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The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.
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Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as â¼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.
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Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.
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Antígeno B7-H1 , Linfócitos T CD8-Positivos , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Imunoterapia , Microambiente Tumoral , Quimiocina CXCL10/farmacologiaRESUMO
Polarization singularities have topological properties, because they can maintain their features invariably during propagation. The topological property can be destroyed by shifting the polarization singularities away from the central axis, and this destruction originates from the space separation of spin angular momentum components. We find that paired centrosymmetric off-axis polarization singularities can recover the topological property in the Fourier plane (reciprocal space), which belongs to the pseudo-topological property. We reveal that the pseudo-topological property is related to the invisible redistribution of both spin and orbital angular momentum states. We experimentally generate a series of Julia fractal vector optical fields with the pseudo-topological property. They may have potential applications in optical encryption and quantum information.
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The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.
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Franquincenso , Humanos , Franquincenso/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/químicaRESUMO
Traditional Chinese medicine (TCM) has been widely used for cancer treatment. Identification of anti-cancer targets of TCM is the first and principal step in discovering molecular mechanisms of TCM as well as obtaining novel targets for cancer therapy. In this study, glycogen phosphorylase L (PYGL) was identified as one of the targeted proteins for several TCMs and was upregulated in various cancer types. The expression level of PYGL was positively correlated with the stage of lung cancer and the poor prognosis of patients. Meanwhile, knockdown of PYGL significantly inhibited proliferation and migration in lung cancer cells. In addition, PYGL was associated with spindle, kinetochore, and microtubule, the cellular components that are closely related to mitosis, in lung cancer. Moreover, PYGL was more susceptible to be upregulated by 144 mutated genes. Taken together, PYGL is a potential target for lung cancer treatment and its molecular mechanism probably influences the mitotic function of cells by regulating energy metabolism.
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Glicogênio Fosforilase , Neoplasias Pulmonares , Humanos , Glicogênio Fosforilase/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genéticaRESUMO
BACKGROUND: As one of the effective pharmacological constituents of Ginseng Radix et Rhizoma, ginsenoside Rh2 (Rh2) exerts a remarkable anticancer effect on various cancer cell lines in vitro and strongly inhibits tumor growth in vivo without severe toxicity. OBJECTIVE: This article reviewed existing evidence supporting the anticancer effects of Rh2 to classify and conclude previous and current knowledge on the mechanisms and therapeutic effects of Rh2, as well as to promote the clinical application of this natural product. CONCLUSION: This article reviewed the anticancer efficacies and mechanisms of Rh2, including the induction of cell cycle arrest and programmed cell death, repression of metastasis, alleviation of drug resistance, and regulation of the immune system. Finally, this paper discussed the research and application prospects of Rh2.
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Ginsenosídeos , Panax , Apoptose , Pontos de Checagem do Ciclo Celular , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêuticoRESUMO
Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.
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Antígeno B7-H1/antagonistas & inibidores , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Interferon gama/farmacologia , Neoplasias Pulmonares/metabolismo , Células A549 , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HCT116 , Células HEK293 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Células Jurkat , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
Despite many decades of research of diodes, which are fundamental components of electronic and photoelectronic devices with p-n or Schottky junctions using bulk or 2D materials, stereotyped architectures and complex technological processing (doping and multiple material operations) have limited future development. Here, a novel rectification device, an orientation-induced diode, assembled using only few-layered black phosphorus (BP) is investigated. The key to its realization is to utilize the remarkable anisotropy of BP in low dimensions and change the charge-transport conditions abruptly along the different crystal orientations. Rectification ratios of 6.8, 22, and 115 can be achieved in cruciform BP, cross-stacked BP junctions, and BP junctions stacked with vertical orientations, respectively. The underlying physical processes and mechanisms can be explained using "orientation barrier" band theory. The theoretical results are experimentally confirmed using localized scanning photocurrent imaging. These orientation-induced optoelectronic devices open possibilities for 2D anisotropic materials with a new degree of freedom to improve modulation in diodes.