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PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1
Chen, Gang,Kim, Yong Ho,Li, Hui,Luo, Hao,Liu, Da-Lu,Zhang, Zhi-Jun,Lay, Mark,Chang, Wonseok,Zhang, Yu-Qiu,Ji, Ru-Rong NATURE AMERICA 2017 NATURE NEUROSCIENCE Vol.20 No.7
<P>Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia. Mice lacking Pd1 (Pdcd1) exhibited thermal and mechanical hypersensitivity. PD-1 activation in DRG nociceptive neurons by PD-L1 induced phosphorylation of the tyrosine phosphatase SHP-1, inhibited sodium channels and caused hyperpolarization through activation of TREK2 K+ channels. PD-L1 also potently suppressed nociceptive neuron excitability in human DRGs. Notably, blocking PD-L1 or PD-1 elicited spontaneous pain and allodynia in melanoma-bearing mice. Our findings identify a previously unrecognized role of PD-L1 as an endogenous pain inhibitor and a neuromodulator.</P>
Chen Sheng-tao,Li Dong-ju,Tian Hao,Hou Jiao-yi,Ning Da-yong,Gong Yong-jun 대한조선학회 2022 International Journal of Naval Architecture and Oc Vol.14 No.1
Maneuverability, which is closely related to navigation safety, is an important part of the overall performance of an underwater vehicle. The purpose of this study is to analyze the dynamic response of an underwater vehicle to internal waves at different angles and speeds. A combination of experiments and numerical simulations is used to compare the forces on the underwater vehicle. In terms of fluidstructure coupling, the internal wave interface is tracked by the VOF method. In this paper, waves of the same amplitude ratio as the numerical results are simulated using a wave-making sphere. The validity of the numerical method is verified by comparing with the rotation moment test of the underwater vehicle. The results show that different angles of attack have significant effects on the forces and moments of the underwater vehicle and that choosing the right angle of attack and rotation speed can limit the dangerous depth. The conclusion is of certain significance for the safety of underwater navigation.
New Therapeutic Schedule for Prostatic Cancer-3 Cells with ET-1 RNAi and Endostar
Zhang, Hao-Jie,Qian, Wei-Qing,Chen, Ran,Sun, Zhong-Quan,Song, Jian-Da,Sheng, Lu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23
Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment. Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.
Observation of multi-channel non-local transport in J-TEXT plasmas
Shi, Yuejiang,Chen, Zhongyong,Yang, Zhoujun,Shi, Peng,Zhao, Kaijun,Diamond, Patrick H.,Kwon, JaeMin,Yan, Wei,Zhou, Hao,Pan, Xiaoming,Cheng, Zhifeng,Chen, Zhiping,Yang, SeongMoo,Zhang, Chi,Li, Da,Dong, IOP 2018 Nuclear fusion. Fusion nucléaire. &n.Illiga Vol.58 No.4
<P>In cold pulse experiments in J-TEXT, not only are rapid electron temperature increases in the core observed, but also steep rises in the inner density are found. Moreover, some evidence of acceleration of the core toroidal rotation is also observed during the non-local transport process of electron temperature. These new findings of cold pulse experiments in J-TEXT suggest that turbulence spreading is a possible mechanism for the non-local transport dynamics.</P>
Preparation and Properties of the Fast-Curing γ-Ray-Shielding Materials Based on Polyurethane
Minxuan Ni,Xiaobin Tang,Hao Chai,Yun Zhang,Tuo Chen,Da Chen 한국원자력학회 2016 Nuclear Engineering and Technology Vol.48 No.6
In this study, fast-curing shielding materials were prepared with a two-component polyurethane matrix and a filler material of PbO through a one-step, laboratory-scale method. With an increase in the filler content, viscosity increased. However, the two components showed a small difference. Curing time decreased as the filler content increased. The minimum tack-free time of 27 s was obtained at a filler content of 70 wt%. Tensile strength and compressive strength initially increased and then decreased as the filler content increased. Even when the filler content reached 60 wt%, mechanical properties were still greater than those of the matrix. Cohesional strength decreased as the filler content increased. However, cohesional strength was still greater than 100 kPa at a filler content of 60 wt%. The γ-ray-shielding properties increased with the increase in the filler content, and composite thickness could be increased to improve the shielding performance when the energy of γ-rays was high. When the filler content was 60 wt%, the composite showed excellent comprehensive properties.
( Wen-tao Yan ),( Jia-he Wang ),( Ming-da Wang ),( Zheng Wang ),( Bing Quan ),( Ya-hao Zhou ),( Wei-min Gu ),( Hong Wang ),( Ting-hao Chen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: According to the BCLC treatment guidelines, surgery does not be recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/ advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: He statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.
Wuxiao, Zhi-Jun,Zhou, Hai-Yan,Wang, Ke-Feng,Chen, Xiao-Qin,Hao, Xin-Bao,Lu, Yan-Da,Xia, Zhong-Jun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2
Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.