bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells
Authors: Guillén-Mancina Emilio , García-Lozano María del Rosario , Burgos-Morón Estefanía , Mazzotta Sarah , Martínez-Aguado Pablo , Calderón-Montaño José Manuel , Vega-Pérez José Manuel , López-Lázaro Miguel , Iglesias-Guerra Fernando , Vega-Holm Margarita
Published: December 2023

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents.
The Development, Optimization and Future of Prime Editing
Authors: Petrova Irina O. , Smirnikhina Svetlana A.
Published: December 2023

Prime editing is a rapidly developing method of CRISPR/Cas-based genome editing. The increasing number of novel PE applications and improved versions demands constant analysis and evaluation. The present review covers the mechanism of prime editing, the optimization of the method and the possible next step in the evolution of CRISPR/Cas9-associated genome editing. The basic components of a prime editing system are a prime editor fusion protein, consisting of nickase and reverse transcriptase, and prime editing guide RNA, consisting of a protospacer, scaffold, primer binding site and reverse transcription template. Some prime editing systems include other parts, such as additional RNA molecules. All of these components were optimized to achieve better efficiency for different target organisms and/or compactization for viral delivery. Insights into prime editing mechanisms allowed us to increase the efficiency by recruiting mismatch repair inhibitors. However, the next step in prime editing evolution requires the incorporation of new mechanisms. Prime editors combined with integrases allow us to combine the precision of prime editing with the target insertion of large, several-kilobase-long DNA fragments.
Z-Ligustilide Combined with Cisplatin Reduces PLPP1-Mediated Phospholipid Synthesis to Impair Cisplatin Resistance in Lung Cancer
Authors: Geng Pengyu , Zhao Jinhui , Li Qi , Wang Xiaolin , Qin Wangshu , Wang Ting , Shi Xianzhe , Liu Xinyu , Chen Jia , Qiu Hongdeng , Xu Guowang
Published: December 2023

Lung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80–85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems. Z-ligustilide is the main active ingredient of the Chinese medicine Angelica sinensis, and has anti-tumor activity. In the present study, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on the resistance of cisplatin-resistant lung cancer cells and its mechanism of action. We found that Z-ligustilide+cisplatin decreased the cell viability, induced cell cycle arrest, and promoted the cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of phospholipid phosphatase 1 (PLPP1). A further study showed that PLPP1 expression was positively correlated with good prognosis, whereas the knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Specifically, Z-ligustilide+cisplatin inhibited the activation of protein kinase B (AKT) by reducing the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3). Z-ligustilide+cisplatin induced cell cycle arrest and promoted the cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis. Our findings demonstrate that the combination of Z-Ligustilide and cisplatin is a promising approach to the chemotherapy of malignant tumors that are resistant to cisplatin.
The Reduction of Carbonyl Compounds with Dicyclopentylzinc: A New Example of Asymmetric Amplifying Autocatalysis
Authors: Saigitbatalova Elena Sh. , Latypova Liliya Z. , Zagidullin Almaz A. , Kurbangalieva Almira R. , Gridnev Ilya D.
Published: December 2023

A previously unknown reduction of carbonyl compounds with dicyclopentylzinc is reported. Aldehydes react in mild conditions yielding corresponding primary alcohols and cyclopentene. Although cyclohexanone and acetophenone are inert to dicyclopentylzinc, a variety of heterocyclic ketones reacted readily, yielding reasonable to high yields of corresponding secondary alcohols. When the reaction was catalyzed with (–)-(1R,2S)-ephedrine, 3-acetylpyridine (10) resulted in a high yield of (S)-1-(pyridin-3-yl)ethanol (19) with >99% ee. 5-Acetyl-2-bromopyridine (11) also provided the corresponding optically active alcohol 20, albeit with a much lower optical yield. When 10% of 19 with 92% ee was used as an autocatalyst, 55% yield of the same compound was obtained, with 95% ee and 96% ee in two independent experiments. A three-stage reaction sequence starting from “no chirality” reaction yielded 19 with 6% ee. Thus, amplifying autocatalysis was detected in the reaction of ketone 10 with dicylopentylzinc.
Experimental and Numerical Investigation of a Turbine Vane Frame with Splitters at Different Operating Points
Authors: Pramstrahler Simon , Peters Andreas , García De Albéniz Mikel Lucas , Leitl Peter Adrian , Heitmeir Franz , Marn Andreas
Published: December 2023

A turbine vane frame is a special type of intermediate turbine duct, and is one option to improve the efficiency and reduce the length and weight of an aero-engine. However, due to its geometry, it features a complex flow field, and therefore in-depth aerodynamic investigations are necessary. Especially for aviation, every component needs to function reliably during all operating points. To perform this study at the Institute for Thermal Turbomachinery at the Graz University of Technology, the Subsonic Test Turbine Facility for Aerodynamic, Aeroacoustic and Aeroelastic Investigations was equipped with a turbine vane frame and a low-pressure turbine located downstream. Measurements were taken with aerodynamic five-hole probes for three operating points, and were compared with steady-state and transient simulations as well as analytic solutions for the pressure drop in the TVF. Finally, the most important loss mechanisms are described.
Profile Loss Prediction for Organic Rankine Cycle Turbines: An Experimental Case Study
Authors: Hake Leander , Sundermeier Stephan , Wiesche Stefan aus der
Published: December 2023

The results of profile loss measurements, including trailing edge flow details, are presented for the flow of an organic vapor through a linear turbine cascade. The so-called VKI-I blade profile from the open literature was chosen for the cascade, and the working fluid was NOVEC 649. Pitot probes and hot-wire anemometry were employed to measure the flow field up and downstream of the cascade. Details of the unsteady flow caused by the trailing edge of the blades and the turbulent spectrum were investigated using hot-wire anemometry. The new organic vapor flow results were compared with the literature data obtained for air and with the prediction of conventional literature loss models. It was found that, under certain thermodynamic conditions, specific traditional loss models can reasonably predict organic Rankine cycle (ORC) turbines’ profile loss. Still, significant deviations between the loss models and the experimental data can also occur.
Characterization of CrufCSP1 and Its Potential Involvement in Host Location by Cotesia ruficrus (Hymenoptera: Braconidae), an Indigenous Parasitoid of Spodoptera frugiperda (Lepidoptera: Noctuidae) in China
Authors: Han Kai-Ru , Wang Wen-Wen , Yang Wen-Qin , Li Xian , Liu Tong-Xian , Zhang Shi-Ze
Published: December 2023

Chemosensory proteins (CSPs) are a class of soluble proteins that facilitate the recognition of chemical signals in insects. While CSP genes have been identified in many insect species, studies investigating their function remain limited. Cotesia ruficrus (Hymenoptera: Braconidae) holds promise as an indigenous biological control agent for managing the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae) in China. This study aimed to shed light on the gene expression, ligand binding, and molecular docking of CrufCSP1 in C. ruficrus. A RT-qPCR analysis revealed that the expression of CrufCSP1 was higher in the wings, with male adults exhibiting significantly higher relative expression levels than other developmental stages. A fluorescence competitive binding analysis further demonstrated that CrufCSP1 has a high binding ability with several host-related volatiles, with trans-2-hexenal, octanal, and benzaldehyde showing the strongest affinity to CrufCSP1. A molecular docking analysis indicated that specific amino acid residues (Phe24, Asp25, Thr53, and Lys81) of CrufCSP1 can bind to these specific ligands. Together, these findings suggest that CrufCSP1 may play a crucial role in the process of C. ruficrus locating hosts. This knowledge can contribute to the development of more efficient and eco-friendly strategies for protecting crops and managing pests.
A Comprehensive Review of the Diagnosis and Management of Acute Liver Failure
Authors: Ozturk Nazli Begum , Herdan Emre , Saner Fuat H. , Gurakar Ahmet
Published: December 2023

Acute liver failure (ALF) is a rare and specific form of severe hepatic dysfunction characterized by coagulopathy and hepatic encephalopathy in a patient with no known liver disease. ALF carries a high morbidity and mortality. Careful attention should be given to hemodynamics and metabolic parameters along with the active surveillance of infections. Timely transfer and supportive management are important in an intensive care unit in a liver transplant center. Identifying patients who will and will not improve with medical management and may need emergent liver transplantation is critical. In this review, we provide a comprehensive update on the etiology, diagnosis, and management of ALF.
Evaluating Cluster-Based Synthetic Data Generation for Blood-Transfusion Analysis
Authors: Kroes Shannon K. S. , van Leeuwen Matthijs , Groenwold Rolf H. H. , Janssen Mart P.
Published: December 2023

Synthetic data generation is becoming an increasingly popular approach to making privacy-sensitive data available for analysis. Recently, cluster-based synthetic data generation (CBSDG) has been proposed, which uses explainable and tractable techniques for privacy preservation. Although the algorithm demonstrated promising performance on simulated data, CBSDG has not yet been applied to real, personal data. In this work, a published blood-transfusion analysis is replicated with synthetic data to assess whether CBSDG can reproduce more complex and intricate variable relations than previously evaluated. Data from the Dutch national blood bank, consisting of 250,729 donation records, were used to predict donor hemoglobin (Hb) levels by means of support vector machines (SVMs). Precision scores were equal to the original data results for both male (0.997) and female (0.987) donors, recall was 0.007 higher for male and 0.003 lower for female donors (original estimates 0.739 and 0.637, respectively). The impact of the variables on Hb predictions was similar, as quantified and visualized with Shapley additive explanation values. Opportunities for attribute disclosure were decreased for all but two variables; only the binary variables Deferral Status and Sex could still be inferred. Such inference was also possible for donors who were not used as input for the generator and may result from correlations in the data as opposed to overfitting in the synthetic-data-generation process. The high predictive performance obtained with the synthetic data shows potential of CBSDG for practical implementation.
Process Chains for Micro-Manufacturing: Modeling and Case Studies
Authors: Basile Vito , Modica Francesco , Rebaioli Lara , Surace Rossella , Fassi Irene
Published: December 2023

As the complexity of micro-products increases, the micro-manufacturing processes, tool setups, and measurement processes have to be more precise and efficient. Combining them in a multi-stage process chain can effectively improve production accuracy and performance and reduce limitations and production costs. This paper focuses on the process chains for the manufacturing of micro-products and presents the state of the art, highlighting the specific characteristics of the existing models of process chains for micro-manufacturing. Based on the critical review of these characteristics, an evolution of the process chain model for micro-manufacturing is proposed, considering machining, measurement/characterization, referencing processes, and their combination into a suitable sequence. The proposed model accounts for relevant aspects of micro-manufacturing, such as size effects and technological fingerprints at the microscale. This paper also discusses the hierarchical properties of multiple micro-manufacturing process chains and some specific techniques to address the critical issue of referencing processes. Furthermore, some relevant case studies involving micro-electrical discharge machining, micro-injection molding, additive manufacturing, and micro-milling are presented to demonstrate how the micro-manufacturing potentiality can be increased using process chains.
Carbon Nanotubes and Graphene Materials as Xenobiotics in Living Systems: Is There a Consensus on Their Safety?
Authors: Gendron David , Bubak Grzegorz
Published: December 2023

Carbon nanotubes and graphene are two types of nanomaterials that have unique properties and potential applications in various fields, including biomedicine, energy storage, and gas sensing. However, there is still a debate about the safety of these materials, and there is yet to be a complete consensus on their potential risks to human health and the environment. While some studies have provided recommendations for occupational exposure limits, more research is needed to fully understand the potential risks of these materials to human health and the environment. In this review, we will try to summarize the advantages and disadvantages of using carbon nanotubes and graphene as well as composites containing them in the context of their biocompatibility and toxicity to living systems. In addition, we overview current policy guidelines and technical regulations regarding the safety of carbon-based nanomaterials.
Navigating through the Controversies and Emerging Paradigms in Early Detection of Prostate Cancer: Bridging the Gap from Classic RCTs to Modern Population-Based Pilot Programs
Authors: Gómez Rivas Juan , Leenen Renée C. A. , Venderbos Lionne D. F. , Helleman Jozien , de la Parra Irene , Vasilyeva Vera , Moreno-Sierra Jesús , Basu Partha , Chandran Arunah , van den Bergh Roderick C. N. , Collen Sarah , Van Poppel Hein , Roobol Monique J. , Beyer Katharina ,   on behalf of the PRAISE-U Consortium
Published: December 2023

Over the last three decades, the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening have steered the conversation around the early detection of prostate cancer. These two randomized trials assessed the effect of screening on prostate cancer disease-specific mortality. Elevated PSA levels were followed by a systematic sextant prostate biopsy. Standard repeat testing intervals were applied. After controversies from 2009 to 2016 due to contradicting results of the two trials, the results aligned in 2016 and showed that early PSA detection reduces prostate cancer-specific mortality. However, overdiagnosis rates of up to 50% were reported, and this sparked an intense debate on harms and benefits for almost 20 years. The balance between harms and benefits is highly debated and has initiated further research to investigate new ways of early detection. In the meantime, the knowledge and tools for the diagnostic algorithm improved. This is a continuously ongoing effort which focuses on individual risk-based screening algorithms that preserve the benefits of the purely PSA-based screening algorithms, while reducing the side effects. An important push towards investigating new techniques for early detection came from the European Commission on the 20th of September 2022. The European Commission published its updated recommendation to investigate prostate, lung, and gastric cancer early detection programs. This opened a new window of opportunity to move away from the trial setting to population-based early detection settings. With this review, we aim to review 30 years of historical evidence of prostate cancer screening, which led to the initiation of the ‘The Prostate Cancer Awareness and Initiative for Screening in the European Union’ (PRAISE-U) project, which aims to encourage the early detection and diagnosis of PCa through customized and risk-based screening programs.
Assessing Non-Specific Neck Pain through Pose Estimation from Images Based on Ensemble Learning
Authors: Kang Jiunn-Horng , Hsieh En-Han , Lee Cheng-Yang , Sun Yi-Ming , Lee Tzong-Yi , Hsu Justin Bo-Kai , Chang Tzu-Hao
Published: December 2023

Background: Mobile phones, laptops, and computers have become an indispensable part of our lives in recent years. Workers may have an incorrect posture when using a computer for a prolonged period of time. Using these products with an incorrect posture can lead to neck pain. However, there are limited data on postures in real-life situations. Methods: In this study, we used a common camera to record images of subjects carrying out three different tasks (a typing task, a gaming task, and a video-watching task) on a computer. Different artificial intelligence (AI)-based pose estimation approaches were applied to analyze the head’s yaw, pitch, and roll and coordinate information of the eyes, nose, neck, and shoulders in the images. We used machine learning models such as random forest, XGBoost, logistic regression, and ensemble learning to build a model to predict whether a subject had neck pain by analyzing their posture when using the computer. Results: After feature selection and adjustment of the predictive models, nested cross-validation was applied to evaluate the models and fine-tune the hyperparameters. Finally, the ensemble learning approach was utilized to construct a model via bagging, which achieved a performance with 87% accuracy, 92% precision, 80.3% recall, 95.5% specificity, and an AUROC of 0.878. Conclusions: We developed a predictive model for the identification of non-specific neck pain using 2D video images without the need for costly devices, advanced environment settings, or extra sensors. This method could provide an effective way for clinically evaluating poor posture during real-world computer usage scenarios.
Bottom Electrode Effects on Piezoelectricity of Pb(Zr0.52,Ti0.48)O3 Thin Film in Flexible Sensor Applications
Authors: Yuan Yanling , Gao Ling , Li Naixin , Gao Jiuning , Yan Yu , Zhao Yiming , Ren Zongqiang , Gong Hongxin , Zhang Yunfei , Liu Yongbin , Wu Ming , Zhong Lisheng
Published: December 2023

Piezoelectric thin films grown on a mechanical, flexible mica substrate have gained significant attention for their ability to convert mechanical deformation into electrical energy though a curved surface. To extract the generated charge from the PZT thin films, bottom electrodes are typically grown on mica substrates. However, this bottom electrode also serves as a buffering layer for the growth of PZT films, and its impact on the piezoelectric properties of PZT thin films remains understudied. In this work, the effect of Pt and LaNiO3 bottom electrodes on the piezoelectric effect of a Pb(Zr0.52,Ti0.48)O3 thin film was investigated. It was observed that the PZT thin films on LNO/Mica substrate possessed weaker stress, stronger (100) preferred orientation, and higher remanent polarization, which is beneficial for a higher piezoelectric response theoretically. However, due to insufficient grain growth resulting in more inactive grain boundaries and lattice imperfections, the piezoelectric coefficient of the PZT thin film on LNO/Mica was smaller than that of the PZT thin film on a Pt/Mica substrate. Therefore, it is concluded that, under the current experimental conditions, PZT films grown with Pt as the bottom electrode are better suited for applications in flexible piezoelectric sensor devices. However, when using LNO as the bottom electrode, it is possible to optimize the grain size of PZT films by adjusting the sample preparation process to achieve piezoelectric performance exceeding that of the PZT/Pt/Mica samples.
Development of Computational Approach for Analyzing In-Process Thermal-Mechanical Condition during Friction Stir Welding for Prediction of Material Bonding Defect
Authors: Chen Gaoqiang , Liu Huijie , Shi Qingyu
Published: December 2023

Unlike the conventional fusion welding process, friction stir welding (FSW) relies on solid-state bonding (SSB) to join metal surfaces. In this study, a straightforward computational methodology is proposed for predicting the material bonding defects during FSW using quantitative evaluation of the in-process thermal-mechanical condition. Several key modeling methods are integrated for predicting the material bonding defects. FSW of AA2024 is taken as an example to demonstrate the performance of the computational analysis. The dynamic sticking (DS) model is shown to be able to predict the geometry of the rotating flow zone near the welding tool. Butting interface tracking (BIT) analysis shows a significant orientation change occurring to the original butting interface, owing to the material flow in FSW, which has a major impact on the bonding pressure at the butting interface. The evolution of the interfacial temperature and the interfacial pressure at the butting interface was obtained to analyze their roles in the formation of material bonding. Four bonding-quality indexes for quantifying the thermal-mechanical condition are tested to show their performance in characterizing the bonding quality during FSW. When the BQI is below a critical value, a bonding defect will be generated. The paper indicates that the simulation-based prediction of a material bonding defect is highly feasible if the developed methodology is extended to quantitatively determine the critical value of the bonding quality index for successful SSB for various alloys.
Solving Partially Observable 3D-Visual Tasks with Visual Radial Basis Function Network and Proximal Policy Optimization
Authors: Hautot Julien , Teulière Céline , Azzaoui Nourddine
Published: December 2023

Visual Reinforcement Learning (RL) has been largely investigated in recent decades. Existing approaches are often composed of multiple networks requiring massive computational power to solve partially observable tasks from high-dimensional data such as images. Using State Representation Learning (SRL) has been shown to improve the performance of visual RL by reducing the high-dimensional data into compact representation, but still often relies on deep networks and on the environment. In contrast, we propose a lighter, more generic method to extract sparse and localized features from raw images without training. We achieve this using a Visual Radial Basis Function Network (VRBFN), which offers significant practical advantages, including efficient and accurate training with minimal complexity due to its two linear layers. For real-world applications, its scalability and resilience to noise are essential, as real sensors are subject to change and noise. Unlike CNNs, which may require extensive retraining, this network might only need minor fine-tuning. We test the efficiency of the VRBFN representation to solve different RL tasks using Proximal Policy Optimization (PPO). We present a large study and comparison of our extraction methods with five classical visual RL and SRL approaches on five different first-person partially observable scenarios. We show that this approach presents appealing features such as sparsity and robustness to noise and that the obtained results when training RL agents are better than other tested methods on four of the five proposed scenarios.
The Efficacy of Immunotherapy and Clinical Utility of Comprehensive Genomic Profiling in Adenoid Cystic Carcinoma of Head and Neck
Authors: Naito Takahiro , Noji Rika , Kugimoto Takuma , Kuroshima Takeshi , Tomioka Hirofumi , Fujiwara Shun , Suenaga Mitsukuni , Harada Hiroyuki , Kano Yoshihito
Published: December 2023

Background and Objectives: Adenoid cystic carcinoma (ACC) of the head and neck is generally slow-growing but has a high potential for local recurrence and metastasis to distant organs. There is currently no standard pharmacological treatment for recurrent/metastatic (R/M) ACC, and there are cases in which immune checkpoint inhibitors (ICIs) are administered for ACC according to head and neck squamous cell carcinoma (HNSCC). However, the efficacy of ICIs for ACC remains unclear, and the predictive biomarkers need to be elucidated. Materials and Methods: The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database enabled the retrospective but nationwide analysis of 263 cases of ACC of the head and neck. Then, we examined and reported four cases of ACC that received ICIs and comprehensive genomic profiling (CGP) in our institution. Results: The C-CAT database revealed that 59 cases out of 263 received ICIs, and the best response was 8% of objective response rate (ORR) and 53% of disease control rate (DCR) (complete response, CR 3%, partial response, PR 5%, stable disease, SD 44%, progressive disease, PD 19%, not evaluated, NE 29%). The tumor mutational burden (TMB) in ACC was lower overall compared to HNSCC and could not be useful in predicting the efficacy of ICIs. Some cases with MYB structural variants showed the response to ICIs in the C-CAT database. A patient with MYB fusion/rearrangement variants in our institution showed long-term stable disease. Conclusions: ICI therapy is a potential treatment option, and the MYB structural variant might be a candidate for predictive biomarkers for immunotherapy in patients with R/M ACC.
Effect of CaO Content and Annealing Treatment on the Room-Temperature Mechanical Properties of AZ61 and AZ61-CaO Alloys
Authors: Chaudry Umer Masood , Tariq Hafiz Muhammad Rehan , Ansari Nooruddin , Mansoor Adil , Khan Muhammad Kashif , Hamad Kotiba , Jun Tea-Sung
Published: December 2023

In the present study, the effect of annealing treatment on the room-temperature mechanical performance of AZ61, AZ61-0.5CaO and AZ61-1CaO was thoroughly investigated. The as-rolled samples were annealed at 400 °C for 1 h followed by furnace cooling. Microstructural characterization was carried out using optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron back-scattered diffraction (EBSD). Moreover, room-temperature uniaxial tensile tests were carried out on the non-annealed and annealed samples along the rolling direction at the strain rate of 10−3 s−1. Microstructural analysis showed the presence of profuse {101¯2} twinning in non-annealed samples and the twinning fraction was increased by the addition of CaO content. SEM showed the formation of precipitates in the AZ61-CaO alloys and TEM confirmed the precipitates to be (Mg, Al)2Ca. The room-temperature tensile tests showed that the mechanical properties of AZ61 were slightly reduced by the addition of CaO, which was attributed to the higher local stress concentration due to the twin–twin interactions. Furthermore, the annealing treatment led to significant enhancement in the YS and UTS of AZ61-1CaO, which is related to the precipitation hardening induced by the intermetallic precipitates.
Effect of Al/Mg Ratio on the Microstructure and Phase Distribution of Zn-Al-Mg Coatings
Authors: Zhang Ziyue , Zhang Jie , Zhao Xingyuan , Liu Xin , Cheng Xuequn , Jiang Sheming , Zhang Qifu
Published: December 2023

In contrast with studies such as those on the effect of a single elemental variable on Zn-Al-Mg coatings, Mg/Al is considered a variable parameter for evaluating the microstructure of Zn-Al-Mg coatings in this work, and the combined effect of the two elements is also taken into account. The Mg/Al ratios in the continuous hot-dip plating of low-alumina Zn-Al-Mg coatings were 0.63, 0.75, 1.00, 1.25, and 1.63. respectively, and the microstructures of the different coatings were observed using scanning electron microscopy (SEM). The surface elemental distributions of the coatings were analyzed with energy dispersive spectrometry (EDS) and X-ray diffraction (XRD) analysis to understand the phase distributions of the coatings, which mainly consisted of a zinc monomeric phase, a binary eutectic phase (Zn/MgZn2), and a ternary eutectic phase (Zn/Al/MgZn2). Statistical calculations of the phase distributions in colored SEM images were performed using ImageJ-win64 software, comparative analysis of the solidification simulation results was carried out with thermodynamic simulation software (PANDAT-2023), and evaluation of the corrosion resistance of the platings was performed using macroscopic cyclic immersion corrosion experiments. The results show that with the increase in the Mg/Al ratio, the binary eutectic phase in the coatings gradually increased, the variation trend of the ternary eutectic phase was not obvious, and the corrosion resistance of the coatings gradually improved.
Parametric Investigation of the Effects of Electrical Discharge Machining on Plain D2 Steel
Authors: Hassan Abual , Mushtaq Ray Tahir , Mashood Khan Aqib , Anwar Saqib
Published: December 2023

Electrical discharge machining (EDM) has emerged as a pivotal non-conventional production technique due to its unique capability to machine without the cutting tool’s physical contact with the workpiece, making it apt for brittle, delicate, and complex materials. This research delved into the influence of operational parameters—pulse duration (Ton), peak current (Ip), duty cycle (T), and gap voltage (Vg)—on machining attributes, namely material removal rate (MRR), electrode wear rate (EWR), and radial overcut (ROC) for AISI D2 steel. Utilizing the Taguchi L9 orthogonal array for experimental design, nine experiments were conducted, followed by signal-to-noise ratio (S/N ratio) computations. Key findings highlighted a 4.02 dB improvement in the S/N ratio for MRR, leading to a 29.13% improvement; a 10.35 dB enhancement in the S/N ratio for EWR, resulting in a 33.33% reduction; and a 2.20 dB increase in the S/N ratio for ROC, leading to a 28.57% increment. ANOVA analyses further underscored the predominant influence of all four parameters. The significance of these findings lies in optimizing the EDM process for increased efficiency, reduced tool wear, and enhanced precision, potentially leading to cost savings and improved production quality in industrial applications.
Microstructural Characterization of In Situ Aluminum Matrix Composites with Interconnected Aluminum Nitride Produced by Arc Plasma-Induced Accelerated Volume Nitridation
Authors: Jeong Sujin , Kim Taeyoon , Lee Je In
Published: December 2023

We present a strategy for fabricating aluminum (Al) matrix composites (AMCs) reinforced with interconnected aluminum nitride (AlN) via arc plasma-induced accelerated volume nitridation. AMCs with 10 vol.% AlN are formed in situ by the reaction between liquid Al alloy and nitrogen gas within 1 min of arc melting, revealing very high formation rate of AlN (3.28 × 10−1 g/min·cm3). The rapid nitridation is attributed to the improved wettability and spontaneous infiltration of the melt, which results in the formation of AlN agglomerates and lamellas. In particular, Al-12Si/AlN composites exhibit over two times higher yield strength (195 MPa) than the Al/AlN composites (70 MPa) when compressed along the longitudinal direction to the lamellas. The coefficient of thermal expansion (CTE) is about 30% lower in the Al-12Si/AlN composites (17.0 × 10−6/K) than pure Al (23.6 × 10−6/K). This is attributed to the interconnected AlN architecture and Al–Si eutectic microstructure, which constrain the thermal expansion of the Al matrix. The present AMCs afford an attractive combination of specific thermal conductivity and CTE. These findings would facilitate the development of novel AMCs reinforced with interconnected AlN as cost-effective heat sink materials.
Fabrication of Dimples by Jet-ECM of Zr-Based Bulk Metallic Glasses with NaCl-Ethylene Glycol Electrolyte
Authors: Guo Cheng , He Jingwen , Zhuang Weizhen , Li Kangsen , Li Duo
Published: December 2023

Zr-based bulk metallic glasses (BMGs) possess unique mechanical and biochemical properties, which have been widely noticed. Jet electrochemical machining (jet-ECM), characterized by a high-speed jet, is a non-contact subtractive method with a high resolution and a high material removal rate (MRR). Past work on the electropolishing of Zr-based BMGs has indicated the feasibility of the NaCl-Ethylene Glycol (EG) electrolyte. In this research, the jet-ECM of Zr-based BMGs in the NaCl-EG electrolyte was studied to explore the dissolving mechanisms and surface integrity according to the voltage, pulse-on time and effective voltage time. The diameter, depth and surface morphologies of dimples were evaluated. The results showed that using this alcohol-based electrolyte led to a desirable surface morphology. The diameter and depth of the dimples varied with the voltage and the effective voltage time in a significantly positive proportional manner. Additionally, cases based on multiple parameter sets exhibited different stray corrosion severity. Afterward, machining performance can be enhanced in the next stage by tuning machining parameters to obtain microscale dimples with better quality.
Low-Cost Optical pH Sensor with a Polyaniline (PANI)-Sensitive Layer Based on Commercial Off-the-Shelf (COTS) Components
Authors: Stoukatch Serguei , Debliquy Marc , Dupont Francois , Redouté Jean-Michel
Published: December 2023

In this paper, we presented a novel, compact, conceptually simple, and fully functional low-cost prototype of a pH sensor with a PANI thin film as a sensing layer. The PANI deposition process is truly low-cost; it performs from the liquid phase, does not required any specialized equipment, and comprises few processing steps. The resulting PANI layer has excellent stability, resistance to solvents, and bio- and chemical compatibility. The pH sensor’s sensing part includes only a few components such as a red-light-emitting diode (LED) as a light source, and a corresponding photodiode (PD) as a detector. Unlike other PANI-based sensors, it requires no sophisticated and expensive techniques and components such lasers to excite the PANI or spectrometry to identify the PANI color change induced by pH variation. The pH sensor is sensitive in the broad pH range of 3 to 9, which is useful for numerous practical applications. The sensor requires a tiny volume of the test specimen, as little as 55 µL. We developed a fully integrated packaging solution for the pH sensor that comprises a limited number of components. The pH sensor comprises exclusively commercial off-the-shelf (COTS) components and standard printed circuit boards. The pH sensor is assembled using standard surface mounting technology (SMT).
High-Precision Ultra-Long Air Slit Fabrication Based on MEMS Technology for Imaging Spectrometers
Authors: Ren Xiaoyu , Yao Selina X. , Zhu Jiacheng , Deng Zejun , Wang Yijia , Zhang Baoshun , Zeng Zhongming , Zhai Hao
Published: December 2023

The increasing demand for accurate imaging spectral information in remote sensing detection has driven the development of hyperspectral remote sensing instruments towards a larger view field and higher resolution. As the core component of the spectrometer slit, the designed length reaches tens of millimeters while the precision maintained within the μm level. Such precision requirements pose challenges to traditional machining and laser processing. In this paper, a high-precision air slit was created with a large aspect ratio through MEMS technology on SOI silicon wafers. In particular, a MEMS slit was prepared with a width of 15 μm and an aspect ratio exceeding 4000:1, and a spectral spectroscopy system was created and tested with a Hg-Cd light source. As a result, the spectral spectrum was linear within the visible range, and a spectral resolution of less than 1 nm was obtained. The standard deviation of resolution is only one-fourth of that is seen in machined slits across various view fields. This research provided a reliable and novel manufacturing technique for high-precision air slits, offering technical assistance in developing high-resolution wide-coverage imaging spectrometers.
Microfiber-Patterned Versatile Perfusable Vascular Networks
Authors: Tian Ye , Wang Liqiu
Published: December 2023

Rapid construction of versatile perfusable vascular networks in vitro with cylindrical channels still remains challenging. Here, a microfiber-patterned method is developed to precisely fabricate versatile well-controlled perfusable vascular networks with cylindrical channels. This method uses tensile microfibers as an easy-removable template to rapidly generate cylindrical-channel chips with one-dimensional, two-dimensional, three-dimensional and multilayered structures, enabling the independent and precise control over the vascular geometry. These perfusable and cytocompatible chips have great potential to mimic vascular networks. The inner surfaces of a three-dimensional vascular network are lined with the human umbilical vein endothelial cells (HUVECs) to imitate the endothelialization of a human blood vessel. The results show that HUVECs attach well on the inner surface of channels and form endothelial tubular lumens with great cell viability. The simple, rapid and low-cost technique for versatile perfusable vascular networks offers plenty of promising opportunities for microfluidics, tissue engineering, clinical medicine and drug development.
Mass Spectrometric Detection of Formaldehyde-Crosslinked PBMC Proteins in Cell-Free DNA Blood Collection Tubes
Authors: Röth Daniel , Molina-Franky Jessica , Williams John C. , Kalkum Markus
Published: December 2023

Streck tubes are commonly used to collect blood samples to preserve cell-free circulating DNA. They contain imidazolidinyl urea as a formaldehyde-releasing agent to stabilize cells. We investigated whether the released formaldehyde leads to crosslinking of intracellular proteins. Therefore, we employed a shotgun proteomics experiment on human peripheral blood mononuclear cells (PBMCs) that were isolated from blood collected in Streck tubes, EDTA tubes, EDTA tubes containing formaldehyde, or EDTA tubes containing allantoin. The identified crosslinks were validated in parallel reaction monitoring LC/MS experiments. In total, we identified and validated 45 formaldehyde crosslinks in PBMCs from Streck tubes, which were also found in PBMCs from formaldehyde-treated blood, but not in EDTA- or allantoin-treated samples. Most were derived from cytoskeletal proteins and histones, indicating the ability of Streck tubes to fix cells. In addition, we confirm a previous observation that formaldehyde crosslinking of proteins induces a +24 Da mass shift more frequently than a +12 Da shift. The crosslinking capacity of Streck tubes needs to be considered when selecting blood-collection tubes for mass-spectrometry-based proteomics or metabolomic experiments.
Effect of Fragment 1 on the Binding of Epigallocatechin Gallate to the PD-L1 Dimer Explored by Molecular Dynamics
Authors: Guo Yan , Guo Yilin , Guo Zichao , Liu Boping , Xu Jianguo
Published: December 2023

Blocking the interaction between programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) by directly targeting the PD-L1 dimer has emerged as a hot topic in the field of cancer immunotherapy. Epigallocatechin gallate (EGCG), a natural product, has been demonstrated binding to the PD-L1 dimer in our previous study, but has a weaker binding capacity, moreover, EGCG is located at the end of the binding pocket of the PD-L1 dimer. The inhibitor fragment 1 (FRA) lies at the other end. So, we proposed that the introduction of FRA might be able to improve the binding ability. To illuminate this issue, molecular dynamics (MD) simulation was performed in the present study. Binding free energy calculations show that the binding affinity is significantly increased by 17 kcal/mol upon the introduction of FRA. It may be due to the energy contributions of emerging key residues ATyr56, AMet115, BTyr123, AIle54 and the enhanced contributions of initial key residues ATyr123 and BVal68. Binding mode and non-bonded interaction results indicate that FRA_EGCG (EGCG in combination with FRA) binds to the C-, F- and G-sheet of the PD-L1 dimer. Importantly, the introduction of FRA mainly strengthened the nonpolar interactions. The free energy landscape and secondary structure results further show that FRA_EGCG can interact with the PD-L1 dimer more stably. These data demonstrated here provide the theoretical basis for screening two or more natural products with additive inhibitory effect on this pathway and therefore exerting more effective anticancer immunity.
Target Screen of Anti-Hyperuricemia Compounds from Cortex Fraxini In Vivo Based on ABCG2 and Bioaffinity Ultrafiltration Mass Spectrometry
Authors: Huang Xiuxiu , Dong Wenqing , Luo Xiao , Xu Lu , Wang Yinan
Published: December 2023

The ATP-binding cassette (ABC) transporter ABCG2 is a significant urate transporter with a high capacity, and it plays a crucial role in the development of hyperuricemia and gout. Therefore, it has the potential to be targeted for therapeutic interventions. Cortex Fraxini, a traditional Chinese medicine (TCM), has been found to possess anti-hyperuricemia properties. However, the specific constituents of Cortex Fraxini responsible for this effect are still unknown, particularly the compound that is responsible for reducing uric acid levels in vivo. In this study, we propose a target screening protocol utilizing bio-affinity ultrafiltration mass spectrometry (BA-UF-MS) to expediently ascertain ABCG2 ligands from the plasma of rats administered with Cortex Fraxini. Our screening protocol successfully identified fraxin as a potential ligand that interacts with ABCG2 when it functions as the target protein. Subsequent investigations substantiated fraxin as an activated ligand of ABCG2. These findings imply that fraxin exhibits promise as a drug candidate for the treatment of hyperuricemia. Furthermore, the utilization of BA-UF-MS demonstrates its efficacy as a valuable methodology for identifying hit compounds that exhibit binding affinity towards ABCG2 within TCMs.
Exploring the Potential of Immersive Virtual Reality in Italian Schools: A Practical Workshop with High School Teachers
Authors: Romano Marco , Frolli Alessandro , Aloisio Alessandro , Russello Claudio , Rega Angelo , Cerciello Francesco , Bisogni Fabio
Published: December 2023

In recent years, there has been a surge of interest in affordable and accessible extended reality devices. Big tech companies like Apple and Meta have announced advanced devices expected to become more prevalent in everyday life. As younger generations embrace immersive digital realities for socialization, entertainment, and information retrieval, there is a need to explore immersive digital technologies that support experiential learning and reevaluate educational approaches. In Italy, the COVID-19 pandemic has sparked a growing interest in immersive virtual reality (VR) and the metaverse for distance education. However, the integration of VR in Italian schools could be faster, primarily due to cost and teacher knowledge challenges. Our study aims to involve high school teachers in a practical workshop to assess their knowledge, skills, and intention to use VR in their teaching after brief training. The focus is on evaluating the acceptability of VR for educational purposes among Italian high school teachers. The workshop involved up to 16 teachers at once and was repeated eight times to reach 120 teachers. Participants received VR training and explored three educational VR applications. The results show that teachers are interested in learning and integrating VR into their lessons. They believe it can enhance teaching practices by actively engaging students and enabling experiential learning. This work provides an overview of the current state of VR in education, describes the workshop with high school teachers, and presents the obtained results.
Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus
Authors: Hayden Melvin R.
Published: December 2023

Astrocytes (ACs) are the most abundant cells in the brain and, importantly, are the master connecting and communicating cells that provide structural and functional support for brain cells at all levels of organization. Further, they are recognized as the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste. They comprise the glymphatic system, which is critically dependent on proper waste removal by the pvACef polarized aquaporin-4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role in synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI), and are associated with white matter hyperintensities, lacunes, and aging, and are accepted as biomarkers for cerebral small vessel disease, increased obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.