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Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

Mechanical metamaterials can be defined as a class of architected materials that exhibit unprecedented mechanical properties derived from designed artificial architectures rather than their constituent mate- rials. While macroscale and simple layouts can be realized by conventional top-down manufacturing approaches, many of the sophisticated designs at various length scales remain elusive, due to the lack of adequate manufacturing methods. Recent progress in additive manufacturing (AM) has led to the reali- zation of a myriad of novel metamaterial concepts. AM methods capable of fabricating microscale archi- tectures with high resolution, arbitrary complexity, and high feature fidelity have enabled the rapid development of architected metamaterials and drastically reduced the design-computation and experimental-validation cycle. This paper first provides a detailed review of various topologies based on the desired mechanical properties, including stiff, strong, and auxetic (negative Poisson’s ratio) meta- materials, followed by a discussion of the AM technologies capable of fabricating these metamaterials. Finally, we discuss current challenges and recommend future directions for AM and mechanical metamaterials.

A gradient nano-grained (GNG) structure demonstrates satisfactory surface strength. However, the underlying mechanism responsible for its strengthening lacks sufficient research. To explain how gradient nano-grained structures improve surface strength in detail, large-scale parallel molecular dynamics simulations are utilized in this study to investigate the mechanical deformation behavior of BCC tungsten with varying grain sizes during spherical nanoindentation. The findings suggest that a well-designed gradient structure can promote rational plasticity and an appropriate distribution of internal atomic stress. The critical point of maximum stress and hardness is observed when the initial grain size is 4.5 nm, with an average grain size of 7.1 nm. The interaction between grain boundary slip and migration in small grains, along with the enhanced activity of grain boundary dislocations in large grains, collectively contributes to the enhancement of the strength and hardness of the GNG structure. Compared with a homogeneous nano-grained structure, the gradient nano-grained structure exhibits a more rational distribution of dislocations and stress relaxation effects to enhance strength. The present work utilizes the molecular dynamics nanoindentation method to study GNG materials, providing a methodology for investigating the surface strengthening effects of GNG structures at the atomic scale and effectively revealing potential mechanisms for resisting surface deformation in GNG structures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants. STUDY DESIGN: This was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018. RESULTS: A total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P = 0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166-4.522, p = 0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p = 0.162). CONCLUSION: Our findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.