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        Neuroprotective potential of imatinib in global ischemiareperfusion- induced cerebral injury: possible role of Janus-activated kinase 2/signal transducer and activator of transcription 3 and connexin 43

        Jieying Wang,Taomin Bai,Nana Wang,Hongyan Li,Xiangyang Guo 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.1

        The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusioninduced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion- induced cerebral injury, which may be possibly attributed to activation of JAK2/ STAT3 signaling pathway along with the increase in the expression of connexin 43.

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        Research on metal flow law of micro-riblets based on multi-pass rolling

        Xujie Gao,Huihang Wang,Guangming Zhu,Zheng Chang,Nana Guo,Zongshen Wang,Lihua Zhu 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.5

        Micro-riblets (grooves) can reduce surface friction in turbulent flow by up to 10 %. Furthermore, roll forming is an effective method for manufacturing large-area groove structures. In this study, the fluidity of metal during the multi-pass rolling of microgrooves was studied, and the reason for the accumulation of materials at the end of rolling was explained. A comparative analysis was conducted between single-pass rolling and multi-pass rolling. Then, according to the distribution of stress field and strain field, the force and flow tendency of the metal during rolling were studied. The gradually changing streamlined roller tooth profile promoted the flow of metal to both sides of the gear hob. Given the same reduction, the forming height of micro-grains during multi-pass rolling was 64.2 % higher than that during single-pass rolling.

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        Self-bending extrusion molding of distorted channels

        Fanlei Min,Huiping Liu,Guangming Zhu,Zheng Chang,Xujie Gao,Bowen Yue,Nana Guo,Xiaoqing Zhai 대한기계학회 2021 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.35 No.5

        Using an integrated profile extrusion and bending forming process with a streamlined extrusion die, a new self-bending extrusion molding technology is proposed with an axis-distorted variable channel. By designing the streamlined extrusion die structure of the distorted central axis, the metal was made to flow non-uniformly in the die cavity, thereby directly extruding a bent profile. The central axis of the streamlined extrusion die is described by a trigonometric function and a Gaussian function. A numerical simulation was applied to analyze the metal flow pattern, equivalent strain, and strain-rate distribution during the self-bending extrusion process. The influences of the extrusion velocity and the addition of a bearing on the self-bending deformation profiles were investigated. During the extrusion process, the streamline at the center of the billet could describe the overall flow of the metal in the die cavity, and the distance between the point on the end face of the die outlet and the center of the die outlet directly determined the degree of extrusion and bending. The greater the distance was, the larger was the degree of bending. The metal strain on the convex edge of the die was greater than that on the concave edge of the die, with the extruded profile always bending toward the concave edge. The strain rate of the metal changed the fastest near the most convex point of the die. As the extrusion velocity increased or more bearings were added, the radius of curvature of the extruded profile increased nonlinearly.

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        IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

        Liang Li,Zhang Fengmei,Feng Naibo,Kuang Biao,Fan Mengtian,Chen Cheng,Pan Yiming,Zhou Pengfei,Geng Nana,Li Xingyue,Xian Menglin,Deng Lin,Li Xiaoli,Kuang Liang,Luo Fengtao,Tan Qiaoyan,Xie Yangli,Guo Fen 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

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