Tight Junctions (TJ) are important components of paracellular pathways, and their destruction enhances vascular permeability. Resolvin D1 (RvD1) is a novel lipid mediator that has treatment effects on inflammatory diseases, but its effect on inflammation induced increase in vascular permeability is unclear. To understand whether RvD1 counteracts the lipopolysaccharide (LPS) induced increase in vascular cell permeability, we investigated the effects of RvD1 on endothelial barrier permeability and tight junction reorganization and expression in the presence or absence of LPS stimulation in cultured Human Vascular Endothelial Cells (HUVECs). Our results showed that RvD1 decreased LPS-induced increased in cellular permeability and inhibited the LPS-induced redistribution of zo-1, occludin, and F-actin in HUVECs. Moreover, RvD1 attenuated the expression of IκBα in LPS-induced HUVECs. The NF-κB inhibitor PDTC enhanced the protective effects of RvD1 on restoration of occludin rather than zo-1 expression in LPS-stimulated HUVECs. By contrast, the ERK1/2 inhibitor PD98059 had no effect on LPS-induced alterations in zo-1 and occludin protein expressions in HUVECs. Our data indicate that RvD1 protects against impairment of endothelial barrier function induced by LPS through upregulating the expression of TJ proteins in HUVECs, which involves the IκBα pathway but not the ERK1/2 signaling.
Concurrent engineering has been widely accepted as a viable strategy for companies to reduce time to market and achieve overall cost savings. This article analyzes various risks and challenges in product development under the concurrent engineering environment. A three-dimensional early warning approach for product development risk management is proposed by integrating graphical evaluation and review technique (GERT) and failure modes and effects analysis (FMEA). Simulation models are created to solve our proposed concurrent engineering product development risk management model. Solutions lead to identification of key risk controlling points. This article demonstrates the value of our approach to risk analysis as a means to monitor various risks typical in the manufacturing sector. This article has three main contributions. First, we establish a conceptual framework to classify various risks in concurrent engineering (CE) product development (PD). Second, we propose use of existing quantitative approaches for PD risk analysis purposes: GERT, FMEA, and product database management (PDM). Based on quantitative tools, we create our approach for risk management of CE PD and discuss solutions of the models. Third, we demonstrate the value of applying our approach using data from a typical Chinese motor company.
Incorporating the impact of the COVID-19 pandemic on the mask supply chain into our framework and taking mask output as a state variable, our study introduces the differential game to study the long-term dynamic cooperation of a two-echelon supply chain composed of the supplier and the manufacturer under government subsidies. The study elaborates that government subsidies can provide more effective incentives for supply chain members to cooperate in the production of masks compared with the situation of no government subsidies. A relatively low wholesale price can effectively increase the profits of supply chain members and the supply chain system. The joint contract of two-way cost-sharing contract and transfer payment contract can promote production technology investment efforts of the supply chain members, the optimum trajectory of mask production, and total profit to reach the best state as the centralized decision scenario within a certain range. Meanwhile, it is determined that the profits of supply chain members in the joint contract can be Pareto improvement compared with decentralized decision scenario. With the increase of production technology investment cost coefficients and output self-decay rate, mask outputs have shown a downward trend in the joint contract decision model. On the contrary, mask outputs would rise with growing sensitivity of mask output to production technology investment effort and increasing sensitivity of mask demand to mask output.
As the backbone for the treatment of patients with coronavirus disease 2019 (COVID-19), nurses have been playing key roles in cabin hospitals, isolation wards, and intensive care units for critical cases. Anesthesia nurses have their own professional specialties, such as airway management, the use and maintenance of life support equipment, including ventilators, and the use of high-flow oxygen equipment. With rich experience in emergency responses and nursing, anesthesia nurses, along with emergency nurses and critical care nurses, play important roles during the treatment of patients with COVID-19. In our hospital, 27 of 34 anesthesia nurses participated in the front-line fight against COVID-19 and did an excellent job. Anesthesia care by nurses is relatively new in China, and the role of anesthesia nurses during a disaster response has not been fully appreciated. Given their specialty, anesthesia nurses have played important roles in the treatment of patients with COVID-19. We hope that authorities will consider including anesthesia nurses in national disaster response medical rescue teams.
CXCL14 is a relatively novel chemokine with a wide spectrum of biological activities. The present study was designed to investigate whether CXCL14 overexpression attenuates sepsis-associated acute kidney injury (AKI) in mice. Sepsis model has been established by cecal ligation and puncture (CLP). CLP induced AKI in mice as assessed by increased renal neutrophil gelatinase-associated lipocalin (NGAL) expression and serum creatinine levels. We found that renal CXCL14 expression in the kidney was significantly decreased at 12 hours after CLP. Correlation analysis demonstrated a negative association between renal CXCL14 expression and AKI markers including serum creatinine and renal NGAL. Moreover, CXCL14 overexpression reduced cytokine (TNF-α, IL-6, and IL-1β) production and NGAL expression in the kidney and decreased serum creatinine levels. In vivo and in vitro experiments found that CXCL14 overexpression inhibited M1 macrophage polarization but increased M2 polarization. Together, these results suggest that CXCL14 overexpression attenuates sepsis-associated AKI probably through the downregulation of macrophages-derived cytokine production. However, further studies are required to elucidate the underlying mechanism.
Janus kinase 2/signal transducer and activators of transcription 1 (JAK2/STAT1) signaling is a common pathway that contributes to numerous inflammatory disorders, including different forms of acute lung injury (ALI). However, the role of JAK2/STAT1 in ventilator-induced lung injury (VILI) and its underlying mechanism remain unclear. In this study, using lipopolysaccharide (LPS) inhalation plus mechanical ventilation as VILI mouse model, we found that the administration of JAK2 inhibitor AZD1480 markedly attenuated lung destruction, diminished protein leakage, and inhibited cytokine release. In addition, when mouse macrophage-like RAW 264.7 cells were exposed to LPS and cyclic stretch (CS), AZD1480 prevented cell autophagy, reduced apoptosis, and suppressed lactate dehydrogenase release by downregulating JAK2/STAT1 phosphorylation levels and inducing HMGB1 translocation from the nucleus to the cytoplasm. Furthermore, HMGB1 and STAT1 knockdown attenuated LPS+CS-induced autophagy and apoptosis in RAW 264.7 cells. In conclusion, these findings reveal the connection between the JAK2/STAT1 pathway and HMGB1 translocation in mediating lung inflammation and cell death in VILI, suggesting that these molecules may serve as novel therapeutic targets for VILI.
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