Abstract Purpose To improve early detection and risk prediction of prostate cancer, we incorporated the urine urothelial carcinoembryonic antigen 1 (UCA1) gene expression levels and the serum PSA level. Patients and Methods In 897 patients the urine UCA1 gene expression was normalized and the performance of UCA1 score was evaluated by receiver operating characteristic (ROC) curve analysis, the Mann–Whitney U test, or decision curve analysis (DCA). Results In the Shengli training cohort ( n = 517), the area under ROC curve (AUC) was 0.880, 0.728, and 0.705 for detecting prostate cancer, D'Amico, and cancer of the prostate risk assessment (CAPRA), respectively. The UCA1 scores of benign patients were significantly lower than those of nonhigh‐risk prostate cancer patients (−2.63 vs. 0.16, p < 0.001; AUC 0.834). DCA yielded a better result with the UCA1 score compared to PSA. Combining PSA <4 with UCA1 score ≥−0.475, all nine of 62 patients were successfully diagnosed with prostate cancer and 70.97% of prostate biopsies were excluded. Using PSA ≥4 and UCA1 score ≥−3.47, 122 cancer patients were accurately diagnosed with a sensitivity of 0.992, while 102 prostate biopsies (22.42%) were excluded. Similar results were validated in the Fuzhou validation cohort ( n = 380). In all patients of two cohort ( n = 897), the UCA1 score was superior to PSA only for detection of clinically significant cancer (28% VS. 22%, p = 0.007) and detection of high‐risk cancer (25% VS. 19%, p = 0.009). Conclusion The performance of the UCA1 score is superior to that of the existing PSA only in the detection and risk prediction of prostate cancer. Combination of the PSA level and the UCA1 score may significantly reduce the burden of prostate biopsy.
Abstract Triple‐negative breast cancer has an immunologically “cold” microenvironment, which leads to resistance to current immunotherapy. The activation of stimulator of interferon genes (STING) pathway has been thought a promising strategy to enhance immunotherapy efficacy. In this study, we adopted a comprehensive strategy that integrates innate immune responses with tumor‐targeting photothermal therapy (PTT) to simultaneously tackle multiple immune‐suppressive mechanisms in breast cancer. This semiconducting polymeric nanoagonists (DPTT‐Mn Lipo NPs) mediated PTT can effectively initiate tumor cell apoptosis and induce ICD, thereby reprogramming the immunosuppressive TME and activating STING. We confirmed the modulation of the TME through the PTT‐mediated ICD effect and the transactivation of the cGAS‐STING pathway in immune cells of the TME due to the released dsDNA via ICD, such as macrophages and DCs. Indeed, DPTT‐Mn Lipo NPs‐mediated PTT promoted M1 polarization of tumor‐associated macrophages, augmented T‐cell infiltration, facilitated dendritic cell (DC) maturation, and regulated type I interferon factor secretion, leading to efficient tumor suppression. Most importantly, the combination of DPTT‐Mn Lipo NPs‐based PTT with a checkpoint blockade therapy (anti‐PD‐1) can elicit long‐term immune memory besides tumor eradication. Collectively, this nano‐system can systemically activate antitumor immunity through STING activation and potentially establish long‐term memory against tumor recurrence.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract The Himalayan Orogen is a typical continental collision orogenic belt that formed during India-Asia collision. The orogeny involved a transition in tectonic regime, which led to E-W–trending extension during the middle Miocene. At the same time, widespread post-collisional adakitic magmatism occurred in southern Tibet, particularly in the Lhasa Terrane, and these rocks provide a valuable record of the collisional geodynamic processes within the lithosphere. Few studies have focused on the middle Miocene adakitic rocks of the Himalayan Orogen, so further research is required to constrain their origin and geodynamics. This study presents new geochronological and geochemical data, including the whole rock Sr-Nd and zircon Hf isotopic compositions from the Mayum pluton in the Mayum-Gong Tso area, Northern Himalaya. Zircon U-Pb ages show that the Mayum granodiorite porphyries crystallized at 16.67 ± 0.14 Ma (mean square weighted deviation [MSWD] = 0.82, n = 29) and 16.68 ± 0.16 Ma (MSWD = 1.13, n = 28), indicating that they formed during the middle Miocene. The major and trace element characteristics are as follows: SiO2 = 65.79–67.31 wt%, Al2O3 = 15.28–16.00 wt%, MgO = 1.77–1.89 wt%, Y = 12.0–13.5 ppm, Yb = 0.11–0.99 ppm, Sr = 719–822 ppm, (La/Yb)N = 21.89–27.02, Sr/Y = 56.1–65.5, and the rocks have weak negative Eu anomalies (Eu/Eu* = 0.76–0.85), indicating that they are adakitic rocks and show high Sr-Ba granite affinity. The Mayum granodiorite porphyries have high K2O contents (3.42–3.65 wt%), Na2O (3.76–4.04 wt%), and K2O/Na2O ratios of 0.91–0.95, indicating a high-K calc-alkaline affinity. All samples are enriched in large-ion lithophile elements and depleted in high field strength elements. The initial 87Sr/86Sr ratios are 0.709262–0.709327 and εNd(t) values are −6.36 to −7.07, which correspond to two-stage Nd model ages [TDM2(Nd)] of 1405–1348 Ma. In situ zircon Lu-Hf isotopic compositions are variable, with 176Hf/177Hf ratios of 0.2823845–0.282824, εHf(t) values of −13.37 to +2.17, and two-stage Hf model ages [TDM2(Hf)] of 1704–841 Ma. These geochemical and Sr-Nd-Hf isotopic characteristics indicate that the Mayum granodiorite porphyries may be derived from partial melting of the subducted Indian thickened ancient mafic lower crust (∼92%) mixed with depleted mid-ocean ridge basalt mantle material input (∼8%) slightly. Crust-mantle interaction was induced by asthenospheric upwelling followed by the underplating of the Himalayan lower crust beneath Southern Tibet during the middle Miocene in response to significant changes in the geodynamics of the India-Asia collisional orogen. These deep geodynamic processes reflect the break-off or rollback of the subducted Indian continental slab, which caused asthenospheric upwelling, the input of juvenile heat, and the addition of depleted mantle material. This study indicates that the middle Miocene Himalayan adakitic rocks, which include the Miocene Yardoi two-mica granite, Gyangzê granite porphyry dike, Bendui two-mica granite, Langkazi enclave, Kuday dacitic dike, Lasa pluton, and Mayum pluton, form a belt of adakitic rocks in the Northern Himalaya to the south of the Indus-Tsangpo Suture Zone. These adakitic rocks have similar temporal and spatial distributions, geochemical features, and Sr-Nd isotopic compositions, indicating that their petrogenesis and geodynamic settings were similar. At that time there was widespread initiation of N-S–trending rifting, exhumation of central Himalayan eclogites, and large changes in the compositions of Himalayan leucogranites in the Himalayan Orogen. These can be attributed to significant changes in the characteristics of the subducted Indian continental lithosphere during the middle Miocene. The middle Miocene Himalayan adakitic rocks provide valuable insights into this transition in the tectonic regime and deep geodynamic processes.
Based on the contents of2006 international forum of micro alloy steel application into oil and gas industryin Brazil,it introduces updated developments of pipeline in sour condition over the world and standard of developments of extra-high strength pipeline steel.The contents shall be good reference for pushing high grade steel applied into national oil and gas pipeline,basic research of pipe application,pipe making and application technology developments.
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