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.
Photocatalytic technology has been considered to be an ideal approach to solve the energy and environmental crises, and TiO2 is regarded as the most promising photocatalyst. Compared with bare TiO2, TiO2 based p-n heterojunction exhibits a much better performance in charge separation, light absorption and photocatalytic activity. Herein, we developed an efficient method to prepare p-type TiO2 quantum dots (QDs) and decorated graphitic carbonitrile (g-C3N4) nanocomposites, while the composition and structure of the TiO2@g-C3N4 were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy, X-ray photoelectron spectroscopy and UV-visible diffuse reflectance spectroscopy characterizations. The characterization results reveal the surface decorated TiO2 quantum dots is decomposed by titanium glycerolate, which exhibits p-type conductivity. The presence of p-n heterojunction over interface is confirmed, and photoluminescence results indicate a better performance in transfer and separation of photo-generated charge carriers than pure semiconductors and type-II heterojunction. Moreover, the synergy of p-n heterojunction over interface, strong interface interaction, and quantum-size effect significantly contributes to the promoted performance of TiO2 QDs@g-C3N4 composites. As a result, the as-fabricated TiO2 QDs@g-C3N4 composite with a p/n mass ratio of 0.15 exhibits improved photo-reactivity of 4.3-fold and 5.4-fold compared to pure g-C3N4 in degradation of organic pollutant under full solar spectrum and visible light irradiation, respectively.
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.
Formic acid production through methyl formate hydrolysis has been shown to be energy and capital cost intensive, and its performance could be significantly promoted by process intensification. However, integration of reaction and separation exhibits a complex nonlinear behavior, which requires corresponding optimization and control to be effectively addressed before further industrial implementation. In the present work, optimization was first performed for a conventional reactive distillation (RD) process and reactive dividing wall column (RDWC) by coupling genetic algorithm and rigorous simulations, in which a user-defined model was incorporated to take kinetics into account. Although the results demonstrate that RDWC is inferior to RD in terms of economic criteria, it provides the basis for proposing new easy-to-operate configurations in the subsequent part 2 of this series. Then multiloop proportional–integral (PI) control structures and linear model predictive control (MPC) schemes were designed for the conventional RD process and RDWC, respectively. The performances of two control structures were compared subject to feed disturbance, by using quantitative indexes such as oscillation, settling time, overshoot, and integral of the squared error (ISE). The dynamic response validates that MPC outperforms classical multiloop control schemes and could tackle the excessive overshoot deficiency in PI control for both the conventional RD process and RDWC.
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