Numerical computation of wheel-rail impact noises with considering wheel flats based on the boundary element method

When a wheel rolls to a flat, it can generate the impact force several multiples larger than that generated at the common time. The paper established a wheel-rail coupling vibration model with wheel flat, and vibration acceleration responses of the rail was computed. The computational result was then compared with the experimental result. Good consistency between simulation and experiment indicated that the finite element model is reliable. Then, based on the finite element model and boundary element model, the paper established a structural-acoustic coupling boundary element model and computed the radiation noise of wheel-rail under effects of wheel flats. Results show that: the wheel flats were an important reason for wheel rail impact noises, impact noises of wheel flats were mainly concentrated in frequency bands of over 250 Hz, and impact noises of wheel flats were closely related with wheel flat length, quantity of wheel flats as well as running speeds. With the increase of these parameters, the radiation noise of wheel flats would be increased correspondingly

Improvement of the fatigue life of an electron-beam welded Ti2AlNb joint subjected to an electromagnetic coupling treatment

The local stress concentration created by the seam welding process often reduces the fatigue life of the material along and around the seam. Post-welding heat treatment is usually used to improve the weld performance, but the improvement effect on fatigue life may not be obvious. In this study, a new treatment method of electromagnetic coupling was applied to regulate the Ti2AlNb electron beam weld after heat treatment, so as to improve the fatigue properties of the welded joint. The results show that after electromagnetic coupling treatment, the fatigue limit of the welded joint is increased by 10.4 %, the residual compressive stress is increased, and the fatigue crack propagation rate is decreased. The microstructure analysis shows that after electromagnetic coupling treatment, the fatigue crack source starts in the subsurface layer, the substructural crystals in the fusion zone and the heat affected zone decrease, the recrystallization content and the large angle grain boundary increase, and the dislocation density increases and tends to be homogenized. An increase of at least 2.3 % in hardness of the welded joints also indicates the increase in the dislocation density. Local high density dislocation is found in the grain, which causes dislocation entanglement and hinders crack initiation and propagation and this provides an important basis for improving fatigue properties. This study provides a new method for improving the fatigue properties of Ti2AlNb electron beam welds which can also be used to study the properties of other welded joints

Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (4, AChE: IC50 = 0.223 μM) with pyrimidone compound 5 (GSK-3β: IC50 = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3β (GSK-3β). The optimal compound 18a possessed potent dual AChE/GSK-3β inhibition (AChE: IC50 = 0.047 ± 0.002 μM, GSK-3β: IC50 = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure–activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs

Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment

Neoadjuvant chemoimmunotherapy cycle number selection for non-small cell lung cancer and clinical outcomes: a real-world analysis

ObjectivesNeoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC.MethodsThis study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate.ResultsA total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041).ConclusionOur data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3–4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles

CMRxRecon: An open cardiac MRI dataset for the competition of accelerated image reconstruction

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a limitation of CMR is its slow imaging speed, which causes patient discomfort and introduces artifacts in the images. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have not been publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. Manual segmentations of the myocardium and chambers of all the subjects are also provided within the dataset. Scripts of state-of-the-art reconstruction algorithms were also provided as a point of reference. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community. Researchers can access the dataset at https://www.synapse.org/#!Synapse:syn51471091/wiki/.Comment: 14 pages, 8 figure

Redox probe-based amperometric sensing for solid-contact ion-selective electrodes

The transformation from the traditional potentiometric response of an ion-selective electrode (ISE) to other signal readout is promising to realize the potential signal amplification. In this work, the redox probes, including ferrocyanide/ferricyanide (Fe(CN)(6)(3-/4-)), hexaammineruthenium (Ru(NH3)(6)(3+)) and ferrocene derivatives, were introduced to read out the potentiometric response for the solid-contact Ca2+-ISE. The mechanism is that the oxidation current of the redox probe on a glassy carbon electrode is modulated by the potential of the ISE through changing the concentrations/activities of Ca2+ under the control of the constant applied potential. Results show that the linear range and the slope sensitivity for detection Ca2+ by using the amperometric signal based on Fe(CN)(6)(4-/3)-redox probe are adjustable through changing the applied potentials. Moreover, the redox probe-based amperometric signal for the solid-contact Ca2+-ISE is found to be related to both of the types of the redox probes and the electrode areas. This work provides a convenient and general method for translating the potential response at mV grade to the amperometric signal at the mu A level, and is promising for detection of ions with high sensitivity by using the ISEs