bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Curvature Self-Folding Method of a Thick Metal Layer for Hinged Origami/Kirigami Stretchable Electronic Devices
Authors: Eda Atsushi , Yasuga Hiroki , Sato Takashi , Sato Yusuke , Suto Kai , Tachi Tomohiro , Iwase Eiji
Published: June 2022

A self-folding method that can fold a thick (~10 μm) metal layer with a large curvature (>1 mm−1) and is resistant to repetitive folding deformation is proposed. Given the successful usage of hinged origami/kirigami structures forms in deployable structures, they show strong potential for application in stretchable electronic devices. There are, however, two key difficulties in applying origami/kirigami methods to stretchable electronic devices. The first is that a thick metal layer used as the conductive layer of electronic devices is too hard for self-folding as it is. Secondly, a thick metal layer breaks on repetitive folding deformation at a large curvature. To overcome these difficulties, this paper proposes a self-folding method using hinges on a thick metal layer by applying a meander structure. Such a structure can be folded at a large curvature even by weak driving forces (such as those produced by self-folding) and has mechanical resistance to repetitive folding deformation due to the local torsional deformation of the meander structure. To verify the method, the large curvature self-folding of thick metal layers and their mechanical resistance to repetitive folding deformation is experimentally demonstrated. In addition, an origami/kirigami hybrid stretchable electronic device with light-emitting diodes (LEDs) is fabricated using a double-tiling structure called the perforated extruded Miura-ori.
Thermal Induced Interface Mechanical Response Analysis of SMT Lead-Free Solder Joint and Its Adaptive Optimization
Authors: Liu Shaoyi , Yan Yuefei , Zhou Yijiang , Han Baoqing , Wang Benben , Zhang Daxing , Xue Song , Wang Zhihai , Yu Kunpeng , Shi Yu , Wang Congsi
Published: June 2022

Surface mount technology (SMT) plays an important role in integrated circuits, but due to thermal stress alternation caused by temperature cycling, it tends to have thermo-mechanical reliability problems. At the same time, considering the environmental and health problems of lead (Pb)-based solders, the electronics industry has turned to lead-free solders, such as ternary alloy Sn-3Ag-0.5Cu (SAC305). As lead-free solders exhibit visco-plastic mechanical properties significantly affected by temperature, their thermo-mechanical reliability has received considerable attention. In this study, the interface delamination of an SMT solder joint using a SAC305 alloy under temperature cycling has been analyzed by the nonlinear finite element method. The results indicate that the highest contact pressure at the four corners of the termination/solder horizontal interface means that delamination is most likely to occur, followed by the y-direction side region of the solder/land interface and the top arc region of the termination/solder vertical interface. It should be noted that in order to keep the shape of the solder joint in the finite element model consistent with the actual situation after the reflow process, a minimum energy-based morphology evolution method has been incorporated into the established finite element model. Eventually, an Improved Efficient Global Optimization (IEGO) method was used to optimize the geometry of the SMT solder joint in order to reduce the contact pressure at critical points and critical regions. The optimization result shows that the contact pressure at the critical points and at the critical regions decreases significantly, which also means that the probability of thermal-induced delamination decreases.
Contributions of Red Blood Cell Sedimentation in a Driving Syringe to Blood Flow in Capillary Channels
Authors: Kang Yang
Published: June 2022

The erythrocyte sedimentation rate (ESR), which has been commonly used to detect physiological and pathological diseases in clinical settings, has been quantified using an interface in a vertical tube. However, previous methods do not provide biophysical information on blood during the ESR test. Therefore, it is necessary to quantify the individual contributions in terms of viscosity and pressure. In this study, to quantify RBC sedimentation, the image intensity (Ib) and interface (β) were obtained by analyzing the blood flow in the microfluidic channels. Based on threshold image intensity, the corresponding interfaces of RBCs (Ib > 0.15) and diluent (Ib < 0.15) were employed to obtain the viscosities (µb, µ0) and junction pressures (Pb, P0). Two coefficients (CH1, CH2) obtained from the empirical formulas (µb = µ0 [1 + CH1], Pb = P0 [1 + CH2]) were calculated to quantify RBC sedimentation. The present method was then adopted to detect differences in RBC sedimentation for various suspended blood samples (healthy RBCs suspended in dextran solutions or plasma). Based on the experimental results, four parameters (µ0, P0, CH1, and CH2) are considered to be effective for quantifying the contributions of the hematocrit and diluent. Two coefficients exhibited more consistent trends than the conventional ESR method. In conclusion, the proposed method can effectively detect RBC sedimentation.
Novel Surface Acoustic Wave Temperature–Strain Sensor Based on LiNbO3 for Structural Health Monitoring
Authors: Li Xiangrong , Tan Qiulin , Qin Li , Yan Xiawen , Liang Xiaorui
Published: June 2022

In this paper, we present the design of an integrated temperature and strain dual-parameter sensor based on surface acoustic waves (SAWs). First, the COMSOL Multiphysics simulation software is used to determine separate frequencies for multiple sensors to avoid interference from their frequency offsets caused by external physical quantity changes. The sensor consists of two parts, a temperature-sensitive unit and strain-sensitive unit, with frequencies of 94.97 MHz and 90.05 MHz, respectively. We use standard photolithography and ion beam etching technology to fabricate the SAW temperature–strain dual-parameter sensor. The sensing performance is tested in the ranges 0–250 °C and 0–700 μԑ. The temperature sensor monitors the ambient temperature in real time, and the strain sensor detects both strain and temperature. By testing the response of the strain sensor at different temperatures, the strain and temperature are decoupled through the polynomial fitting of the intercept and slope. The relationship between the strain and the frequency of the strain-sensitive unit is linear, the linear correlation is 0.98842, and the sensitivity is 100 Hz/μԑ at room temperature in the range of 0–700 μԑ. The relationship between the temperature and the frequency of the temperature-sensitive unit is linear, the linearity of the fitting curve is 0.99716, and the sensitivity is 7.62 kHz/°C in the range of 25–250 °C. This sensor has potential for use in closed environments such as natural gas or oil pipelines.
Shape, Resonant Frequency and Thermoelastic Dissipation Analysis of Free-Formed Microhemispherical Shells Based on Forming Process Modeling
Authors: Gao Yang , Zhang Jiachao , Ruan Zhihu , Meng Lin , Jia Jia
Published: June 2022

Free-form microhemispherical shell resonators have the advantages of high quality factor and mass production. The shape of microhemispherical shells created via this process is based on a single mold and is difficult to adjust, which affects the resonant frequency and quality factor. In this paper, a process analysis model is established through in-depth analysis of the process mechanism and flow of the free-forming method. Based on this model, the influence of the designed preforming parameters on the shape, resonant frequency and thermoelastic dissipation of the microhemispherical shell are analyzed in detail, providing theoretical guidance for parameter design. The results show that the depth and the ratio of internal to external pressure of the substrate’s annular groove affect the height and thickness of the microhemispherical shell, and the structural thickness affects the thickness of the microhemispherical shell; these in turn affect the resonant frequency and thermoelastic dissipation of the microhemispherical shell resonator. In addition, the inner diameter of the substrate’s annular groove mainly affects the radius of the support column of the microhemispherical shell, and the influence on the resonant frequency and thermoelastic dissipation of the resonator is relatively low.
Research on Intelligent Distribution of Liquid Flow Rate in Embedded Channels for Cooling 3D Multi-Core Chips
Authors: Zhang Jian , Xie Zhihui , Lu Zhuoqun , Li Penglei , Xi Kun
Published: June 2022

A numerical simulation model of embedded liquid microchannels for cooling 3D multi-core chips is established. For the thermal management problem when the operating power of a chip changes dynamically, an intelligent method combining BP neural network and genetic algorithm is used for distribution optimization of coolant flow under the condition with a fixed total mass flow rate. Firstly, a sample point dataset containing temperature field information is obtained by numerical calculation of convective heat transfer, and the constructed BP neural network is trained using these data. The “working condition–flow distribution–temperature” mapping relationship is predicted by the BP neural network. The genetic algorithm is further used to optimize the optimal flow distribution strategy to adapt to the dynamic change of power. Compared with the commonly used uniform flow distribution method, the intelligently optimized nonuniform flow distribution method can further reduce the temperature of the chip and improve the temperature uniformity of the chip.
Optimizing Broadband Near-Infrared Emission in Bi/Sn-Doped Aluminosilicate Glass by Modulating Glass Composition
Authors: Xiang Song , Zhang Min , Zeng Tixian , Chen Jiang , Zhang Feiquan
Published: June 2022

The Bi/Sn-doped aluminosilicate glass samples were prepared using a melting–quenching method and their near-infrared (NIR) emission properties were studied. An ultra-broadband NIR emission ranging from 950 nm to 1600 nm was observed in all samples under 480 nm excitation, which covered the whole fiber low-loss window. The NIR emission spectrum showed that the maximum emission peak was about 1206 nm and the full width at half maximum (FWHM) was about 220 nm. Furthermore, the NIR emission intensity strongly depends on the composition of the glass, which can be optimized by modulating the glass composition. The Bi0 and Bi+ ions were the NIR luminescence source of the glass samples in this paper. The Bi/Sn-doped aluminosilicate glass has the potential to become a new type of core fiber material and to be applied to optical fiber amplifiers (OFAs), based on its excellent performance in ultra-broadband NIR emission.
Probabilistic Circuit Implementation Based on P-Bits Using the Intrinsic Random Property of RRAM and P-Bit Multiplexing Strategy
Authors: Liu Yixuan , Hu Qiao , Wu Qiqiao , Liu Xuanzhi , Zhao Yulin , Zhang Donglin , Han Zhongze , Cheng Jinhui , Ding Qingting , Han Yongkang , Peng Bo , Jiang Haijun , Xue Xiaoyong , Lv Hangbing , Yang Jianguo
Published: June 2022

Probabilistic computing is an emerging computational paradigm that uses probabilistic circuits to efficiently solve optimization problems such as invertible logic, where traditional digital computations are difficult to solve. This paper proposes a true random number generator (TRNG) based on resistive random-access memory (RRAM), which is combined with an activation function implemented by a piecewise linear function to form a standard p-bit cell, one of the most important parts of a p-circuit. A p-bit multiplexing strategy is also applied to reduce the number of p-bits and improve resource utilization. To verify the superiority of the proposed probabilistic circuit, we implement the invertible p-circuit on a field-programmable gate array (FPGA), including AND gates, full adders, multi-bit adders, and multipliers. The results of the FPGA implementation show that our approach can significantly save the consumption of hardware resources.
Design, Analysis and Experimental Investigations of a Double-Arm Based Micro-Gripper for Thin and Flexible Metal Wires Manipulation
Authors: Wang Yuezong , Chen Jiqiang , Qu Daoduo
Published: June 2022

A robotic system for the automatic wire pulling of coreless motor winding is designed, including the design of an opening-closing control system and a micro-gripper’s tip structure with a double-armed elastic-beam structure for the support part and an enveloping clamping structure for the tip part. The micro-gripper captures the electrode wire from the root, encircles the wire after the envelope region is closed, and the thin and flexible electrode wire is pulled to the top of the electrode pad by the movement of the micro-gripper and released. The mechanical index of the micro-gripper is simulated to obtain the optimal structural parameters. The experimental results show that the electrode wire’s maximum bearing force is about 0.3 N. Under this reaction force, the deformation of the tip-envelope region of the micro-gripper is about 27.5 μm, which is sufficient for electrode wire pulling micro-manipulation. By comparison with the steel micro-gripper, the silicon micro-gripper has more advantages in shape integrity, machinability and mechanical properties.
A Double-Layer Patch Antenna for 5–6 GHz Wireless Communication
Authors: Li Xue-Ping , Ma Ming-Rong , Zhang Qi-Meng , Yan Lin , Wang Chang-Qing , Li Wei
Published: June 2022

This paper proposes a compact double-layer microstrip patch antenna with a wide bandwidth of 4.83–6.1 GHz and a gain reaching 4.7 dBi. By folding its mirror image through the electric field symmetry principle of the microstrip antenna, its electrical properties are maintained, and the physical size is halved to the compact size of only 25 × 40 mm2. The proposed antenna has the radiation characteristics of a planar inverted-F antenna (PIFA), which can generate the first resonant frequency and realize omnidirectional radiation characteristics. By coupling and feeding the upper patch, the second resonant frequency of the proposed antenna is produced and the directional radiation characteristics of the microstrip patch antenna can be achieved. The consistency of the results between the simulation and test indicates that the proposed antenna design is an ideal potential choice for home wireless local area network (WLAN) communication.
Theoretical and Experimental Investigation of a Rotational Magnetic Couple Piezoelectric Energy Harvester
Authors: Sun Feng , Dong Runhong , Zhou Ran , Xu Fangchao , Mei Xutao
Published: June 2022

With the rapid development of Internet of Things (IoT) and the popularity of wireless sensors, using internal permanent or rechargeable batteries as a power source will face a higher maintenance workload. Therefore, self-powered wireless sensors through environmental energy harvesting are becoming an important development trend. Among the many studies of energy harvesting, the research on rotational energy harvesting still has many shortcomings, such as rarely working effectively under low-frequency rotational motion or working in a narrow frequency band. In this article, a rotational magnetic couple piezoelectric energy harvester is proposed. Under the low-frequency excitation (<10 Hz) condition, the harvester can convert low-frequency rotational into high-frequency vibrational of the piezoelectric beam by frequency up-conversion, effectively increasing the working bandwidth (0.5–16 Hz) and improving the efficiency of low-speed rotational energy harvesting. In addition, when the excitation frequency is too high (>16 Hz), it can solve the condition that the piezoelectric beam cannot respond in time by frequency down-conversion. Therefore, the energy harvester still has a certain degree of energy harvesting ability (18–22 Hz and 29–31 Hz) under high-frequency conditions. Meanwhile, corresponding theoretical analyses and experimental verifications were carried out to investigate the dynamic characteristics of the harvester with different excitation and installation directions. The experimental results illustrate that the proposed energy harvester has a wider working bandwidth benefiting from the frequency up-conversion mechanism and frequency down-conversion mechanism. In addition, the forward beam will have a wider bandwidth than the inverse beam due to the softening effect. In addition, the maximum powers of the forward and inverse beams at 310 rpm (15.5 Hz) are 93.8 μW and 58.5 μW, respectively. The maximum powers of the two beams at 420 rpm (21 Hz) reached 177 μW and 85.2 μW, respectively. The self-powered requirement of micromechanical systems can be achieved. Furthermore, this study provides the theoretical and experimental basis for rotational energy harvesting.
Effects of Recycled Sponge Iron on Phosphorus Recovery from Polluted Water
Authors: Cheng Ping , Wang Biao , Wang Xiaohuan , Xiao Wei
Published: June 2022

Phosphorus in water not only degrades water quality but also leads to a waste of resources. In this study, adsorption thermodynamics and kinetics were used to study the effect of sponge iron on phosphorus removal, and a filtration bed was used to simulate the phosphorus removal in polluted water. The results showed that the maximum theoretical adsorption capacity of the modified sponge iron was increased from 4.17 mg/g to 18.18 mg/g. After desorption with 18.18 mol/L of sodium hydroxide and reactivation with 6% (w%) sulfuric acid, the activation rate of modified sponge iron can reach 98%. In a continuous operation experiment run for approximately 200 days, the sponge iron phosphorus removal percolation bed showed a good phosphorus removal ability. Under the condition of TP = 10 mg/L, HRT = 1 H, the comprehensive phosphorus removal rate was 30–89%, and the accumulated phosphorus adsorption per unit volume was 6.95 kg/m3. Wastewater from the regeneration of the sponge iron base can be used to recover guano stone. The optimum conditions were pH = 10, n (Mg2+):n (PO43−):n (NH4+) = 1.3:1:1.1. Under the optimum conditions, the phosphorus recovery rate could reach 97.8%. The method provided in this study has theoretical and practical significance for the removal and recycling of phosphorus in polluted water.
Assessment of Machine Learning Models for the Prediction of Rate-Dependent Compressive Strength of Rocks
Authors: Yang Ziquan , Wu Yanqi , Zhou Yisong , Tang Hui , Fu Shanchun
Published: June 2022

The prediction of rate-dependent compressive strength of rocks in dynamic compression experiments is still a notable challenge. Four machine learning models were introduced and employed on a dataset of 164 experiments to achieve an accurate prediction of the rate-dependent compressive strength of rocks. Then, the relative importance of the seven input features was analyzed. The results showed that compared with the extreme learning machine (ELM), random forest (RF), and the original support vector regression (SVR) models, the correlation coefficient R2 of prediction results with the hybrid model that combines the particle swarm optimization (PSO) algorithm and SVR was highest in both the training set and the test set, both exceeding 0.98. The PSO-SVR model obtained a higher prediction accuracy and a smaller prediction error than the other three models in terms of evaluation metrics, which showed the possibility of the model as a rate-dependent compressive strength prediction tool. Additionally, besides the static compressive strength, the stress rate is the most important influence factor on the rate-dependent compressive strength of the rock among the listed input parameters. Moreover, the strain rate has a positive effect on the rock strength.
Three-Dimensional Magnetotelluric Inversion for Triaxial Anisotropic Medium in Data Space
Authors: Xie Jingtao , Cai Hongzhu , Hu Xiangyun , Han Shixin , Liu Minghong
Published: June 2022

The interpretation of three-dimensional (3-D) magnetotelluric (MT) data is usually based on the isotropic assumption of the subsurface structures, and this assumption could lead to erroneous interpretation in the area with considerable electrical anisotropy. Although arbitrary anisotropy is much closer to the ground truth, it is generally more challenging to recover full anisotropy parameters from 3-D inversion. In this paper, we present a 3-D triaxial anisotropic inversion framework using the edge-based finite element method with a tetrahedral mesh. The 3-D inverse problem is solved by the Gauss-Newton (GN) method which shows fast convergence behavior. The computation cost of the data-space method depends on the size of data, which is usually smaller than the size of model; therefore, we transform the inversion algorithm from the model space to the data space for memory efficiency. We validate the effectiveness and applicability of the developed algorithm using several synthetic model studies.
3D Sedimentary Architecture of Sandy Braided River, Based on Outcrop, Unmanned Aerial Vehicle and Ground Penetrating Radar Data
Authors: Guo Wei , Dong Chunmei , Lin Chengyan , Zhang Tao , Zhao Zhongxiang , Li Jia
Published: June 2022

Ground Penetrating Radar (GPR) is a geophysical method that uses antennas to transmit and receive high-frequency electromagnetic waves to detect the properties and distribution of materials in media. In this paper, geological observation, UAV detection and GPR technology are combined to study the recent sediments of the Yungang braided river study area in Datong. The application of the GPR technique to the description of fluvial facies and reservoir architecture and the development of geological models are discussed. The process of GPR detection technology and application includes three parts: GPR data acquisition, data processing and integrated interpretation of GPR data. The geological surface at different depths and scales can be identified by using different combinations of frequencies and antenna configurations during acquisition. Based on outcrop observation and lithofacies analysis, the Yandong Member of the Middle Jurassic Yungang Formation in the Datong Basin has been identified as a typical sandy braided river sedimentary system. The sandy braided river sandbody changes rapidly laterally, and the spatial distribution and internal structure of the reservoir are very complex, which has a very important impact on the migration and distribution of oil and gas as a reservoir. It is very important to make clear the characteristics of each architectural unit of the fluvial sand body and quantitatively characterize them. The architectural elements of the braided river sedimentary reservoir in the Datong-Yungang area can be divided into three types: Channel unit, bar unit and overbank assemblages. The geological radar response characteristics of different types of sedimentary units are summarized and their interfaces are identified. The channel sediments form a lens-shaped wave reflection with a flat at the top and convex-down at the bottom in the radar profile, and the angles of the radar reflection directional axes are different on both sides of the sedimentary interface. In the radar profile, the deposit of the unit bar is an upward convex reflection structure. The overbank siltation shows a weak amplitude parallel reflection structure. The flood plain sediments are distributed continuously and stably in the radar profile, showing weak reflection characteristics. Different sedimentary units are identified by GPR data and combined with Unmanned Aerial Vehicle (UAV) detection data, and the establishment of the field outcrop geological model is completed. The development pattern of the diara is clarified, and the swing and migration of the channel in different stages are identified.
Reduction of Acid Iron Ore Pellets under Simulated Wall and Center Conditions in a Blast Furnace Shaft
Authors: Iljana Mikko , Abdelrahim Ahmed , Bartusch Hauke , Fabritius Timo
Published: June 2022

The operational conditions, including temperature and gas composition, vary along the radial position in a blast furnace. Nevertheless, very few studies can be found in the literature that discuss how the reduction behavior of the ferrous burden varies along the radial position. In this study, the effect of the radial charging position on the reducibility of acid iron ore pellets was investigated using a laboratory-scale, high-temperature furnace in CO-CO2-N2 and CO-CO2-H2-H2O-N2 atmospheres up to 1100 °C. The experimental conditions were accumulated based on earlier measurements from a multi-point vertical probing campaign that was performed for a center-working European blast furnace. The main finding of this study is that the pellet reduction proceeded faster under simulated blast furnace conditions resembling those in the center area, compared to the wall area, because of a higher share of CO and H2 in the gas. Therefore, the pellet charging position affects its reduction path in a blast furnace. Additionally, it was shown that the presence of H2 and H2O in the reducing gas enhanced the progress of reduction reactions significantly and enhanced the formation of cracks slightly, both of which are desirable in blast furnace operation. The reducibility data attained in this study are important in understanding how temperature and gas composition is connected to the reduction degree under realistic process conditions.
Separation of Rare Earth and Aluminum by Selective Complexation
Authors: Li Jinhui , Wen Yaoru , Chu Yuhang , Liu Wenxin , Liu Jinbiao , Wang Ruixiang , Xu Zhifeng
Published: June 2022

The presence of aluminum in the weathering crust leaching rare earth ore harms the subsequent extraction and separation of rare earths. High-quality rare earth production processes must reduce the aluminum content in their feed liquid. Groups containing lone pairs of electrons can form stable insoluble complexes with metal ions under certain conditions. In this paper, 3-hydroxyphenylphosphoryl propionic acid is used to selectively separate rare earths by complexation in feed liquid. The results show that: using 3-hydroxyphenylphosphoryl propionic acid as the complexing agent, and when the amount of 3-hydroxyphenyl phosphoryl propionic acid is six times the theoretical complete reaction amount, the reaction time is 10 min, the reaction temperature is 50 °C, and the solution is adjusted to pH 1, the extraction rate of RE3+ is 90.48%, and the extraction rate of Al3+ is nearly 9.52%. The separation of rare earth and aluminum is well realized. 3-hydroxyphenyl phosphoryl propionic acid has good water solubility and low cost, and the product after complexation reaction with metal ions is solid and easy to separate. It has potential as an alternative complexing agent in the industry.
Geological History of the Great Altai: Implications for Mineral Exploration
Authors: D’yachkov Boris A. , Mizernaya Marina A. , Khromykh Sergey V. , Bissatova Ainel Y. , Oitseva Tatiana A. , Miroshnikova Anastassiya P. , Frolova Olga V. , Kuzmina Oxana N. , Zimanovskaya Natalya A. , Pyatkova Anna P. , Zikirova Karina , Ageyeva Olga V. , Yeskaliyev Yertay T.
Published: June 2022

The Great Altai region, located at the boundary of Russia, Mongolia, China, and Kazakhstan, belongs to the system of the Central Asian Orogenic Belt. It has undergone a long complex geological and metallogenic history. Extremely rich resources of base, precious, and rare metals (Fe, Cu, Pb, Zn, Ag, Au, Li, Cs, Ta, Nb, REE, etc.) maintain developed mining and metallurgical industry, especially in East Kazakhstan, which is the key metallogenic province. The East Kazakhstan province comprises the Rudny Altai, Kalba-Narym, West-Kalba, and Zharma-Saur metallogenic belts, each having its typical mineralization profiles and deposits. The reconstructed geodynamic and metallogenic history of the Great Altai province, along with the revealed relationships between tectonic settings and mineralization patterns, allowed us to formulate a number of geodynamic, structural, lithostratigraphic, magmatic, mineralogical, and geochemical criteria for exploration and appraisal of mineral potential in Eastern Kazakhstan. Geodynamic criteria are based on the origin of different mineralization types in certain geodynamic settings during the Late Paleozoic–Early Mesozoic orogenic cycle. Structural criteria mean that the location of base-metal deposits in Rudny Altai, gold deposits in the West Kalba belt, rare and base metals in the Kalba-Narym and Zharma-Saur zones is controlled by faults of different sizes. Lithostratigraphic criteria consist of the relation of orebodies with certain types of sedimentary or volcanic-sedimentary rocks. Magmatic criteria are due to the relation between mineralization types and igneous lithologies. Mineralogical and geochemical criteria include typical minerals and elements that can serve as tracers of mineralization. The joint use of all these criteria will open new avenues in prospecting and exploration at a more advanced level.
Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study
Authors: Galati Salvatore , Sainas Stefano , Giorgis Marta , Boschi Donatella , Lolli Marco L. , Ortore Gabriella , Poli Giulio , Tuccinardi Tiziano
Published: June 2022

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors.
Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line
Authors: Dewi Citra , Fristiohady Adryan , Amalia Riezki , Khairul Ikram Nur Kusaira , Ibrahim Sugeng , Muchtaridi Muchtaridi
Published: June 2022

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, having a poor prognosis and rapid metastases. TNBC is characterized by the absence of estrogen, progesterone, and human epidermal growth receptor-2 (HER2) expressions and has a five-year survival rate. Compared to other breast cancer subtypes, TNBC patients only respond to conventional chemotherapies, and even then, with limited success. Shortages of chemotherapeutic medication can lead to resistance, pressured index therapy, non-selectivity, and severe adverse effects. Finding targeted treatments for TNBC is difficult owing to the various features of cancer. Hence, identifying the most effective molecular targets in TNBC pathogenesis is essential for predicting response to targeted therapies and preventing TNBC cell metastases. Nowadays, natural compounds have gained attention as TNBC treatments, and have offered new strategies for solving drug resistance. Here, we report a systematic review using the database from Pubmed, Science Direct, MDPI, BioScince, Springer, and Nature for articles screening from 2003 to 2022. This review analyzes relevant signaling pathways and the prospect of utilizing natural compounds as a therapeutic agent to improve TNBC treatments in the future.
Decontamination Efficiency of Thermal, Photothermal, Microwave, and Steam Treatments for Biocontaminated Household Textiles
Authors: Neral Branko , Gorgieva Selestina , Kurečič Manja
Published: June 2022

With the outbreak of the COVID-19 pandemic, textile laundering hygiene has proved to be a fundamental measure in preventing the spread of infections. The first part of our study evaluated the decontamination efficiency of various treatments (thermal, photothermal, and microwave) for bio contaminated textiles. The effects on textile decontamination of adding saturated steam into the drum of a household textile laundering machine were investigated and evaluated in the second part of our study. The results show that the thermal treatment, conducted in a convection heating chamber, provided a slight reduction in efficiency and did not ensure the complete inactivation of Staphylococcus aureus on cotton swatches. The photothermal treatment showed higher reduction efficiency on contaminated textile samples, while the microwave treatment (at 460 W for a period of 60 s) of bio contaminated cotton swatches containing higher moisture content provided satisfactory bacterial reduction efficiency (more than 7 log steps). Additionally, the treatment of textiles in the household washing machine with the injection of saturated steam into the washing drum and a mild agitation rhythm provided at least a 7 log step reduction in S. aureus. The photothermal treatment of bio contaminated cotton textiles showed promising reduction efficiency, while the microwave treatment and the treatment with saturated steam proved to be the most effective.
Prediction Models for Brain Distribution of Drugs Based on Biomimetic Chromatographic Data
Authors: Vallianatou Theodosia , Tsopelas Fotios , Tsantili-Kakoulidou Anna
Published: June 2022

The development of high-throughput approaches for the valid estimation of brain disposition is of great importance in the early drug screening of drug candidates. However, the complexity of brain tissue, which is protected by a unique vasculature formation called the blood–brain barrier (BBB), complicates the development of robust in silico models. In addition, most computational approaches focus only on brain permeability data without considering the crucial factors of plasma and tissue binding. In the present study, we combined experimental data obtained by HPLC using three biomimetic columns, i.e., immobilized artificial membranes, human serum albumin, and α1-acid glycoprotein, with molecular descriptors to model brain disposition of drugs. Kp,uu,brain, as the ratio between the unbound drug concentration in the brain interstitial fluid to the corresponding plasma concentration, brain permeability, the unbound fraction in the brain, and the brain unbound volume of distribution, was collected from literature. Given the complexity of the investigated biological processes, the extracted models displayed high statistical quality (R2 > 0.6), while in the case of the brain fraction unbound, the models showed excellent performance (R2 > 0.9). All models were thoroughly validated, and their applicability domain was estimated. Our approach highlighted the importance of phospholipid, as well as tissue and protein, binding in balance with BBB permeability in brain disposition and suggests biomimetic chromatography as a rapid and simple technique to construct models with experimental evidence for the early evaluation of CNS drug candidates.
Comparison of Physical Adsorption and Covalent Coupling Methods for Surface Density-Dependent Orientation of Antibody on Silicon
Authors: Gajos Katarzyna , Petrou Panagiota , Budkowski Andrzej
Published: June 2022

The orientation of antibodies, employed as capture molecules on biosensors, determines biorecognition efficiency and bioassay performance. In a previous publication we demonstrated for antibodies attached covalently to silicon that an increase in their surface amount Γ, evaluated with ellipsometry, induces changes in their orientation, which is traced directly using Time-of-Flight Secondary Ion Mass Spectroscopy combined with Principal Component Analysis. Here, we extend the above studies to antibodies adsorbed physically on a 3-aminopropyltriethoxysilane (APTES) monolayer. Antibodies physisorbed on APTES (0 ≤ Γ ≤ 3.5 mg/m2) reveal the Γ ranges for flat-on, side-on, and vertical orientation consistent with random molecular packing. The relation between orientation and Γ is juxtaposed for silicon functionalized with APTES, APTES modified with glutaraldehyde (APTES/GA) and N-hydroxysuccinimide-silane (NHS-silane). Antibody reorientation occurs at lower Γ values when physisorption (APTES) is involved rather than chemisorption (APTES/GA, NHS-silane). At high Γ values, comparable proportions of molecules adapting head-on and tail-on vertical alignment are concluded for APTES and the NHS-silane monolayer, and they are related to intermolecular dipole–dipole interactions. Intermolecular forces seem to be less decisive than covalent binding for antibodies on the APTES/GA surface, with dominant head-on orientation. Independently, the impact of glutaraldehyde activation of APTES on vertical orientation is confirmed by separate TOF-SIMS measurements.
Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs
Authors: Beck Tyler , Springs Kendra , Morningstar Jordan , Mills Catherine , Stoddard Andrew , Guo Lilong , Moore Kelsey , Gensemer Cortney , Biggs Rachel , Petrucci Taylor , Kwon Jennie , Stayer Kristina , Koren Natalie , Dunne Jaclyn , Fulmer Diana , Vohra Ayesha , Mai Le , Dooley Sarah , Weninger Julianna , Peterson Yuri , Woster Patrick , Dix Thomas , Norris Russell
Published: June 2022

Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk. These toxicities may be mitigated by pharmacokinetic optimization and reductions in off-target interactions. As such, there is a need for early-stage implementation of pharmacokinetic (PK) prediction tools. Several PK prediction platforms exist, including pkCSM, SuperCypsPred, Pred-hERG, Similarity Ensemble Approach (SEA), and SwissADME. These tools can be used in screening hits, allowing for the selection of compounds were reduced toxicity and/or risk of attrition. In this short commentary, we used PK prediction tools in the optimization of mitogen activated extracellular signal-related kinase kinase 1 (MEK1) inhibitors. In doing so, we identified MEK1 inhibitors with retained activity and optimized predictive PK properties, devoid of hERG inhibition. These data support the use of publicly available PK prediction platforms in early-stage drug discovery to design safer drugs.
The Potential of a Protein Model Synthesized Absent of Methionine
Authors: Savino Ronald J. , Kempisty Bartosz , Mozdziak Paul
Published: June 2022

Methionine is an amino acid long thought to be essential, but only in the case of protein synthesis initiation. In more recent years, methionine has been found to play an important role in antioxidant defense, stability, and modulation of cell and protein activity. Though these findings have expanded the previously held sentiment of methionine having a singular purpose within cells and proteins, the essential nature of methionine can still be challenged. Many of the features that give methionine its newfound functions are shared by the other sulfur-containing amino acid: cysteine. While the antioxidant, stabilizing, and cell/protein modulatory functions of cysteine have already been well established, recent findings have shown a similar hydrophobicity to methionine which suggests cysteine may be able to replace methionine in all functions outside of protein synthesis initiation with little effect on cell and protein function. Furthermore, a number of novel mechanisms for alternative initiation of protein synthesis have been identified that suggest a potential to bypass the traditional methionine-dependent initiation during times of stress. In this review, these findings are discussed with a number of examples that demonstrate a potential model for synthesizing a protein in the absence of methionine.
Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner
Authors: Shang Nan , Bhullar Khushwant S. , Wu Jianping
Published: June 2022

Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed that IRW treatment protects osteoblasts against Ang II induced decline in cell proliferation and restores protein levels of collagen type I alpha 2 chain (COL1A2) and alkaline phosphatase (ALP) levels in MC3T3-E1 cells (p < 0.05). Apart from augmentation of these mineralization factors, the angiotensin II (Ang II) induced apoptotic stress in osteoblasts was mitigated by IRW as well. At the molecular level, IRW abolished the cytochrome-c release via modulation of pro-and anti-apoptotic genes in MC3T3-E1 cells (p < 0.05). Interestingly, IRW also increased cellular levels of cytoprotective local RAAS factors such as MasR, Ang (1–7), ACE2, and AT2R, and lowered the levels of Ang II effector receptor (AT1R). Further, our results indicated a lower content of inflammation and osteoclastogenesis biomarkers such as cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-κB), and receptor activator of nuclear factor kappa-B ligand (RANKL) following IRW treatment in MC3T3-E1 cells (p < 0.05). The use of an antagonist-guided cell study indicated that IRW contributed to the process of cytoprotection and proliferation of osteoblasts via Runt-related transcription factor 2 (RUNX2) in face of Ang II stress in an AT2R dependent manner. The key findings of our study showed that IRW could potentially have a therapeutic role in the treatment and/or prevention of bone disorders.
TP-CSO: A Triptolide Prodrug for Pancreatic Cancer Treatment
Authors: Wang Xinlong , Zeng Huahui , Zhu Xin , Xu Duanjie , Tian Qikang , Wang Can , Zhao Lingzhou , Zhao Junwei , Miao Mingsan , Wu Xiangxiang
Published: June 2022

Triptolide (TP) is a potential drug candidate for the treatment of cancer, but its use was hampered by its systemic toxicity and poor water solubility. Hence, a TP-CSO prodrug was synthesized by conjugating TP to chitosan oligosaccharide (CSO), and characterized by 1H NMR, FTIR, DSC and XRD analyses. The TP-CSO containing about 4 wt% of TP exhibited excellent water solubility (15 mg/mL) compared to TP (0.017 mg/mL). Compared with TP, the pharmacokinetics of the conjugate after oral administration showed a three-fold increase in the half-life in the blood circulation and a 3.2-fold increase in AUC (0–∞). The orally administered TP-CSO could more effectively inhibit tumor progression but with much lower systemic toxicity compared with TP, indicating significant potential for further clinical trials. In conclusion, CSO-based conjugate systems may be useful as a platform for the oral delivery of other sparingly soluble drugs.
The Effect of Combining Post-Harvest Calcium Nanoparticles with a Salicylic Acid Treatment on Cucumber Tissue Breakdown via Enzyme Activity during Shelf Life
Authors: Abdelkader Mohamed F. M. , Mahmoud Mohamed H. , A. Lo’ay A. , Abdein Mohamed A. , Metwally Khaled , Ikeno Shinya , Doklega Samar M. A.
Published: June 2022

In the present study, an experiment was carried out on the postharvest of cucumber fruit during a 14-day shelf life. The aim was to assess the impact of calcium nanoparticles (CaNPs) blended with different concentrations of salicylic acid (SA) on the shelf life of cucumbers during the seasons of 2018 and 2019. The investigation further monitored the influences of CaNPs-SA on some physical properties of cucumber, including the percentage weight loss, color, and fruit firmness. In addition, chemical properties, such as total soluble solids (SSC%), total acidity (TA%), total soluble sugars, and chlorophyll pigmentation of the fruit skin, were assessed during a 14-day shelf lifeCell wall degradation enzymes (CWEAs) such as polygalacturonase (PG), cel-lulase (CEL), xylanase (XYL), and pectinase (PT) were also researched. In addition, the generation rates of H2O2 and O2•− were calculated, as well as the reduction of DPPH. The lipid peroxidation (malondialdehyde, MDA) and cell membrane permeability (IL%) of cell wall composites were also determined. CaNPs-SA at 2 mM suppressed CWEAs, preserved fruit quality, reduced weight loss throughout the shelf-life period, and reduced the percent leakage value. At this concentration, we also found the lowest levels of MDA and the highest levels of DPPH.
Precise Quantification of Molybdate In Vitro by the FRET-Based Nanosensor ‘MolyProbe’
Authors: Oliphant Kevin D. , Karger Marius , Nakanishi Yoichi , Mendel Ralf R.
Published: June 2022

Molybdenum (Mo) is an essential trace element in all kingdoms of life. Mo is bioavailable as the oxyanion molybdate and gains biological activity in eukaryotes when bound to molybdopterin, forming the molybdenum cofactor. The imbalance of molybdate homeostasis results in growth deficiencies or toxic symptoms within plants, fungi and animals. Recently, fluorescence resonance energy transfer (FRET) methods have emerged, monitoring cellular and subcellular molybdate distribution dynamics using a genetically encoded molybdate-specific FRET nanosensor, named MolyProbe. Here, we show that the MolyProbe system is a fast and reliable in vitro assay for quantitative molybdate determination. We added a Strep-TagII affinity tag to the MolyProbe protein for quick and easy purification. This MolyProbe is highly stable, resistant to freezing and can be stored for several weeks at 4 °C. Furthermore, the molybdate sensitivity of the assay peaked at low nM levels. Additionally, The MolyProbe was applied in vitro for quantitative molybdate determination in cell extracts of the plant Arabidopsis thaliana, the fungus Neurospora crassa and the yeast Saccharomyces cerevisiae. Our results show the functionality of the Arabidopsis thaliana molybdate transporter MOT1.1 and indicate that FRET-based molybdate detection is an excellent tool for measuring bioavailable Mo.
Inspired by Nature—Functional Analogues of Molybdenum and Tungsten-Dependent Oxidoreductases
Authors: Pätsch Sebastian , Correia Jevy V. , Elvers Benedict J. , Steuer Mareile , Schulzke Carola
Published: June 2022

Throughout the previous ten years many scientists took inspiration from natural molybdenum and tungsten-dependent oxidoreductases to build functional active site analogues. These studies not only led to an ever more detailed mechanistic understanding of the biological template, but also paved the way to atypical selectivity and activity, such as catalytic hydrogen evolution. This review is aimed at representing the last decade’s progress in the research of and with molybdenum and tungsten functional model compounds. The portrayed systems, organized according to their ability to facilitate typical and artificial enzyme reactions, comprise complexes with non-innocent dithiolene ligands, resembling molybdopterin, as well as entirely non-natural nitrogen, oxygen, and/or sulfur bearing chelating donor ligands. All model compounds receive individual attention, highlighting the specific novelty that each provides for our understanding of the enzymatic mechanisms, such as oxygen atom transfer and proton-coupled electron transfer, or that each presents for exploiting new and useful catalytic capability. Overall, a shift in the application of these model compounds towards uncommon reactions is noted, the latter are comprehensively discussed.