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Aiming at the problem that students lack business practice participation in different industries in production management experimental teaching, we put forward a production management experimental teaching platform which integrates multiple industry data sources. The platform separats the system database from multiple business database and constructs a multi-level platform service technology architecture. The platform is constructed by using SaaS (Software as a Service) model. Using the workflow technology to complete templated business process modeling, it implements the whole process simulation of enterprise production management, and involves multiple industries and roles. Finally, we verify the feasibility and applicability of production management experimental teaching platform by taking motor manufacturing industry as an example. [ABSTRACT FROM AUTHOR]

Abstract: Calcium-dependent mechanisms, particularly those mediated by Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs. [Copyright &y& Elsevier]

Abstract: To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of α-tubulin, β-tubulin and β-actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, α-tubulin, β-tubulin and β-actin contents remain unchanged. A significant positive correlation (R =0.9427, P <0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD. [Copyright &y& Elsevier]

Abstract: Occupational exposure to n-hexane produces a neuropathy characterized as a central-peripheral distal axonopathy, which is mediated by 2,5-hexanedione (HD). To investigate the mechanisms of the neuropathy induced by HD, the contents and activities of cyclin-dependent kinase 5 (CDK5) and activators (p35 precursor, p35 and p25) in rats’ cerebrum cortex (CC), spinal cord (SC) and sciatic nerve (SN) were determined. The results showed that the levels and activities of CDK5 in CC of 200 or 400mg/kg HD-treated rats were significantly decreased in both the cytosolic and membrane fractions and negatively correlated with gait abnormality in the cytosolic fraction. However, CDK5 contents and activities in SN of rats treated with 200 or 400mg/kg HD were significantly increased and positively correlated with gait abnormality in both the cytosolic and membrane fractions. Although increases of CDK5 contents in both the cytosolic and membrane fractions of SC in 200 and 400mg/kg HD-treated rats were also observed, CDK5 activities were significantly decreased in the cytosolic fraction and negatively correlated with gait abnormality. The changes of p35 precursor, p35 and p25 contents in CC, SC and SN showed the same pattern with that of CDK5 activities. Thus, HD intoxication was associated with deregulation of CDK5 and its activator p35 or p25 in nerve tissues. The inconsistent changes of CDK5 activities in CNS and PNS might delegate the different mechanisms of HD-induced peripheral neuropathy. [Copyright &y& Elsevier]

• The neurotrophic effect of FLZ on dopaminergic neurons is mediated by astroglia. • GDNF released from astroglia is crucial for the neurotrophic effect of FLZ. • PI3K/Akt/CREB signaling triggers GDNF production in response to FLZ treatment. • The induction of GDNF by FLZ contributes to its neuroprotection on PD. Glial cell line-derived neurotrophic factor (GDNF) has neurotrophic activity for the survival of dopaminergic neurons, which is under active investigation for Parkinson's disease (PD) therapy. FLZ is a potential new drug for PD treatment. However, it is unclear whether neurotrophic activity contributes to the neuroprotective effects of FLZ. Here we found that FLZ markedly improved the function of dopaminergic neurons in primary mesencephalic neuron/glia cultures. Further investigation demonstrated that astroglia were required for FLZ to function as a neurotrophic regulator, as FLZ failed to show neurotrophic effects in the absence of astroglia. We clarified that GDNF was responsible for the neurotrophic effects of FLZ since FLZ selectively stimulated GDNF production, which was confirmed by the finding that the neurotrophic effect of FLZ was attenuated by GDNF-neutralizing antibody. Mechanistic study demonstrated that GDNF induction by FLZ was CREB-dependent and that PI3K/Akt was the main pathway regulating CREB activity, which was confirmed by in vivo studies. We also validated that the induction of GDNF by FLZ contributed to PD treatment in vivo. In conclusion, the present data provided evidence that FLZ had robust neurotrophic effects on dopaminergic neurons through sustained induction of GDNF in astroglia by activating the PI3K/Akt/CREB pathway. [ABSTRACT FROM AUTHOR]

Abstract: Allyl chloride (AC) is widely used in industries as raw material and has been reported to produce occupational peripheral neuropathies in man chronically exposure to it. Although many studies have been done addressing to it, the mechanisms still remain unclear. To elucidate the molecular mechanism of neuropathy induced by AC, we measured the contents of glutathione (GSH), Bcl-2, Bax, cytochrome c (CytC) and Caspase-3 in a time-dependent manner by biochemical and quantitative immunoblotting techniques in rats’ cerebrum and spinal cord after 3, 6, 9 and 12 weeks of AC intoxication. The results showed that the levels of Bcl-2 of cerebrum and spinal cord significantly (P <0.05) decreased after 9 and 6 weeks of AC intoxication, respectively, while GSH levels decreased after 12 week. However, the levels of Bax, CytC and Caspase-3 significantly (P <0.05) increased both in cerebrum and spinal cord. Bax levels of cerebrum and spinal cord increased after 12 and 9 weeks of AC administration, respectively. The levels of CytC and Caspase-3 also went up after 9 weeks of AC treatment in cerebrum and 9, 6 weeks in spinal cord, respectively. Thus, subchronic exposure to AC affected the expressions of apoptotic-related proteins in the central nervous system (CNS) and peripheral nervous system (PNS) tissues and the time dependent changes of these indexes occurred. The regulatory mechanism of apoptosis might be involved and served as one of mechanisms of toxic neuropathy induced by AC. [Copyright &y& Elsevier]

Objective: To explore the role of cyclin dependent kinase 5 (CDK5) in 2, 5-hexanedione (HD)-induced neuropathy., Methods: Thirty male Wistar rats weighted 200 approximately 240 g were divided randomly into three groups, i.e. control group, 200 mg/kg HD group and 400 mg/kg HD group (n = 10 for each group). HD was administered to rats by intraperitoneal injection at dosage of 200 or 400 mg/kg for 8 weeks (five times per week) to establish the intoxicated rats model. The relative contents of CDK5, p35 and p25 were determined in cerebrum, spinal cord and sciatic nerve of rats by Western Blotting., Results: Compared with that of the control group rats, p35 contents were significantly decreased (P < 0.01) in the cytosolic fractions of cerebrum and spinal cord in both the 200 and 400 mg/kg HD intoxicated rats, while in the membrane fractions of spinal cord and sciatic nerve, p35 contents were increased significantly (P < 0.01). The changes of p25 showed the same pattern with p35. P25 contents were significantly reduced (P < 0.05) in the cytosolic (cerebrum and spinal cord) and membrane (cerebrum) fractions of both HD-treated rats and were elevated (P < 0.01) in the membrane fraction of spinal cord and cytosolic fraction of sciatic nerve. The relative amounts of CDK5 were significantly decreased (P < 0.01) in the cytosolic and membrane fractions of cerebrum in both the 200 and 400 mg/kg HD intoxicated rats. Except for membrane fraction of sciatic nerve, the significant increased (P < 0.01) of CDK5 were observed in the spinal cord and sciatic nerve of both the 200 and 400 mg/kg HD treated rats., Conclusion: HD can induce significant changes of CDK5 and its activators p35, p25 in nerve tissues, which may be related to the neuropathy induced by HD.