bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyphenol Content, Antiradical Properties, and α-Amylase Inhibition Activity of Vaccinium myrtillus L. (Bilberry) and Vaccinium vitis-idaea L. (Lingonberry) Leaf and Aerial Parts Extracts
Authors: Cvetkova Marina , Bandere Dace , Lauberte Liga , Niedra Santa , Teterovska Renāte
Published: June 2024

The utilisation of medicinal plants has gained importance due to emerging drug resistance in diseases, including type 2 diabetes mellitus (T2DM). Vaccinium myrtillus (VM) and Vaccinium vitis-idaea (VV) are particularly noteworthy as their leaves and aerial parts (no flowering leaves with stems) are rich in polyphenols and antioxidants with potential positive impacts on blood sugar levels. The aim of this study was to compare the chemical composition, antiradical, and α-amylase inhibitory activities of the leaves and aerial parts of the Latvian VM and VV. Two samples of VM and two samples of VV were collected from two different locations. Dried plants were used to prepare 70% ethanol extracts and freeze-dried samples. The total tannin and phenolic contents were determined, and the phytochemical compounds were characterised by LC-MS. The α-amylase inhibition activity and the antiradical activity in the extracts were measured. The VV ethanol extracts had the highest polyphenol content at 632.80 mg/100 g, followed by the freeze-dried extracts at 968.52 mg/100 g. The highest polyphenol content in the VV ethanol extracts was 632.80 mg/100 g and 968.52 mg/100 g in the freeze-dried extracts. The ethanol extracts of VM (1.34%) and VV (2.85%) had the highest content of tannin, whereas the freeze-dried extracts showed significantly lower tannin content in VM (0.21%) and VV (0.18%). A high correlation was observed between DPPH (2,2-diphenyl-1-picrylhydrazyl) and α-amylase inhibition activity (R = 0.86, p = 0.015). This information can be used for additional control of sugar levels in T2DM patients. Comparing both plants with each other and different types of samples (ethanol extracts, freeze-dried samples), it was concluded that the difference exists in both variants. The VM samples showed higher results (α-amylase inhibition activity, DPPH radical scavenging activity) than the VV samples, and the freeze-dried samples had higher results than the ethanol extracts.
The Pin Structure Design of LaVAi-1.5-1400 Microwave Vertical Tubular Furnace Based on COMSOL
Authors: Li Guo , Zhou Jian , Wang Lin
Published: June 2024

The microwave heating process will involve a variety of physical phenomena, including the distribution of the electromagnetic field in the heating cavity, the heat generated by electromagnetic loss, and the transfer of heat inside the material during heating. In this paper, the simulation software COMSOL Multiphysics 5.6 based on the finite element analysis method is used to establish the microwave heating model of Al2O3/SiC composites and design the pinning structure of the experimental furnace for multi-mode microwave heating. From the uniformity of microwave heating of the sample and the coupling with microwave, the heating characteristics of the sample with different pin spacing, pin radius, and pin insertion depth were simulated and analyzed. This pin structure design can be used to control the heating conditions of Al2O3/SiC composites in microwave heating ovens to meet industrial requirements.
Characteristics and Genesis of Pore–Fracture System in Alkaline Lake Shale, Junggar Basin, China
Authors: Jiao Yifan , Tang Xianglu , He Wenjun , Huang Liliang , Jiang Zhenxue , Yang Leilei , Lin Caihua
Published: June 2024

Unconventional oil and gas resources are indispensable, and shale oil is one of them. The Junggar Basin is a typical superposition oil and gas basin in China, with reserves of 100 million tons in many areas and various types of oil and gas reservoirs. The Permian Fengcheng Formation in Mahu Sag has great potential for oil generation, making the study of the Fengcheng Formation reservoir in Mahu Sag particularly important. Based on previous studies, the core sample from well Maye-1 is divided into four lithologies according to mineral composition: felsic shale, dolomitic felsic shale, clay-bearing felsic shale, and siltstone interlayers. Through core observation and description, it is found that the macroscopic porosity of each lithology is well-developed, with felsic shale exhibiting the highest macroscopic fracture density, followed by siltstone interlayers, and clay-bearing felsic shale showing the least development. Argon ion polishing scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR) techniques show that the siltstone interlayer pore development is the best, with pore sizes ranging from 100 to 4000 nm. The fracture development of dolomitic felsic shale is the most significant, with fractures contributing up to 80.14%. The porosity of clay-bearing felsic shale is only 1.12%. The development of pores and fractures in the study area is related to sedimentary tectonic factors and diagenesis. It mainly exhibits three types of subfacies deposits, namely semi-deep lake subfacies, shallow lake subfacies, and lakeshore lake subfacies, predominantly composed of felsic shale. Strong tectonic movements contribute to the formation of macroscopic fractures. Diagenesis plays a crucial role in the formation of microscopic pores. The Fengcheng Formation is primarily influenced by compaction, pressure dissolution, dissolution, and metasomatism. These various diagenetic processes collectively promote the formation of pores, ultimately leading to the development of a multi-scale porosity system in the Fengcheng Formation.
A Point Cloud Registration Algorithm Based on Weighting Strategy for 3D Indoor Spaces
Authors: Lv Wenshan , Zhang Haifeng , Chen Weiren , Li Xiaoming , Sang Shengtian
Published: June 2024

Point cloud registration is a technology that aligns point cloud data from different viewpoints by computing coordinate transformations to integrate them into a specified coordinate system. Many cutting-edge fields, including autonomous driving, industrial automation, and augmented reality, require the registration of point cloud data generated by millimeter-wave radar for map reconstruction and path planning in 3D environments. This paper proposes a novel point cloud registration algorithm based on a weighting strategy to enhance the accuracy and efficiency of point cloud registration in 3D environments. This method combines a statistical weighting strategy with a point cloud registration algorithm, which can improve registration accuracy while also increasing computational efficiency. First, in 3D indoor spaces, we apply PointNet to the semantic segmentation of the point cloud. We then propose an objective weighting strategy to assign different weights to the segmented parts of the point cloud. The Iterative Closest Point (ICP) algorithm uses these weights as reference values to register the entire 3D indoor space’s point cloud. We also show a new way to perform nonlinear calculations that yield exact closed-form answers for the ICP algorithm in generalized 3D measurements. We test the proposed algorithm’s accuracy and efficiency by registering point clouds on public datasets of 3D indoor spaces. The results show that it works better in both qualitative and quantitative assessments.
Visualization of Demodulated Sound Based on Sequential Acoustic Ray Tracing with Self-Demodulation in Parametric Array Loudspeakers
Authors: Geng Yuting , Shimokata Makoto , Nakayama Masato , Nishiura Takanobu
Published: June 2024

With the development of acoustic simulation methods in recent decades, it has become feasible to simulate the sound pressure distribution of loudspeakers before actually setting physical speakers and measuring the sound field. The parametric array loudspeaker (PAL) has attracted attention due to its sharp directivity and unique applications. However, the sound reproduced by PALs is generated by the nonlinear interactions of ultrasound in the air, which makes it difficult to simulate the reproduced sound of a PAL with low computational load. Focusing on the sharp directivity of ultrasound, we extended conventional acoustic ray-tracing methods to consider the self-demodulation phenomenon of PALs. In this study, we developed a visualization method for the demodulated sound of a PAL. Specifically, the demodulated sound pressure distribution can be simulated to estimate and visualize the area covered by the reproduced sound of PAL before setting a real PAL. In the proposed method, acoustic rays were generated sequentially to express the generation of demodulated sound. Therefore, the proposed method is expected to simulate the demodulated sound of a PAL with acceptable accuracy and low calculation complexity. Quantitative evaluation between simulation results and practical measurement has been carried out, and the results demonstrate the effectiveness of the proposed method.
Privacy-Preserving Byzantine-Resilient Swarm Learning for E-Healthcare
Authors: Zhu Xudong , Lai Teng , Li Hui
Published: June 2024

An automatic medical diagnosis service based on deep learning has been introduced in e-healthcare, bringing great convenience to human life. However, due to privacy regulations, insufficient data sharing among medical centers has led to many severe challenges for automated medical diagnostic services, including diagnostic accuracy. To solve such problems, swarm learning (SL), a blockchain-based federated learning (BCFL), has been proposed. Although SL avoids single-point-of-failure attacks and offers an incentive mechanism, it still faces privacy breaches and poisoning attacks. In this paper, we propose a new privacy-preserving Byzantine-resilient swarm learning (PBSL) that is resistant to poisoning attacks while protecting data privacy. Specifically, we adopt threshold fully homomorphic encryption (TFHE) to protect data privacy and provide secure aggregation. And the cosine similarity is used to judge the malicious gradient uploaded by malicious medical centers. Through security analysis, PBSL is able to defend against a variety of known security attacks. Finally, PBSL is implemented by uniting deep learning with blockchain-based smart contract platforms. Experiments based on different datasets show that the PBSL algorithm is practical and efficient.
Three-Dimensional and Two-Dimensional Stability Analysis of Bentonite Slurry Trenches Using a Shear Strength Reduction Technique and Limit Equilibrium Methods
Authors: Cała Marek , Le Thi Cat Tuong , Stopkowicz Agnieszka
Published: June 2024

Bentonite slurry trenches are becoming increasingly popular in the excavation of trenches, especially for diaphragm wall construction. The problem that needs to be addressed is the stability of bentonite slurry trenches. This paper presents a stability analysis of trenches with temporary support from bentonite slurry, with unit weights ranging from 10.5 to 12.0 kN/m3 in the realistic stratum, and C3 in the Hue city area. Our analysis employs the Shear Strength Reduction Technique (SSR) with Mohr–Coulomb materials to numerically evaluate the factor of safety (FS). The finite element method (FEM) software program (RS2 v. 121 and RS3 v. 4.0) and the finite difference method (FDM) FLAC v. 7.0 software were used. Additionally, the limit equilibrium method (LEM) of Bell–Washbourne and three-dimensional (3D) Bishop were used to calculate trench stability. The results of the analysis show a good agreement between RS2 and FLAC2D, and between RS3 and FLAC3D. Secondly, upon comparison, it was noted that the factor of safety of the 3D software programs (RS3 v. 4.0, FLAC v. 7.0) was higher than that of the 2D software programs (RS2 v. 11.0, FLAC v. 7.0), ranging from 52.3 to 63.0% for trench lengths of 6 m. However, for trench lengths of 54 m, the factor of safety values in 2D and 3D configurations were nearly equal. Thirdly, the factor of safety of the Bell–Washbourne method (LEM) was lower than that of the numerical analysis methods (FLAC and RS programs). Using the three-dimensional numerical method appears to be effective for estimating stability.
Characterization of Spatial and Temporal Variations in Air Pollutants and Identification of Health Risks in Xi’an, a Heavily Polluted City in China
Authors: Han Li , Qi Yongjie
Published: June 2024

The study of the temporal and spatial characteristics of air pollutants in heavily polluted cities is extremely important for analyzing the causes of pollution and achieving a viable means of control. Such characteristics in the case of Xi’an, a typical heavily polluted city in Fenwei Plain, China, have remained unclear due to limitations in data accuracy and research methods. The monthly, daily, and hourly patterns of O3 and particulate matter (PM2.5 and PM10) are analyzed in this study using on-site data provided by an urban air quality monitoring network. The analysis of variance (ANOVA) method was used to compare differences in pollutant concentrations during different seasons and time periods. The spatial distributions of O3, PM2.5, and PM10 at different time points following interpolation of the air quality monitoring sites have been analyzed. The results show that the O3 concentration from 12 p.m. to 3 p.m. was significantly higher than that in the morning and evening, and the concentrations of PM2.5 and PM10 from 7 p.m. to 10 p.m. were significantly higher than those in the morning and afternoon. The number of qualified days for PM2.5 was less than 30 and unqualified days for O3 was more than 100 in 2019. There is a potential risk of exposure to pollution with associated health risks. Even on the same day, the spatial pollutant distributions at different time points can differ significantly. This study provides a scientific basis for reducing O3 and particulate matter exposure. Outdoor activities in the morning in summer are more beneficial to reduce O3 exposure, and outdoor activities should be curtailed in the evening in winter to reduce particulate exposure. This study provides a scientific basis for the government to formulate public health policies to reduce pollution exposure from outdoor activities.
Influence of Natural Tropical Oscillations on Ozone Content and Meridional Circulation in the Boreal Winter Stratosphere
Authors: Ermakova Tatiana , Koval Andrey , Didenko Kseniia , Aniskina Olga , Okulicheva Arina
Published: June 2024

The dependence of ozone content in the polar stratosphere upon different phases of the quasi-biennial oscillation (QBO) of the zonal wind and the El Niño–Southern Oscillation (ENSO) during winter was studied. The monthly (from November to January) mean residual meridional circulation (RMC) was calculated for four different combinations of the main phases of ENSO and QBO using MERRA2 reanalysis data. It has been demonstrated that the QBO phase manifests itself in different vertical distributions of ozone in the equatorial stratosphere, as well as in strengthening/weakening of the secondary meridional circulation in the tropics. The enhancement of the RMC from the tropical to the polar stratosphere is stronger at altitudes where ozone is higher in the tropics under El Niño conditions. The RMC modification and intensification are observed from ozone-depleted areas under La Niña conditions. A “cumulative” effect is observed by February under La Niña conditions and the easterly QBO, which is expressed in the lowest ozone content in the polar stratosphere. The numerical experiments carried out using the Middle and Upper Atmosphere Model (MUAM) confirmed tendencies in changes in the meridional transport detected from the reanalysis data for different combinations of QBO and ENSO.
Near-Surface Thermodynamic Influences on Evaporation Duct Shape
Authors: Wessinger Sarah E. , Greenway Daniel P. , Haack Tracy , Hackett Erin E.
Published: June 2024

This study utilizes in situ measurements and numerical weather prediction forecasts curated during the Coupled Air–Sea Processes Electromagnetic Ducting Research (CASPER) east field campaign to assess how thermodynamic properties in the marine atmospheric surface layer influence evaporation duct shape independent of duct height. More specifically, we investigate evaporation duct shape through a duct shape parameter, a parameter known to affect the propagation of X-band radar signals and is directly related to the curvature of the duct. Relationships between this duct shape parameter and air sea temperature difference (ASTD) reveal that during unstable periods (ASTD < 0), the duct shape parameter is generally larger than in near-neutral or stable atmospheric conditions, indicating tighter curvature of the M-profile. Furthermore, for any specific duct height, a strong linear relationship between the near-surface-specific humidity gradient and the duct shape parameter is found, suggesting that it is primarily driven by near-surface humidity gradients. The results demonstrate that an a priori estimate of duct shape, for a given duct height, is possible if the near-surface humidity gradient is known.
Seasonal Patterns and Allergenicity of Casuarina Pollen in Sydney, Australia: Insights from 10 Years of Monitoring and Skin Testing
Authors: Lampugnani Edwin R. , Silver Jeremy D. , Burton Pamela , Nattala Usha , Katelaris Constance H.
Published: June 2024

Casuarina (Australian pine, She-oak) is native to Australia and South East Asia and is known for its abundant wind-borne pollen. Despite not being considered a major aeroallergen, some patients report respiratory symptoms upon exposure, with positive skin prick tests (SPT) to Casuarina pollen extract. This study investigates Casuarina pollen dispersal patterns in Sydney, Australia, over a 10-year period, from 2008 to 2018, revealing a bimodal distribution of pollen from September to October (southern hemisphere spring) and February to March (mid-late summer). Analysis of historical SPT data shows 20% of individuals with respiratory allergies reacting positively to Casuarina pollen extract, with almost 90% of these also reacting to grass pollen, suggesting potential cross-reactivity. Notably, there are no exclusive reactions to Casuarina pollen. Understanding the prolonged pollen season underscores the importance of year-round monitoring for accurate characterization. Currently lacking are commercially available skin test extracts or specific IgE assays for Casuarina sensitization, necessitating challenge studies to confirm clinical symptoms directly attributable to Casuarina pollen. By elucidating the seasonal dynamics and meteorological drivers of Casuarina pollen dispersion, alongside the potential allergenicity suggested by skin prick tests, this study paves the way for improved management of Casuarina-related allergies and highlights the critical need for further research on native Australian plant allergens.
Study on the Health Effect of Temperature on Cardiovascular and Cerebrovascular Diseases in Haikou City
Authors: Zhang Mingjie , Lin Shaowu , Zhang Yajie , Zhang Jinghong
Published: June 2024

Research on the impact of temperature in tropical regions on the risk of cardiovascular and cerebrovascular diseases was limited. The aim of the study was to investigate this topic using Haikou, a tropical city, as the research area. Outpatient data on cardiovascular and cerebrovascular diseases (CVD and CeVD) from Hainan Provincial People’s Hospital during 2016–2018 (total of 77,820) and meteorological and air-quality data were used to establish a distributed-lag nonlinear model (DLNM) based on the nested generalized addition model (GAM) of meteorological elements. The results revealed the impact on the risk of CVD and CeVD was mainly due to the cold effect, which significantly lagged behind. The thermal effect had a strong impact on the onset of CVD and CeVD on the day of high temperature. Males were easily affected by low temperatures, while females were the opposite. The lag period of the working-age group affected by low temperatures was longer and greater than that of the elderly group. The high-temperature effect only had an impact on the working-age group. The lag effect of low temperatures on the risk of hypertension was the greatest. These results can provide technical support for carrying out meteorological forecasting, warning, and services for individuals with CVD and CeVD, suggesting attaching importance to health protection for special populations.
Rainfall Estimation Model in Seasonal Zone and Non-Seasonal Zone Regions Using Weather Radar Imagery Based on a Gradient Boosting Algorithm
Authors: Putra Maulana , Rosid Mohammad Syamsu , Handoko Djati
Published: June 2024

Indonesia, a country located in the equatorial region with hilly and valley lands surrounded by vast oceans, has complex rainfall patterns that can generally be classified into three types: equatorial, monsoon, and local. Rainfall estimates have only been derived based on local data and characteristics so far, and have not yet been developed based on universal data for all of Indonesia. This study aimed to develop a rainfall estimation model based on weather radar data throughout Indonesia using ensemble machine learning with the gradient boosting algorithm. The proposed rainfall estimation model is universal, can be applied to different rainfall pattern areas, and has a temporal resolution of 10 min. It is based on determining the root mean square error (RMSE) and R-squared (R2) values. Research was conducted in six areas with different rainfall patterns: Bandar Lampung and Banjarmasin with monsoon rain patterns, Pontianak and Deli Serdang with equatorial rain patterns, and the Gorontalo and Biak areas with local rain patterns. The analysis of the proposed model reveals that the best hyperparameters for the learning rate, maximum depth, and number of trees are 0.7, 3, and 50, respectively. The results demonstrate that the estimated rainfall in the six areas was very accurate, with RMSE < 2 mm/h and R2 > 0.7.
Spatiotemporal Modeling of Carbon Fluxes over Complex Underlying Surfaces along the North Shore of Hangzhou Bay
Authors: Zhang Kaidi , Zhao Min , Zhao Zhenyu , Shen Xucheng , Lu Yanyu , Gao Jun
Published: June 2024

Urban areas contribute to over 80% of carbon dioxide emissions, and considerable efforts are being undertaken to characterize spatiotemporal variations of CO2 (carbon dioxide) at a city, regional, and national level, aiming at providing pipelines for carbon mission reduction. The complex underlying surface composition of urban areas makes process-based and physiology-based models inadequate for simulating carbon flux in this context. In this study, long short-term memory (LSTM), support vector machine (SVM), random forest (RF), and artificial neural network (ANN) were employed to develop and investigate their viability in estimating carbon flux at the ecosystem level. All the data used in our study were derived from the long-term chronosequence observations collected from the flux towers within urban complex underlying surface, along with meteorological reanalysis datasets. To assess the generalization ability of these models, the following statistical metrics were utilized: coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE). Our analysis revealed that the RF model performed the best in simulating carbon flux over long time series, with the highest R2 values reaching up to 0.852, and exhibiting the smallest RMSE and MAE values at 0.293 μmol·m−2·s−1 and 0.157 μmol·m−2·s−1. As a result, the RF model was chosen for simulating carbon flux at spatial scale and assessing the impact of urban impervious surfaces in the simulation. The results showed that the RF model performs well in simulating carbon flux at the spatial scale. The input of impervious surface area index can improve the performance of the RF model in simulating carbon flux, with R2 values of 84.46% (with the impervious surface area index in) and 83.74% (without the impervious surface area index in). Furthermore, the carbon flux in Fengxian District, Shanghai, exhibited significant spatial heterogeneity: the CO2 flux in the western part of Fengxian District was less than in the eastern part, and the CO2 flux gradually increased from the west to the east. In addition, we creatively introduced the diurnal impervious surface area index based on the Kljun model, and clarified the influence of impervious surface on the spatiotemporal simulation of CO2 flux over the complex urban underlying surface. Based on these findings, we conclude that the RF models can be effectively applied for estimating carbon flux on the complex underlying urban surface. The results of our study reduce the uncertainty in modeling carbon cycling in terrestrial ecosystems, and make the variety of models for the carbon cycling of terrestrial ecosystems more diverse.
A New Class of Coordinated Non-Convex Fuzzy-Number-Valued Mappings with Related Inequalities and Their Applications
Authors: Rakhmangulov Aleksandr , Aljohani A. F. , Mubaraki Ali , Althobaiti Saad
Published: June 2024

Both theoretical and applied mathematics depend heavily on integral inequalities with generalized convexity. Because of its many applications, the theory of integral inequalities is currently one of the areas of mathematics that is evolving at the fastest pace. In this paper, based on fuzzy Aumann’s integral theory, the Hermite–Hadamard’s type inequalities are introduced for a newly defined class of nonconvex functions, which is known as U·D preinvex fuzzy number-valued mappings (U·D preinvex F·N·V·Ms) on coordinates. Some Pachpatte-type inequalities are also established for the product of two U·D preinvex F·N·V·Ms, and some Hermite–Hadamard–Fejér-type inequalities are also acquired via fuzzy Aumann’s integrals. Additionally, several new generalized inequalities are also obtained for the special situations of the parameters. Additionally, some of the interesting remarks are provided to acquire the classical and new exceptional cases that can be considered as applications of the main outcomes. Lastly, a few suggested uses for these inequalities in numerical integration are made.
On Using Relative Information to Estimate Traits in a Darwinian Evolution Population Dynamics
Authors: Kwessi Eddy
Published: June 2024

Since its inception, evolution theory has garnered much attention from the scientific community for a good reason: it theorizes how various living organisms came to be and what changes are to be expected in a certain environment. While many models of evolution have been proposed to track changes in species’ traits, not much has been said about how to calculate or estimate these traits. In this paper, using information theory, we propose an estimation method for trait parameters in a Darwinian evolution model for species with one or multiple traits. We propose estimating parameters by minimizing the relative information in a Darwinian evolution population model using either a classical gradient ascent or a stochastic gradient ascent. The proposed procedure is shown to be possible in a supervised or unsupervised learning environment, similarly to what occurs with Boltzmann machines. Simulations are provided to illustrate the method.
Optimizing the Amino Acid Sequence Enhances the Productivity and Bioefficacy of the RBP-Albumin Fusion Protein
Authors: Park Ji Hoon , Kwon Sohyun , Choi So-Young , Kim Bongcheol , Oh Junseo
Published: June 2024

The significant growth of the global protein drug market, including fusion proteins, emphasizes the crucial role of optimizing amino acid sequences to enhance the productivity and bioefficacy. Among these fusion proteins, RBP-IIIA-IB, comprising retinol-binding protein in conjunction with the albumin domains, IIIA and IB, has displayed efficacy in alleviating liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). This study aimed to address the issue of the low productivity in RBP-IIIA-IB. To induce structural changes, the linking sequence, EVDD, between domain IIIA and IB in RBP-IIIA-IB was modified to DGPG, AAAA, and GGPA. Among these, RBP-IIIA-AAAA-IB demonstrated an increase in yield (>4-fold) and a heightened inhibition of HSC activation. Furthermore, we identified amino acid residues that could form disulfide bonds when substituted with cysteine. Through the mutation of N453S-V480S in RBP-IIIA-AAAA-IB, the productivity further increased by over 9-fold, accompanied by an increase in anti-fibrotic activity. Overall, there was a more than 30-fold increase in the fusion protein’s yield. These findings demonstrate the effectiveness of modifying linker sequences and introducing extra disulfide bonds to improve both the production yield and biological efficacy of fusion proteins.
Promising New Methods Based on the SOD Enzyme and SAUR36 Gene to Screen for Canola Materials with Heavy Metal Resistance
Authors: Dai Yue , Chen Hao , Li Yufang , Hui Rongkui , Zhang Zhenqian
Published: June 2024

Canola is the largest self-produced vegetable oil source in China, although excessive levels of cadmium, lead, and arsenic seriously affect its yield. Therefore, developing methods to identify canola materials with good heavy metal tolerance is a hot topic for canola breeding. In this study, canola near-isogenic lines with different oil contents (F338 (40.62%) and F335 (46.68%) as the control) and heavy metal tolerances were used as raw materials. In an experiment with 100 times the safe standard values, the superoxide dismutase (SOD) and peroxidase (POD) activities of F335 were 32.02 mmol/mg and 71.84 mmol/mg, while the activities of F338 were 24.85 mmol/mg and 63.86 mmol/mg, exhibiting significant differences. The DEGs and DAPs in the MAPK signaling pathway of the plant hormone signal transduction pathway and other related pathways were analyzed and verified using RT-qPCR. SAUR36 and SAUR32 were identified as the key differential genes. The expression of the SAUR36 gene in canola materials planted in the experimental field was significantly higher than in the control, and FY958 exhibited the largest difference (27.82 times). In this study, SOD and SAUR36 were found to be closely related to heavy metal stress tolerance. Therefore, they may be used to screen for new canola materials with good heavy metal stress tolerance for canola breeding.
When Chromatin Decondensation Affects Nuclear γH2AX Foci Pattern and Kinetics and Biases the Assessment of DNA Double-Strand Breaks by Immunofluorescence
Authors: Granzotto Adeline , El Nachef Laura , Restier-Verlet Juliette , Sonzogni Laurène , Al-Choboq Joëlle , Bourguignon Michel , Foray Nicolas
Published: June 2024

Immunofluorescence with antibodies against phosphorylated forms of H2AX (γH2AX) is revolutionizing our understanding of repair and signaling of DNA double-strand breaks (DSBs). Unfortunately, the pattern of γH2AX foci depends upon a number of parameters (nature of stress, number of foci, radiation dose, repair time, cell cycle phase, gene mutations, etc…) whose one of the common points is chromatin condensation/decondensation. Here, we endeavored to demonstrate how chromatin conformation affects γH2AX foci pattern and influences immunofluorescence signal. DSBs induced in non-transformed human fibroblasts were analyzed by γH2AX immunofluorescence with sodium butyrate treatment of chromatin applied after the irradiation that decondenses chromatin but does not induce DNA breaks. Our data showed that the pattern of γH2AX foci may drastically change with the experimental protocols in terms of size and brightness. Notably, some γH2AX minifoci resulting from the dispersion of the main signal due to chromatin decondensation may bias the quantification of the number of DSBs. We proposed a model called “Christmas light models” to tentatively explain this diversity of γH2AX foci pattern that may also be considered for any DNA damage marker that relocalizes as nuclear foci.
De Novo Synthesis of Resveratrol from Sucrose by Metabolically Engineered Yarrowia lipolytica
Authors: Ibrahim Gehad G. , Perera Madhavi , Abdulmalek Saadiah A. , Yan Jinyong , Yan Yunjun
Published: June 2024

Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. Yarrowia lipolytica stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer Y. lipolytica for resveratrol production. The resveratrol biosynthetic pathway was integrated into Y. lipolytica by adding genes encoding tyrosine ammonia lyase from Rhodotorula glutinis, 4-coumarate CoA ligase from Nicotiana tabacum, and stilbene synthase from Vitis vinifera. This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from Arabidopsis thaliana, malonyl-CoA synthase, and a malonate transporter protein from Bradyrhizobium diazoefficiens. These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of Y. lipolytica as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production.
The Structural Basis of the Activity Cliff in Modafinil-Based Dopamine Transporter Inhibitors
Authors: Lee Kuo-Hao , Camacho-Hernandez Gisela Andrea , Newman Amy Hauck , Shi Lei
Published: June 2024

Modafinil analogs with either a sulfoxide or sulfide moiety have improved binding affinities at the human dopamine transporter (hDAT) compared to modafinil, with lead sulfoxide-substituted analogs showing characteristics of atypical inhibition (e.g., JJC8-091). Interestingly, the only distinction between sulfoxide and sulfide substitution is the presence of one additional oxygen atom. To elucidate why such a subtle difference in ligand structure can result in different typical or atypical profiles, we investigated two pairs of analogs. Our quantum mechanical calculations revealed a more negatively charged distribution of the electrostatic potential surface of the sulfoxide substitution. Using molecular dynamics simulations, we demonstrated that sulfoxide-substituted modafinil analogs have a propensity to attract more water into the binding pocket. They also exhibited a tendency to dissociate from Asp79 and form a new interaction with Asp421, consequently promoting an inward-facing conformation of hDAT. In contrast, sulfide-substituted analogs did not display these effects. These findings elucidate the structural basis of the activity cliff observed with modafinil analogs and also enhance our understanding of the functionally relevant conformational spectrum of hDAT.
The Role of Intestinal Cytochrome P450s in Vitamin D Metabolism
Authors: Uga Minori , Kaneko Ichiro , Shiozaki Yuji , Koike Megumi , Tsugawa Naoko , Jurutka Peter W. , Miyamoto Ken-Ichi , Segawa Hiroko
Published: June 2024

Vitamin D hydroxylation in the liver/kidney results in conversion to its physiologically active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 controls gene expression through the nuclear vitamin D receptor (VDR) mainly expressed in intestinal epithelial cells. Cytochrome P450 (CYP) 24A1 is a catabolic enzyme expressed in the kidneys. Interestingly, a recently identified mutation in another CYP enzyme, CYP3A4 (gain-of-function), caused type III vitamin D-dependent rickets. CYP3A are also expressed in the intestine, but their hydroxylation activities towards vitamin D substrates are unknown. We evaluated CYP3A or CYP24A1 activities on vitamin D action in cultured cells. In addition, we examined the expression level and regulation of CYP enzymes in intestines from mice. The expression of CYP3A or CYP24A1 significantly reduced 1,25(OH)2D3-VDRE activity. Moreover, in mice, Cyp24a1 mRNA was significantly induced by 1,25(OH)2D3 in the intestine, but a mature form (approximately 55 kDa protein) was also expressed in mitochondria and induced by 1,25(OH)2D3, and this mitochondrial enzyme appears to hydroxylate 25OHD3 to 24,25(OH)2D3. Thus, CYP3A or CYP24A1 could locally attenuate 25OHD3 or 1,25(OH)2D3 action, and we suggest the small intestine is both a vitamin D target tissue, as well as a newly recognized vitamin D-metabolizing tissue.
The Role of Macrophage Inhibitory Factor in TAA-Induced Liver Fibrosis in Mice: Modulatory Effects of Betaine
Authors: Radosavljevic Tatjana , Vukicevic Dusan , Djuretić Jasmina , Gopcevic Kristina , Labudovic Borovic Milica , Stankovic Sanja , Samardzic Janko , Radosavljevic Milica , Vucevic Danijela , Jakovljevic Vladimir
Published: June 2024

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.
Exploring Periodontal Conditions, Salivary Markers, and Systemic Inflammation in Patients with Cardiovascular Diseases
Authors: Caloian Carmen Silvia , Șurlin Petra , Ciurea Andreea , Pop Dana , Caloian Bogdan , Leucuța Daniel Corneliu , Țigu Adrian Bogdan , Rasperini Giulio , Micu Iulia Cristina , Stanomir Alina , Soancă Andrada , Roman Alexandra
Published: June 2024

(1) Background: This cross-sectional investigation appreciated the role of serum C-reactive protein (CRP), several hematologic-cell markers, and salivary inflammation-related molecules [calprotectin (S100A8/A9), interleukin-1β (IL-1β), kallikrein] to predict periodontitis in patients with atherosclerotic cardiovascular disease (ACVD), arrhythmia, or both. Also, we appreciated the relationship between the inflammatory burden and periodontal destruction with the type of cardiac pathology. (2) Methods: Demographic, behavioral characteristics, periodontal indicators, blood parameters, and saliva samples were collected. (3) Results: All 148 patients exhibited stage II or III/IV periodontitis. Stage III/IV cases exhibited significantly increased S100A8/A9 levels (p = 0.004). A positive correlation between S100A8/A9 and IL-1β [0.35 (<0.001)], kallikrein [0.55 (<0.001)], and CRP [0.28 (<0.001)] was observed. Patients with complex cardiac involvement had a significantly higher number of sites with attachment loss ≥ 5 mm [19 (3–30)] compared to individuals with only arrhythmia [9 (3.25–18)] or ACVD [5 (1–12)] [0.048♦ {0.162/0.496/0.14}]. (4) Conclusions: Severe, extensive attachment loss may be indicative of patients with complex cardiac conditions, which underscores the essential role of periodontal status in relation to systemic diseases. The correlations between the rising trends of the inflammatory parameters suggest a potential interconnection between oral and systemic inflammation.
Design of Apoptotic Cell-Inspired Particles as a Blood Coagulation Test
Authors: Yue Liang , Nakagawa Yasuhiro , Ebara Mitsuhiro
Published: June 2024

The blood coagulation test is an indispensable test for monitoring the blood coagulation and fibrinolysis functions. Currently, activated partial thromboplastin time (APTT) is the most widely used approach to coagulation testing. However, APTT reagents need to be optimized due to the fact that they are unstable, highly variable, and cannot be easily controlled. In this study, we created apoptotic cell-inspired methacryloyloxyethyl phosphorylserine (MPS) particles for blood coagulation as an alternative to conventional APTT reagents. Particle size could be controlled by changing the concentration of the polymer. The blood coagulation ability of particles was stable at different environmental temperatures. Moreover, the procoagulant activity could be enhanced by increasing the concentration to 0.06 mg/mL and reducing the size of the particles to around 900 nm. Fibrin clotted by particles showed no significant difference from that formed by APTT regent Actin FSL. We propose that MPS particles are a potential alternative to Actin FS for the application of blood coagulation tests.
Design and Application of Microfluidic Capture Device for Physical–Magnetic Isolation of MCF-7 Circulating Tumor Cells
Authors: Bendre Akhilesh , Somasekhara Derangula , Nadumane Varalakshmi K. , Sriram Ganesan , Bilimagga Ramesh S. , Kurkuri Mahaveer D.
Published: June 2024

Circulating tumor cells (CTCs) are a type of cancer cell that spreads from the main tumor to the bloodstream, and they are often the most important among the various entities that can be isolated from the blood. For the diagnosis of cancer, conventional biopsies are often invasive and unreliable, whereas a liquid biopsy, which isolates the affected item from blood or lymph fluid, is a less invasive and effective diagnostic technique. Microfluidic technologies offer a suitable channel for conducting liquid biopsies, and this technology is utilized to extract CTCs in a microfluidic chip by physical and bio-affinity-based techniques. This effort uses functionalized magnetic nanoparticles (MNPs) in a unique microfluidic chip to collect CTCs using a hybrid (physical and bio-affinity-based/guided magnetic) capturing approach with a high capture rate. Accordingly, folic acid-functionalized Fe3O4 nanoparticles have been used to capture MCF-7 (breast cancer) CTCs with capture efficiencies reaching up to 95% at a 10 µL/min flow rate. Moreover, studies have been conducted to support this claim, including simulation and biomimetic investigations.
Challenges and Advances in Biomarker Detection for Rapid and Accurate Sepsis Diagnosis: An Electrochemical Approach
Authors: Kumar Deivasigamani Ranjith , Banaś Angelika , Krukiewicz Katarzyna
Published: June 2024

Sepsis is a life-threatening condition with high mortality rates due to delayed treatment of patients. The conventional methodology for blood diagnosis takes several hours, which suspends treatment, limits early drug administration, and affects the patient’s recovery. Thus, rapid, accurate, bedside (onsite), economical, and reliable sepsis biomarker reading of the clinical sample is an emergent need for patient lifesaving. Electrochemical label-free biosensors are specific and rapid devices that are able to perform analysis at the patient’s bedside; thus, they are considered an attractive methodology in a clinical setting. To reveal their full diagnostic potential, electrode architecture strategies of fabrication are highly desirable, particularly those able to preserve specific antibody–antigen attraction, restrict non-specific adsorption, and exhibit high sensitivity with a low detection limit for a target biomarker. The aim of this review is to provide state-of-the-art methodologies allowing the fabrication of ultrasensitive and highly selective electrochemical sensors for sepsis biomarkers. This review focuses on different methods of label-free biomarker sensors and discusses their advantages and disadvantages. Then, it highlights effective ways of avoiding false results and the role of molecular labels and functionalization. Recent literature on electrode materials and antibody grafting strategies is discussed, and the most efficient methodology for overcoming the non-specific attraction issues is listed. Finally, we discuss the existing electrode architecture for specific biomarker readers and promising tactics for achieving quick and low detection limits for sepsis biomarkers.
Depression Severity, Slow- versus Fast-Wave Neural Activity, and Symptoms of Melancholia
Authors: Sharpley Christopher , Bitsika Vicki , Evans Ian , Vessey Kirstan , Jesulola Emmanuel , Agnew Linda
Published: June 2024

Melancholia is a major and severe subtype of depression, with only limited data regarding its association with neurological phenomena. To extend the current understanding of how particular aspects of melancholia are correlated with brain activity, electroencephalographic data were collected from 100 adults (44 males and 56 females, all aged 18 y or more) and investigated for the association between symptoms of melancholia and the ratios of alpha/beta activity and theta/beta activity at parietal–occipital EEG sites PO1 and PO2. The results indicate differences in these associations according to the depressive status of participants and the particular symptom of melancholia. Depressed participants exhibited meaningfully direct correlations between alpha/beta and theta/beta activity and the feeling that “Others would be better off if I was dead” at PO1, whereas non-depressed participants had significant inverse correlations between theta/beta activity and “Feeling useless and not needed” and “I find it hard to make decisions” at PO1. The results are discussed in terms of the relative levels of fast-wave (beta) versus slow-wave (alpha, theta) activity exhibited by depressed and non-depressed participants in the parietal–occipital region and the cognitive activities that are relevant to that region.