bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of Dipterocarpus tuberculatus with High Antioxidative Activity Against UV-Induced Photoaging of NHDF Cells and Nude Mice
Authors: Lee Su Jin , Kim Ji Eun , Choi Yun Ju , Gong Jeong Eun , Park So Hae , Douangdeuane Bounleuane , Souliya Onevilay , Park Ju Min , Lee Hee Seob , Kim Bae-Hwan , Hwang Dae Youn
Published: May 2021

To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against UV-induced photoaging, we assessed for alterations in the antioxidant activity, anti-apoptotic effects, ECM modulation, skin appearances, and anti-inflammatory response in normal human dermal fibroblast (NHDF) cells and nude mice orally treated with MED. High levels of tannin content and high free radical scavenging activity to DPPH were determined in MED, while seven active components, namely, gallic acid, bergenin, ellagic acid, ε-viniferin, asiatic acid, oleanolic acid, and 2α-hydroxyursolic acid, were identified using LC–MS analyses. UV-induced alterations in the NO concentration, SOD activity, and Nrf2 expression were remarkably recovered in MED-treated NHDF cells. Moreover, the decreased number of apoptotic cells and G2/M phase arrest were observed in the UV + MED-treated groups. Similar recoveries were detected for β-galactosidase, MMP-2/9 expression, and intracellular elastase activity. Furthermore, MED treatment induced suppression of the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation in UV-radiated NHDF cells. The anti-photoaging effects observed in NHDF cells were subsequently evaluated and validated in UV + MED-treated nude mice through skin phenotypes and histopathological structure analyses. Taken together, these results indicate that MED exerts therapeutic effects against UV-induced photoaging and has the potential for future development as a treatment for photoaging.
Decentralized Voltage Optimization Based on the Auxiliary Problem Principle in Distribution Networks with DERs
Authors: Di Fazio Anna Rita , Risi Chiara , Russo Mario , De Santis Michele
Published: May 2021

This paper addresses the problem of optimizing the voltage profile of radially-operated distribution systems by acting on the active and reactive powers provided by distributed energy resources (DERs). A novel voltage optimization procedure is proposed by adopting a decentralized control strategy. To this aim, a centralized voltage optimization problem (VOP), minimizing the distance of all the nodal voltages from their reference values, is firstly formulated as a strictly-convex quadratic program. Then, the centralized VOP is rewritten by partitioning the network into voltage control zones (VCZs) with pilot nodes. To overcome the lack of strictly convexity determined by the reduction to the pilot nodes, the dual centralized VOP working on the augmented Lagrangian function is reformulated and iteratively solved by the method of multipliers. Finally, a fully-distributed VOP solution is obtained by applying a distributed algorithm based on the auxiliary problem principle, which allows for solving in each VCZ a quadratic programming problem of small dimension and to drive the VCZ solutions toward the overall optimum by an iterative coordination process that requires to exchange among the VCZs only scalar values. The effectiveness and feasibility of the proposed method have been demonstrated via numerical tests on the IEEE 123-bus system.
Flexural Performance of Reinforced Concrete Members with Steel Bars
Authors: Lim Myunghwan , Lee Changhee
Published: May 2021

The use of high-tension bars to strengthen flexural members is gaining increasing interest. However, the applicability of current standards to such bars is uncertain, because there may not be a definite yield strength and it may be unclear whether the tensile or compressive failure mode dominates. Determining the balanced–destruction steel ratio is particularly difficult. We measure the bending behaviour of flexural members containing high-tension bars with different yield strengths and tensile steel ratios. We conclude that the maximum-steel-ratio regulation and nominal -strength equation in the current standard remain applicable.
Multilevel Gene Regulation Using Switchable Transcription Terminator and Toehold Switch in Escherichia coli
Authors: Hong Seongho , Kim Jeongwon , Kim Jongmin
Published: May 2021

Nucleic acid-based regulatory components provide a promising toolbox for constructing synthetic biological circuits due to their design flexibility and seamless integration towards complex systems. In particular, small-transcriptional activating RNA (STAR) and toehold switch as regulators of transcription and translation steps have shown a large library size and a wide dynamic range, meeting the criteria to scale up genetic circuit construction. Still, there are limited attempts to integrate the heterogeneous regulatory components for multilevel regulatory circuits in living cells. In this work, inspired by the design principle of STAR, we designed several switchable transcription terminators starting from natural and synthetic terminators. These switchable terminators could be designed to respond to specific RNA triggers with minimal sequence constraints. When combined with toehold switches, the switchable terminators allow simultaneous control of transcription and translation processes to minimize leakage in Escherichia coli. Further, we demonstrated a set of logic gates implementing 2-input AND circuits and multiplexing capabilities to control two different output proteins. This study shows the potential of novel switchable terminator designs that can be computationally designed and seamlessly integrated with other regulatory components, promising to help scale up the complexity of synthetic gene circuits in living cells.
Air Pollution: Sensitive Detection of PM2.5 and PM10 Concentration Using Hyperspectral Imaging
Authors: Chen Chi-Wen , Tseng Yu-Sheng , Mukundan Arvind , Wang Hsiang-Chen
Published: May 2021

This paper proposes a method to detect air pollution by applying a hyperspectral imaging algorithm for visible light, near infrared, and far infrared. By assigning hyperspectral information to images from monocular, near infrared, and thermal imaging, principal component analysis is performed on hyperspectral images taken at different times to obtain the solar radiation intensity. The Beer–Lambert law and multivariate regression analysis are used to calculate the PM2.5 and PM10 concentrations during the period, which are compared with the corresponding PM2.5 and PM10 concentrations from the Taiwan Environmental Protection Agency to evaluate the accuracy of this method. This study reveals that the accuracy in the visible light band is higher than the near-infrared and far-infrared bands, and it is also the most convenient band for data acquisition. Therefore, in the future, mobile phone cameras will be able to analyze the PM2.5 and PM10 concentrations at any given time using this algorithm by capturing images to increase the convenience and immediacy of detection.
Big Data in Smart City: Management Challenges
Authors: Amović Mladen , Govedarica Miro , Radulović Aleksandra , Janković Ivana
Published: May 2021

Smart cities use digital technologies such as cloud computing, Internet of Things, or open data in order to overcome limitations of traditional representation and exchange of geospatial data. This concept ensures a significant increase in the use of data to establish new services that contribute to better sustainable development and monitoring of all phenomena that occur in urban areas. The use of the modern geoinformation technologies, such as sensors for collecting different geospatial and related data, requires adequate storage options for further data analysis. In this paper, we suggest the biG dAta sMart cIty maNagEment SyStem (GAMINESS) that is based on the Apache Spark big data framework. The model of the GAMINESS management system is based on the principles of the big data modeling, which differs greatly from standard databases. This approach provides the ability to store and manage huge amounts of structured, semi-structured, and unstructured data in real time. System performance is increasing to a higher level by using the process parallelization explained through the five V principles of the big data paradigm. The existing solutions based on the five V principles are focused only on the data visualization, not the data themselves. Such solutions are often limited by different storage mechanisms and by the ability to perform complex analyses on large amounts of data with expected performance. The GAMINESS management system overcomes these disadvantages by conversion of smart city data to a big data structure without limitations related to data formats or use standards. The suggested model contains two components: a geospatial component and a sensor component that are based on the CityGML and the SensorThings standards. The developed model has the ability to exchange data regardless of the used standard or the data format into proposed Apache Spark data framework schema. The verification of the proposed model is done within the case study for the part of the city of Novi Sad.
Effects of Tendon Release Surgery on Inter-Limb Leg Stiffness Control in Children with Spastic Diplegic Cerebral Palsy during Gait
Authors: Kuo Chien-Chung , Huang Hsing-Po , Lu Hsuan-Yu , Chen Tsan-Yang , Wang Ting-Ming , Lu Tung-Wu
Published: May 2021

Impaired motor control and musculotendon tightness in the lower extremities are characteristic features of patients with diplegic cerebral palsy (CP). Tendon release surgery (TRS) helps improve joint and leg stiffness, but the effects of TRS on inter-limb coordination in terms of the total leg stiffness, and the bilateral symmetry in leg stiffness during gait, remain unknown. Ten children with spastic diplegic CP scheduled for TRS and ten healthy controls participated in this study. The inter-limb sharing of total leg stiffness during double-limb support phase and bilateral leg stiffness symmetry during stance phase of gait were calculated using the kinematic and ground reaction force data measured by a motion analysis system. Before TRS, the patients with diplegic CP walked with a decreased share of total leg stiffness during weight-acceptance (p < 0.05) and with increased bilateral leg stiffness asymmetry during single-limb support and weight-transfer during gait (p < 0.05) when compared to healthy controls. After TRS, the bilateral leg stiffness asymmetry was significantly reduced in the CP group, especially in the terminal stance phase, with inter-limb sharing of total leg stiffness becoming similar to that in controls (p > 0.05). The surgery seemed to improve the lower limb control and increased the bilateral limb symmetry during gait.
Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts
Authors: Matsuzaki Yuichi , Ulziibayar Anudari , Shoji Toshihiro , Shinoka Toshiharu
Published: May 2021

The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications.
Halloysite Nanotubes with Immobilized Plasmonic Nanoparticles for Biophotonic Applications
Authors: Kornilova Anastasiia V. , Novikov Sergey M. , Kuralbayeva Galiya A. , Jana Subhra , Lysenko Ivan V. , Shpichka Anastasia I. , Stavitskaya Anna V. , Gorbachevskii Maxim V. , Novikov Andrei A. , Ikramova Saltanat B. , Timashev Peter S. , Arsenin Aleksey V. , Volkov Valentyn S. , Vasiliev Alexander N. , Timoshenko Victor Yu.
Published: May 2021

Halloysite nanotubes (HNTs) with immobilized gold (Au) and silver (Ag) nanoparticles (NPs) belong to a class of nanocomposite materials whose physical properties and applications depend on the geometry of arrangements of the plasmonic nanoparticles on HNT’ surfaces. We explore HNTs:(Au, Ag)-NPs as potential nano-templates for surface-enhanced Raman scattering (SERS). The structure and plasmonic properties of nanocomposites based on HNTs and Au- and Ag-NPs are studied by means of the transmission electron microscopy and optical spectroscopy. The optical extinction spectra of aqueous suspensions of HNTs:(Au, Ag)-NPs and spatial distributions of the electric fields are simulated, and the simulation results demonstrate the corresponding localized plasmonic resonances and numerous “hot spots” of the electric field nearby those NPs. In vitro experiments reveal an enhancement of the protein SERS in fibroblast cells with added HNTs:Ag-NPs. The observed optical properties and SERS activity of the nanocomposites based on HNTs and plasmonic NPs are promising for their applications in biosensorics and biophotonics.
Semi-Active System of Vehicle Vibration Damping
Authors: Grzesikiewicz Wiesław , Makowski Michał
Published: May 2021

This article discusses the vibration of a vehicle equipped with four semi-active dampers. The friction forces generated in these dampers have crucial influence on the intensity of the vehicle vibration. To estimate the effect of the vehicle vibration damping, a criterial function depending on the values of these forces has been selected. Solving the problem has the purpose of determining four values of the forces at which the criteria function reaches the minimum at any moment. On the basis of the above, signals for the devices controlling the operation of the semi-active dampers are determined. In this work, the analysis of the discussed problem was conducted in regard to the method for determining the optimal force values. Moreover, the results of the simulation of the vibration of the vehicle equipped with semi-active magneto-rheological dampers are presented. In addition, the analysis of the influence of the form of the criterial function on the vehicle vibration damping efficiency is proposed. Based on the tests carried out on the vehicle with MR dampers, the comfort index improved by 51.6%, compared to the classic suspension.
Improvement of a Tunable Stiffness Organ-Grasping Device by Design of a Wavy-Shaped Beam Structure
Authors: Kawase Toshihiro , Sugino Takaaki , Onogi Shinya , Kawashima Kenji , Nakajima Yoshikazu
Published: May 2021

Tunable stiffness mechanisms can increase the noninvasiveness and stability of organ manipulation in laparoscopic liver resection. We have developed an organ-grasping device using beam-shaped tunable stiffness mechanism. Increasing the change ratio of stiffness will improve the performance of the device by offering high flexibility when adhering to the liver surface and high rigidity during the manipulation of the liver; however, optimal design of the beam has not been investigated. In this study, we investigate the wavy structure shape of the device that enhances the change in the ratio of stiffness. To increase the stiffness in a high-stiffness state, we used principal stress lines in the device to design the edge curve of the wavy shape material in the beams. We also investigated the arrangement of the wavy shape to decrease the stiffness in a low-stiffness state. Simulation using finite element method showed that the change ratio of stiffness was improved up to 13.0 by the new wavy shape arranged with the uniformly thick bottom of the waves.
Low-Rank Approximation of Difference between Correlation Matrices Using Inner Product
Authors: Tanioka Kensuke , Hiwa Satoru
Published: May 2021

In the domain of functional magnetic resonance imaging (fMRI) data analysis, given two correlation matrices between regions of interest (ROIs) for the same subject, it is important to reveal relatively large differences to ensure accurate interpretation. However, clustering results based only on differences tend to be unsatisfactory and interpreting the features tends to be difficult because the differences likely suffer from noise. Therefore, to overcome these problems, we propose a new approach for dimensional reduction clustering. Methods: Our proposed dimensional reduction clustering approach consists of low-rank approximation and a clustering algorithm. The low-rank matrix, which reflects the difference, is estimated from the inner product of the difference matrix, not only from the difference. In addition, the low-rank matrix is calculated based on the majorize–minimization (MM) algorithm such that the difference is bounded within the range −1 to 1. For the clustering process, ordinal k-means is applied to the estimated low-rank matrix, which emphasizes the clustering structure. Results: Numerical simulations show that, compared with other approaches that are based only on differences, the proposed method provides superior performance in recovering the true clustering structure. Moreover, as demonstrated through a real-data example of brain activity measured via fMRI during the performance of a working memory task, the proposed method can visually provide interpretable community structures consisting of well-known brain functional networks, which can be associated with the human working memory system. Conclusions: The proposed dimensional reduction clustering approach is a very useful tool for revealing and interpreting the differences between correlation matrices, even when the true differences tend to be relatively small.
Longer Time-Scale Variability of Atmospheric Vertical Motion over the Tibetan Plateau and North Pacific and the Climate in East Asia
Authors: Tian Rongxiang , Ma Yaoming , Ma Weiqiang , Zhao Xiuyi , Zha Duo
Published: May 2021

The vertical motion of air is closely related to the amount of precipitation that falls in a particular region. The Tibetan Plateau and the North Pacific are important determinants of the East Asian climate. We use climate diagnosis and statistical analysis to study the vertical motion of the air over the North Pacific and Tibetan Plateau and the relationship between the vertical motion of air over them and the climate in East Asia. Here we show that there is a downward movement of air over the Tibetan Plateau during the winter, with a maximum velocity of downward movement at 500 hPa, whereas there is an upward movement of air with a maximum velocity of upward movement at 600 hPa during the summer. Precipitation in East Asia has a significant negative correlation (The correlation coefficient exceeds −0.463 and confidence level is greater than 99%) with the vertical motion of air over the Tibetan Plateau and the North Pacific during both the winter and summer. There is also a negative correlation of precipitation in the region south of the Yangtze River with the vertical motion of air over the Tibetan Plateau in winter, whereas the area of negative correlation to the vertical motion of air over the North Pacific in winter is located to the east of the Tibetan Plateau and the Yangtze–Huaihe river basin. The research results provide a climatic framework for the vertical motion of air over both the Tibetan Plateau and the North Pacific.
Characteristics of Summer Hourly Extreme Precipitation Events and Its Local Environmental Influencing Factors in Beijing under Urbanization Background
Authors: Zheng Zuofang , Xu Guirong , Gao Hua
Published: May 2021

Studies on urban extreme precipitation and its influencing factors are significant for prevention and reduction of meteorological disasters; however, few studies focus on hourly extreme precipitation (HEP) events due to the limitation of observation. By using the summer hourly precipitation data in Beijing from 1980 to 2020, the spatial distribution and temporal variation of HEP as well as its local environmental influencing factors are investigated. It is found that both summer precipitation amount and frequency of HEP are affected by topography, with high values in windward slope area. The summer precipitation amount of HEP is 160–200 mm, accounting for 42–47% of the annual summer precipitation amount, while the frequency proportion of HEP is only 5.5–6.0%. Although the summer precipitation amount and frequency in Beijing both decrease in the past 41 years, those for HEP present an opposite trend mainly due to the increasing HEP since 2003 and this is a phenomenon worthy of attention. A similar bimodal pattern in diurnal variation is found for the summer precipitation amount and frequency of HEP, with two peaks in 19–22 LT and 01–05 LT, respectively, indicating that HEPs are more concentrated in the evening and early morning especially in urban area. Moreover, the urbanization process of Beijing is consistent with the change trend of HEP, implying that the stronger the urban heat island intensity (UHI), the higher the probability of HEP. Furthermore, the convergence lines of terrain are also conducive to local heavy rainfall, and lower tropospheric stability (LTS) and convective available potential energy (CAPE) as well as aerosols may also affect HEP in Beijing.
“Military Parade Blue Skies” in Beijing: Decisive Influence of Meteorological Factors on Transport Channel and Atmospheric Pollutant Concentration Level
Authors: Yang Shujian , Zhang Yang , Shang Jing , Li Zhengqiang , de Foy Benjamin , Schauer James Jay , Zhang Yuanxun
Published: May 2021

The severity of high atmospheric pollution has been a major social problem in northern China. To improve the air quality in the Beijing–Tianjin–Hebei (BTH) region and guarantee a suitable environment during the military parade and other celebrating activities for the 70th anniversary of the victory for anti-Fascist Warcraft in the year 2015, a series of strict air quality control policies were carried out. To analyze the reduction extents of PM2.5 and organic matter components during the control period and to examine the meteorological conditions in this region and their decisive influence on the air quality, PM2.5 samples were collected and the Lagrangian particle dispersion model FLEXPART was performed to calculate potential source locations within the BTH region. PM2.5, organic carbon (OC), elementary carbon (EC), and three species types were specifically analyzed. Although the results showed that PM2.5, OC, and EC reduced by 64.55%, 48.74%, and 60.75% during the control period, the air mass transport patterns showed great difference at certain periods, which altered the dominant transport direction of air mass and the potential source region of pollutants and organic matters. This alteration completely changed major atmospheric pollutants sources contribution and caused huge concentration changes. Parallel cases also showed that meteorological conditions could avoid massive atmospheric transported from a major emission source region to a receptor site. The meteorological conditions changed the main contribution source region in control and non-control periods and proved the air quality control measures were less necessary in some southern Hebei cities during special events periods.
Emissions of Volatile Organic Compounds (VOCs) from an Open-Circuit Dry Cleaning Machine Using a Petroleum-Based Organic Solvent: Implications for Impacts on Air Quality
Authors: Lee Hyeonji , Kim Kyunghoon , Choi Yelim , Kim Daekeun
Published: May 2021

Volatile organic compounds (VOCs) are known to play an important role in tropospheric chemistry, contributing to ozone and secondary organic aerosol (SOA) generation. Laundry facilities, using petroleum-based organic solvents, are one of the sources of VOCs emissions. However, little is known about the significance of VOCs, emitted from laundry facilities, in the ozone and SOA generation. In this study, we characterized VOCs emission from a dry-cleaning process using petroleum-based organic solvents. We also assessed the impact of the VOCs on air quality by using photochemical ozone creation potential and secondary organic aerosol potential. Among 94 targeted compounds including toxic organic air pollutants and ozone precursors, 36 compounds were identified in the exhaust gas from a drying machine. The mass emitted from one cycle of drying operation (40 min) was the highest in decane (2.04 g/dry cleaning). Decane, nonane, and n-undecane were the three main contributors to ozone generation (more than 70% of the total generation). N-undecane, decane, and n-dodecane were the three main contributors to the SOA generation (more than 80% of the total generation). These results help to understand VOCs emission from laundry facilities and impacts on air quality.
The Formal Framework for Collective Systems
Authors: Palak Rafał , Wojtkiewicz Krystian
Published: May 2021

Automated reasoning is becoming crucial for information systems. Building one uniform decision support system has become too complicated. The natural approach is to divide the task and combine the results from different subsystems into one uniform answer. It is the basic idea behind the system approach, where one solution is a composition of multiple subsystems. In this paper, the main emphasis is on establishing the theoretical framework that combines various reasoning methods into a collective system. The system’s formal abstraction uses graph theory and provides a discussion on possible aggregation function definitions. The proposed framework is a tool for building and testing specific approaches rather than the solution itself.
Integrated Signals of Jasmonates, Sugars, Cytokinins and Auxin Influence the Initial Growth of the Second Buds of Chrysanthemum after Decapitation
Authors: Sun Daojin , Zhang Luyao , Yu Qi , Zhang Jiali , Li Peiling , Zhang Yu , Xing Xiaojuan , Ding Lian , Fang Weimin , Chen Fadi , Song Aiping
Published: May 2021

Decapitation is common in horticulture for altering plant architecture. The decapitation of chrysanthemum plants breaks apical dominance and leads to more flowers on lateral branches, resulting in landscape flowers with good coverage. We performed both third- and second-generation transcriptome sequencing of the second buds of chrysanthemum. This third-generation transcriptome is the first sequenced third-generation transcriptome of chrysanthemum, revealing alternative splicing events, lncRNAs, and transcription factors. Aside from the classic hormones, the expression of jasmonate-related genes changed because of this process. Sugars also played an important role in this process, with upregulated expression of sucrose transport-related and TPS genes. We constructed a model of the initial growth of the second buds after decapitation. Auxin export and sugar influx activated the growth of these buds, while the JA-Ile caused by wounding inhibited the expression of CycD genes from 0 h to 6 h. After wound recovery, cytokinins accumulated in the second buds and might have induced ARR12 expression to upregulate CycD gene expression from 6 h to 48 h, together with sugars. Therefore, jasmonates, cytokinins, sugars, and auxin work together to determine the fate of the buds of plants with short internodes, such as chrysanthemum.
Tobacco Use and Periodontal Disease—The Role of Microvascular Dysfunction
Authors: Silva Henrique
Published: May 2021

Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author’s knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies.
Camel Milk Mitigates Cyclosporine-Induced Renal Damage in Rats: Targeting p38/ERK/JNK MAPKs, NF-κB, and Matrix Metalloproteinases
Authors: Arab Hany H. , Ashour Ahmed M. , Alqarni Abdulmalik M. , Arafa El-Shaimaa A. , Kabel Ahmed M.
Published: May 2021

Renal damage is a devastating adverse effect for cyclosporine; a widely used immunosuppressant drug. The present work examined the potential of camel milk, a natural agent with marked anti-inflammatory/antioxidant properties, to attenuate cyclosporine-induced renal injury. The kidney tissue was examined with the aid of Western blotting, immunohistochemistry, biochemical assays, including colorimetric and ELISA kits. The present findings revealed that camel milk (10 mL/kg/day; for 3 weeks by gavage) significantly lowered serum creatinine, BUN, and KIM-1 renal dysfunction markers. Mechanistically, camel milk inhibited renal inflammation, as seen by significant decrease of the pro-inflammatory cytokines (MCP-1, TNF-α, IL-1β, and IL-18) and extracellular degradation signals (MMP-2 and MMP-9) and enhanced the generation of the anti-inflammatory IL-10. Moreover, it inhibited the upstream pro-inflammatory p38/ERK/JNK MAPK pathway by lowering the phosphorylation of the 3 subfamilies of MAPKs (p38 MAPK, JNK1/2, and ERK1/2). Furthermore, camel milk curbed the NF-κB pathway activation by downregulating the protein expression of activated NF-κBp65, p-NF-κBp65, and p-IκBα proteins. Additionally, camel milk inhibited renal oxidative stress by lowering the MPO activity and augmenting the reduced/oxidized glutathione ratio and total antioxidant capacity. These findings propose that camel milk may be a promising agent that inhibits cyclosporine-triggered renal inflammation via curtailing the p38/ERK/JNK MAPK and NF-κB pathways, matrix metalloproteinases, and pro-inflammatory cytokines.
Metabolomics-Guided Hypothesis Generation for Mechanisms of Intestinal Protection by Live Biotherapeutic Products
Authors: Ye Jiayu , Erland Lauren A. E. , Gill Sandeep K. , Bishop Stephanie L. , Verdugo-Meza Andrea , Murch Susan J. , Gibson Deanna L.
Published: May 2021

The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs’ persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.
Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics
Authors: Weeks Joi , Strom Alexandra I. , Widjaja Vinnie , Alexander Sati , Pucher Dahra K. , Sohl Christal D.
Published: May 2021

Isocitrate dehydrogenase (IDH1) catalyzes the reversible NADP+-dependent oxidation of isocitrate to α-ketoglutarate (αKG). IDH1 mutations, primarily R132H, drive > 80% of low-grade gliomas and secondary glioblastomas and facilitate the NADPH-dependent reduction of αKG to the oncometabolite D-2-hydroxyglutarate (D2HG). While the biochemical features of human WT and mutant IDH1 catalysis have been well-established, considerably less is known about mechanisms of regulation. Proteomics studies have identified lysine acetylation in WT IDH1, indicating post-translational regulation. Here, we generated lysine to glutamine acetylation mimic mutants in IDH1 to evaluate the effects on activity. We show that mimicking lysine acetylation decreased the catalytic efficiency of WT IDH1, with less severe catalytic consequences for R132H IDH1.
L-Proline Activates Mammalian Target of Rapamycin Complex 1 and Modulates Redox Environment in Porcine Trophectoderm Cells
Authors: Liu Ning , Yang Ying , Si Xuemeng , Jia Hai , Zhang Yunchang , Jiang Da , Dai Zhaolai , Wu Zhenlong
Published: May 2021

L-proline (proline) is a key regulator of embryogenesis, placental development, and fetal growth. However, the underlying mechanisms that support the beneficial effects of proline are largely unknown. This study used porcine trophectoderm cell line 2 (pTr2) to investigate the underlying mechanisms of proline in cell proliferation and redox homeostasis. Cells were cultured in the presence of 0, 0.25, 0.50, or 1.0 mmol/L proline for an indicated time. The results showed that 0.5 and 1.0 mmol/L proline enhanced cell viability. These effects of proline (0.5 mmol/L) were accompanied by the enhanced protein abundance of p-mTORC1, p-p70S6K, p-S6, and p-4E-BP1. Additionally, proline dose-dependently enhanced the mRNA expression of proline transporters [solute carrier family (SLC) 6A20, SLC36A1, SLC36A2, SLC38A1, and SLC38A2], elevated proline concentration, and protein abundance of proline dehydrogenase (PRODH). Furthermore, proline addition (0.25 or 0.5 mmol/L) resulted in lower abundance of p-AMPKα when compared with a control. Of note, proline resulted in lower reactive oxygen species (ROS) level, upregulated mRNA expression of the catalytic subunit of glutamate–cysteine ligase (GCLC) and glutathione synthetase (GSS), as well as enhanced total (T)-GSH and GSH concentration when compared with a control. These data indicated that proline activates themTORC1 signaling and modulates the intracellular redox environment via enhancing proline transport.
Generation of Stilbene Glycoside with Promising Cell Rejuvenation Activity through Biotransformation by the Entomopathogenic Fungus Beauveria bassiana
Authors: Ha Sang Keun , Kang Min Cheol , Lee Seulah , Darlami Om , Shin Dongyun , Choi Inwook , Kim Ki Hyun , Kim Sun Yeou
Published: May 2021

A stilbene glycoside (resvebassianol A) (1) with a unique sugar unit, 4-O-methyl-D-glucopyranose, was identified through biotransformation of resveratrol (RSV) by the entomopathogenic fungus Beauveria bassiana to obtain a superior RSV metabolite with enhanced safety. Its structure, including its absolute configurations, was determined using spectroscopic data, HRESIMS, and chemical reactions. Microarray analysis showed that the expression levels of filaggrin, HAS2-AS1, and CERS3 were higher, while those of IL23A, IL1A, and CXCL8 were lower in the resvebassianol A-treated group than in the RSV-treated group, as confirmed by qRT-PCR. Compound 1 exhibited the same regenerative and anti-inflammatory effects as RSV with no cytotoxicity in skin keratinocytes and TNF-α/IFN-γ-stimulated HIEC-6 cells, suggesting that compound 1 is a safe and stable methylglycosylated RSV. Our findings suggest that our biotransformation method can be an efficient biosynthetic platform for producing a broad range of natural glycosides with enhanced safety.
Simvastatin Enhances the Chondrogenesis But Not the Osteogenesis of Adipose-Derived Stem Cells in a Hyaluronan Microenvironment
Authors: Wu Shun-Cheng , Chang Chih-Hsiang , Chang Ling-Hua , Wu Che-Wei , Chen Jhen-Wei , Chen Chung-Hwan , Lin Yi-Shan , Chang Je-Ken , Ho Mei-Ling
Published: May 2021

Directing adipose-derived stem cells (ADSCs) toward chondrogenesis is critical for ADSC-based articular cartilage regeneration. Simvastatin (SIM) was reported to promote both chondrogenic and osteogenic differentiation of ADSCs by upregulating bone morphogenetic protein-2 (BMP-2). We previously found that ADSC chondrogenesis is initiated and promoted in a hyaluronan (HA) microenvironment (HAM). Here, we further hypothesized that SIM augments HAM-induced chondrogenesis but not osteogenesis of ADSCs. ADSCs were treated with SIM in a HAM (SIM plus HAM) by HA-coated wells or HA-enriched fibrin (HA/Fibrin) hydrogel, and chondrogenic differentiation of ADSCs was evaluated. SIM plus HAM increased chondrogenesis more than HAM or SIM alone, including cell aggregation, chondrogenic gene expression (collagen type II and aggrecan) and cartilaginous tissue formation (collagen type II and sulfated glycosaminoglycan). In contrast, SIM-induced osteogenesis in ADSCs was reduced in SIM plus HAM, including mRNA expression of osteogenic genes, osteocalcin and alkaline phosphatase (ALP), ALP activity and mineralization. SIM plus HAM also showed the most effective increases in the mRNA expression of BMP-2 and transcription factors of SOX-9 and RUNX-2 in ADSCs, while these effects were reversed by CD44 blockade. HAM suppressed the levels of JNK, p-JNK, P38 and p-P38 in ADSCs, and SIM plus HAM also decreased SIM-induced phosphorylated JNK and p38 levels. In addition, SIM enhanced articular cartilage regeneration, as demonstrated by implantation of an ADSCs/HA/Fibrin construct in an ex vivo porcine articular chondral defect model. The results from this study indicate that SIM may be an enhancer of HAM-initiated MSC-based chondrogenesis and avoid osteogenesis.
Assessment of a Reliable Fractional Anisotropy Cutoff in Tractography of the Corticospinal Tract for Neurosurgical Patients
Authors: Wende Tim , Kasper Johannes , Wilhelmy Florian , Dietel Eric , Hamerla Gordian , Scherlach Cordula , Meixensberger Jürgen , Fehrenbach Michael Karl
Published: May 2021

Background: Tractography has become a standard technique for planning neurosurgical operations in the past decades. This technique relies on diffusion magnetic resonance imaging. The cutoff value for the fractional anisotropy (FA) has an important role in avoiding false-positive and false-negative results. However, there is a wide variation in FA cutoff values. Methods: We analyzed a prospective cohort of 14 patients (six males and eight females, 50.1 ± 4.0 years old) with intracerebral tumors that were mostly gliomas. Magnetic resonance imaging (MRI) was obtained within 7 days before and within 7 days after surgery with T1 and diffusion tensor image (DTI) sequences. We, then, reconstructed the corticospinal tract (CST) in all patients and extracted the FA values within the resulting volume. Results: The mean FA in all CSTs was 0.4406 ± 0.0003 with the fifth percentile at 0.1454. FA values in right-hemispheric CSTs were lower (p < 0.0001). Postoperatively, the FA values were more condensed around their mean (p < 0.0001). The analysis of infiltrated or compressed CSTs revealed a lower fifth percentile (0.1407 ± 0.0109 versus 0.1763 ± 0.0040, p = 0.0036). Conclusion: An FA cutoff value of 0.15 appears to be reasonable for neurosurgical patients and may shorten the tractography workflow. However, infiltrated fiber bundles must trigger vigilance and may require lower cutoffs.
Recent Advances in Nucleic Acid Modulation for Functional Nanozyme
Authors: Wang Xin , Xu Yuancong , Cheng Nan , Wang Xinxian , Huang Kunlun , Luo Yunbo
Published: May 2021

Nanozymes have the potential to replace natural enzymes, so they are widely used in energy conversion technologies such as biosensors and signal transduction (converting biological signals of a target into optical, electrical, or metabolic signals). The participation of nucleic acids leads nanozymes to produce richer interface effects and gives energy conversion events more attractive characteristics, creating what are called “functional nanozymes”. Since different nanozymes have different internal structures and external morphological characteristics, functional modulation needs to be compatible with these properties, and attention needs to be paid to the influence of nucleic acids on nanozyme activity. In this review, “functional nanozymes” are divided into three categories, (nanozyme precursor ion)/ (nucleic acid) self-assembly, nanozyme-nucleic acid irreversible binding, and nanozyme-nucleic acid reversible binding, and the effects of nucleic acids on modulation principles are summarized. Then, the latest developments of nucleic acid-modulated nanozymes are reviewed in terms of their use in energy conversion technology, and their conversion mechanisms are critically discussed. Finally, we outline the advantages and limitations of “functional nanozymes” and discuss the future development prospects and challenges in this field.
Enzymatic Polymerization of Dihydroquercetin (Taxifolin) in Betaine-Based Deep Eutectic Solvent and Product Characterization
Authors: Khlupova Maria , Vasil’eva Irina , Shumakovich Galina , Zaitseva Elena , Chertkov Vyacheslav , Shestakova Alla , Morozova Olga , Yaropolov Alexander
Published: May 2021

Deep eutectic solvents (DESs) are an alternative to conventional organic solvents in various biocatalytic reactions. Meanwhile, there have been few studies reporting on synthetic reactions in DESs or DES-containing mixtures involving oxidoreductases. In this work, we have studied the effects of several DESs based on betaine as the acceptor of hydrogen bonds on the catalytic activity and stability of laccase from the basidial fungus Trametes hirsuta and performed enzymatic polymerization of the flavonoid dihydroquercetin (DHQ, taxifolin) in a DES–buffer mixture containing 60 vol.% of betaine-glycerol DES (molar ratio 1:2). The use of the laccase redox mediator TEMPO enabled an increased yield of DHQ oligomers (oligoDHQ), with a number average molecular weight of 1800 g mol−1 and a polydispersity index of 1.09. The structure of the synthesized product was studied using different physicochemical methods. NMR spectroscopy showed that oligoDHQ had a linear structure with an average chain length of 6 monomers. A scheme for enzymatic polymerization of DHQ in a DES–buffer mixture was also proposed.
Human-Specific Genes, Cortical Progenitor Cells, and Microcephaly
Authors: Heide Michael , Huttner Wieland B.
Published: May 2021

Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene ARHGAP11B and on the gene family comprising the three human-specific genes NOTCH2NLA, -B, and -C. These genes are thought to have significantly contributed to the expansion of the cerebral cortex during human evolution. We will summarize the evolution of these genes, as well as their expression and functional role during human cortical development, and discuss their potential relevance for microcephaly. Furthermore, we will give an overview of other human-specific genes that are expressed during fetal human cortical development. We will discuss the potential involvement of these genes in microcephaly and how these genes could be studied functionally to identify a possible role in microcephaly.
Never Change a Flowing System? The Effects of Retrograde Flow on Isolated Perfused Lungs and Vessels
Authors: Krabbe Hanif , Klassen Sergej , Bleidorn Johannes , Jacobs Michael J. , Krabbe Julia , Babendreyer Aaron , Martin Christian
Published: May 2021

Retrograde perfusion may occur during disease, surgery or extracorporeal circulation. While it is clear that endothelial cells sense and respond to changes in blood flow, the consequences of retrograde perfusion are only poorly defined. Similar to shear stress or disturbed flow, retrograde perfusion might result in vasomotor responses, edema formation or inflammation in and around vessels. In this study we investigated in rats the effects of retrograde perfusion in isolated systemic vessels (IPV) and in pulmonary vessels of isolated perfused lungs (IPL). Anterograde and retrograde perfusion was performed for 480 min in IPV and for 180 min in the IPL. Perfusion pressure, cytokine levels in perfusate and bronchoalveolar lavage fluid (BALF), edema formation and mRNA expression were studied. In IPV, an increased perfusion pressure and initially also increased cytokine levels were observed during retrograde perfusion. In the IPL, increased edema formation occurred, while cytokine levels were not increased, though dilution of cytokines in BALF due to pulmonary edema cannot be excluded. In conclusion, effects of flow reversal were visible immediately after initiation of retrograde perfusion. Pulmonary edema formation was the only effect of the 3 h retrograde perfusion. Therefore, further research should focus on identification of possible long-term complications of flow reversal.
Stability across the Whole Nuclear Genome in the Presence and Absence of DNA Mismatch Repair
Authors: Lujan Scott Alexander , Kunkel Thomas A.
Published: May 2021

We describe the contribution of DNA mismatch repair (MMR) to the stability of the eukaryotic nuclear genome as determined by whole-genome sequencing. To date, wild-type nuclear genome mutation rates are known for over 40 eukaryotic species, while measurements in mismatch repair-defective organisms are fewer in number and are concentrated on Saccharomyces cerevisiae and human tumors. Well-studied organisms include Drosophila melanogaster and Mus musculus, while less genetically tractable species include great apes and long-lived trees. A variety of techniques have been developed to gather mutation rates, either per generation or per cell division. Generational rates are described through whole-organism mutation accumulation experiments and through offspring–parent sequencing, or they have been identified by descent. Rates per somatic cell division have been estimated from cell line mutation accumulation experiments, from systemic variant allele frequencies, and from widely spaced samples with known cell divisions per unit of tissue growth. The latter methods are also used to estimate generational mutation rates for large organisms that lack dedicated germlines, such as trees and hyphal fungi. Mechanistic studies involving genetic manipulation of MMR genes prior to mutation rate determination are thus far confined to yeast, Arabidopsis thaliana, Caenorhabditis elegans, and one chicken cell line. A great deal of work in wild-type organisms has begun to establish a sound baseline, but far more work is needed to uncover the variety of MMR across eukaryotes. Nonetheless, the few MMR studies reported to date indicate that MMR contributes 100-fold or more to genome stability, and they have uncovered insights that would have been impossible to obtain using reporter gene assays.