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The crucial role of CD4+ and CD8+ T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3+CD4-CD8- double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer. [ABSTRACT FROM AUTHOR]

As excellent solvents of lithum-ion electrolyte, ethyl-methyl carbonate (EMC) and diethyl carbonate (DEC) are synthesized through transesterification of dimethly carbonate (DMC) and ethanol. Process intensification, optimization and the corresponding control scheme of the synthesized process are essential when sustainability is becoming a necessity. In the present work, the intensified flowsheet for EMC and DEC production process was firstly proposed and optimized with conventional reactive distillation (RD) and reactive dividing wall column (RDWC), respectively. Compared with RD process, RDWC could achieve 25.3% and 8.2% total annualized cost reduction for EMC and DEC production process, respectively. And carbon dioxide emission could be decreased by 29.4% and 11.7% by further integrating RD and separation column into RDWC arrangement for DEC and EMC production. Then multi-loop PI control schemes were developed as benchmark and linear model predictive controller was designed to handle the persistent feed disturbance. The superiorities of model-based controllers for the strongly interactive and coupled system are demonstrated by the dynamic response comparisons in terms of settling time, overshoot and integral of squared error (ISE), especially for the controlled variables with poor control performance under conventional multi-loop PI control structure. To summarize, the comprehensive control performance index-ISE with MPC is reduced by 55.9%–99.1%, as compared to those under PI control strategy. • Sustainable processes were realized by RD and RDWC for EMC and DEC production. • Optimization was conducted for series sustainable processes with genetic algorithm. • RDWC shows superiority in energy efficiency enhancement and CO 2 emission reduction. • Controllability investigation for sustainable processes with novel control strategy. • Model predictive control shows to be effective for strongly coupled system. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. Beta-1,3-galactosyltransferase 5 (b3galt5) plays crucial roles in protein glycosylation, but its function in HCC remains unclear. Here, we investigated the role and underlying mechanism of b3galt5 in HCC. We found that b3galt5 is highly expressed and associated with a poor prognosis in HCC patients. In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. We also demonstrated that b3galt5 deficiency suppressed hepatocarcinogenesis in DEN/TCPOBOP-induced HCC. Further investigation confirmed that b3galt5 promoted aerobic glycolysis in HCC. Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Studies have shown that epigenetic enzymes such as histone deacetylase (HDAC) are closely related to cancers and that several HDAC inhibitors exert antitumor effects. Studies have further suggested that class IIa HDAC inhibitors are related to immune functions, including immune responses and the expression of chemokines and complement pathway components. TMP195, a selective class IIa HDAC inhibitor, has been reported to be effective against breast cancer. However, the role and mechanism of TMP195 in colorectal cancer remain unknown. In this study, we found that TMP195 significantly reduced the tumor burden in two mouse models of colitis-associated colorectal cancer (CAC) and subcutaneous tumor. Mechanistically, TMP195 decreased the proportion of total macrophages but increased the proportion of M1 macrophages by promoting polarization, resulting in the increased release of inflammatory cytokines. TMP195 had no direct effect on the proliferation of colorectal cancer cells, and its antitumor effect on the colorectal cancer disappeared when macrophages were partly depleted by clodronate liposomes. In addition, TMP195 enhanced the efficacy of PD-1 blockade. The present study revealed that the combination of TMP195 and PD-1 blockade may provide a therapeutic strategy for colorectal cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The crucial role of CD4 + and CD8 + T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3 + CD4 - CD8 - double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Zheng, Sheng, Han, Yang, Pan and Yao.)