Search

Rubble-pile asteroids may be the type of near-Earth object most likely to threaten Earth in a future collision event. Small-scale impact experiments and numerical simulations for large-scale impacts were conducted to clarify the size ratio of the boulder/projectile diameter effects on ejecta size–velocity distribution. A series of small-scale impact cratering experiments were performed on porous gypsum–basalt targets at velocities of 2.3 to 5.5 km·s−1. Three successive ejection processes were observed by high-speed and ultra-high-speed cameras. The momentum transfer coefficient and cratering size were measured. A three-dimensional numerical model reflecting the random distribution of the interior boulders of the rubble-pile structure asteroid is established. The size ratio (length to diameter) of the boulder size inside the asteroid to the projectile diameter changed from 0.25 to 1.7. We conducted a smoothed particle hydrodynamics numerical simulation in the AUTODYN software to study the boulder size effect on the ejecta size–velocity distribution. Simulation results suggest that the microscopic porosity on regolith affects the propagation of shock waves and reduces the velocity of ejecta. Experiments and numerical simulation results suggest that both excavation flow and spalling ejection mechanism can eject boulders (0.12–0.72 m) out of the rubble-pile asteroid. These experiments and simulation results help us select the potential impact site in a planetary defense scenario and reduce deflection risk. are comprised primarily of boulders of a range of sizes. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. Conclusions: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. Trial registration: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577). [ABSTRACT FROM AUTHOR]

Mechanoluminescence (ML) is a fascinating phenomenon with diverse applications in pressure sensing, damage detection, and stress distribution visualization. However, most ML materials exhibit instantaneous photon emission that requires real‐time recording with a photodetector, and thereby circumscribing their applicability predominantly to real‐time stress‐sensing scenarios. In this work, a novel method is introduced for non‐real‐time stress sensing utilizing Li0.1Na0.9NbO3:Pr3+ phosphor, which allows for the retrieval of pressure location and intensity even 20 days after the event. The influence of heat and pressure on the trap depth distribution is analyzed using thermoluminescence (TL) and ML measurements, and it is proved that both heat and pressure release the captured electrons in the same traps. Leveraging the intricate competition between mechanical and thermal detrapping processes, stress information can be accessed through TL imaging. Furthermore, an algorithm is proposed based on this phenomenon to authenticate the stress information. This research not only advances the fundamental understanding of ML phenomena but also introduces a novel approach for applications such as mechano‐history indicators, security papers, and advanced data storage systems. [ABSTRACT FROM AUTHOR]

P2Y 14 receptor (P2Y 14 R) is activated by uridine 5'-diphosphate-glucose, which is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2Y 14 R antagonists and the crystallographic overlap study between the reported P2Y 14 R antagonist compounds 6 and 9 , a series of N-substituted-acetamide derivatives were designed, synthesized, and identified as novel and potent P2Y 14 R antagonists. The most potent antagonist, compound I-17 ( N -(1 H -benzo[ d ]imidazol-6-yl)-2-(4-bromophenoxy)acetamide, IC 50 = 0.6 nM) without zwitterionic character, showed strong binding ability to P2Y 14 R, high selectivity, moderate oral bioactivity, and improved pharmacokinetic profiles. In vitro and in vivo evaluation demonstrated that compound I-17 had satisfactory inhibitory activity on the inflammatory response of monosodium urate (MSU)-induced acute gouty arthritis. I-17 decreased inflammatory factor release and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. Thus, compound I-17 , with potent P2Y 14 R antagonistic activity, in vitro and in vivo efficacy, and favorable bioavailability ( F = 75%), could be a promising lead compound for acute gouty arthritis.