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Initially discovered in chronic viral infection and then extended to tumor, 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation. By definition, whether T-cell exhaustion occurs in diffuse large B-cell lymphoma (DLBCL) remains largely unknown because little has been described. Here, the immune-suppressing checkpoint molecules involved in T-cell exhaustion, including PD-1, PD-L1, TIM-3 and TIGIT, whose expression levels were analyzed in DLBCL, were retrieved from the GEPIA database. Compared with the normal control, CD8A, TNFA, IFNG and GZMA were markedly elevated in DLBCL, indicating that infiltrated CD8+ T cells predominate in DLBCL. Meanwhile, inhibitory immune checkpoints, such as PD-1, PD-L1, TIGIT and TIM-3 were drastically higher in DLBCL. PTEN, WNT2 and DKK3 expression were also appraised. It was revealed that PTEN was lower in DLBCL, without being statistically significant. In contrast with PTEN, DKK3 and WNT2 were shown to be pronouncedly higher in DLBCL relative to the normal control. Prognostically, only TIGIT was found to be associated with overall survival in DLBCL. Collectively, all the data we curetted from the GEPIA and TIMER 2.0 databases explicitly indicate that CD8+ T cell exhaustion took place, which may be linked with lower PTEN in DLBCL. To the best of our knowledge, this is the first bioinformatic report explicitly proposing that CD8+ T cell exhaustion occurs in DLBCL, which may be associated with lower PTEN. [ABSTRACT FROM AUTHOR]

Abstract Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating lymphocytes (TILs), including but not limited to neutrophils, M2 macrophages, cytotoxic CD8 T cells and dendritic cells, will play a role in the acidic tumor microenvironment mediated by monocarboxylate transporter 4 (MCT4) in esophageal squamous cell carcinoma (ESCC). However, the roles they play and their significance in ESCC remain less clear. To understand the clinicopathological and prognostic significance of neutrophils, M2 macrophages, CD8 T cells and dendritic cells in the tumor acidic microenvironment mediated by MCT4, we investigated the distribution of these TILs in the epithelial and stromal compartments of ESCC by means of multiplexed immunohistochemistry on a tissue microarray containing 87 paired dots of ESCC and its adjacent normal tissue (ANT) and an additional 6 cases of unpaired ESCC dots. The density of cells stained with MCT4 in the epithelium was significantly associated with overall survival. Dendritic cells stained with S100 in epithelial compartmentalization were found to markedly correlate with clinical stage and tumor invasion depth. No other significant association could be identified in terms of prognostic and clinicopathological significance. The potential correlation between the number of cells stained with MCT4 versus the number of TILs was also explored, showing that only in epithelial cells were there significant and positive correlations identified between the number of cells stained with MCT4 versus the number of neutrophils stained with CD15, M2 macrophages stained with CD163 and CD8 T cells stained by CD8a. However, no significant correlation was found along the stromal line. Together, the data we described here, although somewhat discouraging, showed that in epithelial cells from which ESCC originated, acidicity mediated by MCT4 may be responsible for lactate release and may have an effect on the infiltration of TILs we assessed. [ABSTRACT FROM AUTHOR]

• Influence of ship motions on Stewart platform is fully considered. • Velocity feedforward compensation is first proposed. • It is the first dual-loop control method. • Stability of system's equilibrium point is ensured. Offshore installations e.g.marine transportation, oil platforms, etc., are strongly dependent on sea conditions. To increase the workable time of carrying out these operations, a Stewart platform is installed on a ship to serve as a motion compensation base, and equipment on the base can have the same precision with those on the land-fixed base. Herein, movements of the Stewart platform are influenced by ship motions. Consequently, they present more complicated dynamical characteristics. Besides, uncertainties coming from the load and the hydraulic system may deteriorate system performance. To deal with the aforementioned problems, this paper proposes an adaptive robust dual-loop control scheme. Specifically, a multiple-degree-of-freedom velocity feedforward compensator is proposed to decouple motion disturbance from the base platform. Furthermore, the original dynamics model is transformed into a linearly parameterized form, and adaptive laws are utilized to estimate essential parameters. Then, a command-filtered based adaptive robust controller is developed. Finally, it is rigorously proven that control errors are bounded employing Lyapunov-based analysis, and simulations are included to illustrate the effectiveness of the proposed control scheme. [ABSTRACT FROM AUTHOR]

Offshore installations e.g., marine transportation, oil platforms, etc., are strongly dependent on sea conditions, which means low working efficiency and economic loss due to unworkable sea conditions. To increase the workable time of carrying out these operations, a Stewart platform is installed on a ship deck to serve as a motion compensation base, and equipment such as cranes and drilling platforms can be placed on the base to eliminate the effect of wave-induced ship motions. Herein, ship-mounted Stewart platforms work in the non-inertial frame, and their movements are influenced by persistent and unpredictable ship motions. As a result, they present much more complicated dynamical characteristics, which bring much more challenges for the controller design. To deal with the aforementioned problem, this paper presents a sliding-mode control scheme for the ship-mounted Stewart platform. Specifically, by employing Kane's method, the dynamics model is established with the effect of ship's motion on the top platform considered. Furthermore, a novel velocity feedforward compensator is proposed to improve control performance. A command-filtered based sliding-mode backstepping controller is subsequently developed. Finally, it is rigorously proven that the control errors are bounded employing Lyapunov-based analysis, and simulations are included to illustrate the effectiveness of the proposed control scheme. [Display omitted] • Ship and platform interaction problem is considered. • Velocity feedforward compensator is first proposed. • Stability of system's equilibrium point is ensured. [ABSTRACT FROM AUTHOR]

Metadherin (MTDH) was found to be highly expressed in various squamous cell carcinomas (SCCs); however, meta-analysis evaluating the association of MTDH in SCC has not been performed. The purpose of this study was to explore the biological functions of MTDH in esophageal squamous cell carcinoma (ESCC) and to meta-analyze the association between MTDH and SCC. Immunohistochemistry was performed to examine MTDH expression using an ESCC tissue array consisting of 86 ESCC and 78 paired normal adjacent tissues (NATs). MTDH was significantly overexpressed in ESCC tissues compared with NATs and was significantly associated with lymph node metastasis, differentiation, and prognosis. Knockdown of MTDH using an MTDH-short hairpin RNA plasmid caused cell cycle arrest at the G0/G1 phase and induced apoptosis of EC9706 cells. Knockdown of MTDH suppressed the proliferation, invasion, and migration of ESCC cells. Furthermore, meta-analysis revealed that overexpression of MTDH was significantly associated with the lymph node metastasis, advanced clinical stage, and T classification of tissues in SCC, suggesting that MTDH might be used as a potential therapeutic target in the lymph node metastasis of ESCC. [ABSTRACT FROM AUTHOR]

• PIK3CA mutation correlates with effector memory and naïve CD4 T cell infiltration in ESCC. • PIK3CA mutation is linked to increased tumor mutation burden in ESCC. • ESCC cells with PIK3CA mutations show reduced sensitivity to p38 MAPK and JNK inhibitors. • Glycosaminoglycan degradation is involved in PIK3CA mutations in ESCC. Recent studies have increasingly focused on PIK3CA mutations in esophageal squamous cell carcinoma (ESCC); however, the clinicopathological significance of these mutations within the tumor microenvironment remains underexplored. This study aimed to evaluate and compare the clinicopathological significance of mutated PIK3CA in ESCC using in silico analyses of the ESCC dataset from the TCGA database. We assessed prognosis, differential expression, correlation with immune cell infiltration and immune checkpoint expression, heterogeneity, and drug sensitivity in comparison with wild-type PIK3CA. Our findings revealed that PIK3CA mutation is associated with increased tumor mutation burden and significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells. Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC. [ABSTRACT FROM AUTHOR]