group showed significantly lower eGFR and prevalence of smoking.
The Establishment of Intervertebral Endplate Degeneration: A Novel in-vivo Diurnal-Axial Controllable Loading Model in Rat Tail
Authors: Hu Zhouyang , He Fan , Li Xinhua , Jiang Bei , Yan Shuaifeng , Tan Jun , Yang Mingjie , Li Lijun
Published: May 2020

Background. Cartilage endplate (CEP) acts as an important mechanical barrier and nutrient channel for the intervertebral disc (IVD). Its vulnerability to excessive loading and subsequent degeneration might be an initial trigger for IVD degeneration. This study aims to build a new in-vivo animal model of rat-tail CEP degeneration through implementing a controllable axial compressive device.Methods. An axial controllable compressive load was conducted on the 8–9 th coccygeal IVD of adult rat tail through puncturing 4 Kirschner wires into its superior and inferior vertebra. The exact compression loads were controlled and adjusted by a remote controller. The compression and decompression periods were set as 8 h/16 h per day. The control group was set as no device installation, while the Kirschner wires were punctured without compression in the sham group. After each 4, 8 and 12 weeks, 3 rats in each group were sacrificed and compressed disc were analyzed.Results. After compression, the targeted CEP degenerated gradually with time. Through 12 weeks' loading, the CEP structure collapsed completely and the Schmorl's nodes formed and penetrated from the cartilage layer into the vertebra. When compared with the control group, the number of micro porosities in the CEP becomes extremely scarce with loading, while the content of aggrecan and collagen II decreased significantly. However, these significant changes did not show up when sham and control groups were compared.Conclusions. A new excessive force induced CEP degeneration animal model was developed with its contribution as a practical alternative for further studying mechanisms of CEP degeneration.
Griseococcin(1) from Bovistella radicata (Mont.) Pat and Antimicrobial Activity
Authors: qingmei zeng , ye yong , Zeng Qinghua
Published: May 2020

Bovistella radicata (Mont.) Pat was a natural plant with multiple medicinal values. The purified compound purified from Bovistella radicata (Mont.) Pat by DEAE-cellulose and sephadex LC-20 column which could inhibit main pathogens leading to tinea pedis. Based on the spectral (HPLC, FT-IR, 1D and 2D NMR etc.) studies, purified compounds were identified as the Griseococcin(1) which were naphthoquinone derivatives, the Chemical formula and MW of Griseococcin(1) was determined as C37O10H43N and 661 Da. Minimum inhibitory concentration(MIC) and zone of inhibition(ZOI) of Griseococcin(1) were 31.2, 31.2 µg/ml and 18.06 ± 0.85 mm, 15.01 ± 1.02 mm respectively against main pathogenic fungus Trichophyton rubrum and Trichophyton mentagrophytes.
GDF15-Mediated Cholesterol Metabolism Promotes EMT and Metastasis in Esophageal Cancer
Authors: Dong Gang , Huang Xiaoquan , Jiang Siyu , Ni Liyuan , Ma Lili , Zhu Chouwen , Chen Shiyao
Published: May 2020

Background: GDF15 is a potential biomarker for patients with esophageal cancer (EC). However, the mechanistic role of GDF15 in the invasion and metastasis of EC remains poorly understood. Methods: We determined the expression and function of GDF15 in esophageal cancer cells (ESCCs) and in patient tissue samples using western blotting, migration and invasion assays, immunohistochemistry, Co-IP assays, and quantitative real-time-PCR. In addition, a pulmonary metastatic nude mouse model was used to determine the function of GDF15. We then supplemented our experimental results with database analysis to validate our findings.Results: GDF15 was upregulated in EC, and was associated with poor differentiation, high metastasis rates and worse prognosis. GDF15 knock-down reduced the migration and invasion of ESCCs. Co-IP assays demonstrated its association with SCAP, while GDF15 knock-down decreased SCAP levels. SCAP overexpression reversed the migration, invasion and EMT in GDF15-siRNA ESCCs. However, after incubation with β-cyclodextrin (β-CD), the ability of migration and invasion was weakened, EMT was reversed again. Migration, invasion, and EMT were enhanced in GDF15-siRNA ESCCs cultured in the presence of cholesterol and were similar to GDF15-siRNA ESCCs overexpressing SCAP. In vivo, knockdown of GDF15 inhibited lung metastasis of ESCCs and was reversed by SCAP overexpression or high cholesterol diet. Increased lung metastasis after SCAP overexpression was partially suppressed by intraperitoneal injection of β-CD. In addition, we determined that GDF15 was a direct target of miR-1324, miR-1324 was down-regulated in EC tissues. MiR-1324 upregulation resulted in decreased GDF15 expression and metastasis in ESCCs. Conclusions: We demonstrated that SCAP mediated GDF15-induced the invasion and metastasis of EC by regulating cholesterol metabolism. In addition, GDF15 was shown to be a direct target of miR-1324.
E2F1-mediated repression of WNT5A expression Promotes Brain Metastasis Dependent on the ERK1/2 pathway in EGFR-Mutant Non-Small Cell Lung Cancer
Authors: Li Huanhuan , Tong Fan , Meng Rui , Peng Ling , Zhang Ruiguang , Dong xiaorong
Published: May 2020

Background: Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutation reportedly enhances the development of BM. However, the exact mechanism of how EGFR-mutant NSCLC contributes to BM remains unknown. This study was aimed at exploring the mechanism of BM development in EGFR-mutant NSCLC.Methods: WNT5A, was identified by analyzing RNA sequencing data of BM tissue from NSCLC. The expression of WNT5A in NSCLC plasma (n=94) and cells were detected by quantitative real-time PCR (qRT-PCR) and western blotting. WNT5A functions were examined by cell viability, migration, invasion, and immunohistochemistry assay in vitro. A xenograft nude mouse model and BM model were used to observe tumor growth and brain metastasis in vivo. The potential transcription factor of WNT5A was explored using bioinformatics analysis and verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. WNT5A targets in NSCLC cells were confirmed using luciferase reporter assay, qRT-PCR, and western blotting.Results: WNT5A was downregulated in BM tissues and EGFR-mutant samples and cells. The overexpression of WNT5A inhibited the growth, migration, and invasion of EGFR-mutant cells in vitro and retarded tumor growth and metastasis in vivo compared to the EGFR wide-type cells. ChIP and luciferase reporter assays showed that E2F1 negatively regulated WNT5A at transcriptional levels, which was suppressed by ERK1/2 inhibitor (U0126) in EGFR-mutant cells. Furthermore, WNT5A inhibited β-catenin activity and the transcriptional levels of its downstream genes in cancer progression.Conclusions: Our research revealed the role of WNT5A in NSCLC BM with EGFR mutation and proved that E2F1-mediated repression of WNT5A was dependent on the ERK1/2 pathway, supporting the notion that targeting the ERK1/2-E2F1-WNT5A pathway could be an effective strategy for treating BM in EGFR-mutant NSCLC.