Search

Lung cancer is the highest incidence and mortality of all cancers around the world. In the present immunotherapy era, an increasing number of immunotherapeutic agents including monoclonal antibody‐targeted drugs have been used in the clinical treatment of malignancy, but it still has many limitations. Chimeric antigen receptor‐modified T (CAR‐T) cells, a novel adoptive immunotherapy strategy, have not only been used successfully against hematological tumors, but have also opened up new avenues for immunotherapy of solid tumors, including lung cancer. However, targeting lung cancer‐specific antigens using engineered CAR‐T cells is complicated by the lack of proper tumor‐specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR‐T cell infiltration into tumor tissues, along with off‐target effect, etc. Simultaneously, the clinical application of CAR‐T cells remains limited because of many challenges such as tumor lysis syndrome, neurotoxicity syndrome, and cytokine release syndrome. In this review, we outline the basic structure and generation characteristic of CAR‐T cells and summarize the common tumor‐associated antigens in clinical trials of CAR‐T cell therapy for lung cancer, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for the pre‐clinical experiments and clinical trials of CAR‐T cell therapy in lung cancer. [ABSTRACT FROM AUTHOR]

The phenomenon of DNA phosphorothioation (DNA sulfur modification) is widespread among prokaryotes and may serve as a mechanism to restrict gene transfer among bacteria. DndE is one of five essential proteins that are required for the DNA phosphorothioation process. However, its exact biochemical role in sulfur modification of DNA remains unclear. In this study, the DndE protein homologue from Salmonella enterica serovar Cerro 87 was overexpressed, purified and crystallized. The crystals of the DndE protein diffracted to 2.7 Å resolution and belonged to space group P3121. These results will facilitate detailed structural analysis of DndE and further elucidation of its biochemical function. [ABSTRACT FROM AUTHOR]

The Ghohroud granitoids (GG), containing mafic microgranular enclaves (MMEs) are located in the central part of the Urumieh‐Dokhtar Magmatic Arc (UDMA) in central Iran. They are associated with the subduction‐related magmatism in the Alpine‐Himalayan orogenic belt. The GG are comprised of a variety of intermediate and felsic rocks, including tonalite, granodiorite, granite, diorite porphyry and monzodiorite. The MMEs are gabbroic diorite and tonalite in composition and characterized by a fine‐grained hypidiomorphic microgranular texture with occasional chilled margins. They show rounded, sharp or irregular contact with the host granitoids. The occurrences of quartz, K‐feldspar and corroded plagioclase indicate that MMEs are the products of mixing between mantle and crust‐derived magmas. New ages of zircon U–Pb dating reveal that the GG in the Kashan area emplaced at ca. 19–17 Ma (Burdigalian). All the samples of MMEs and granitoid host rocks in this study are metaluminous and calc‐alkaline with I‐type affinities. They are enriched in light rare earth elements (LREEs) and show slight negative Eu anomalies (Eu/Eu* = 0.36–0.95). These features in a combination with the relative depletion in Nb, Ta, Ti and P, indicate the granitoids and MMEs are closely associated with subduction‐related magmas at an active continental margin. The host rocks yield relatively homogeneous isotopic compositions of initial 87Sr/86Sr ratios ranging from 0.706036 to 0.707055, εNd(t) values varying from −2.25 to 0.8, and the Nd model ages (TDM) vary in a limited range of 0.70–0.96 Ga. The MMEs show similar initial 87Sr/86Sr ratios (0.706420–0.707366), εNd(t) values (−1.32 to −0.27), TDM (0.68–1.09 Ga) and Pb isotopic compositions with host granitoids, which imply they attained isotopic equilibration during magma mingling and mixing. In combination with the petrographic, chemical and isotopic results, we suggest that the origin of MMEs and their host rocks were related to the interaction between crust‐derived melts and mantle‐derived mafic magmas. The magma‐mixing event possibly occurred during the transition from subduction to collision in the UDMA along with the closure of the Neotethyan ocean. [ABSTRACT FROM AUTHOR]

Yanshanian magmatisms are intensive in the eastern Jiangnan orogen and can be divided into early (150–136 Ma) and late (136–120 Ma) stages. About these granitic rocks, the petrogenesis and associated tectonic setting are still hotly debated. The Taiping–Huangshan complex, a representative granitic rock in this region, is selected to perform geochemical studies. Three lithologic units have been identified in the Taiping–Huangshan complex: granodiorite, monzogranite, and alkali‐feldspar granite with zircon U–Pb dating results of 149–144 Ma, 148 Ma, and 135–131 Ma, respectively, belonging to the early stage for the granodiorite and monzogranite, and late stage for the alkali‐feldspar granite. The granodiorite and monzogranite have similar major and trace element characteristics with intermediate‐acidic SiO2 contents ranging from 65.9 to 69.7 wt.%, low Mg# values of 35.8–38.4, enriched LREE, Pb, Th, and U contents, and weak Eu anomalies (δEu = 0.71–0.79). The alkali‐feldspar granite is characterized by high SiO2 contents (73.3–76.6 wt.%), low Mg# (2.6–10.0), enriched Th, U, Ta, Pb, and Nd, depleted high‐field‐strength elements, and pronounced negative Eu anomalies (δEu = 0.01–0.19). The granodiorite and monzogranite have consistent εHf(t) (−5.38 to −9.41) and δ18O (7.18‰ to 11.00‰) values, while the alkali‐feldspar granite has elevated εHf(t) values (−0.96 to −6.48) and δ18O values (6.27‰ to 8.34‰). Integrated geochemical characteristics and batch partial melting modelling constrain that the early stage granitic rocks derived from ca. 8% batch melting of the Neoproterozoic juvenile crust, and the late‐stage granites derived from a similar crust source with a little contribution from mantle. From early to late stage, the tectonic setting translated from post‐orogenic to anorogenic and the later corresponded to a back‐arc extensional setting as increasing of the slab subducted angle of the Palaeo‐Pacific Plate. [ABSTRACT FROM AUTHOR]