Purpose -The purpose of this paper is to address "how Toyota can continuously and consistently achieve its dramatic success through its competences -continuous waste elimination and the objective of long term philosophy"; the paper aims to summarize some solid suggestions and comprehensive ideas for those industries planning to implement lean production. Design/methodology/approach -The methodology used is the case based approach (CBA), which described lean supply chain (LSC) through value stream mapping (VSM) using a case study from the Ford Motor Company in Chung Li, Taiwan. The paper follows a four-step problem solving process to demonstrate how lean supply chain affects product cost and quality. Findings -Using VSM case study to demonstrate LSC, all the measurable indices helpful for cost reduction, quality enhancement and lead time reduction are shown. The paper also provides some recommendations and basic principles to implement VSM successfully through P-D-C-A improving cycle.Research limitations/implications -Since a comprehensive demonstration of VSM implementation is likely to be both expensive and timeconsuming, this study provides a case study from the Ford Motor Company in Taiwan. Practical implications -VSM through lean process is considered to be one of the best practices in supply chain management. It has been shown to be successful for implementing lean production in Toyota Production System (TPS). However, other competitors struggle despite adopting similar principles. It seems that there is a special ingredient within TPS that Toyota's competitors do not fully comprehend. Originality/value -This paper not only shows the value of VSM as a supply chain tool in implementing lean production; but also provides industrial insight for enterprising companies to follow a four-step problem-solving process to effectively develop their lean supply chain.
Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)–polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe
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nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a
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-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers.
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