Search

Hepatocellular carcinoma (HCC) is clinically distinguished by its covert onset, rapid progression, high recurrence rate, and poor prognosis. Studies have revealed that SETDB1 (SET Domain Bifurcated 1) is a histone H3 methyltransferase located on chromosome 1 and plays a crucial role in carcinogenesis. Therefore, we aimed to evaluate the clinical significance of SETDB1 expression in HCC. In patients with HCC, elevated levels of SETDB1 correlated with a poorer overall survival (OS) rate, marking it as an independent prognostic factor for HCC, as revealed by both univariate and multivariate Cox analyses. Furthermore, we utilized the SangerBox and TISIDB databases to profile the tumor immune microenvironment in HCC, including scoring the tumor microenvironment and assessing immune cell infiltration. The TIDE algorithm was employed to examine the association between SETDB1 expression and immune responses. Our findings indicated that SETDB1 expression negatively correlated with the majority of immune cells, a wide range of immune cell marker genes, and numerous immune pathways, thereby leading to the reduced effectiveness of immune checkpoint inhibitors. Lastly, both in vivo and ex vivo experiments were conducted to substantiate the role of SETDB1 in HCC tumorigenesis. In conclusion, the upregulation of SETDB1 is associated with a poorer prognosis in HCC patients and inversely correlates with immune cell infiltration, potentially serving as a predictive marker for immunotherapy response. [ABSTRACT FROM AUTHOR]

Objectives: To explore downstream management and outcomes of machine learning (ML)–based CT derived fractional flow reserve (FFRCT) strategy compared with an anatomical coronary computed tomography angiography (CCTA) alone assessment in participants with intermediate coronary artery stenosis. Methods: In this prospective study conducted from April 2018 to March 2019, participants were assigned to either the CCTA or FFRCT group. The primary endpoint was the rate of invasive coronary angiography (ICA) that demonstrated non-obstructive disease at 90 days. Secondary endpoints included coronary revascularization and major adverse cardiovascular events (MACE) at 1-year follow-up. Results: In total, 567 participants were allocated to the CCTA group and 566 to the FFRCT group. At 90 days, the rate of ICA without obstructive disease was higher in the CCTA group (33.3%, 39/117) than that (19.8%, 19/96) in the FFRCT group (risk difference [RD] = 13.5%, 95% confidence interval [CI]: 8.4%, 18.6%; p = 0.03). The ICA referral rate was higher in the CCTA group (27.5%, 156/567) than in the FFRCT group (20.3%, 115/566) (RD = 7.2%, 95% CI: 2.3%, 12.1%; p = 0.003). The revascularization-to-ICA ratio was lower in the CCTA group than that in the FFRCT group (RD = 19.8%, 95% CI: 14.1%, 25.5%, p = 0.002). MACE was more common in the CCTA group than that in the FFRCT group at 1 year (HR: 1.73; 95% CI: 1.01, 2.95; p = 0.04). Conclusion: In patients with intermediate stenosis, the FFRCT strategy appears to be associated with a lower rate of referral for ICA, ICA without obstructive disease, and 1-year MACE when compared to the anatomical CCTA alone strategy. Key Points: • In stable patients with intermediate stenosis, ML-based FFRCT strategy was associated with a lower referral ICA rate, a lower normalcy rate of ICA, and higher revascularization-to-ICA ratio than the CCTA strategy. • Compared with the CCTA strategy, ML-based FFRCTshows superior outcome prediction value which appears to be associated with a lower rate of 1-year MACE. • ML-based FFRCT strategy as a non-invasive "one-stop-shop" modality may be the potential to change diagnostic workflows in patients with suspected coronary artery disease. [ABSTRACT FROM AUTHOR]

Sediment relamination in subduction zones is posited to be important for the compositional evolution, physical structure and material recycling of the Earth. Despite support from numerical experimental modeling and geophysical observation, magmatic evidence for relamination is rare and difficult to identify in ancient and modern convergent systems. Here we report newly identified ca.32–27 Ma adakite‐like granites with high δ18O values (up to 10.38‰) from the Ailaoshan‐Red River (ASRR) shear zone in western Yunnan (SE Tibet). Their geochronological and compositional data strongly exhibits significant contributions from Permian‐Eocene sedimentary rocks in the lower crust (30–45 km). Our study provides further evidence that the lower crust may be partially composed of more felsic lithologies likely originating from rapid supracrustal material recycling via diapiric relamination of (meta)sedimentary material during Cenozoic‐age continental subduction. The ASRR adakite‐like granites thus represent clear magmatic evidence for sediment relamination in a subduction system. Plain Language Summary: Subducted sediments may detach from the downgoing slab due to the large density contrast with surrounding mantle, and ascend as diapirs to become emplaced into the base of the overriding plate. Sediment relamination would help building a more felsic continental lower crust, and be important to Earth material recycling. However, identifying and verifying sediment relamination is difficult. Here, we carry out an integrated in situ analysis of zircon U‐Pb and Hf‐O isotopes, along with whole‐rock geochemistry for the Cenozoic granites from the Ailaoshan‐Red River (ASRR) shear zone in western Yunnan (SE Tibet). Our data reveal that the newly identified ca. 32–27 Ma adakite‐like granites are characterized by high δ18O values (up to 10.38‰), and other geochemical compositions similar to sediment‐derived melts formed under the pressure of 1.0–1.5 Gpa corresponding to depths of 30–45 km. Occurrence of Paleocene‐Eocene inherited zircon cores (ca. 67–41 Ma) further imply that the (meta)sedimentary rocks in the lower crustal depth may be resulted from rapid supracrustal material recycling via diapiric relamination during Cenozoic‐age continental subduction. We propose that the high δ18O adakite‐like granites identified in the ASRR represent clear magmatic evidence for sediment relamination in a subduction system. Key Points: The newly identified ca. 32–27 Ma adakite‐like granites were formed in the Cenozoic continental subduction zoneThe granites have high δ18O, Sr/Y and La/Yb values, showing significant contributions from metasedimentary materials in the lower crustSediment relamination was responsible for the rapid supracrustal material recycling in a subdcution system [ABSTRACT FROM AUTHOR]

A suite of Jurassic–Cretaceous migmatites was newly identified in the Liaodong Peninsula of the eastern North China Craton (NCC). Anatexis is commonly associated with crustal thickening. However, the newly identified migmatites were formed during strong lithospheric thinning accompanied by voluminous magmatism and intense deformation. Field investigations show that the migmatites are spatially associated with low-angle detachment faults. Numerous leucosomes occur either as isolated lenses or thin layers (dykes), parallel to or cross-cutting the foliation. Peritectic minerals such as titanite and sillimanite are distributed mainly along the boundaries of reactant minerals or are accumulated along the foliation. Most zircons show distinct core–rim structures, and the rims have low Th/U ratios (0.01–0.24). Zircon U–Pb dating results indicate that the protoliths of the migmatites were either the Late Triassic (224–221 Ma) diorites or metasedimentary rocks deposited sometime after c. 1857 Ma. The zircon overgrowth rims record crystallization ages of 173–161 Ma and 125 Ma, which represent the formation time of leucosomes. These ages are consistent with those reported magmatic events in the Liaodong Peninsula and surrounding areas. The leucosomes indicate a strong anatectic event during the Jurassic–Cretaceous period. Partial melting occurred through the breakdown of muscovite and biotite with the presence of water-rich fluid under a thermal anomaly regime. The possible mechanism that caused the 173–161 Ma and 125 Ma anatectic events was intimately related to the regional crustal extension during the lithospheric thinning of the NCC. Meanwhile, the newly generated melts further weakened the rigidity of the crust and enhanced the extension. [ABSTRACT FROM AUTHOR]