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The problems of parallel two-sided assembly lines balancing (TALB) are nonpolynomial (NP-hard) problems that belong to the field of combinatorial optimization. In most cases, these problems can be resolved with algorithms. To this end, this research adopts colored Petri nets (CPN) and a minimal spanning tree (MST) to address the type I problems for two-sided assembly line balancing problem (TALBP). This research proposes a three-step method. In the first step, a reachability tree chart is built to show potential tasks order assignment. In the second step, the color firing mechanism is employed to determine if the colored conditions are satisfied. The final step uses a MST and a least-time prioritized rule to select the proper tasks for assignment efficiently. These steps will be performed repetitively until all the tasks are properly assigned. Since the whole assignment process is based on graphical and paradigm methods, it can be adopted to lessen the burdens of complex calculations. The end of the research will present the comparison results between the examples from the literature and the method proposed in this research. As indicated by the research findings, employing CPN and an MST for TALBPs (type-I) can obtain even favorable and consistent results over legacy methods, and further optimize workstation design and enhance balance efficiency.

本案例為一名56歲女性因反覆眩暈及耳鳴，經檢查後初步診斷為良性陣發性姿勢性眩暈（Benign Paroxysmal Positional Vertigo, BPPV），接受右耳耳石復位術（Canalith Reposition Procedure），然而，隨著病程進展，接續出現關鍵性的前額眉心處的頭痛及視力模糊的症狀，藉由詳細地病史詢問、身體評估、及相關的檢驗及影像檢查，採用排除及納入相關診斷的鑑別過程，最後確診為蝶鞍空洞症，在詳細地病情解釋後，病人接受經鼻腔內視鏡蝶竇蝶鞍減壓併自體脂肪填充及鼻中隔皮瓣重建手術。不幸地，術後產生腦脊髓液鼻漏的併發症，在及時地重新評估、鑑別診斷及處置，有效的控制併發症避免神經功能惡化，最後病人順利出院，因此引發筆者撰寫動機，期望分享此病例照護經驗，提醒同仁臨床照護病人時需要時刻保持警覺，確保病人回復健康。 The case in this study is a 56-year-old woman who was initially diagnosed with benign paroxysmal postural dizziness because of repeated vertigo and tinnitus after serial examinations. She underwent reduction of otolith of right ear (Canalith Reposition Procedure). However, her symptoms remained and subsequent symptoms of frontal headache and blurred vision occurred. Although symptoms such as vertigo, tinnitus, and headache are common in Meniere’s disease, benign paroxysmal postural vertigo (BPPV), cerebral infarction, etc. eventually we revised the diagnosis to the Empty Sella Syndrome through detailed inquiry of medical history, physical assessment, and image examinations.After well-addressed explanation of the clinical condition, the patient received endoscopic transnasal transsphenoidal approach and packing sella with autologous fat, reconstruction by cartilage and nasal septal flap. Unfortunately, the sequel of cerebrospinal fluid rhinorrhea occurred after the operation. By promptly reassessment, differential diagnosis with proper treatment, the complication was effectively controlled to avoid neurological deterioration, and the patient was discharged without further complication. I sincerely share the experience of this specific case with my colleagues. Keeping vigilant in clinical care of patients to ensure they could return to health. &nbsp

Ischemic stroke is a severe threat to the health of older individuals. Bone marrow mesenchymal stem cells (BMSCs) have been implicated in ischemic stroke. Urokinase‑type plasminogen activator (uPA) and its specific receptor (uPAR) are associated with the pathological process of ischemic stroke. However, the relationship between BMSCs and uPA/uPAR in ischemic stroke remains unclear. For simulating the occurrence of an ischemic stroke in vitro, human cerebral microvascular endothelial cells (HBMECs) were subjected to oxygen and glucose deprivation followed by re‑oxygenation (OGD/R) and were then cocultured with BMSCs. 3,4,5‑dimethylthiazol‑2,5‑diphenyltetrazolium bromide and bromodeoxyuridine staining were used for measuring cell viability and proliferation. Flow cytometry was performed for assessing cell apoptosis. Endothelial cell tube formation was determined using angiogenesis assays. Alterations in the protein and gene expression in HBMECs were evaluated using western blot analysis and quantitative reverse transcription‑polymerase chain reaction, respectively. OGD/R considerably inhibited the viability and proliferation of HBMECs by inducing apoptosis, which was reversed by BMSCs. Consistently, OGD/R‑induced inhibition of angiogenesis was attenuated by BMSCs. In addition, BMSCs could protect HBMECs against OGD/R‑induced injury by positively regulating the uPA/uPAR/stromal cell‑derived factor‑1α (SDF‑1α)/C‑X‑C chemokine receptor type 4 (CXCR4) pathway, and uPA/uPAR could mediate the SDF‑1α/CXCR4 pathway in OGD/R‑treated HBMECs. Therefore, this study provides novel strategies to investigate the specific role of BMSCs in ameliorating OGD/R‑induced vascular endothelial cell injury.

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P P = 0.02), age > 50 years old (HR/CI 3.64/2.03–6.54, P P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03–1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04–19.09, P = 0.04) and BMI (HR/CI 1.11/1.03–1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Background Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. Aim To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss. Methods We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo. Results The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features. Conclusion Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

Cervical spondylotic myelopathy (CSM) is a clinically symptomatic entity arising from the spinal cord compression by degenerative diseases. Although endoplasmic reticulum (ER) stress has been commonly observed in several neurodegenerative diseases, the relationship between ER stress and CSM remains unknown. Shikonin is known to protect PC12 by inhibiting apoptosis in vitro. This study hypothesised that ER stress was vital in neuronal apoptosis in CSM. Shikonin might inhibit such responses by regulating ER stress through the protein kinase-like ER kinase-eukaryotic translation initiation factor 2 α-subunit-C/EBP homologous protein (PERK-eIF2α-CHOP) signalling pathway. Thus, the aim of this study was evaluating the neuroprotective effect of shikonin in rats with double-level chronic cervical cord compression, as well as primary rat cortical neurons with glutamate-induced neurotoxicity. The result showed that ER stress-related upregulation of PERK-eIF2α-CHOP resulted in rat neuronal apoptosis after chronic cervical cord compression; then, shikonin promoted motor recovery and inhibited neuronal apoptosis by attenuating PERK-eIF2α-CHOP and prevented Bax translocation from cytoplasm to mitochondrion induced by CHOP of neurons in rats with chronic compression. Also, it was found that shikonin could protect rat primary cortical neuron against glutamate toxicity by regulating ER stress through the PERK-eIF2α-CHOP pathway in vitro. In conclusion, shikonin might inhibit neuronal apoptosis by regulating ER stress through attenuating the activation of PERK-eIF2α-CHOP.

Cervical spondylotic myelopathy (CSM) is the most prevalent type of non-traumatic spinal cord injury. The pathological process of CSM is relatively complicated. Most of the chronic cervical cord compression animal models established using hydrophilic expanding polymer are single-segment compression, which was deviated from clinical practice with double-segment or multi-segment compression. This study aims to better mimic the actual clinical compression by using a new type of hydrophilic expanding polymer to establish an animal model of double-level cervical cord compression.Progressive cord compression was done with implantation of polyvinyl alcohol-polyacrylamide hydrogel in the spinal canal at the C3-4 and C5-6 levels. Sprague-Dawley rats (n = 32) were divided into three groups: sham (no compression, n = 12) and screw compression group (n = 8), and hydrogel compression group (n = 12). Functional deficits were characterized using motor function scores, forelimb grip strength, hindlimb pain threshold, and gait analysis, while compression was imaged with magnetic resonance imaging. The apoptosis, inflammation, and demyelination were assessed by hematoxylin and eosin staining, Luxol fast blue staining, TUNEL assay, immunofluorescence staining, and Western blot analysis.Motor function scores for rats with cervical cord hydrogel compression were significantly decline in motor function scores, an increase in allodynia, neurons and oligodendrocytes apoptosis related to B cell lymphoma-2 (Bcl-2)/Bcl-2 associated X (Bax)/cleaved caspase-3, and impaired axonal conduction, as well as neuroinflammation zone related to microglia or macrophages aggregation related to the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome activation, and activation of astrocytes, as well as oxidative stress were observed.We believe that this model utilizing compression on double-level cervical cord will allow researchers to investigate of translationally relevant therapeutic methods for CSM.

Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P

Trends in digital games and game-based learning development are gradually moving toward physical interactivity and man-machine experiential input. In this study, a motion-sensing wireless handle created by the Industrial Technology Research Institute of Taiwan was applied to a PC-based digital somatosensory learning system. Through wireless signal transmission, a decision tree algorithm was used to verify and analyze the information for determining the corresponding functions and motion-sensing identification. The enhanced accuracy and validity rate of action judgments of physical action signals (action-end device) sent to the somatosensory system can increase the efficiency of instant interaction and fluency between the interface and game system. The research results can be used to develop somatosensory games, add to the collective knowledge in this field, and improve future system efficacy. This study can help developers working on digital games and in other related fields to understand the engines and hardware principles of somatosensory games. Moreover, because ideas are presented without excessive complexity, the results may encourage students to develop somatosensory games.

Background Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins in NRK-49F cells. Discussion These finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells.

Communities of Practices (CoPs) become building blocks of the knowledge economy. CoPs offer a productive solution for improving knowledge and knowledge management. This article presents the results of an empirical study that explored the impact of leadership on overall community effectiveness and knowledge creation and management. The research method employed was a multi-case study, with purposive sampling on two communities of Radiology and Anesthesia in a nonprofit healthcare organization of Taiwan. A total of 24 semi-structured interviews were taken with longitudinal non-participant observation of the routine meetings over a period of one year. The research revealed that two communities develop different leadership styles. In particular, two leadership styles are compared: shared leadership and single leadership. Shared leadership represents communities whose members are empowered to share the tasks and responsibilities of leadership. The results of the study suggest that CoP with shared leadership can nurture CoP to promote innovative learning and knowledge-sharing environment. First, shared leadership is capable of building a social setting for utilizing and articulating individuals and groups' embedded knowledge. Second, shared leadership can work together on setting learning support system entailing various types of meeting, such as regular meeting, morning meeting, and monthly meeting, make environmental influence on individual' motivation to engage in CoPs. Third, the sharing norms purposely developed by leadership overcome the power differences among members and provide chances for constructive interactions. On the other hand, a CoP that took the traditional approach of relying on a single leader has poor performance on the cohesiveness and ability to communicate. The article concludes with a discussion of some guidance for purposeful design of CoPs, implications, and future research opportunities.

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex- and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P < 0.05). After adjusting for the risk factors, miRNA-4739 levels were found to be associated with an increased odds ratio (OR) of T2DM with CLI (OR =12.818, 95% confidence intervals (CI) 1.148 to 143.143, P = 0.038). ROC curve analysis revealed that the area under the curve (AUC) of miR-4739+confounding risk factors was 0.94 (95% CI 0.891 to 0.998, P < 0.001), which was higher than that of confounding risk factors (AUC 0.94 vs. 0.91, 95% CI -0.122 to 0.060, P > 0.05) and of miR-4739 (AUC 0.94 vs. 0.69, 95% CI -0.399 to -0.101, P < 0.001), respectively. We conclude that elevated plasma miRNA-4739 levels are independently associated with CLI in T2DM patients. miRNA-4739 is implicated as a novel diagnostic marker and a potential therapeutic target for CLI in diabetes.

Peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1α) is a transcriptional coactivator that regulates energy metabolism and mitochondrial biogenesis. Recently, mitochondrial dysfunction has been indicated as an established risk factor for the development of renal fibrosis. However, whether PGC-1α is involved in the pathogenesis of renal fibrosis is unknown. In this study, we treated NRK-49F (normal rat kidney fibroblast) cells with transforming growth factor-beta 1 (TGF-β1) for 24 h to establish an in vitro fibrosis model. TGF-β1 induced the upregulation of type I collagen, fibronectin, TGF-β receptor I (TGFβ-RI), TGFβ-RII, Smad4, and pSmad2/3, as well as PGC-1α. NRK-49F cells transfected with pcDNA-PGC-1α showed significantly increased expression of fibronectin and type I collagen, as revealed by western blot assay. Interestingly, transfection with PGC-1α-siRNA caused a stark reversal of TGF-β1-induced cellular fibrosis, with concomitant suppression of fibronectin and type I collagen, as revealed by western blot and immunofluorescence assays. Moreover, SB431542 (TGFβ-RI), LY294002 (PI3K/Akt), and SB203580 (p38 MAPK), inhibitors of TGF-β-associated pathways, markedly suppressed TGF-β1-induced PGC-1α upregulation. These results implicate a role of PGC-1α in renal interstitial fibrosis mediated via the TGFβ-RI, PI3K/Akt, and p38 MAPK pathways. Our findings that PGC-1α-siRNA downregulates fibronectin and type I collagen suggest that it can be used as a novel molecular treatment for renal fibrosis.

Fibrosis is the important pathway for end-stage renal failure. Glucose has been demonstrated to be the most important fibrogenesis-inducing agent according to previous studies. Despite diosgenin has been demonstrated to be anti-inflammatory, the possible role in fibrosis regulation of diosgenin remain to be investigated. In this study, renal proximal tubular epithelial cells (designated as HK-2) were treated with high concentration of glucose (HG, 27.5mM) to determine whether diosgenin (0.1, 1 and 10 μM) has the effects to regulate renal cellular fibrosis. We found that 10 μM of diosgenin exert optimal inhibitory effects on high glucose-induced fibronectin expression in HK-2 cells. In addition, diosgenin markedly inhibited HG-induced increase in α-smooth muscle actin (α-SMA) and HG-induced decrease in E-cadherin. In addition, diosgenin antagonizes high glucose-induced epithelial-to-mesenchymal transition (EMT) signals partly by enhancing the catabolism of Snail in renal cells. Collectively, these data suggest that diosgenin has the potential to inhibit high glucose-induced renal tubular fibrosis possibly through EMT pathway.

Because of the lack of generality, the existing data publish/subscribe systems are mostly used in a particular field. In order to satisfy the general support of interdisciplinary model, proposed a general data publish/subscribe model based on DDS. The model supports the configuration and modification of the underlying data types. Simulation results show that the general data publish/subscribe model based on DDS can be well applied in various types of data publish/subscribe occasions.

For the reliability analysis of domain software researching to present a comprehensive reliability analysis method of domain software based on evidence,and to establish the working framework. To form reliability evidence through analyzing and measuring the evidence that collecting from the software lifecycle, and to build up a evaluation mode to expression the reliability requirements;to define reliability degree and mapping method based on evaluation mode, and to describe software reliability by reliability degree; to analysis modeling the reliability based on formal methods, as well as to verification and validation models. The method combined of informal evaluation and formal analysis modeling has good maneuverability and good practicability. It can describe the reliability of domain software clearly, and provide support for constructing complete formal high reliability software.

Time-space-source dynamic controlling sand theory emphasized the size, supply and distribution of the source changes with time and space. Based on this theory, ramp-type, half-graben type and slots, grooves parallel-type sand control modes were established at Surennuoer oil field. According to the attribute maps and the sandstone thickness maps, the sand scope of nantun group can be determined, after identified the sand control point by using the fault throw statistic and 3D visualization technology. Sedimentary facies and the single well integrated histogram were used to verify the accuracy of the sand body divided. The results showed that: the sand control scope divide very accurately,and the sand control scope dovetail nicely with turbidite fan, braided channel and other sand-rich sedimentary facies.

In the paper, the main research topic is product data exchange of each heterogeneous systems in the process of collaborative design and manufacturing under the condition of mass customization.Based on the research for existing technology of product model information sharing and conversion,put forward the solution to combine STEP with XML,completed product data transfer and exchange among web-based cooperation enterprises. Also,it was researched how to express EXPRESS data model to XML, as well as its application in the network environment, the function of converting STEP Part21 physical file to XML file was realized.

In order to examine whether the wheel hub meet the security requirement during its design stage, the 3D model of a wheel hub was built by UG software, on which strength test of the wheel hub was proceeded based on the simulation experimental conditions , and used finite element method to analyse the wheel hub strength. The analysis results are the basis for modifying and lightening wheel hub.The study demostrates that test simulation and analysis to the wheel hub by computer technology can overcome the shortcomings of traditional experience analogy method in which the strength test only can be done after the product is produced. The method improves working efficiency，shortens the product development cycle, reduces costs.

Medical images play a very important role in clinical medicine. They often have the features of low contrast, narrow gray scale and edge blurring between tissues. Aimed at the disadvantages, the paper presents a new medical image enhancement algorithm combining pseudocolor processing and marker-based watershed transform. The new algorithm and traditional pseudocolor processing in frequency domain are implemented using MATLAB, and their effectivity is evaluated by two parameters, mean and entropy. Results show that the proposed enhancement algorithm can improve the visual effect of different types of medical images, especially for the tissues in the low contrast regions in the image. The output image is more suitable for doctor’s diagnosing. The algorithm has been used in the medical image fusion system we developed, and the performance is very satisfactory.

1.1.Background:Renal fibrosis is characterized by interstitial cells hypercellularity and matrix protein accumulation, cause of loss normal function and finally kidney failure. Transforming growth factor-β (TGF-β) is a profibrotic cytokine as a key mediator for Smads pathways. Verbascoside is a pure compound most from Osmanthus spp. In addition, Verbascoside has an antioxidants, anti-inflammatory and immunosuppressive functions. In here, we investigated the underlying mechanism of Verbascoside in the regulation of TGFβ1-induced cellular fibrosis in NRK-49F. 1.2.Materials and Methods:NRK-49F (Rat kidney fibroblast Cells) were cultured in TGF-β1 (5ng/ml) for days. The cells treatment with different concentrations of Verbascoside (0.1mM, 1mM, 10mM) in last 24 hours. The effect of Verbascoside on cell viability in renal fibrosis by MTT test. Here we evaluated the in vitro cytotoxic effect of Verbascoside in renal fibrosis using the LDH release assay. We determined to EMT relevant markers including fibronectin and TGF-β1/Smads transducer including Smad4, Smad2/3 and Smad7 by Western blot assay. The expression of the extracellular fibronectin by ELISA. Results: MTT analysis showed that Verbascoside did not significantly affect levels of cell viability. Treating cells with Verbascoside did not release a significant amount of LDH compared to control. Western blotting showed that Verbascoside dose-dependent reverse TGFβ1-induced expression of fibronectin in NRK49F cells. Immunofluorescence assay showed that Verbascoside (10mM)) reverse TGFβ1-induced expression of fibronectin in NRK49F cells. 1.3.Conclusion:We propose that Verbascoside is a potential fibrosis antagonist for renal cells by TGF-β1/Smads signaling pathway.

Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F cells was dose- and time-dependently increased by the administration of exogenous TSLP (P

Renal fibrosis progresses to end stage of diabetes kidney disease, which causes irreversible progressive proximal tubular injury. In a previous study, 20-hydroxyecdysterone (20-HE), a phytoecdysteroid, attenuated renal injury in diabetes models. However, the fibrosis regulatory role remains to be investigated. Methods: The proximal tubular epithelial cells (designated as HK-2) were treated for 48 h with TGF-β1 (5ng/ml) in different concentrations of 20-HE (0 to 500 nM/ml) in the last 24 h of culture. The extracellular fibronectin was measured by ELISA assay. Western blot and immunofluorescence were used to evaluate the expression of TGF-β1/Smads transducer (including Smad2/3, 4, and 7), epithelial and mesenchymal markers (e.g. E-cadherin and α-smooth muscle actin) and Snail (transcriptional regulators for EMT). Results: 20-HE reverses TGF-β1-induced increase in fibronectin (both intracellular and extracellular fibronectin). Simultaneously, 20-HE reverses TGF-β1-induced down-regulation of Smad7. In addition, 20-HE significantly attenuates TGF-β1-induced upregulation of Smad2/3 and pSmad2/3, and downregulation of E-Cadherin. Moreover, 20-HE dramatically suppresses TGF-β1-induced increases in the expression of Snail. Conclusion: We propose that 20-HE is a potential fibrosis antagonist for renal proximal tubule cells. 20-HE might act through suppressing post-receptor signaling of TGF-β1 and restoring tubule epithelial character by blocking the expression of Snail.

Objective Oleanolic acid (OA) and its glycosides have been reported to prevent bone loss by inhibiting the formation of osteoclasts. However, because bone formation and resorption are balanced processes in bone metabolism, no studies have described the effect of OA on osteogenesis. The aim of the present study was to evaluate the osteoprotective effect of OA in rats with ovariectomy (OVX)-induced osteoporosis and to search for the molecular targets of OA in bone mesenchymal stem cells (bMSCs). Methods Two-month-old female mice that underwent OVX were treated with OA (20 mg/kg a day). After 2 weeks and after 3 months, bone mass was evaluated by micro-CT, morphometry, and immunohistochemical detection. In addition, the expression of 256 genes was measured via microarray and confirmed by real-time reverse transcription-polymerase chain reaction. The effects of OA on the activities of bMSCs were also observed in vitro using alkaline phosphatase and cell proliferation assays. Results Micro-CT displayed only a tendency for bone loss at 2 weeks but a decrease in bone mass at 3 months after OVX. OA treatment increased osteoblast number, increasing osteocalcin and runt-related protein 2 protein levels in vivo and facilitating the osteoblastic differentiation of bMSCs in vitro at doses of 10(-6) and 10(-5) M. Gene expression profile analysis revealed that OVX caused a marked dysregulation of gene expression, especially at 2 weeks, some of which was rescued by OA. Few of these genes overlapped, but their functions were involved in the Notch signaling pathway between two phases of the osteoporotic process. Conclusions OA exerts an osteoprotective effect in OVX-induced osteoporotic rats and stimulates the osteoblastic differentiation of bMSCs in vitro. The molecular mechanism of this effect might be related to the Notch signaling pathway and requires further investigation.

Background Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic condition. Methods Cells were cultured in high glucose (27.5 mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200 ng/ml) was added in the last 24 h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-β 1 . Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail). Results We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-β, TGF-β RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in α-SMA and Snail and decrease in E-cadherin. Conclusion We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway.

Restriction fragment length polymorphism (RFLP) and enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies (mAbs) were used in this study to detect genotypes of HBV, and the efficiency and precision of ELISA using the mAbs for HBV genotype detection were also estimated.The ELISA with mAbs method was used for the detection of HBV genotype in a Taiwanese population. The HBV genotypes of 100 chronic hepatitis B patients were determined by ELISA and were then compared with those obtained using RFLP.Genotype B was found to be the most prevalent in this study (63% by RFLP; 62% by ELISA) followed by genotype C (31% by RFLP; 35% by ELISA). There was no significant difference between the results obtained by RFLP and ELISA (P = 0.75). The ELISA overall genotypeable rate, the correct genotyping rate from genotypeable specimens, and the concordance of the HBV genotyping assay was 96.00, 94.79, and 91.00%; for the ELISA HBV genotyping assay for genotype B specimens was 96.77, 100.00, and 96.77%; and for genotype C specimens was 97.14, 91.18, and 88.57%, respectively. The mean HBV DNA level was higher in the specimens that could be genotyped by both RFLP and ELISA samples (6.24 ± 1.77 vs. 2.34 ± 0.90, log IU/ml), and a significant difference in terms of HBV DNA level of more than 2 × 10(3) IU/ml was identified between the genotyped RFLP samples (P 0.001).ELISA is a practical and a useful method for HBV genotyping in a clinical setting in Taiwan, in particular for patients with lower levels of HBV DNA.

The state-of-art of collaborative hydraulic system design and the necessity to carry on collaborative hydraulic system design are summarized. The architecture and implementation methodology of Web-based collaborative product design system are presented, with some key techniques of implementing collaborative hydraulic system design being discussed in detail.