T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. ...Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and CTL antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently, five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7, were identified. Here we review recent understanding of new B7 family checkpoint molecules as they have come to the front of cancer research with the concept that tumor cells exploit them to escape immune surveillance. The aim of this article is to address the structure and expression of the new B7 family molecules as well as their roles in controlling and suppressing immune responses of T cells as well as NK cells. We also discuss clinical significance and contribution of these checkpoint expressions in human cancers.
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CD4+ T helper 1 (T(H)1) and T(H)2 cells have long been regarded as two sides of a coin in terms of adaptive immune responses. However, as I discuss here, this concept needs to be reconsidered. In ...particular, recent data indicate that interleukin-17 (IL-17) is produced by T(H) cells that are distinct from the traditional T(H)1- and T(H)2-cell subsets. Furthermore, the generation of these IL-17-producing CD4+ T cells from naive precursors during immune responses is not dependent on the cytokines and transcription factors that mediate T(H)1- and T(H)2-cell development. Given that IL-17 has crucial roles in regulating tissue inflammation and the development of disease in several animal models of autoimmunity, I propose that IL-17-producing CD4+ T cells represent a distinct inflammatory T(H)-cell lineage.
Wide bandgap oxide semiconductors constitute a unique class of materials that combine properties of electrical conductivity and optical transparency. They are being widely used as key materials in ...optoelectronic device applications, including flat‐panel displays, solar cells, OLED, and emerging flexible and transparent electronics. In this article, an up‐to‐date review on both the fundamental understanding of materials physics of oxide semiconductors, and recent research progress on design of new materials and high‐performing thin film transistor (TFT) devices in the context of fundamental understanding is presented. In particular, an in depth overview is first provided on current understanding of the electronic structures, defect and doping chemistry, optical and transport properties of oxide semiconductors, which provide essential guiding principles for new material design and device optimization. With these principles, recent advances in design of p‐type oxide semiconductors, new approaches for achieving cost‐effective transparent (flexible) electrodes, and the creation of high mobility 2D electron gas (2DEG) at oxide surfaces and interfaces with a wealth of fascinating physical properties of great potential for novel device design are then reviewed. Finally, recent progress and perspective of oxide TFT based on new oxide semiconductors, 2DEG, and low‐temperature solution processed oxide semiconductor for flexible electronics will be reviewed.
Wide‐bandgap oxide semiconductors uniquely combine electrical conductivity and optical transparency and are widely used in optoelectronic devices. The materials physics of wide‐bandgap oxide semiconductors, the recent progress in the design of new materials and novel thin‐film transistor (TFT) devices, and current challenges and perspectives are reviewed.
Backscattering suppression in silicon-on-insulator (SOI) is one of the central issues to reduce energy loss and signal distortion, enabling for capability improvement of modern information processing ...systems. Valley physics provides an intriguing way for robust information transfer and unidirectional coupling in topological nanophotonics. Here we realize topological transport in a SOI valley photonic crystal slab. Localized Berry curvature near zone corners guarantees the existence of valley-dependent edge states below light cone, maintaining in-plane robustness and light confinement simultaneously. Topologically robust transport at telecommunication is observed along two sharp-bend interfaces in subwavelength scale, showing flat-top high transmission of ~10% bandwidth. Topological photonic routing is achieved in a bearded-stack interface, due to unidirectional excitation of valley-chirality-locked edge state from the phase vortex of a nanoscale microdisk. These findings show the prototype of robustly integrated devices, and open a new door towards the observation of non-trivial states even in non-Hermitian systems.
The gut microbiota regulates the biological processes of organisms acting like 'another' genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have ...been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What's more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum (Fn) and Escherichia coli (E.coli), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota-microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.
Dysregulation of circular RNAs (circRNAs) plays an important role in the development of gastric cancer; thus, revealing the biological and molecular mechanisms of abnormally expressed circRNAs is ...critical for identifying novel therapeutic targets in gastric cancer.
A circRNA microarray was performed to identify differentially expressed circRNAs between primary and distant metastatic tissues and between gastric cancer tissues sensitive or resistant to anti-programmed cell death 1 (PD-1) therapy. The expression of circRNA discs large homolog 1 (DLG1) was determined in a larger cohort of primary and distant metastatic gastric cancer tissues. The role of circDLG1 in gastric cancer progression was evaluated both in vivo and in vitro, and the effect of circDLG1 on the antitumor activity of anti-PD-1 was evaluated in vivo. The interaction between circDLG1 and miR-141-3p was assessed by RNA immunoprecipitation and luciferase assays.
circDLG1 was significantly upregulated in distant metastatic lesions and gastric cancer tissues resistant to anti-PD-1 therapy and was associated with an aggressive tumor phenotype and adverse prognosis in gastric cancer patients treated with anti-PD-1 therapy. Ectopic circDLG1 expression promoted the proliferation, migration, invasion, and immune evasion of gastric cancer cells. Mechanistically, circDLG1 interacted with miR-141-3p and acted as a miRNA sponge to increase the expression of CXCL12, which promoted gastric cancer progression and resistance to anti-PD-1-based therapy.
Overall, our findings demonstrate how circDLG1 promotes gastric cancer cell proliferation, migration, invasion and immune evasion and provide a new perspective on the role of circRNAs during gastric cancer progression.
Reduction of the 17,18‐double bond in the D‐ring during chlorophyll biosynthesis is catalyzed by the rare, naturally occurring photoenzyme protochlorophyllide oxidoreductase (POR). A conserved ...tyrosine residue has been suggested to donate a proton to C18 of the substrate in the past decades. Taylor and colleagues scrutinized the model with a powerful tool that utilized a modified genetic code to introduce fluorinated tyrosine analogues into POR. The presented results show that the suggested catalytically critical tyrosine is unlikely to participate in the reaction chemistry but is required for substrate binding, and instead, a cysteine residue preceding the lid helix is proposed to have the role of proton donor.
Reduction of the 17,18‐double bond in the D‐ring during chlorophyll biosynthesis is catalyzed by the rare, naturally occurring photoenzyme protochlorophyllide oxidoreductase. Previously, a conserved tyrosine residue had been suggested to donate a proton to C18 of the substrate. Aoife Taylor and colleagues show that the suggested tyrosine is unlikely to participate in the reaction chemistry but is required for substrate binding, and instead, a cysteine residue preceding the lid helix is proposed to be the proton donor.
To develop high‐performance thermally activated delayed fluorescence (TADF) exciplex emitters, a novel strategy of introducing a single‐molecule TADF emitter as one of the constituting materials has ...been presented. Such a new type of exciplex TADF emitter will have two reverse intersystem crossing (RISC) routes on both the pristine TADF molecules and the exciplex emitters, benefiting the utilization of triplet excitons. Based on a newly designed and synthesized single‐molecule TADF emitter MAC, a highly efficient exciplex emitter MAC:PO‐T2T has been obtained. The device based on MAC:PO‐T2T with a weight ratio of 7:3 exhibits a low turn‐on voltage of 2.4 V, high maximum efficiency of 52.1 cd A−1 (current efficiency), 45.5 lm W−1 (power efficiency), and 17.8% (external quantum efficiency, EQE), as well as a high EQE of 12.3% at a luminance of 1000 cd m−2. The device shows the best performance among reported organic light‐emitting devices based on exciplex emitters. Such high‐efficiency and low‐efficiency roll‐off should be ascribed to the additional reverse intersystem crossing process on the MAC molecules, showing the advantages of the strategy described in this study.
A new type of high‐performance exciplex thermally activated delayed fluorescence TADF emitter is demonstrated by introducing single‐molecule TADF emitter as one of the constituting materials. The OLED based on the novel emitter shows a low turn‐on voltage of 2.4 V and a maximum external quantum efficiency of 17.8% with mild efficiency roll‐off, which offers a new strategy for designing efficient exciplex emitters.
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