Search

The main cause of Parkinson’s disease (PD) remains unknown and the pathologic changes in the brain limit rapid diagnosis. Herein, differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) database (GSE8397 and GSE22491) were assessed using linear models for microarray analysis (limma). Ankyrin 1 (ANK1) was the only common gene differentially down-regulated in lateral substantia nigra (LSN), medial substantia nigra (MSN) and blood. Additionally, DEGs between high ANK1 and low ANK1 in GSE99039 were picked out and then uploaded to the Database for Annotation, Visualization and Integrated Discovery (DAVID) for gene ontology (GO) functional annotation analysis. GO analysis displayed that these DEGs were mainly enriched in oxygen transport, myeloid cell development and gas transport (biological process (BP)); hemoglobin complex, haptoglobin–hemoglobin complex and cortical cytoskeleton (cellular component (CC)); and oxygen transporter activity, haptoglobin binding and oxygen binding (molecular function (MF)). Receiver operating characteristic (ROC) curve analysis showed ANK1 had good diagnostic accuracy and increased the area under the curve (AUC) value when combined with other biomarkers. Consistently, intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropy-ridi-ne (MPTP) in C57BL/6J mice reduced ANK1 mRNA expression in both substantia nigra and blood compared to the control group. Thus, ANK1 may serve as a candidate biomarker for PD diagnosis.

Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in Parkinson’s disease (PD). In recent years, environmental toxins are employed to increase oxidative stress mediated neuropathology and sporadic PD. Disruption of iron homeostasis has been implicated in PD patients for many years, but the functional role of iron in sporadic PD pathogenesis is still not well clarified in vivo. To address this question, we set out to investigate the effect of iron on a Drosophila rotenone model of sporadic PD. Iron homeostasis is maintained by many transporters. We found that inhibition of transferrin1 (Tsf1) expression in the central nervous system (CNS) results in reduced iron levels in brains and significantly ameliorates the neurodegenerative phenotypes of rotenone exposure Drosophila; moreover, the rotenone induced reactive oxygen species (ROS) levels in the brain, the damaged complex I activity and the decreased ATP generation were dramatically rescued by Tsf1 knockdown. Further study indicated that all the rescue effects of Tsf1 knockdown on sporadic PD could be inhibited by malvolio (Mvl) overexpression, an iron transporter responsible for iron uptake. These results imply that Tsf1 knockdown in the CNS could attenuate rotenone toxicity by decreasing the ROS levels in brains through reducing iron levels, and manipulation of iron transporters in brains may provide a novel therapeutic strategy for sporadic PD.

Disruption of iron homeostasis in the brain of Parkinson's disease (PD) patients has been reported for many years, but the underlying mechanisms remain unclear. To investigate iron metabolism genes related to PTEN-induced kinase 1 (Pink1) and parkin (E3 ubiquitin ligase), two PD-associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, we conducted a genetic screen in Drosophila and found that altered expression of genes involved in iron metabolism, such as Drosophila ZIP13 (dZIP13) or transferrin1 (Tsf1), significantly influences the disease progression related to Pink1 but not parkin. Several phenotypes of Pink1 mutant and Pink1 RNAi but not parkin mutant were significantly rescued by over-expression (OE) of dZIP13 (dZIP13 OE) or silencing of Tsf1 (Tsf1 RNAi) in the flight muscles. The rescue effects of dZIP13 OE or Tsf1 RNAi were not exerted through mitochondrial disruption or mitophagy; instead, the iron levels in mitochondira were significantly increased, resulting in enhanced activities of enzymes participating in respiration and increased ATP synthesis. Consistently, the rescue effects of dZIP13 OE or Tsf1 RNAi on Pink1 RNAi can be inhibited by decreasing the iron levels in mitochondria through mitoferrin (dmfrn) RNAi. This study suggests that dZIP13, Tsf1, and dmfrn might act independently of parkin in a parallel pathway downstream of Pink1 by modulating respiration and indicates that manipulation of iron levels in mitochondria may provide a novel therapeutic strategy for PD associated with Pink1.

The main cause of Parkinson’s disease (PD) remains unknown and the pathologic changes in the brain limit rapid diagnosis. Herein, differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) database (GSE8397 and GSE22491) were assessed using linear models for microarray analysis (limma). Ankyrin 1 (ANK1) was the only common gene differentially down-regulated in lateral substantia nigra (LSN), medial substantia nigra (MSN) and blood. Additionally, DEGs between high ANK1 and low ANK1 in GSE99039 were picked out and then uploaded to the Database for Annotation, Visualization and Integrated Discovery (DAVID) for gene ontology (GO) functional annotation analysis. GO analysis displayed that these DEGs were mainly enriched in oxygen transport, myeloid cell development and gas transport (biological process (BP)); hemoglobin complex, haptoglobin–hemoglobin complex and cortical cytoskeleton (cellular component (CC)); and oxygen transporter activity, haptoglobin binding and oxygen binding (molecular function (MF)). Receiver operating characteristic (ROC) curve analysis showed ANK1 had good diagnostic accuracy and increased the area under the curve (AUC) value when combined with other biomarkers. Consistently, intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropy-ridi-ne (MPTP) in C57BL/6J mice reduced ANK1 mRNA expression in both substantia nigra and blood compared to the control group. Thus, ANK1 may serve as a candidate biomarker for PD diagnosis.

PURPOSE To compare outcomes of deep anterior lamellar keratoplasty (DALK) and corneal cross-linking (CXL) in patients with advanced keratoconus, with the primary aim of assessing CXL as a potential therapeutic alternative. STUDY DESIGN Retrospective, multi-center, comparative study. METHODS Patients with advanced keratoconus (maximum keratometry reading (K-max) > 58D, best spectacle-corrected visual acuity worse than 0.52logMAR), undergoing either DALK or CXL treatment at four tertiary ophthalmic centers in Wenzhou, Hangzhou, Nanjing and Wuhan were included. Visual acuity, refractive error, corneal topography and complications were evaluated at baseline and at least 2 year postoperatively. RESULTS 75 eyes of 72 patients were included, of which 37 eyes underwent DALK and 38 eyes, CXL. A larger reduction in Kmax was observed in the DALK group (-18.18 ± 9.44 D versus -1.10 ± 2.70D, p

Black bean seed coat extract (BBSCE) contains a high amount of bioactive compounds which can reduce the risk of cancers, but the underlying mechanism remains poorly understood in vivo. Here using a Drosophila model of a malignant tumor, wherein the activated oncogene Raf (RafGOF) cooperates with loss-of-function mutations in the conserved tumor suppressor scribble (scrib-/-), we investigated the antitumor mechanism of BBSCE and its main active component cyanidin-3-O-glucoside (C3G) in vivo. The results showed that supplementation of either BBSCE or C3G inhibited the tumor growth and invasion of RafGOFscrib-/- and extended their survival in a dose dependent manner. Strikingly, the activation of both autonomous and non-autonomous autophagy in tumor flies was significantly reduced by C3G treatment. A further study indicated that C3G exhibited an antitumor effect in vivo by blocking autophagy both in tumor cells and in its microenvironment by inhibiting the JNK pathway. Interestingly, the efficacy of chloroquine (CQ, an autophagy inhibitor used as an antitumor agent) combined with C3G is much better than either C3G or CQ treatment alone. C3G may be combined with CQ to treat cancers and to provide a theoretical basis for functional food or natural medicine development.

The expression and influence mechanism of CTGF and HO-1 in rats with diabetic retinopathy (DR) was investigated. One hundred and thirty male Sprague-Dawley (SD) rats were selected and randomly divided into the control group and DR group, with 65 rats in each group. DR was caused by intraperitoneal injection of streptozotocin in rats in the DR group. There were 55 successful models and 10 failed in the modelling. The successful models were sacrificed at the 2nd, 4th and 6th month, respectively. RT-qPCR technology was used for detection of the expression of CTGF and HO-1 in rat retina in each group, H&E staining for observation of the gradation structure in rat retina and TUNEL method for detection of apoptosis of retinal cells. In the DR group, the retina layers were disordered and a few blood vessels dilated at the 2nd month. In the DR group, the inner membrane of the retina swelled, and the ganglion cells were irregularly arranged at the 4th month. In the DR group, dilatation of the blood vessels was more obvious, the inner membrane edema was more severe, and the arrangement was more irregular at the 6th month. The retinal apoptosis rate of DR rats gradually increased at the 2nd, 4th and 6th month, after which, the CTGF expression gradually increased, but the HO-1 expression gradually decreased in retina in the DR group. However, the mRNA expression of CTGF and HO-1 in the rats at the 2nd, 4th and 6th month in the DR group was higher than that in the control group at the same period. Therefore, CTGF and HO-1 are associated with the occurrence and development of DR in rats and can be considered as targets for the treatment of DR.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Eigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is known to exert a beneficial effect on PD patients. Although some mechanisms were suggested to underlie this intervention, it remains unknown if the EGCG-mediated protection was achieved by remodeling gut microbiota. In the present study, 0.1 mM or 0.5 mM EGCG was administered to the Drosophila melanogaster with PINK1 (PTEN induced putative kinase 1) mutations, a prototype PD model, and their behavioral performances, as well as neuronal/mitochondrial morphology (only for 0.5 mM EGCG treatment) were determined. According to the results, the mutant PINK1B9 flies exhibited dopaminergic, survival, and behavioral deficits, which were rescued by EGCG supplementation. Meanwhile, EGCG resulted in profound changes in gut microbial compositions in PINK1B9 flies, restoring the abundance of a set of bacteria. Notably, EGCG protection was blunted when gut microbiota was disrupted by antibiotics. We further isolated four bacterial strains from fly guts and the supplementation of individual Lactobacillus plantarum or Acetobacter pomorum strain exacerbated the neuronal and behavioral dysfunction of PD flies, which could not be rescued by EGCG. Transcriptomic analysis identified TotM as the central gene responding to EGCG or microbial manipulations. Genetic ablation of TotM blocked the recovery activity of EGCG, suggesting that EGCG-mediated protection warrants TotM. Apart from familial form, EGCG was also potent in improving sporadic PD symptoms induced by rotenone treatment, wherein gut microbiota shared regulatory roles. Together, our results suggest the relevance of the gut microbiota-TotM pathway in EGCG-mediated neuroprotection, providing insight into indirect mechanisms underlying nutritional intervention of Parkinson's disease.

Recently, cloud computing with the rapid development is a new computing model and application based on the Internet. The application has a broad concept and definition, which is mainly composed of a number of new computing technologies. However, from the cognitive perspective of industry, in general cloud computing mainly represents a model unified user resources for large-scale distributed computing. First of all, in order to constitute an abstract, virtual and dynamically extensible computing resource pool (which can be arbitrarily combined distribution and dynamic recycling of reuse), cloud computing platform uses the Internet to integrate various wide area heterogeneous computing resources. This paper presents a communication technology overview to support further information interaction between electric demand and supply side in smart grid.

Large receiving end grid has characteristics such as low capacity, poor fault tolerance. In the case of unexpected fault, aiming at the demand of emergency load regulation, a method is proposed here that the load group can quickly participate in the resource control based on logical channel mode. Firstly, the paper analyzes the existing architecture of load regulation, pointing out the limitation of its control process. Then this paper put forward the rapid control structure based on the logical channel mechanism, which further elaborated its concrete realization scheme, including business division, user analysis and control scheme. Finally, the advantages of the proposed method are analyzed and the great effectiveness of the logic channel mode on power emergency response is clarified.

In order to solve the problem caused by UHV emergency fault of large-scale power grid, it is necessary to control the large-scale user load group to fill the power supply gap. Due to the lack of the corresponding communication protocol to support the control of large-scale load group, this paper studied the existing Internet and smart grid related communication protocol to establish a XMPP-based LSLGC communication protocol in the application layer. Registration, Report, Event and Opt four processes are selected to support large-scale load group control. Also, the corresponding control mechanism is studied.

Aims: Apoptosis plays a critical role in cardiomyocyte loss during ischaemic heart injury. A detailed understanding of the mechanism involved has a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast cells. Methods and Results: SIRT4 interference significantly alters H9c2 cell viability, apoptotic cell number and caspase-3/7 activity. Furthermore, SIRT4 expression can affect the ratio of pro-caspase 9/caspase 9 or pro-caspase 3/caspase 3, an affect Bax translocation, which in turn alters the development of H9c2 cell apoptosis. Conclusion: These results suggest that SIRT4 is a key player in hypoxia-induced cardiomyocyte apoptosis, and that strategies based on its enhancement might be of benefit in the treatment of ischaemic heart disease.

A hybrid approach based on neural network (NN) and genetic algorithm (GA) is presented to solve so called expanded job shop scheduling problems, Neurons to represent the restrictions are designed with conflicts resolving ability. Constraint neural network (CNN) is constructed with these neurons for operations' starting time optimization under deterministic processing sequence in virtue of gradient search algorithm. Combined with genetic algorithm for sequence optimization, a hybrid approach to expanded job shop scheduling is formulated. lots of experiment cases has shown the hybrid approach powerful for the complicated expanded job shop scheduling.

When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF-α) among other cytokines leaks into the subretinal space, induces resident retinal pigment epithelial (RPE) cells to migrate, which is the initial step of proliferative vitreoretinopathy (PVR). In the current study, we aim to understand how this is regulated by focusing the cellular mechanisms involved. Here we identified an Akt/Tuberous sclerosis protein 2 (TSC2)/mTOR complex1 (mTORC1) signaling pathway after TNF-α treatment to mediate RPE cell migration. Suppression of mTORC1 activation, either by its inhibitor rapamycin, or by activation of its suppressor AMP activated protein kinase (AMPK), inhibited TNF-α-mediated RPE cell migration, while RNA interference (RNAi)-mediated knocking-down of SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2), had no significant effect on TNF-α-induced RPE cell migration. Our data provide initial evidence that TNF-α-mediated in vitro RPE cell migration mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study may lead to indentify novel signaling targets against PVR.

To solve optimization scheduling problems and improve efficiency of tobacco enterprises, the paper first establishes mathematical modeling of optimization scheduling on tobacco enterprise, through introducing idea of operation sets to scheduling algorithm, increases the possibility of scheduling algorithm. According to making and packing plan, the paper also educes cut tobacco plans and accomplishes pulling scheduling requirement.

It is in accordance with just-in-time (JIT) philosophy to penalize early/tardy jobs. An optimal method genetic-based is presented to solve single machine scheduling problem with general early-tardy penalty weights in the paper. A new heuristic crossover operator is proposed for searching optimal sequences. On different scale of scheduling problems, lots of comparative experiments were carried out and the results manifested the method effectiveness.

A performance management system is regarded as a framework for manufacturing enterprise, and links strategies, resources, and business processes through the management of the enterprise's performance. It is used to guide decisions and activities for both employee and manager in the enterprise. Research and practice of performance management is reviewed. An enterprise performance analysis model, based on the process and multi-view technology, is suggested then a performance evaluation model and benchmarking of performance evaluation are presented. Finally, a framework for a performance management system based on the performance analysis and evaluation is put forward.

This paper presents some applications of the discrete-time point process theory. time-varying Markov chain and Martingale Difference(MD) sequence in urban traffic computer control system. In this paper we propose an approach to discrete the place of arriving vehicles in fornt of the intersection, depending on their speed distributions. Furthermore, the formation and dispersion of real queues at traffic signal is then moiled by a time-varying Markov chain which is related to the observation data from vehicle detectors in the intersection. Some results in the theory of discrete time point process are then used to derive a new nonlinear minimum error variance algorithm to predicte the state of queues in the model. At same time, we present a method to determine the time-varying unknown parameters of the algorithm. The new algorithm was tested in comparison with the previous ones by simulation. Some results of the test are shown. They indicated that an apparent better performance than those of previous ones is achived. We have set up an optimal control system based on a micro-carputer in one main street in Dalian City.China using the approach presented in this paper. And a satisfactory performance was obtained.

In this paper, we study a closed-loop conveyor system with equally spaced transportation devices and only one unloading station. We first discuss the dynamic behaviour and, in particular, we point out the non-blocking conditions of this system. We consider the steady-state of the conveyor system and give the values of the expected in-process inventory and of the expected production cycle according to the length of the conveyor.

A fuzzy production system for multiobjective scheduling is described in this paper. Based on the heuristic search principle in AI, this system takes the heuristic algorithms used for finding optimal or quasi optimal sequences of different single objectives as the production rules, and the fuzzy min-operator with nonlinear membership function as the test criterion. It is able to find an optimal or quasi-optimal processing sequence to meet many different objective functions simultaneously.

This paper presents some applications of the discrete-time point process theory, time-varying Markov chain and Martingale Difference(MD) sequence in urban traffic computer control system. In this paper we propose an approach to discrete the place of arriving vehicles in fornt of the intersection, depending on their speed distributions. Furthermore, the formation and dispersion of real queues at traffic signal is then modeled by a time-varying Markov chain which is related to the observation data from vehicle detectors in the intersection. Some results in the theory of discrete time point process are then used to derive a new nonlinear minimum error variance algorithm to predicte the state of queues in the model. At same time, we present a method to determine the time-varying unknown parameters of the algorithm. The new algorithm was tested in comparison with the previous ones by simulation. Some results of the test are shown. They indicated that an apparant better performance than those of previous ones is achived. We have set up an optimal control system based on a micro-computer in one main street in Dalian City, China using the approach presented in this paper. And a satisfactory performance was obtained.