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The quality of Al–Li castings is significantly influenced by fluidity and hot tearing susceptibility (HTS), underscoring the importance of comprehending castability and the related influencing mechanisms. Hence, this work systematically explores the synergistic effect of in situ TiB2 particles and Ti solute on fluidity and HTS of the Al–Li alloys. The addition of Ti solutes or in situ TiB2 particles yields a discernible improvement in both the fluidity and HTS of the Al–Li alloys. Furthermore, their combined addition further enhances fluidity and reduces HTS, resulting in a significant 67.3% enhancement and a remarkable 59.1% decrease, respectively. To elucidate these underlying influencing mechanisms, experimental results were compared with predictions derived from numerical simulation using ProCAST software, alongside assessments based on the CSC and Kou's criteria. Numerical simulations closely align with experimental results. However, the CSC criterion and Kou's criterion exhibit discrepancies when compared to experimental observations, highlighting their limitations in capturing the nuanced effects of minor Ti addition or TiB2 particles on fluidity and HTS. Therefore, a comprehensive exploration of other influencing factors, encompassing microstructural features, solidification interval, and diverse thermophysical parameters, was thoroughly examined to uncover the influencing mechanisms. These outcomes are poised to offer profound insights into the fluidity and HTS of Al–Li alloys, thereby advancing the utilization and progression of cast Al–Li alloy applications. [ABSTRACT FROM AUTHOR]

Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout, the TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified as a TGF‐β‐inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF‐β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF‐β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly‐ubiquitination and proteasomal degradation. Moreover, hyperactive TGF‐β signaling in turn up‐regulates TGFBRAP1 expression in drug‐resistant CSC‐like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF‐β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF‐β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF‐β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness. [ABSTRACT FROM AUTHOR]

In this work, we report a counter-intuitive activation of abnormal grain growth (AGG) in randomly-oriented fine grains (FGs) in an L-PBF Al–Mg–Sc–Zr alloy, which is unlikely from perspectives of curvature-driven grain growth, crystallographic texture or strain-induced boundary migration. The observed spontaneous AGG is understood in light of the growth instability of an arbitrary grain in an evolving particle-pinned polycrystalline aggregation. A generalized criterion for AGG is hence proposed, which efficaciously explains the observed susceptibility of FGs to AGG, the presence of multiple AGG activation sites, and the asynchrony of AGG activation. [ABSTRACT FROM AUTHOR]

Particle agglomeration poses the principal challenge in the solidification of particulate-reinforced metal matrix composites (MMNCs). Here, we present an approach aimed at achieving a uniform dispersing of nanoparticles (NPs) in an aluminum matrix via ultrasonic-assisted fast cooling schemes. Microstructure analysis reveals that the distribution of NPs in the matrix transforms from intergranular distribution to intragranular distribution at the microscale and the interface between NP and the matrix changes from incoherent to coherent at the nanoscale under the action of ultrasonic melt treatment. Theoretical analysis underscores the significance of NP size and cooling rate as the two prominent factors influencing NP distribution during the solidification of nanocomposites. Through the ultrasonic dispersion of NPs and particle engulfment during the fast cooling process, the ductility of highly dispersed nanocomposites exhibits significant enhancement, with an increase of 82.7 and 18.4 pct compared to that of pure aluminum and non-ultrasonic-treated samples, respectively. [ABSTRACT FROM AUTHOR]

Background Chronic hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, the risk factors and the mechanisms underlying its occurrence have yet to be fully elucidated. The purpose of this study was to identify biomarkers that could be used to predict chronic hydrocephalus after aSAH and to investigate the relationships. Methods We analyzed cerebrospinal fluid (CSF) samples from 19 patients with chronic hydrocephalus after aSAH and 44 controls without hydrocephalus after aSAH. Enzyme-linked immunosorbent assay was used to determine the levels of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor-β (TGF-β), Smad1, Smad4, Smad5, Smad8, activin receptor-like kinase 1 (Alk-1), activin receptor-like kinase 5 (Alk-5), P38, and TGF-β type II receptor (TGFßRII) in CSF samples. Results In the CSF of patients with chronic hydrocephalus after aSAH, the levels of LRG, TGF-β, Alk-1, Smad5, and TGFßRII were significantly increased (p < 0.05) and the levels of Smad1, Smad4, and Smad8 were significantly decreased (p < 0.05). There were no significant differences between the two groups concerning the levels of P38 and Alk-5 (p > 0.05). The analysis also identified significant correlations between specific biomarkers: LRG and Smad1, LRG and Smad5, TGF-β and Alk-1, and Alk-1 and Smad4 (p < 0.05); the Pearson's correlation coefficients for these relationships were −0.341, 0.257, 0.256, and −0.424, respectively. Conclusion The levels of LRG, TGF-β, Alk-1, TGFßRII, Smad1/5/8, and Smad4 in the CSF are potentially helpful as predictive biomarkers of chronic hydrocephalus after aSAH. Moreover, the LRG-TGF-β-Alk-1/TGFßRII-Smad1/5/8-Smad4 signaling pathway is highly likely to be involved in the pathogenic process of chronic hydrocephalus after aSAH. [ABSTRACT FROM AUTHOR]

Abstract Objective Through the study of 4‐dimensional (4D) positron emission tomography (PET)/computed tomography (CT) for lung tumor, the delineation of the lung tumor target area was analyzed, the accurate target area was received, and the radiation dose of normal tissue was compared . Methods The average 4DPET volume, 3DPET volume, average 4DCT volume, and 3DCT volume of 10 tumors were compared. Taking the relative difference between the average 4D volume and the 3D volume as the difference of the volumes, the influence of the tumor size and the range of motion for 4D volume and 3D volume were studied respectively, then the target areas were delineated respectively, and the radiation doses of the normal tissues associated with the respective target areas were compared after the intensity‐modulated radiation therapy plan was formulated. Results The PET volumes of all tumors were smaller than those of CT, no matter 4D or 3D, from small to large, the volume sizes were 3DPET volume, average 4DPET volume, 3DCT volume and average 4DCT volume. The relative volume difference was related to the respiratory movement and the size of the tumors. The average 4DPET volume was 22.8% larger than the average 3DPET volume, and the volume ratio was 1.23. The volume of the average 4DCT was 15.4% larger than that of the average 3DCT, and the volume ratio was 1.16. The average volume of 4DCT was 59.5% larger than that of 4DPET. When the movement amplitude of the tumor was greater than 3 mm and less than 5 mm, the larger the tumor volume, the larger the volume ratio of the average 4DCT volume to the average 4DPET volume, with the maximum value being 1.54. When the tumor movement amplitude was greater than 5 mm, the ratio was about 1.4. When the volume of conventional 3DCT was larger than 5 cm3, the ratio of the average 4DCT volume to the average 4DPET volume was 1.9. The planning target area internal target volume (ITV)3DCT was much larger than that of ITV3DPET, intersected ITV4DCTave and ITV4DPETave, the dose V20 and V5 of normal lung tissue, and the dose V30 of heart were increased accordingly. Of these, the dose of lung and heart of ITV4DPETave was the lowest. The V20 and V5 of lung of ITV4DPETave was about 2% lower than ITV4DCTave. Conclusion To delineate lung tumor targets at various positions, particular attention should be paid to the effect of breathing exercises on large movements and large volumes. The target volume seemed to be overestimated by 4DCT, and the average multiphased 4DPET volume was more accurate for delineating the target area while reducing the radiation dose of the lung.

The gas insulated switch (GIS) vibrates during operation. In order to analyze the difference between the vibration signals for loosed bolts or misaligned conducting rods at the connection of GIS shell and the normal operation without defects,a 3D model of 252 kV three-phase box-type GIS is established in this paper. Computational modal analysis is firstly performed on the model in the field of solid mechanics. Secondly,the natural frequency is determined,and the representative sixth mode shapes are obtained. By applying different loads and changing the parameters of the model,the time-domain signals of the vibration acceleration of GIS shell under the state of no fault,different number of bolts loose and different cases of conducting rod misalignment are solved in the solid mechanics field. Then the frequency-domain signals are obtained through spectrum analysis. By comparing and analyzing the difference of vibration acceleration signals of GIS shell in several cases,the characteristics of vibration acceleration of GIS shell in case of bolt loosening fault and conducting rod misalignment fault are obtained. Finally,the criteria for the above faults are obtained. Some certain reference value about the follow-up GIS equipment running condition monitoring,mechanical fault identification and vibration research have been provided in the conclusion of this paper.