bluuebunny/crossref_metadata_2025 huggingface dataset:
The New Variants of Corona-Virus Mutations: An Understanding to Their Infectivity, Immunological Tolerance and Vaccine Efficacy
Authors: Garg Pankaj
Published: July 2021

The new COVID-19 variants are triggering a fresh panic all around. Scientists still have not found any closely related identification of these variants in the context of their evolution. The scrupulous deletion/mutations recognized inside the spike protein of the variants are emerging with an amplified pace and are observed to be associated with the alterations in the receptor-binding region (RBD) of the spike protein. This paper highlights the reported mechanistic studies conducted on SARS-CoV-2 mutant variants; the mutant virus’s ability in response to the antibody recognition to evade the immune system in humans. The role of cellular immunity in response to its interaction with SARS-CoV-2 variants and importantly the discussion on the antibody-dependent enhancement (ADE) of SARS-CoV-2 disease with therapeutic antibodies and vaccines has been highlighted. It is expected that this may likely be interesting and helpful for readers in clearing all their presumptions related to the spreading severity of the mutant virus strains and more importantly the effectiveness of current and upcoming vaccines for its possible control.
Near-Field Direct Write Microfiber-Reinforced Collagen Hydrogel Scaffolds for Articular Cartilage Regeneration
Authors: Wang Zining , Ye Xinliang , Lin Yingxian , Tan Zhishan , Liu Yuming , Li Jie , Yin Jiawen , Zhu Dejian , Ma Mingze , Wang Xiang , Lu Bingheng , Wang Li , Wang Chong
Published: July 2021

The demand for treating degenerative osteoarthritis is dramatically growing during the past decade due to the increasing aging population. Compared to arthroscopic debridement and injection of lubricating hydrogels, implantation of a cartilage tissue engineering scaffold with a customized architecture and excellent stem cell delivery ability has been deemed as a superior alternative to regenerate defected cartilage tissues. However, relatively low mechanical strength of cell-laden hydrogel limits its potential in treating diseased/defected cartilage or tissues with an anisotropic structure. In this study, a composite cell-laden scaffold composed of three-dimensional (3D) fibrous patterns which was made through near-field electrospinning direct write (NEDW) and mesenchymal stem cell (MSC)-laden collagen I (COL I) hydrogel was fabricated. The hydrogel acted as a favorable microenvironment to load cells and growth factors to facilitate chondrogenic differentiation while the 3D fibrous patterns made of poly(caprolactone)-reinforced hydrogels and provided the composite scaffolds with a precisely designed micro-architecture. Compared to hydrogel scaffold alone, the fabricated composite scaffold had significantly higher mechanical properties. The composite scaffolds were biocompatible and can accelerate the chondrogenic differentiation of MSCs by up-regulating the expression of SOX9, collagen II (COL II) and aggrecan (ACAN), when transforming growth factor (TGF)-[Formula: see text]1 was loaded in COL I hydrogel. However, the morphology of differentiated cells was not identical to that of the natural chondrocytes, suggesting that the modulation of initial MSC morphology is needed to pursue the target phenotype after the chondrogenic differentiation.
Fabrication of N-Doped Carbon Quantum Dots/BiOI Nanocomposite and Its Efficient Photocatalytic Activity Under Visible-Light Irradiation
Authors: Yu Yichang , Zheng Ziyuyang , Liao Weiling , Yao Yuan , Peng Feng , Chen Tingting , Wu Jin , Feng Li
Published: July 2021

A novel spherical N-CQDs/BiOI photocatalyst was successfully synthesized through a facile solvothermal method. The optimization experiments of hydrothermal time and temperature were carried out. The effect of ammonium citrate addition was investigated. The as-synthesized photocatalysts were characterized via X-ray diffraction, scanning and transmission electron microscopy, Fourier transform infrared spectrum and elemental analysis. The adsorption and photocatalytic performance of as-synthesized photocatalysts were studied, 0.2N-CQDs/BiOI showed the best performance. For the removal of anionic dye RhB, adsorption occupied a major position. The maximum adsorption capacity was 97.09[Formula: see text]mg/g for RhB. For the removal of cationic dyes X3B, photocatalysis occupied a major position. The photocatalytic activity of 0.2N-CQDs/BiOI was superior to that of nano-TiO2 under the simulate sunlight irradiation. Different scavengers were used to analyze the effect of active species and photocatalytic degradation mechanism of X3B. The outstanding stability and performance make 0.2N-CQDs/BiOI has highly potential applications in wastewater treatment.
Preparation and performance analysis of Pt-IPMC for driving bionic tulip
Authors: Tian Aifen , Wang Xixi , Sun Yue , Zhang Xinrong , Wang Hongyan , Yang Liang
Published: July 2021

Based on the biological characteristics of tulip, the low driving voltage and fast response of ionic polymer metal composite (IPMC), we analyzed the fabrication, morphology and performance of the platinum IPMC (Pt-IPMC) and selected the right IPMC for driving bionic tulip. The preparation and performance of IPMC was analyzed first in this paper such as blocking force, output displacement and bending angle of IPMC under the different directed current voltage (DC). The optimal IPMC sample size and driving voltage were selected based on tulip blooming angles and the strain energy density of IPMC, which completed the blooming process of bionic tulip. The feasibility of IPMC used in driving bionic field was fully proved in this paper, which laid a foundation for the application of IPMC in driving biomimetic biological robots.
Noncontact Nanoscale Imaging of Cells
Authors: Klenerman David , Korchev Yuri , Novak Pavel , Shevchuk Andrew
Published: July 2021

The reduction in ion current as a fine pipette approaches a cell surface allows the cell surface topography to be imaged, with nanoscale resolution, without contact with the delicate cell surface. A variety of different methods have been developed and refined to scan the topography of the dynamic cell surface at high resolution and speed. Measurement of cell topography can be complemented by performing local probing or mapping of the cell surface using the same pipette. This can be done by performing single-channel recording, applying force, delivering agonists, using pipettes fabricated to contain an electrochemical probe, or combining with fluorescence imaging. These methods in combination have great potential to image and map the surface of live cells at the nanoscale.
Protein Dynamics by Two-Dimensional Infrared Spectroscopy
Authors: Tumbic Goran W. , Hossan Md Yeathad , Thielges Megan C.
Published: July 2021

Proteins function as ensembles of interconverting structures. The motions span from picosecond bond rotations to millisecond and longer subunit displacements. Characterization of functional dynamics on all spatial and temporal scales remains challenging experimentally. Two-dimensional infrared spectroscopy (2D IR) is maturing as a powerful approach for investigating proteins and their dynamics. We outline the advantages of IR spectroscopy, describe 2D IR and the information it provides, and introduce vibrational groups for protein analysis. We highlight example studies that illustrate the power and versatility of 2D IR for characterizing protein dynamics and conclude with a brief discussion of the outlook for biomolecular 2D IR.
Glycan Labeling and Analysis in Cells and In Vivo
Authors: Cheng Bo , Tang Qi , Zhang Che , Chen Xing
Published: July 2021

As one of the major types of biomacromolecules in the cell, glycans play essential functional roles in various biological processes. Compared with proteins and nucleic acids, the analysis of glycans in situ has been more challenging. Herein we review recent advances in the development of methods and strategies for labeling, imaging, and profiling of glycans in cells and in vivo. Cellular glycans can be labeled by affinity-based probes, including lectin and antibody conjugates, direct chemical modification, metabolic glycan labeling, and chemoenzymatic labeling. These methods have been applied to label glycans with fluorophores, which enables the visualization and tracking of glycans in cells, tissues, and living organisms. Alternatively, labeling glycans with affinity tags has enabled the enrichment of glycoproteins for glycoproteomic profiling. Built on the glycan labeling methods, strategies enabling cell-selective and tissue-specific glycan labeling and protein-specific glycan imaging have been developed. With these methods and strategies, researchers are now better poised than ever to dissect the biological function of glycans in physiological or pathological contexts.
Genotype–Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness
Authors: Jakutis Gabrielius , Stainier Didier Y.R.
Published: July 2021

Genetic manipulations with a robust and predictable outcome are critical to investigate gene function, as well as for therapeutic genome engineering. For many years, knockdown approaches and reagents including RNA interference and antisense oligonucleotides dominated functional studies; however, with the advent of precise genome editing technologies, CRISPR-based knockout systems have become the state-of-the-art tools for such studies. These technologies have helped decipher the role of thousands of genes in development and disease. Their use has also revealed how limited our understanding of genotype–phenotype relationships is. The recent discovery that certain mutations can trigger the transcriptional modulation of other genes, a phenomenon called transcriptional adaptation, has provided an additional explanation for the contradicting phenotypes observed in knockdown versus knockout models and increased awareness about the use of each of these approaches. In this review, we first cover the strengths and limitations of different gene perturbation strategies. Then we highlight the diverse ways in which the genotype–phenotype relationship can be discordant between these different strategies. Finally, we review the genetic robustness mechanisms that can lead to such discrepancies, paying special attention to the recently discovered phenomenon of transcriptional adaptation.
Electrochemical Formation of Nd-Fe Alloys in Molten LiF-CaF2-NdF3
Authors: Kawaguchi Kenji , Nohira Toshiyuki
Published: July 2021

In the present study, as a fundamental study for recycling Nd from Nd-Fe-B permanent magnet scrap, the electrochemical Nd-alloying behavior of Fe was investigated in a molten LiF-CaF2-NdF3 (0.3 or 0.5 mol%) system at 1123 K. Herein, the equilibrium potential of Nd3+/Nd was determined as 0.18 V (vs Li+/Li) by open-circuit potentiometry using a Mo electrode. Cyclic voltammetry and open-circuit potentiometry were conducted using an Fe electrode, and the results suggested the formation of multiple phases within the Nd-Fe alloys. Alloy samples were prepared via one- or two-step potentiostatic electrolysis of Fe electrodes at various potentials. The formation of liquid Nd-Fe alloy was confirmed through one-step potentiostatic electrolysis at 0.10 V. The solid Nd2Fe17 alloy was formed via a two-step potentiostatic electrolysis, wherein the potential was changed to 0.25 V after the initial electrolysis at 0.10 V, indicating that the Nd2Fe17 phase is thermodynamically stable at 0.25 V. The equilibrium potentials of the coexistence states of liq. Nd-Fe + Nd2Fe17 and Nd2Fe17 + Fe were determined as 0.19 and 0.31 V, respectively, which are in good agreement with the previously reported thermodynamic data.
Applications of 3D Image Using Internet of Things in the Exhibition of Classical Architecture Art Style
Authors: Xie Xusheng , Wen Xin , Deng Fengfeng
Published: July 2021

Classical architecture is an architectural, cultural heritage with specific historical value. It is also a city with historical and cultural heritage and even a testimony of the profound historical culture of a country. Therefore, urbanization is unavoidable, and it directly influences historical buildings. This study aims to combine the three-dimensional image techniques and the Internet of Things (IoT) technology to research the development of classical architectural artistic style. This article presents the acquisition equipment, methods, precautions, and data processing of real-life 3D image data of the classical architectural heritage. We realized the online publishing of real-world 3D services of classical architectural heritage through the real-world 3D display system developed through the Internet of Things and mobile terminals. The model was verified through simulation tests. The combination of image processing techniques and analysis methods such as simulated annealing improved the accuracy of the prediction model. The proposed model can provide data support for policy formulation, technical intervention, and targeted field investigation on architectural heritage by screening research objects.
Modeling and Control Strategy for Multiterminal Flexible DC Distribution Network with Echelon Utilization Power Battery
Authors: Mou Min , Zhou Yuhao , Zheng Wenguang , Xie Yurong , Wang Shipeng , Liu Lili , Wei Chengzhi
Published: July 2021

With the integration of distributed renewable energy to the distribution network and the development of multiterminal flexible DC transmission technology, multiterminal flexible DC distribution network has broad application prospects. At the same time, with the rapid development of new energy vehicles, the echelon utilization of power battery has become a research hotspot. By analyzing the characteristics of flexible DC distribution network and echelon utilization battery, the structure and control strategy of modular multilevel converter (MMC), DC solid‐state transformer, photovoltaic power generation, wind power generation, and echelon utilization battery energy storage system are established, respectively, in this paper. To achieve a DC network connection of various types of power supply and load, this paper proposes a starting method of multiterminal flexible DC distribution network and a cooperative control strategy of the wind‐solar‐storage system. A six‐terminal ring‐shape DC distribution network model is built in real‐time digital simulation (RTDS) platform. The simulation results show that the modeling methods and control strategies of each component in the real‐time simulation model meet the operation requirements of the multiterminal flexible DC distribution network, which provides a reference for the construction and research of the flexible DC distribution network.
On the JK Iterative Process in Banach Spaces
Authors: Ahmad Junaid , Işık Hüseyin , Ali Faeem , Ullah Kifayat , Ameer Eskandar , Arshad Muhammad
Published: July 2021

In the recent progress, different iterative procedures have been constructed in order to find the fixed point for a given self-map in an effective way. Among the other things, an effective iterative procedure called the JK iterative scheme was recently constructed and its strong and weak convergence was established for the class of Suzuki mappings in the setting of Banach spaces. The first purpose of this research is to obtain the strong and weak convergence of this scheme in the wider setting of generalized

α

-nonexpansive mappings. Secondly, by constructing an example of generalized

α

-nonexpansive maps which is not a Suzuki map, we show that the JK iterative scheme converges faster as compared the other iterative schemes. The presented results of this paper properly extend and improve the corresponding results of the literature.
Extension of Nunokawa Lemma for Functions with Fixed Second Coefficient and Its Applications
Authors: Amani Mostafa , Aghalary Rasoul , Ebadian Ali
Published: July 2021

In this paper, we study some properties of analytic functions with fixed initial coefficients. The methodology of differential subordination is used for modification and improvements of several well-known results for subclasses of univalent functions by restricting the functions with fixed initial coefficients. Actually, by extending the Nunokawa lemma for fixed initial coefficient functions, we obtain some novel results on subclasses of univalent functions, such as differential inequalities for univalency or starlikeness of analytic functions. Also, we provide some new sufficient conditions for strongly starlike functions. The results of this paper extend and improve the previously known results by considering functions with fixed second coefficients.
Prognostic Implications of Immune-Related Gene Pairs Signatures in Bladder Cancer
Authors: Xiong Hui , Gao Hui , Hu Jinding , Dai Yun , Wang Hanbo , Fu Min , Qi Taiguo , Li Lianjun , Xia Qinghua , Jin Xunbo , Cui Zilian , Kang Weiting
Published: July 2021

Compelling evidence indicates that immune function is correlated with the prognosis of bladder cancer (BC). Here, we aimed to develop a clinically translatable immune-related gene pairs (IRGPs) prognostic signature to estimate the overall survival (OS) of bladder cancer. From the 251 prognostic-related IRGPs, 37 prognostic-related IRGPs were identified using LASSO regression. We identified IRGPs with the potential to be prognostic markers. The established risk scores divided BC patients into high and low risk score groups, and the survival analysis showed that risk score was related to OS in the TCGA-training set (

p
<
0.001

; HR = 7.5 [5.3, 10]). ROC curve analysis showed that the AUC for the 1-year, 3-year, and 5-year follow-up was 0.820, 0.883, and 0.879, respectively. The model was verified in the TCGA-testing set and external dataset GSE13507. Multivariate analysis showed that risk score was an independent prognostic predictor in patients with BC. In addition, significant differences were found in gene mutations, copy number variations, and gene expression levels in patients with BC between the high and low risk score groups. Gene set enrichment analysis showed that, in the high-risk score group, multiple immune-related pathways were inhibited, and multiple mesenchymal phenotype-related pathways were activated. Immune infiltration analysis revealed that immune cells associated with poor prognosis of BC were upregulated in the high-risk score group, whereas immune cells associated with a better prognosis of BC were downregulated in the high-risk score group. Other immunoregulatory genes were also differentially expressed between high and low risk score groups. A 37 IRGPs-based risk score signature is presented in this study. This signature can efficiently classify BC patients into high and low risk score groups. This signature can be exploited to select high-risk BC patients for more targeted treatment.
Network Pharmacology-Based Analysis of Gegenqinlian Decoction Regulating Intestinal Microbial Activity for the Treatment of Diarrhea
Authors: Li Xiaoya , Zhang Chenyang , Tan Zhoujin , Yuan Jiali
Published: July 2021

Gegenqinlian decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness-heat syndrome (IDHS) with a satisfying therapeutic effect. The purpose of this study is to clarify the active ingredients and mechanism of GD in the treatment of diarrhea with IDHS. The TCMSP database was used to screen out the active ingredients of the four Chinese herbal medicines in GD, and the targets of the active ingredients were predicted. We selected the targets related to diarrhea through the DisGeNET database, then used the NCBI database to screen out related targets of lactase and sucrase, and constructed the visual network to search for the active ingredients of GD in the treatment of diarrhea and related mechanisms of the targets. Combined with network pharmacology, we screened out 146 active ingredients in GD corresponding to 252 ingredient targets, combined with 328 disease targets in diarrhea, and obtained 12 lactase targets and 11 sucrase targets. The key active ingredients involved quercetin, formononetin, β-sitosterol kaempferol, and wogonin. Furthermore, molecular docking showed that these five potential active ingredients had good affinities with the core targets PTGS2. The active ingredients in GD (such as quercetin, formononetin, and β-sitosterol) may increase the microbial activity of the intestinal mucosa of mice and reduce the microbial activity of the intestinal contents through multiple targets, thereby achieving the effect of treating diarrhea.
Bayesian Fully Convolutional Networks for Brain Image Registration
Authors: Cui Kunpeng , Fu Panpan , Li Yinghao , Lin Yusong
Published: July 2021

The purpose of medical image registration is to find geometric transformations that align two medical images so that the corresponding voxels on two images are spatially consistent. Nonrigid medical image registration is a key step in medical image processing, such as image comparison, data fusion, target recognition, and pathological change analysis. Existing registration methods only consider registration accuracy but largely neglect the uncertainty of registration results. In this work, a method based on the Bayesian fully convolutional neural network is proposed for nonrigid medical image registration. The proposed method can generate a geometric uncertainty map to calculate the uncertainty of registration results. This uncertainty can be interpreted as a confidence interval, which is essential for judging whether the source data are abnormal. Moreover, the proposed method introduces group normalization, which is conducive to the network convergence of the Bayesian neural network. Some representative learning-based image registration methods are compared with the proposed method on different image datasets. Experimental results show that the registration accuracy of the proposed method is better than that of the methods, and its antifolding performance is comparable to that of fast image registration and VoxelMorph. Furthermore, the proposed method can evaluate the uncertainty of registration results.
Enhanced Photocatalytic Degradation of Phenol Using Urchin-Like ZnO Microrod-Reduced Graphene Oxide Composite under Visible-Light Irradiation
Authors: Margaret S. Mary , Paul Winston Albin John P. , Muthupandi S. , Shobha P. , Sagayaraj P.
Published: July 2021

In this study, visible-light-driven ZnO microrod-rGO heterojunction composites were successfully synthesized via a facile and scalable hydrothermal process. The prepared photocatalyst heterojunction was examined using different techniques including XRD, SEM, FTIR, UV-Vis spectroscopy, and TGA to reveal their crystal phase, morphology, and other optical properties. The photocatalytic performance of the obtained ZnO-rGO composites was measured by the photodegradation of phenol under visible light illumination. The addition of graphene over the catalyst exhibited an enhanced photocatalytic activity for phenol degradation due to its high surface area and decreasing rate of electron-hole separation. Kinetic studies proved that the degradation of phenol process happened by following the pseudo-first-order kinetic model. The effective conditions for degradation of phenol using ZnO-rGO composite were 0.2 g L-1catalyst dose, pH -4, and initial concentration 20 ppm of phenol solution. Comparing with ZnO microrods, the heterojunction composite degraded the organic pollutants of phenol solution up to 84.2% of efficiency displaying the highest photocatalytic activity, whereas urchin-like ZnO catalyst exhibited much less photocatalytic activity for phenol degradation under visible light irradiation. This result envisages immense properties, showing a great potential industrial application for the removal of phenolic wastewater.
Robust PD+ Control Algorithm for Satellite Attitude Tracking for Dynamic Targets
Authors: Shan Gao , You Li , Huifeng Xue , ShuYue Yao
Published: July 2021

In this paper, a PD + controller combined with the sliding mode surface is proposed to improve system convergence rate and efficiency on control torque for satellite attitude tracking control. A sliding mode surface with the maneuver stage is constructed by the Euler axis; hence, the constant angular velocity is achieved. The PD + controller with the variable structure and auxiliary term is constructed to track the desired sliding mode surface. The Lyapunov function in PD control analysis is modified to simplify stability analysis. Model uncertainty, external disturbance, control torque constraint, and angular velocity constraint are taken into consideration, and a novel method to reduce the overshoot of angular velocity is proposed. The performance and superiority of the proposed method are demonstrated by numerical simulation results.
Propofol Suppresses Cell Progression by Inhibiting CCL18 Expression in Hepatoblastoma
Authors: Zhang Hua , Lin Pingling , Fu Lei , Li Zhijun , Ding Yan
Published: July 2021

Background. Propofol is an anesthetic commonly used clinically and has been found to have antitumor activity in various cancers. The purpose of this study was to investigate the role of propofol in hepatoblastoma (HB). Methods. CCK-8 and transwell were used to measure cell proliferation, migration, and invasion in HB cells. Cell apoptosis rate was measured by FCM. The expression of CCL18 in HB tissues and cells was detected by RT-qPCR. Western blotting was used to explore the protein expression of CCK18- and PI3K/AKT-related proteins. Results. The expression of CCL18 in HB tissues and cells was overexpressed compared with control groups. CCL18 knockdown was found to notably block cell proliferation and progression, while enhancing cell apoptosis in HuH-6 and HepT1 cells. Furthermore, propofol suppressed the proliferation of HB cells in a dose-dependent manner. According to the results, we chose 5 μg/mL of propofol-treated cells for 48 hours as the subsequent experimental conditions. We found that propofol (5 μg/mL, 48 h) significantly blocked cell migration and invasion, but induced cell apoptosis in HuH-6 and HepT1 cells. In addition, CCK18 overexpression facilitated cell progression in HB cells, while propofol dramatically suppressed the effect of CCK18. Besides that, propofol suppressed the PI3K/AKT pathway. Conclusion. Propofol suppressed the development of HB cells by inhibiting CCK18 expression and the PI3K/AKT pathway. Therefore, we infer that propofol plays a role in the treatment of HB.
GC-MS Based Metabolomics Reveals the Synergistic Mechanism of Gardeniae Fructus-Forsythiae Fructus Herb Pair in Lipopolysaccharide-Induced Acute Lung Injury Mouse Model
Authors: Wu Wenhui , Lin Huiqing , Yin Ailing , Shen Cunsi , Zhou Hongliang , Wang Majie , Yu Heming , Wang Haidan , Zhang Zhihao , Zhou Wei
Published: July 2021

Compatibility remains among the crucial and significant characteristics of traditional Chinese medicines. The Gardeniae Fructus (FG)-Forsythiae Fructus (FF) herb pair, an epitome of formulations for heat-clearing and detoxification, is extensively used to treat bacterial pneumonia in clinical settings. However, there are few reports on their synergistic effects. This study thus investigated their compatibility by GC-MS based metabolomics using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Differential metabolites were identified by both variable importance in the projection (VIP) > 1 in orthogonal partial least-squares discriminant analysis (OPLS-DA) mode and

P
<
0.05

. Results of biochemistry and histopathology indicated that FG-FF herb pair exerted more promising lung protective effect than its individual decoction against the LPS-induced ALI model. From the metabolomics study, 32 differential metabolites in vehicle vs. model groups, 21 differential metabolites in FF vs. model groups, 21 differential metabolites in FG vs. model groups, and 20 differential metabolites in FG-FF herb pair vs. model groups were found. Among them, the levels of 3-hydroxybutyric acid, alanine, isophthalic acid, and terephthalic acid were restored significantly in the FF group, while silanol and cholesterol were restored significantly in the FG group. For FG-FF treatment, the amount of behenic acid, a metabolite with anti-inflammatory properties, was increased, while palmitic acid, a proinflammatory metabolite, was decreased. Meanwhile, the two biomarkers were restored more significantly than that by FG or FF treatment, which indicated that the synergistic effects by FF coupled with FG might be attributed to restoring fatty acids metabolic pathway.
Smart Bracelet System for Temperature Monitoring and Movement Tracking Analysis
Authors: Fang Bin , Sun Fuchun , Quan Zhou , Liu Huaping , Shan Jianhua
Published: July 2021

In several epidemic diseases, one of the main symptoms exhibited by people is abnormal body temperature. Therefore, monitoring body temperature is crucial for preventing the spread of infectious diseases and facilitating timely responses. This study presents a wearable bracelet that can be used as a temperature monitoring and trajectory analysis system. The temperature sensor in the bracelet can effectively monitor the body temperature of the wearer in the target scene, and the data transmission between the bracelet and the data collector can effectively detect the movement range and trajectory of the wearer. Through these, the whole set can also detect the direct and indirect contact of the wearer in any period of time, which is very helpful for the prevention and control of infectious diseases and the isolation of potentially infected persons.
Improvement of Presbyopia Using a Mixture of Traditional Chinese Herbal Medicines, Including Cassiae Semen, Wolfberry, and Dendrobium huoshanense
Authors: Horng Chi-Ting , Ma Jui-Wen , Shieh Po-Chuen
Published: July 2021

Background. Presbyopia is a primary cause of a decline in near vision. In this study, we developed a new mixed herbal medicine to retard presbyopic progression and increase the amplitude of accommodation (AA), which is beneficial for near vision. Methods. A total of 400 participants between the ages of 45 and 70 years were recruited. We designed the mixed herbal drug to include Cassiae Semen (200 mg), wolfberry (200 mg), and Dendrobium huoshanense (DD) (40 mg) in one capsule. In experiment 1, the recruited subjects were directed to perform a push-up test to measure their AA; this was then converted to the additional diopters of reading glasses. In experiment 2, 240 subjects took three capsules daily for six months and then stopped medical therapy for a six-month follow-up. In experiment 3, 160 subjects were randomly categorized into four groups: a placebo group, low-dose group (LDG) (1 capsule daily), middle-dose group (MDG) (two capsules daily), and high-dose group (HDG) (three capsules daily). The 160 volunteers took different doses for six months and then stopped treatment, accompanied by another six-month follow-up. In experiments 2 and 3, the change in AA, uncorrected far visual acuity (UFVA), and uncorrected near visual acuity (UNVA) were recorded each month for one year. Results. In experiment 1, AA was found to decrease with age and a great deal of additional power was needed in older individuals. In experiment 2, the mean AA reached a maximum value of 2.1D (

P

 < 0.05) after six months, while the UNVA improved by about two to three lines of a Jaeger chart in most of the subjects. At nine months, all the means decreased slightly to 2.0 D (

P

 < 0.05). This meant that the mixed herbal medicine could still maintain AA for another three months because the herbal therapy was stopped at the seventh month. In experiment 3, the maximal AA was 2.8D, 2.9D, and 3.2D (

P

 < 0.05) in the LDG, MDG, and HDG after six-month treatments, respectively. Experiment 3 showed that AA gain occurred in a dose-dependent manner; the higher the dose, the greater the AA value. Conclusion. Only two studies on the use of herbal drugs for presbyopia have been reported in PubMed. In our study, we found that taking a mixed herbal drug caused an excellent gain in AA. This is the first study to report that the characteristics of the new herbal regimen could retard and even ameliorate presbyopia.
Experimental and Numerical Analysis of Hollow and Solid Reinforced Concrete Piers under Static and Impact Loadings
Authors: Yao Pengfei , Zhu Junyu , Zhu Lu , Fang Hai , Qian Changgen
Published: July 2021

Collision on reinforced concrete (RC) piers by moving vessels or vehicles is a significant issue. This paper presents the static and impact behavior of RC piers with different hollow ratios. Three specimens were statically tested to obtain the load‐displacement response. Low‐velocity collision on eleven RC piers was conducted under the same velocity of 2.42 m/s. The damage process, failure mode, and force response were comprehensively analyzed. The experimental results indicate that the hollow ratio plays a significant role in the failure mode and ultimate load of RC piers under static and impact loadings. For RC piers with a hollow ratio of 0 and 0.4, the global failure dominated the damage process. However, failure of piers with a hollow ratio of 0.6 was governed by the local damage near the loading point. The static load capacities of the RC piers with a hollow ratio of 0.4 and 0.6 were 1.27% and 60.5% smaller than that of the solid pier, respectively. RC piers with a higher hollow ratio or lighter drop weight suffer smaller peak impact force. The increase of the longitudinal reinforcements leads to a promotion of the peak and mean impact force. Furthermore, the numerically predicted failure modes and impact load response show satisfactory agreement with the experimental results.
The Prevalence and Severity of Depression, Anxiety, and Stress among Medical Undergraduate Students of Arsi University and Their Association with Substance Use, Southeast Ethiopia
Authors: Melaku Leta , Bulcha Guta , Worku Deresa
Published: July 2021

Background. Mental problems can negatively impact physical and psychological well-being of junior medical students and predispose them to many unhealthy behaviors. Objective. We aimed to determine the prevalence and severity of depression, anxiety, and stress among medical undergraduate students of Arsi University and their association with substance use. Methods. Institutional-based cross-sectional study was conducted on 265 sampled medical students. Participants were selected by systematic random sampling. Data were collected by a pretested self-administrative questionnaire and analyzed using SPSS-21 software. Logistic regression analysis was employed, and statistical significance was accepted at

p
<
0.05

. Result. In the present study, 5 questionnaires were rejected for incompleteness giving response rate of 98.1%. The mean age was 22.03 (SD = 2.074) years. The current prevalence rates of depression, anxiety, and stress were 52.3%, 60.8%, and 40.4%, respectively. The overall prevalence of khat chewing, cigarette smoking, and alcohol drinking was found to be 21.5%, 15.4%, and 33.8%, respectively. Depression was significantly associated with monthly income [AOR = 2.13], residency [AOR = 13.10], and alcohol drinking [AOR = 1.68]. Anxiety was associated with gender [AOR = 0.51], marital status [AOR = 0.46], educational year [AOR = 20.43], residency [AOR = 58.72], and cigarette smoking [AOR = 2.60]. Stress was significantly associated with monthly income [AOR = 2.21], educational year [AOR = 3.05], residency [AOR = 4.82], khat chewing [AOR = 1.90], and drinking alcohol [AOR = 1.84]. Conclusion. To sum up, depression, anxiety, and stress are common problems among medical students of Arsi University. Monthly income, residency, and alcohol drinking were identified as risk factors of both depression and stress. In addition to other mentioned factors, educational year and khat chewing were identified as risk factors of stress. However, gender, marital status, educational year, residency, and cigarette smoking were identified as risk factors of anxiety. Counselling and awareness creation are recommended.
Inhibitory Effects of Myricetrin and Dihydromyricetin toward α-Glucosidase and Pancreatic Lipase with Molecular Docking Analyses and Their Interaction
Authors: Mi Siyuan , Liu Jia , Liu Xiaojing , Fu Yishan , Yi Junjie , Cai Shengbao
Published: July 2021

The aim of the current study was to evaluate the interaction effects of myricetrin and dihydromyricetin in inhibiting α-glucosidase and pancreatic lipase at different combination ratios and concentrations and to illuminate the underlying mechanisms of their inhibitions by molecular docking analyses. Results showed that both phenolic compounds possessed good inhibitory effects toward two enzymes in a dose-dependent manner. Myricetrin demonstrated a stronger inhibition against α-glucosidase (IC50, 41.14 ± 2.52 and more than 200 μg/mL, respectively), while dihydromyricetin had a better pancreatic lipase inhibition (IC50, 244.96 ± 4.24 and 373.26 ± 21.36 μg/mL, respectively). Different interaction types were observed when myricetrin and dihydromyricetin inhibited α-glucosidase and pancreatic lipase in combination, which were closely related to the combination ratio and concentration. For α-glucosidase inhibition, synergistic effects were observed at relative low concentrations when the combination ratio of myricetrin to dihydromyricetin was set as 1 : 2, while strong synergistic effects existed at relative high concentrations for pancreatic lipase inhibition. In other combination ratios (1 : 1 or 2 : 1), additive and/or antagonistic effects occurred. Molecular docking analyses showed that myricetrin formed nine hydrogen bonds with α-glucosidase, while only three hydrogen bonds were formed between dihydromyricetin and α-glucosidase. However, these two phenolic compounds had similar hydrogen bonds and hydrophobic interactions with pancreatic lipase. The present study suggested that myricetrin and dihydromyricetin or food materials rich in these two phenolic compounds could be exploited as α-glucosidase and/or pancreatic lipase inhibitors to deal with health problems caused by excessive energy intake, and the combination ratio and concentration of these two phenolic compounds should be considered when producing new functional foods.
The Price Impact of Order Book Events from a Dimension of Time
Authors: Chi Wentao , Zhao Xuemei , Huang Lufei
Published: July 2021

We propose a new linear model to explain the price move by Level-2 high-frequency data in Chinese mainland stock market. In Chinese stock market, the cancellation ratio is very low, and imbalanced order flow prevails most of the time in the trading periods. From time dimension viewpoint, we find the difference of efficiency of limit orders executed, respectively, in bid/ask limit order book, order execution imbalance (OEI), could improve the classic model of Cont et al. (2014) based on market microstructure of Chinese mainland stock market. In particular, when market’s liquidity is booming, our model’s explanatory power and R-squared increased sharply. And the correlations of OEI are very high that may be exploited to predict the price move in the next time window for doing high-frequency trading.
Preclinical and Early Clinical Development of PTC596, a Novel Small-Molecule Tubulin-Binding Agent
Authors: Jernigan Finith , Branstrom Arthur , Baird John D. , Cao Liangxian , Dali Mandar , Furia Bansri , Kim Min Jung , O'Keefe Kylie , Kong Ronald , Laskin Oscar L. , Colacino Joseph M. , Pykett Mark , Mollin Anna , Sheedy Josephine , Dumble Melissa , Moon Young-Choon , Sheridan Richard , Mühlethaler Tobias , Spiegel Robert J. , Prota Andrea E. , Steinmetz Michel O. , Weetall Marla
Published: July 2021

PTC596 is an investigational small-molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical in vitro anticancer activity, and its pharmacokinetic–pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma. Using X-ray crystallography, it was determined that PTC596 binds to the colchicine site of tubulin with unique key interactions. PTC596 exhibited broad-spectrum anticancer activity. PTC596 showed efficacy as monotherapy and additive or synergistic efficacy in combinations in mouse models of leiomyosarcomas and glioblastoma. PTC596 demonstrated efficacy in an orthotopic model of glioblastoma under conditions where temozolomide was inactive. In a first-in-human phase I clinical trial in patients with cancer, PTC596 monotherapy drug exposures were compared with those predicted to be efficacious based on mouse models. PTC596 is currently being tested in combination with dacarbazine in a clinical trial in adults with leiomyosarcoma and in combination with radiation in a clinical trial in children with diffuse intrinsic pontine glioma.
Design of a Cytotoxic Neuroblastoma-Targeting Agent Using an Enzyme Acting on Polysialic Acid Fused to a Toxin
Authors: Lehti Timo A. , Pajunen Maria I. , Jokilammi Anne , Korja Miikka , Lilie Hauke , Vettenranta Kim , Finne Jukka
Published: July 2021

Polysialic acid, an abundant cell surface component of the developing nervous system, which declines rapidly postnatally to virtual absence in the majority of adult tissues, is highly expressed in some malignant tumors including neuroblastoma. We found that the binding of a noncatalytic endosialidase to polysialic acid causes internalization of the complex from the surface of neuroblastoma kSK-N-SH cells, a subline of SK-N-SH, and leads to a complete relocalization of polysialic acid to the intracellular compartment. The binding and uptake of the endosialidase is polysialic acid–dependent as it is inhibited by free excess ligand or removal of polysialic acid by active endosialidase, and does not happen if catalytic endosialidase is used in place of inactive endosialidase. A fusion protein composed of the noncatalytic endosialidase and the cytotoxic portion of diphtheria toxin was prepared to investigate whether the cellular uptake observed could be used for the specific elimination of polysialic acid–containing cells. The conjugate toxin was found to be toxic to polysialic acid–positive kSK-N-SH with an IC50 of 1.0 nmol/L. Replacing the noncatalytic endosialidase with active endosialidase decreased the activity to the level of nonconjugated toxin. Normal nonmalignant cells were selectively resistant to the toxin conjugate. The results demonstrate that noncatalytic endosialidase induces a quantitative removal and cellular uptake of polysialic acid from the cell surface which, by conjugation with diphtheria toxin fragment, can be exploited for the selective elimination of polysialic acid–containing tumor cells.
Novel Humanized Mesothelin-Expressing Genetically Engineered Mouse Models Underscore Challenges in Delivery of Complex Therapeutics to Pancreatic Cancers
Authors: Hagerty Brendan , O'Sullivan T. Norene , Zhang Xianyu , Collins N. Keith , Custer Lawrence Wendi , Bassel Laura L. , Pate Nathan , Xu Jian , Guerin Theresa M. , Kozlov Serguei , Alewine Christine
Published: July 2021

Antibody-based therapies designed for human use frequently fail to cross-react with the murine isoform of their target. Because of this problem, preclinical studies of antibody-based mesothelin (Msl)-targeted therapeutics in immunocompetent systems have been limited by the lack of suitable mouse models. Here, we describe two immunocompetent humanized mesothelin transgenic mouse lines that can act as tolerant hosts for C57Bl/6-syngeneic cell lines expressing the human isoform of mesothelin. Thyroid peroxidase (TPO) mice have thyroid-restricted human mesothelin expression. Mesothelin (Msl) mice express human mesothelin in the typical serosal membrane distribution and can additionally be utilized to assess on-target, off-tumor toxicity of human mesothelin–targeted therapeutics. Both transgenic strains shed human mesothelin into the serum like human mesothelioma and patients with ovarian cancer, and serum human mesothelin can be used as a blood-based surrogate of tumor burden. Using these models, we examined the on-target toxicity and antitumor activity of human mesothelin–targeted recombinant immunotoxins. We found that immunotoxin treatment causes acute and chronic histologic changes to serosal membranes in Msl mice, while human mesothelin-expressing thyroid follicular cells in TPO mice are resistant to immunotoxin despite excellent drug delivery. Furthermore, poor delivery of immunotoxin to syngeneic orthotopic human mesothelin-expressing pancreatic adenocarcinoma limits antitumor activity both alone and in combination with immune checkpoint inhibition. In summary, we have developed two high-fidelity, immunocompetent murine models for human cancer that allow for rigorous preclinical evaluation of human mesothelin–targeted therapeutics.
Nephrologist Interventions to Avoid Kidney Replacement Therapy in Acute Kidney Injury
Authors: Chávez-Íñiguez Jonathan S. , Maggiani-Aguilera Pablo , Pérez-Flores Christian , Claure-Del Granado Rolando , De la Torre-Quiroga Andrés E. , Martínez-Gallardo González Alejandro , Navarro-Blackaller Guillermo , Medina-González Ramón , Raimann Jochen G. , Yanowsky-Escatell Francisco G. , García-García Guillermo
Published: July 2021

Background: Based on the pathophysiology of acute kidney injury (AKI), it is plausible that certain early interventions by the nephrologist could influence its trajectory. In this study, we investigated the impact of 5 early nephrology interventions on starting kidney replacement therapy (KRT), AKI progression, and death. Methods: In a prospective cohort at the Hospital Civil of Guadalajara, we followed up for 10 days AKI patients in whom a nephrology consultation was requested. We analyzed 5 early interventions of the nephrology team (fluid adjustment, nephrotoxic withdrawal, antibiotic dose adjustment, nutritional adjustment, and removal of hyperchloremic solutions) after the propensity score and multivariate analysis for the risk of starting KRT (primary objective), AKI progression to stage 3, and death (secondary objectives). Results: From 2017 to 2020, we analyzed 288 AKI patients. The mean age was 55.3 years, 60.7% were male, AKI KDIGO stage 3 was present in 50.5% of them, sepsis was the main etiology 50.3%, and 72 (25%) patients started KRT. The overall survival was 84.4%. Fluid adjustment was the only intervention associated with a decreased risk for starting KRT (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.48–0.70, and p ≤ 0.001) and AKI progression to stage 3 (OR: 0.59, 95% CI: 0.49–0.71, and p ≤ 0.001). Receiving vasopressors and KRT were associated with mortality. None of the interventions studied was associated with reducing the risk of death. Conclusions: In this prospective cohort study of AKI patients, we found for the first time that early nephrologist intervention and fluid prescription adjustment were associated with lower risk of starting KRT and progression to AKI stage 3.