Background Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small ...cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Methods First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied. Results High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs. Conclusions Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment. Keywords: CD151, Integrins, EGFR/ErbB2, Proliferation, NSCLC
Purpose
Tumor metastasis significantly impacts the prognosis of non-small cell lung cancer (NSCLC) patients, with lymph node (LN) metastasis being the most common and early form of spread. With the ...development of adjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes（TDLN) in early-stage NSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but has potential benefits in adjuvant treatment.
Methods
We showed the remodeled immune environment in TDLNs through using TCR-seq to analyse 24 primary lung cancer tissues and 134 LNs from 24 lung cancer patients with or without LN metastasis. Additionally, we characterized the spatial profiling of immunocytes and tumor cells in TDLNs and primary tumor sites through using multi-IHC.
Results
We found the remodeled immune environment in TDLNs through analyzing primary lung cancer tissues and LNs from NSCLC patients with or without LN metastasis. Considering the intricate communication between tumor and immunocytes, we further subdivided TDLNs, revealing that metastasis-negative LNs from LN-metastatic patients (MNLN) exhibited greater immune activation, exhaustion, and memory in comparison to both metastasis-positive LNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN).
Conclusions
Our data indicate that LN metastasis facilitated tumor-specific antigen presentation in TDLNs and induces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs through multiple mechanisms. These findings contribute to a comprehensive understanding of the immunological mechanisms through which LN metastasis influences tumor progression and plays a role in immunotherapy for NSCLC patients.
AIM: This study aims at exploring the distribution of TCM syndromes in CHB patients with HBV pre-core mutation (1896) and the relationship between pre-core mutation and T lymphocytes subgroup, ...through which to provide objective data on clinical syndrome differentiation of TCM, and further to suggest the therapeutic principle and guide clinical treatment. METHODS: One hundred and forty CriB patients were evenly divided into two study groups, HBV pre-core mutant group and HBV pre-core wild-type group. Besides, 30 healthy blood donors were selected as a healthy control group. HBV-labeled compound, T lymphocytes subgroup, and HBV-DNA pre-core mutant were tested in the study groups. T lymphocytes subgroup were also tested in the control group. All the patients were both diagnosed by syndrome differentiation of TCM and western medicine. RESULTS: The most common syndrome in mutant group was damp-heat combined with blood stasis, and the most common syndrome in the wild-type group was dampheat stasis in the middle-jiao. There were more cases of medium and severe hepatitis in mutant group than that in wild-type group. The content of CD4+ lymphocytes and CD4+/CD8+ ratio were decreased gradually (healthy control group>wild-type group>mutant group). In the wild-type group, severe and medium CriB patients had considerably lower level of them than mild CriB patients. However, in the mutant group, the opposite result appeared. Meanwhile, the content of HBV-DNA in mutant group was higher than that in wild-type group. CONCLUSION: Damp, heat, toxin and blood stasis were the basic pathogens of CriB, whether pre-core mutant or not. CriB with precore mutant may lead to more severe hepatitis. The decreased content of CD4+ lymphocytes and ratio of CD4+/CD8+ may be taken as one of the indices in confirming the deficiency syndrome of CriB patients with pre-core mutation.
The aim of this study was to investigate the cellular toxicity of copper-induced injury to the black tiger shrimp Penaeus monodon. The 24h, 48h, 72h and 96h LC50 (median lethal concentration) of Cu2+ ...on P. monodon (11.63±1.14g) were found to be 3.49, 1.54, 0.73 and 0.40mgL−1, respectively. Total haemocyte count (THC), phagocytic activity, respiratory burst (RB), cytoplasmic free-Ca2+ (cf-Ca2+) concentration and apoptotic cell ratio of shrimp were determined after exposure to different concentrations of Cu2+ (0, 0.05, 0.5, 1.5 and 3.5mgL−1) for 0, 6, 12, 24 and 48h. There was no significant effect on the analytic indicator of shrimp exposed to 0.05mgL−1 Cu2+. THC decreased after Cu-exposure to 0.5mgL−1 for 48h, 1.5mgL−1 for 24h and 3.5mgL−1 for 12h. Phagocytic activity decreased in P. monodon following 48h exposure to 3.5mgL−1 Cu2+. RB was induced after 6h exposure to 0.5, 1.5 and 3.5mgL−1 Cu2+. cf-Ca2+ concentration increased after 48h exposure to 0.5mgL−1 Cu2+, and 12h exposure to 1.5 and 3.5mgL−1 Cu2+. The percentage of apoptotic cells increased to 9.5%, 16.3% and 18.6% respectively following 48h exposure to 0.5, 1.5 and 3.5mgL−1 Cu2+. These results indicate that Cu can induce oxidative stress, elevation of cf-Ca2+ and cell apoptosis, and inhibit phagocytic activity in the shrimp P. monodon, and the lethal injury of Cu2+ to P. monodon may be mainly due to the sharp reduction of THC caused by ROS-induced apoptosis.
In this paper, eight different SRAM cells are studied and evaluated with a 65nm CMOS technology. The cells were designed with radiation-hardening-by-design approaches including schematic and layout ...techniques. The eight types of cells were placed into eight pages of an SRAM test chip. The alpha and proton irradiation demonstrated that the Dual Interlocked Cell (DICE) has the best radiation-tolerant performance, but requires the largest area. The 6T and 11T cells designed with charge cancellation techniques can reduce soft errors up to 2-3 times with less area overhead. Several DICE variants were developed with reduced area overhead and showed SEU resilience performance equivalent to DICE. Simulation results are also presented in this paper to validate the findings.
Significant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory ...characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.
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•Sensory histology showed high grade HPBT had high pekoe, fresh aroma and umami.•Key flavor metabolites of different grades of HPBT were identified.•Correlation analysis revealed linalool, geraniol and nonanal contributed to aroma score.
In order to realize the wide speed range of the sensorless control for permanent magnet synchronous motor (PMSM), a composite control strategy of I/f startup control combined with the sliding mode ...observer (SMO) control is proposed. In low-speed region, I/f control with speed open loop and current closed loop is adopted. The rotor is accelerated from standstill to a certain speed by following gradually increasing frequency. In high-speed region, the SMO is used to achieve sensorless control, where the saturation function is adopted to decrease the chatter. When the rotor speed reaches the target value, the smooth transition of the two control strategies is achieved by designing a proper transition status. As a result, the experimental results verify that the sensorless control system can work reliably and stably with smooth switching transition and good control performance.
Objective:
The purpose of this study was to explore the effect of sacubitril-valsartan on rats with acute myocardial infarction.
Methods:
Sprague-dawley rats were randomly divided into six groups. ...Rats in Group A and B were threaded without deligation and treated with valsartan (34 mg/kg) or sacubitril-valsartan (68 mg/kg) after operation. Rats in Group C and D were given the two drugs (34 mg/kg, 68 mg/kg) after ligation of the left anterior descending branch for 40 minutes. Rats in Group E and F were restored the blood of the coronary artery after ligation, and given the two drugs (34 mg/kg, 68 mg/kg) at the same time. N-terminal pro-brain natriuretic peptide, high sensitivity troponin T, aldosterone and Cyclic guanosine monophosphate were measured and Color Doppler echocardiography was performed. Six weeks later, the rats were killed, the hearts were weighed and stained with Masson staining.
Results:
Compared with Group A and B, the levels of N-terminal pro-brain natriuretic peptide, high sensitivity troponin T, aldosterone and Cyclic guanosine monophosphate in other groups were significantly increased (p < 0.05). Before treatment, the left ventricular end diastolic diameter and left ventricular end systolic diameter were similar in each group. After treatment, the levels of left ventricular end diastolic diameter and left ventricular end systolic diameter, and collagen fiber range stained with blue in other groups were significantly increased in comparison with Group A and B (p < 0.05). In addition, the left ventricular volume and collagen fiber range stained with blue were notably decreased, the levels of ejection fraction (EF) were increased in sacubitril-valsartan groups in comparison with valsartan groups (p < 0.05).
Conclusion:
Early application of sacubitril-valsartan has a protective effect on rats with acute myocardial infarction.
Recent clinical studies have reported that some cytokines are associated with lung cancer prognosis and mortality. However, the relationship between cytokines and clinical outcomes in severe lung ...cancer patients was unclear. IL-6 as an important cytokine in inflammation, expression level in severe lung cancer patients was unknown.
A cohort of 55 severe lung cancer patients were enrolled retrospectively in this study. The clinical characteristics, including performance status (PS), therapeutic effect, and patients' adverse effects, were recorded. The association of cytokines and the concerned clinical outcomes were assessed by logistic regression analysis. The area under the curve (AUC) was assessed to evaluate the strength of prediction.
The mean age of the patients was 59.8, and 42 patents were males. Increased IL-6 levels were associated with worse PS. Logistic regression analysis demonstrated that higher IL-6 was associated with an increased risk of progressive disease (PD) (OR =1.03, 95% CI: 1.0-1.06). The area under the ROC curve (AUC) of the model used for predicting PD was 0.821.
Increased IL-6 levels are correlated with worse PS and are an essential predictor for PD in severe lung cancer patients. Monitoring the IL-6 level may represent an essential strategy in improving the prognosis of patients with severe lung cancer.
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