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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.

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.

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.

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.

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.

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.

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.

Research among Asian users of methylenedioxy methamphetamine (MDMA), also known as Ecstasy, is rare. To evaluate the feasibility of a study on the abuse of and dependence on Ecstasy, two focus groups of users (n= 12) and health professionals (n=7) were conducted in Taiwan. Major results included blatant human testing with "candy and dinosaur girls" and a specific sequence of drugs called a "Trinity" (Ecstasy, ketamine, and marijuana). "Head-shaked bars" and "KTVs" were public places where illegal behaviors were implicitly allowed. Depression after Ecstasy use was not reported. For future studies, participants suggested that magnetic resonance imaging could be a strong incentive for young users to enhance willingness to participate. Cultural issues of Ecstasy use are also discussed.

Diabetic nephropathy is characterized by early hypertrophy in both glomerular and tubuloepithelial elements. However, no studies to date have established a direct causal link between hyperglycaemia and renal hypertrophy. Our previous studies have found that high glucose does not induce cellular hypertrophy or expression of TGF-beta1 (transforming growth factor-beta1) in distal renal tubule cells [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. In the present study, we used AGEs (advanced glycation end-products) to mimic long-term hyperglycaemia. Similar to glucose, AGEs did not induce TGF-beta1 mRNA in distal renal tubule cells [MDCK (Madin-Darby canine kidney) cells]; however, TGF-beta1 bioactivity was increased significantly. This result indicated post-translational regulation. Since TSP-1 (thrombospondin-1) has been demonstrated to activate latent TGF-beta1 in a variety of systems, the following experiments were performed. We found that AGEs dose-dependently increased both intracellular and extracellular levels of TSP-1. Purified TSP-1, like AGEs, increased the cellular protein content. Furthermore, anti-TSP-1 neutralizing antibodies attenuated the AGE-induced increase in TGF-beta1 bioactivity and hypertrophy. Thus TSP-1 might mediate AGE-induced distal renal tubule hypertrophy. In addition, we observed several putative transcription factor binding sites in the TSP-1 promoter, including those for AP-1 (activator protein-1), CREB (cAMP response element binding protein), NF-kappaB (nuclear factor-kappaB), SRF (serum response factor) and HSF (heat-shock factor), by sequence mapping. We used an enhancer assay to screen possible transcription factors involved. We showed that AP-1 and CREB were specifically induced by AGEs; furthermore, TFD (transcription factor decoy) for AP-1 could attenuate the AGE-induced increases in TSP-1 levels and cellular hypertrophy. Thus regulation of TSP-1 might be critical for hyperglycaemic distal tubule hypertrophy. Furthermore, TSP-1 TFD might be a potential approach to ameliorate diabetic renal hypertrophy.

TGF-beta (transforming growth factor-beta) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-beta receptor (TbetaRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. We have elucidated the mechanism by using cultured Madin-Darby canine kidney cells. Enhancer assay and electrophoretic-mobility-shift assay were used to estimate the involvement of transcription factors. Western blotting and an in vitro kinase assay were used to evaluate the level and activity of protein kinase. We showed that glucose (100-900 mg/dl) induced an increase in mRNA level and promoter activity of TbetaRII (note: 'mg/dl' are the units commonly used in diabetes studies). The promoter region -209 to -177 appeared to contribute to positive transactivation of TbetaRII promoter by comparing five TbetaRII-promoter-CAT (chloramphenicol acetyl-transferase) plasmids. Moreover, the transcription factor AP-1 (activator protein 1) was significantly activated and specifically binds to TbetaRII promoter (-209 to -177). More importantly, we found that atypical PKC iota might be pivotal for high glucose-induced increase in both AP-1 binding and TbetaRII promoter activity. First, high glucose induced cytosolic translocation, activation and autophosphorylation of PKC iota. Secondly, antisense PKC iota expression plasmids attenuated high-glucose-induced increase in AP-1 binding and TbetaRII promoter activity; moreover, sense PKC iota expression plasmids enhanced these instead. Finally, we showed that antisense PKC iota expression plasmids might partly attenuate a high-glucose/TGF-beta1-induced increase in fibronectin. We conclude that PKC iota might mediate high-glucose-induced increase in TbetaRII promoter activity. In addition, antisense PKC iota expression plasmid effectively suppressed up-regulation of TbetaRII and fibronectin in hyperglycaemic distal-tubule cells.

Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. NRF-1 is a key transcription factor regulating the function of mitochondria.However, the role of this process in renal fibrosis is unknown. Thus, we hereby discuss the correlations of NRF-1 and renal interstitial fibrosis. Materials and Methods: NRK-49F (Normal Rat kidney fibroblast) cells were used. In vitro fibrosis model was established by treatment with transforming growth factor-b1 (TGF-b1). The fibrogenic marker (e.q. fibronectin) and fibrogenic signal proteins (e.q. pSmad2/3,Smad2/3,Smad7) were investigated. Here, we used that two distinct mechanisms regulate NRF1 activition and degradation of NRF1. NRF-1 was transfect by NRF-1 overexpression gene to evaluate NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by NRF-1 shRNA to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Western blot was used to examine the intracellular fibrogenic signal proteins (e.q. pSmad2/3,Smad2/3,Smad7). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin). Results: Our study demonstrated that expression of NRF-1 is significantly decreased in renal fibrosis. However, transfection with pcDNA-NRF-1 (2mg/mL) expression vector did dramatically reverse TGF-b1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin) and fibrogenic signal protein. Intriguingly, NRF-1 shRNA dramatically increased TGF-b1-induced cellular fibrosis. Collectively, 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.

Hemoglobin A1c (HbA1c) is used for the long-term management of patients with diabetes mellitus (DM) (1)(2). Hb variants other than HbA1c and e-N-lysine-glycated Hb A may cause analytical interference in determinations of HbA1c (3)(4)(5)(6). In one study, the authors estimated the prevalence of thalassemia in Taiwan as 7%; moreover, ∼1% of the people in northern Taiwan are β-thalassemia heterozygotes (7). The occurrence of 24 abnormal Hbs (13 α-chain variants and 11 β-chain variants), including Hb G-Taipei, in populations in the Silk Road area of Northwestern China has been presented in a review (8). The frequency of thalassemia has been estimated to be ∼1 in 2350 in Japan (9) and even higher in North Africa (10). Hb E is the second most prevalent Hb variant worldwide and the third most prevalent variant in the US, after Hb S and C. Hb E is found primarily in Southeast Asia, especially among the Thai population (11). In the northeastern region of India, the gene frequency of Hb E is 10.9% (12). In a study of 222 000 blood samples in Canada, 23 cases of Hb J were identified (13). Given that the majority of hemoglobinopathic cases are from families of Asian, Southeast …

Osteoarthritis (OA) is the most common form of joint disease. OA frequently affects knees, hips, hands, and the spine. It is characterized by the progressive destruction of articular cartilage and subchondral bone accompanied by low-grade inflammation that together result in pain and deformity. Recent studies have shed light on the nature of OA genetic susceptibility and confirmed a number of candidate genes involved in the destruction of the synovium, articular cartilage, and subchondral bone in OA pathogenesis. During the progression of OA, there are several cellular changes in joints, including an increase in the number of activated osteoclasts and macrophages and an infiltration of the synovium by activated T-cells and B-cells. Pro-inflammatory mediators (e.g. interleukin IL-1, IL-1beta, IL-6, IL-17, and IL-18, and Tumor necrosis actor-alpha), proteinases (e.g. matrix metalloproteinase 9 and cathepsin K), and regulators of cartilage and bone formation (e.g. BMPs) have been shown to have important roles in OA progression at the molecular level. Studies have suggested that OA shares several common characteristics with rheumatoid arthritis (RA). To systematically understand OA, this review summarizes OA disease genes, mouse models of human disease experimental mouse models, mechanisms of OA pathogenesis, and current OA therapies.

Icariin (ICA) is an active component of Herba Epimedium effective in preventing osteoporosis. Bone mesenchymal stem cells (bMSCs) are an important target by which ICA promotes osteogenesis. However, its molecular mechanisms are poorly defined. In the present study, we induced osteoporosis in rats by corticosterone (CORT) and ovariectomy (OVX), treated both with ICA for 2 weeks or 3 months. As results, both models displayed bone loss tendency within 2 weeks and a significant bone loss after 3 months. ICA promoted bMSCs diffenentiation from CORT rat, and increased the secretion of osteocalcin, collagen I, runt-related transcription factor 2 in OVX model. Gene profile revealed a marked shift of gene expression by ICA, with much more significance in CORT rats. These potential molecular targets were involved in cell communication, adhesion, cycle and cytokines secretion. But very few genes overlapped in these two models, suggesting the effects and molecular mechanisms of ICA on osteoporosis might be pathogenesis-dependent. However, the Notch signaling pathway was common in both models, and should be paid close attention to for further study.