bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the Rate of Convergence of the PH/M/1 Model by Reducing to Quasi-Birth-Death Processes
Authors: Usov Ilya , Satin Yacov , Zeifman Alexander
Published: March 2023

We are studying the quasi-birth-death process and the property of weak ergodicity. Using the C-matrix method, we derive estimates for the rate of convergence to the limiting regime for the general case of the PH/M/1 model, as well as the particular case when m=3. We provide a numerical example for the case m=3, and construct graphs showing the probability of an empty queue and the probability of p1(t).
Sustainable Cooperation in a Bicriteria Game of Renewable Resource Extraction
Authors: Kuzyutin Denis , Smirnova Nadezhda
Published: March 2023

We study a multi-objective finite-horizon game model of renewable, common resource extraction where the players have two separate objectives (one is economic success; the other describes the players’ environmental concern). We derive the cooperative strategy and the subgame-perfect Pareto equilibrium in linear-state non-stationary feedback strategies by employing the dynamic programming approach. Since the utility is transferable only based on the economic criterion, we need to revise the concept of time consistency and the payoff-distribution procedure to provide a mechanism for sustainable long-term cooperation. All the results are illustrated with a numerical example.
Mathematical Circuit Root Simplification Using an Ensemble Heuristic–Metaheuristic Algorithm
Authors: Behmanesh-Fard Navid , Yazdanjouei Hossein , Shokouhifar Mohammad , Werner Frank
Published: March 2023

Symbolic pole/zero analysis is a crucial step in designing an analog operational amplifier. Generally, a simplified symbolic analysis of analog circuits suffers from NP-hardness, i.e., an exponential growth of the number of symbolic terms of the transfer function with the circuit size. This study presents a mathematical model combined with a heuristic–metaheuristic solution method for symbolic pole/zero simplification in operational transconductance amplifiers. First, the circuit is symbolically solved and an improved root splitting method is applied to extract symbolic poles/zeroes from the exact expanded transfer function. Then, a hybrid algorithm based on heuristic information and a metaheuristic technique using simulated annealing is used for the simplification of the derived symbolic roots. The developed method is tested on three operational transconductance amplifiers. The obtained results show the effectiveness of the proposed method in achieving accurate simplified symbolic pole/zero expressions with the least complexity.
Development of Grey Machine Learning Models for Forecasting of Energy Consumption, Carbon Emission and Energy Generation for the Sustainable Development of Society
Authors: Saxena Akash , Zeineldin Ramadan A. , Mohamed Ali Wagdy
Published: March 2023

Energy is an important denominator for evaluating the development of any country. Energy consumption, energy production and steps towards obtaining green energy are important factors for sustainable development. With the advent of forecasting technologies, these factors can be accessed earlier, and the planning path for sustainable development can be chalked out. Forecasting technologies pertaining to grey systems are in the spotlight due to the fact that they do not require many data points. In this work, an optimized model with grey machine learning architecture of a polynomial realization was employed to predict power generation, power consumption and CO2 emissions. A nonlinear kernel was taken and optimized with a recently published algorithm, the augmented crow search algorithm (ACSA), for prediction. It was found that as compared to conventional grey models, the proposed framework yields better results in terms of accuracy.
Fusion and Enhancement of Consensus Matrix for Multi-View Subspace Clustering
Authors: Deng Xiuqin , Zhang Yifei , Gu Fangqing
Published: March 2023

Multi-view subspace clustering is an effective method that has been successfully applied to many applications and has attracted the attention of scholars. Existing multi-view subspace clustering seeks to learn multiple representations from different views, then gets a consistent matrix. Until now, most of the existing efforts only consider the multi-view information and ignore the feature concatenation. It may fail to explore their high correlation. Consequently, this paper proposes a multi-view subspace clustering algorithm with a novel consensus matrix construction strategy. It learns a consensus matrix by fusing the different information from multiple views and is enhanced by the information contained in the original feature direct linkage of the data. The error matrix of the feature concatenation data is reconstructed by regularization constraints and the sparse structure of the multi-view subspace. The feature concatenation data are simultaneously used to fuse the individual views and learn the consensus matrix. Finally, the data is clustered by using spectral clustering according to the consensus matrix. We compare the proposed algorithm with its counterparts on six datasets. Experimental results verify the effectiveness of the proposed algorithm.
Exploring Energy in the Direct Correction Method for Correcting Geometric Constraint Violations
Authors: Zhang Lina , Rui Xiaoting , Zhang Jianshu , Gu Junjie , Zhang Xizhe
Published: March 2023

The direct correction method is widely used for eliminating geometric constraint violations. This method involves iteratively adjusting the generalized coordinates, which are assumed to be consistent and remain so during the velocity-level corrections. However, the corrected generalized coordinates cause a significant effect on the velocity constraint violations. In this paper, simultaneously correcting both the generalized coordinates and velocities is proposed. A semi-analytic approach to solve the Jacobian matrix, which is used to correct the generalized coordinates and velocities, was employed. Further, the position level, velocity level, and energy constraint equations were corrected simultaneously to ensure that the corrected generalized coordinates and velocities complied with the dynamic equations. The corresponding semi-analytic Jacobian matrix was derived to solve the constraint equations. The methods were demonstrated to be effective using examples, with the simultaneous correction of position-level and velocity-level constraints showing the best results when combined with the energy correction.
Parameter Optimization in a Leaky Integrator Echo State Network with an Improved Gravitational Search Algorithm
Authors: Lun Shuxian , Zhang Zhenqian , Li Ming , Lu Xiaodong
Published: March 2023

In the prediction of a nonlinear time series based on a leaky integrator echo state network (leaky-ESN), building a reservoir related to the specific problem is a key step. For problems such as poor performance of randomly generated reservoirs, it is tough to determine the parameter values of the reservoirs. The work in this paper uses the gravitational search algorithm (GSA) to optimize the global parameters of a leaky-ESN, such as the leaking rate, the spectral radius, and the input scaling factor. The basic GSA has some problems, such as slow convergence and poor balance between exploration and exploitation, and it cannot solve some complex optimization problems well. To solve these problems, an improved gravitational search algorithm (IGSA) is proposed in this paper. First, the best agent and elite agents were archived and utilized to accelerate the exploration phase and improve the convergence rate in the exploitation phase. Second, to improve the effect of the poor fitness agents on the optimization result, a differential mutation strategy was proposed, which generated new individuals to replace original agents with worse fitness, increasing the diversity of the population and improving the global optimization ability of the algorithm. Finally, two simulation experiments showed that the leaky-ESN optimized by the IGSA had better prediction accuracy.
On the Fractal Measures and Dimensions of Image Measures on a Class of Moran Sets
Authors: Attia Najmeddine , Selmi Bilel
Published: March 2023

In this work, we focus on the centered Hausdorff measure, the packing measure, and the Hewitt–Stromberg measure that determines the modified lower box dimension Moran fractal sets. The equivalence of these measures for a class of Moran is shown by having a strong separation condition. We give a sufficient condition for the equality of the Hewitt–Stromberg dimension, Hausdorff dimension, and packing dimensions. As an application, we obtain some relevant conclusions about the Hewitt–Stromberg measures and dimensions of the image measure of a τ-invariant ergodic Borel probability measures. Moreover, we give some statistical interpretation to dimensions and corresponding geometrical measures.
Global Dynamics of a Diffusive Within-Host HTLV/HIV Co-Infection Model with Latency
Authors: AlShamrani Noura H. , Elaiw Ahmed , Raezah Aeshah A. , Hattaf Khalid
Published: March 2023

In several publications, the dynamical system of HIV and HTLV mono-infections taking into account diffusion, as well as latently infected cells in cellular transmission has been mathematically analyzed. However, no work has been conducted on HTLV/HIV co-infection dynamics taking both factors into consideration. In this paper, a partial differential equations (PDEs) model of HTLV/HIV dual infection was developed and analyzed, considering the cells’ and viruses’ spatial mobility. CD4+T cells are the primary target of both HTLV and HIV. For HIV, there are three routes of transmission: free-to-cell (FTC), latent infected-to-cell (ITC), and active ITC. In contrast, HTLV transmits horizontally through ITC contact and vertically through the mitosis of active HTLV-infected cells. In the beginning, the well-posedness of the model was investigated by proving the existence of global solutions and the boundedness. Eight threshold parameters that determine the existence and stability of the eight equilibria of the model were obtained. Lyapunov functions together with the Lyapunov–LaSalle asymptotic stability theorem were used to investigate the global stability of all equilibria. Finally, the theoretical results were verified utilizing numerical simulations.
Recombinant Analogs of Sea Anemone Kunitz-Type Peptides Influence P2X7 Receptor Activity in Neuro-2a Cells
Authors: Pislyagin Evgeny , Menchinskaya Ekaterina , Gladkikh Irina , Kvetkina Aleksandra , Sintsova Oksana , Popkova Darya , Kozlovskiy Sergei , Gorpenchenko Tatiana , Likhatskaya Galina , Kaluzhskiy Leonid , Ivanov Alexis , Andreev Yaroslav , Kozlov Sergey , Dmitrenok Pavel , Aminin Dmitry , Leychenko Elena
Published: March 2023

Purinergic P2X7 receptors (P2X7) have now been proven to play an important role and represent an important therapeutic target in many pathological conditions including neurodegeneration. Here, we investigated the impact of peptides on purinergic signaling in Neuro-2a cells through the P2X7 subtype in in vitro models. We have found that a number of recombinant peptides, analogs of sea anemone Kunitz-type peptides, are able to influence the action of high concentrations of ATP and thereby reduce the toxic effects of ATP. The influx of calcium, as well as the fluorescent dye YO-PRO-1, was significantly suppressed by the studied peptides. Immunofluorescence experiments confirmed that the peptides reduce the P2X7 expression level in neuronal Neuro-2a cells. Two selected active peptides, HCRG1 and HCGS1.10, were found to specifically interact with the extracellular domain of P2X7 and formed stable complexes with the receptor in surface plasmon resonance experiments. The molecular docking approach allowed us to establish the putative binding sites of the most active HCRG1 peptide on the extracellular domain of the P2X7 homotrimer and propose a mechanism for regulating its function. Thus, our work demonstrates the ability of the Kunitz-type peptides to prevent neuronal death by affecting signaling through the P2X7 receptor.
Effects of Age, Metabolic and Socioeconomic Factors on Cardiovascular Risk among Saudi Women: A Subgroup Analysis from the Heart Health Promotion Study
Authors: Wahabi Hayfaa , Esmaeil Samia , Zeidan Rasmieh , Fayed Amel
Published: March 2023

Background: Cardiovascular disease (CVD) remains the leading cause of death in women. Along with the effect of age on the risk of CVD, the reproductive profile of women can influence cardiac health among women. Objectives: The objective of this study is to investigate the influence of age and reproductive stages on the development and progression of cardiovascular disease risks in Saudi women. Methods: For this study, we included 1907 Saudi women from the Heart Health Promotion Study. The study cohort was divided into five age groups (less than 40 years, 40–45 years, 46–50 years, 51–55 years, and ≥56 years). The cohort stratification was meant to correspond to the social and hormonal changes in women’s life, including reproductive, perimenopausal, menopausal, and postmenopausal age groups. The groups were compared with respect to the prevalence of metabolic, socioeconomic, and cardiac risks, and the age group of less than 40 years was considered as the reference group. The World Health Organization stepwise approach to chronic disease risk factor Surveillance-Instrument v2.1 was used in this study to collect the anthropometric and biochemical measurements and the Framingham Coronary Heart Risk Score was used to calculate the cardiovascular risk (CVR). Logistic regression analysis was conducted to assess the independent effect of age on CVD risks after adjustment of sociodemographic factors. Results: Metabolic and CVR increased progressively with the increase in age. There was a sharp increase in obesity, hypertension, diabetes, and metabolic syndrome, from the age group <40 years to 41–45 years and then again between the age groups of 46–50 and ≥56 years. A similar noticeable increase in metabolic risk factors (high cholesterol, high triglyceride, high Low-Density Lipoprotein) was observed between the age group <40 years and 41–45 years, but with a steady increase with the increase in age between the other age groups. The high and intermediate Framingham Coronary Heart Risk Scores showed a progressive increase in prevalence with the increase in age, where the proportion doubled from 9.4% at the age group 46–50 years, to 22% at the age group 51–55 years. It doubled again at the age group ≥56 years to 53%—these sharp inflections in the risk of CVD correspond to the women’s reproductive lives. Conclusions: In Saudi women, CVR increases with the increase of age. The influence of pregnancy and menopause is apparent in the prevalence of increased risks for cardiovascular and metabolic diseases.
Donnan Dialysis for Recovering Ammonium from Fermentation Solutions Rich in Volatile Fatty Acids
Authors: Barros Kayo Santana , Carvalheira Mónica , Marreiros Bruno Costa , Reis Maria Ascensão M. , Crespo João Goulão , Pérez-Herranz Valentín , Velizarov Svetlozar
Published: March 2023

For the production of polyhydroxyalkanoates (PHA) using nitrogen-rich feedstocks (e.g., protein-rich resources), the typical strategy of restricting cell growth as a means to enhance overall PHA productivity by nitrogen limitation is not applicable. In this case, a possible alternative to remove the nitrogen excess (NH4+/NH3) is by applying membrane separation processes. In the present study, the use of Donnan dialysis to separate ammonium ions from volatile fatty acids present in the media for the production of PHA was evaluated. Synthetic and real feed solutions were used, applying NaCl and HCl receiver solutions separated by commercial cation-exchange membranes. For this specific purpose, Fumasep and Ralex membranes showed better performance than Ionsep. Sorption of ammonium ions occurred in the Ralex membrane, thus intensifying the ammonium extraction. The separation performances with NaCl and HCl as receiver solutions were similar, despite sorption occurring in the Ralex membrane more intensely in the presence of NaCl. Higher volumetric flow rates, NaCl receiver concentrations, and volume ratios of feed:receiver solutions enhanced the degree of ammonium recovery. The application of an external electric potential difference to the two-compartment system did not significantly enhance the rate of ammonium appearance in the receiver solution. The results obtained using a real ammonium-containing solution after fermentation of cheese whey showed that Donnan dialysis can be successfully applied for ammonium recovery from such solutions.
Hydrogen Sulphide Sequestration with Metallic Ions in Acidic Media Based on Chitosan/sEPDM/Polypropylene Composites Hollow Fiber Membranes System
Authors: Pașcu Dumitru , Nechifor Aurelia Cristina , Grosu Vlad-Alexandru , Oprea Ovidiu Cristian , Tanczos Szidonia-Katalin , Man Geani Teodor , Dumitru Florina , Grosu Alexandra Raluca , Nechifor Gheorghe
Published: March 2023

This paper presents the preparation and characterization of composite membranes based on chitosan (Chi), sulfonated ethylene–propylene–diene terpolymer (sEPDM), and polypropylene (PPy), and designed to capture hydrogen sulfide. The Chi/sEPDM/PPy composite membranes were prepared through controlled evaporation of a toluene dispersion layer of Chi:sEPDM 1;1, w/w, deposited by immersion and under a slight vacuum (100 mmHg) on a PPy hollow fiber support. The composite membranes were characterized morphologically, structurally, and thermally, but also from the point of view of their performance in the process of hydrogen sulfide sequestration in an acidic media solution with metallic ion content (Cu2+, Cd2+, Pb2+, and/or Zn2+). The operational parameters of the pertraction were the pH, pM, matrix gas flow rate, and composition. The results of pertraction from synthetic gases mixture (nitrogen, methane, carbon dioxide) indicated an efficient removal of hydrogen sulfide through the prepared composite membranes, as well as its immobilization as sulfides. The sequestration and the recuperative separation, as sulfides from an acid medium, of the hydrogen sulfide reached up to 96%, decreasing in the order: CuS > PbS > CdS > ZnS.
Interactions of Surfactants with Biomimetic Membranes—2. Generation of Electric Potential with Non-Ionic Surfactants
Authors: Kocherginsky Nikolai , Sharma Brajendra
Published: March 2023

It is discovered that noncharged surfactants lead to electric effects that interact with biomimetic membranes made of nitrocellulose filters, which are impregnated with fatty acid esters. At a surfactant concentration as low as 64 microM in one of the solutions, they lead to the transient formation of transmembrane electric potential. Maximum changes of this potential are proportional to the log of noncharged surfactant concentrations when it changes by three orders of magnitude. We explain this new and nontrivial effect in terms of an earlier suggested physicochemical mechanics approach and noncharged surfactants transient changes induced by membrane permeability for inorganic ions. It could be used to imitate the interactions of non-ionic drugs with biological membranes. The effect may also be used in determining the concentration of these surfactants and other non-ionic chemicals of concern, such as pharmaceuticals and personal care products.
Pharmacological Characterization of a Recombinant Mitochondrial ROMK2 Potassium Channel Expressed in Bacteria and Reconstituted in Planar Lipid Bilayers
Authors: Krajewska Milena , Szewczyk Adam , Kulawiak Bogusz , Koprowski Piotr
Published: March 2023

In the inner mitochondrial membrane, several potassium channels that play a role in cell life and death have been identified. One of these channels is the ATP-regulated potassium channel (mitoKATP). The ROMK2 potassium channel is a potential molecular component of the mitoKATP channel. The current study aimed to investigate the pharmacological modulation of the activity of the ROMK2 potassium channel expressed in Escherichia coli bacteria. ROMK2 was solubilized in polymer nanodiscs and incorporated in planar lipid bilayers. The impact of known mitoKATP channel modulators on the activity of the ROMK2 was characterized. We found that the ROMK2 channel was activated by the mitoKATP channel opener diazoxide and blocked by mitoKATP inhibitors such as ATP/Mg2+, 5-hydroxydecanoic acid, and antidiabetic sulfonylurea glibenclamide. These results indicate that the ROMK2 potassium protein may be a pore-forming subunit of mitoKATP and that the impact of channel modulators is not related to the presence of accessory proteins.
Development of a New Micro Drilling Tool with H-Shaped Chisel Edge
Authors: Ma Yue , Liang Zhiqiang , Wan Kun , Cai Rongbin , Yi Linfeng , Li Jianfei , Wang Fei , Zhao Xu , Chen Rui , Wang Xibin
Published: March 2023

In order to improve the tool life and micro-hole machining quality, the H-shaped chisel edge micro-drill (HCE-MD) was developed in this paper. The HCE-MD was characterized by the inner edge formed through the chisel edge thinning. In the micro-drilling process, the inner edge can perform positive rake cutting, so the machining area of the workpiece extruded by cutting edge with a negative rake angle is reduced. Based on this, the distribution of rake angle near the chisel edge corner is improved. Then, the HCE-MD was fabricated on the six-axis CNC grinding machine. The grinding process parameters of the micro-drill were optimized based on the orthogonal grinding test and grey relational grade theory. The size and shape accuracy of the micro-drill were controlled by the multi-axis linkage grinding method and the movement-axis micro compensation method. Finally, the 0.25 mm HCE-MD was fabricated with the cutting edge radius of 1.94 μm and the flank surface roughness of 0.25 μm. The drilling performance of HCE-MD was evaluated through comparative drilling experiments. The experimental results show that, compared with common micro drill, the HCE-MD produced lower thrust force and better micro-hole roundness accuracy, and reduced the micro-drill wear on the chisel edge and the flank.
Characteristics for Gallium-Based Liquid Alloys of Low Melting Temperature
Authors: Shentu Jianfei , Pan Jiatong , Chen Hao , He Chunlin , Wang Youbin , Dodbiba Gjergj , Fujita Toyohisa
Published: March 2023

Gallium alloys are ideal base carriers for temperature-sensitive ferrofluids, which can be used for energy convection, soft robotics, microchannels, magnetorheological devices, etc. In this study, gallium was mixed with different substances (In, Sn, Zn, Ge, and Al) to obtain a low melting point, reduce the wetness and adhesion of its alloys, and realize low viscosity. The melting point, contact angle on certain solid plates, viscosity, and viscoelasticity of the gallium alloys were measured, and some useful gallium alloys were obtained. The experimental results showed that Ga80In10Sn10 had lower wettability at a larger contact angle of 148.6° on the Teflon plate. Here, (Ga80In10Sn10)97Zn3 with a melting point of 8.2 °C, lower than the melting point of Galinstan, was developed. It had a viscosity about three times that of water at room temperature and an elastic response from 0.1 to 100 Hz at a 1% strain amplitude for the viscoelasticity. It was expected that a kind of temperature-sensitive magnetic fluid with a gallium-based liquid alloy as the base carrier liquid would be prepared in the future with Teflon as the container to achieve energy conversion under the drive of the magnetic field.
Behaviour Aspects of an EB-PVD Alumina (Al2O3) Film with an Interlayer (NiCrAlY) Deposited on AISI 316L Steel Investigated in Liquid Lead
Authors: Petrescu Daniel , Nitu Alexandru , Golgovici Florentina , Demetrescu Ioana , Corban Mircea
Published: March 2023

The use of lead as a primary coolant is one of the most attractive options for next-generation lead-cooled fast reactor systems (LFR). Despite many favourable features, liquid Pb is a harsh environment that induces many problems on metallic components. Therefore, candidate materials for LFR must be qualified, and the solutions to improve their properties must be found. This paper’s objective is to present the results obtained from the tensile tests of AISI 316L steel in liquid lead at 400 °C, 450 °C, and 500 °C, and the short-term corrosion tests performed on coated and uncoated AISI 316L steel at 550 °C. The coating was made of Al2O3 with a CrNiAlY interlayer using the electron beam-physical vapor deposition (EB-PVD) technique. Both the mechanical and corrosion tests were performed in stagnant lead saturated with oxygen. After testing, the specimens were characterised by several analyses, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), optical microscopy (OM), scratching test, and Vickers micro-hardness test. The tensile test results highlight the ductile behaviour of the material, and in the case of the corrosion tests, the coatings prove to be effective in protecting the substrate from the harsh environment.
Binder Jet Additive Manufacturing Process and Material Characterization for High Temperature Heat Exchangers Used in Concentrated Solar Power Applications
Authors: Gerstler William D. , Barua Ananda , Huang Shenyan , Erno Daniel J. , Wang Yongxiang , Ju Siyeong , Thiagarajan Naveenan
Published: March 2023

The U.S. Department of Energy’s (DOE) Sunshot 2030 initiative has a goal of reducing the cost of concentrating solar power (CSP) to 5 cents per kWh for baseload power plants. One of the potential pathways to this goal includes a reduction in the cost of the supercritical CO2 (sCO2) power block to 0.9 cents per kWh. Recuperators—high and low temperatures, used in the sCO2 power cycle, contribute to >50% of the cost of the power cycle. This work studies the feasibility towards a ≥10% cost reduction for High Temperature Recuperators (HTR) used in the sCO2 power cycle. One way to address the cost reduction is by leveraging low-cost additive manufacturing, specifically, Binder Jet Additive Manufacturing (BJAM) to 3D print HTRs at scale. This study focuses on the development of a BJAM process towards 3D printing HTR cores using Stainless Steel alloy 316L (SS316L). To evaluate the suitability of the BJ process towards the HTR, high level specifications of the application are translated to materials capability requirements. Subsequently, at-temperature materials testing is conducted on as-printed and sintered additively manufactured coupons. Data from the coupons are compared against cast and wrought SS316L data obtained from the literature. Results show that the tensile properties from the BJ process compare well against cast properties. Furthermore, a baseline analysis of creep testing data is established for the BJ process, and insights are drawn from the results towards future improvements of the process.
Monte-Carlo-Assisted Phase Field Simulations of Grain Structure Evolution during the Welding Process
Authors: Zheng Ying , Liu Jiangping , Liang Yongfeng , Wu Pingping
Published: March 2023

A Monte-Carlo-assisted phase field model for the simulation of grain growth in metals and alloys is presented. The simulation time in this model is connected to real time through an experimental data-based kinetic model. Site selection probability is introduced to simulate grain structure evolution under non-isothermal conditions. The grain evolutions with temporal and spatial distributions of temperature during the welding process are comprehensively reproduced. The average size and topological texture of the generated grains in the fusion zone and heat-affected zone are examined. The computed results are compared to experimental data for laser-welding two alloys: Fe–6.5 wt.%Si and low-carbon steel. The applications of real-time–temperature based phase field simulation to material processing indicate significant promise for understanding grain structures during the welding process or additive manufacturing processes.
Detecting and Profiling of Milk Thistle Metabolites in Food Supplements: A Safety-Oriented Approach by Advanced Analytics
Authors: Raclariu-Manolică Ancuța Cristina , Socaciu Carmen
Published: March 2023

Milk thistle (Silybum marianum (L.) Gaertn.) is among the top-selling botanicals used as a supportive treatment for liver diseases. Silymarin, a mixture of unique flavonolignan metabolites, is the main bioactive component of milk thistle. The biological activities of silymarin have been well described in the literature, and its use is considered safe and well-tolerated in appropriate doses. However, commercial preparations do not always contain the recommended concentrations of silymarin, failing to provide the expected therapeutic effect. While the poor quality of raw material may explain the low concentrations of silymarin, its deliberate removal is suspected to be an adulteration. Toxic contaminants and foreign matters were also detected in milk thistle preparations, raising serious health concerns. Standard methods for determination of silymarin components include thin-layer chromatography (TLC), high-performance thin-layer chromatography (HPTLC), and high-performance liquid chromatography (HPLC) with various detectors, but nuclear magnetic resonance (NMR) and ultra-high-performance liquid chromatography (UHPLC) have also been applied. This review surveys the extraction techniques of main milk thistle metabolites and the quality, efficacy, and safety of the derived food supplements. Advanced analytical authentication approaches are discussed with a focus on DNA barcoding and metabarcoding to complement orthogonal chemical characterization and fingerprinting of herbal products.
Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification
Authors: Kim Hwi Young , Kim Da Jung , Lee Hye Ah , Cho Joo-Youn , Kim Won
Published: March 2023

Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463–0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340–0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417–0.779), and tyrosine (OR = 2.743; 95% CI, 1.875–4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.
Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives
Authors: Cossu Marcello , Pintus Roberta , Zaffanello Marco , Mussap Michele , Serra Fabiola , Marcialis Maria Antonietta , Fanos Vassilios
Published: March 2023

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022.
Participation of Krüppel-like Factors in Atherogenesis
Authors: Kotlyarov Stanislav , Kotlyarova Anna
Published: March 2023

Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral blood flow are involved. Endothelial cells, which line the vascular wall in a monolayer, play an important role in vascular biology. A growing body of evidence strengthens the understanding of the multifaceted functions of endothelial cells, which not only organize the barrier between blood flow and tissues but also act as regulators of hemodynamics and play an important role in regulating the function of other cells in the vascular wall. Krüppel-like factors (KLFs) perform several biological functions in various cells of the vascular wall. The large family of KLFs in humans includes 18 members, among which KLF2 and KLF4 are at the crossroads between endothelial cell mechanobiology and immunometabolism, which play important roles in both the normal vascular wall and atherosclerosis.
Relation between Selected Sleep Parameters, Depression, Anti-Tumor Necrosis Factor Therapy, and the Brain-Derived Neurotrophic Factor Pathway in Inflammatory Bowel Disease
Authors: Sochal Marcin , Ditmer Marta , Binienda Agata , Gabryelska Agata , Białasiewicz Piotr , Talar-Wojnarowska Renata , Fichna Jakub , Małecka-Wojciesko Ewa
Published: March 2023

Inflammatory bowel disease (IBD) patients often have sleep and mood disorders. Brain-derived neurotrophic factor (BDNF) and proBDNF were shown to modulate interactions between the central nervous system and the gastrointestinal tract, possibly contributing to psychological issues. Anti-tumor necrosis factor (TNF) therapy in IBD can alter BDNF expression and further affect the brain–gut axis. Eighty IBD patients and 44 healthy controls (HCs) were enrolled and divided into subsets based on disease activity and condition (ulcerative colitis (UC)/Crohn’s disease (CD)). Questionnaires evaluating sleep parameters and depression as well as venous blood were collected. The IBD group had a lower expression of BDNF mRNA, but higher proBDNF and BDNF protein concentration than HCs. The UC group had a higher BDNF protein concentration than the CD. BDNF protein was positively correlated to sleep efficiency in the IBD group. Depression severity was associated positively with BDNF mRNA and negatively with BDNF protein in the remission group. Anti-TNF therapy enhanced BDNF mRNA expression. The BDNF pathway might be disturbed in IBD, linking it to sleep disorders and depression. Systemic inflammation could be the main cause of this disruption. BDNF mRNA is a more reliable parameter than protein due to numerous post-translational modifications.
Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients
Authors: Martinez Jessica A. , Wertheim Betsy C. , Roe Denise J. , Taljanovic Mihra S. , Chow H-H. Sherry , Chew Wade , Ehsani Sima , Jiralerspong Sao , Segar Jennifer , Chalasani Pavani
Published: March 2023

Aromatase inhibitor-induced arthralgia (AIA) presents a major problem for patients with breast cancer but is poorly understood. This prospective study explored the inflammatory metabolomic changes in the development of AIA. This single-arm, prospective clinical trial enrolled 28 postmenopausal women with early-stage (0–3) ER+ breast cancer starting adjuvant anastrozole. Patients completed the Breast Cancer Prevention Trial (BCPT) Symptom Checklist and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 0, 3, and 6 months. The plasma levels of four polyunsaturated fatty acids (PUFAs) and 48 oxylipins were quantified at each timepoint. The subscores for WOMAC-pain and stiffness as well as BCPT-total, hot flash, and musculoskeletal pain significantly increased from baseline to 6 months (all p < 0.05). PUFA and oxylipin levels were stable over time. The baseline levels of 8-HETE were positively associated with worsening BCPT-total, BCPT-hot flash, BCPT-musculoskeletal pain, WOMAC-pain, and WOMAC- stiffness at 6 months (all p < 0.05). Both 9-HOTrE and 13(S)-HOTrE were related to worsening hot flash, and 5-HETE was related to worsening stiffness (all p < 0.05). This is the first study to prospectively characterize oxylipin and PUFA levels in patients with breast cancer starting adjuvant anastrozole. The oxylipin 8-HETE should be investigated further as a potential biomarker for AIA.
Mechanisms of Maternal Diet-Induced Obesity Affecting the Offspring Brain and Development of Affective Disorders
Authors: Radford-Smith Daniel E. , Anthony Daniel C.
Published: March 2023

Depression and metabolic disease are common disorders that share a bidirectional relationship and continue to increase in prevalence. Maternal diet and maternal behaviour both profoundly influence the developmental trajectory of offspring during the perinatal period. At an epidemiological level, both maternal depression and obesity during pregnancy have been shown to increase the risk of neuropsychiatric disease in the subsequent generation. Considerable progress has been made to understand the mechanisms by which maternal obesity disrupts the developing offspring gut–brain axis, priming offspring for the development of affective disorders. This review outlines such mechanisms in detail, including altered maternal care, the maternal microbiome, inflammation, breast milk composition, and maternal and placental metabolites. Subsequently, offspring may be prone to developing gut–brain interaction disorders with concomitant changes to brain energy metabolism, neurotransmission, and behaviour, alongside gut dysbiosis. The gut microbiome may act as a key modifiable, and therefore treatable, feature of the relationship between maternal obesity and the offspring brain function. Further studies examining the relationship between maternal nutrition, the maternal microbiome and metabolites, and offspring neurodevelopment are warranted to identify novel therapeutic targets.
Acid-Base and Photocatalytic Properties of the CeO2-Ag Nanocomposites
Authors: Kravtsov Alexander A. , Blinov Andrey V. , Nagdalian Andrey A. , Gvozdenko Alexey A. , Golik Alexey B. , Pirogov Maxim A. , Kolodkin Maxim A. , Alharbi Naiyf S. , Kadaikunnan Shine , Thiruvengadam Muthu , Shariati Mohammad Ali
Published: March 2023

In this work, CeO2 nanoparticles, as well as CeO2 nanocomposites with plasmonic silver nanoparticles, were synthesized using a simple sol-gel process. The concentration of silver in the composites varied from 0.031–0.25 wt%. Cerium hydroxide dried gel was calcined at temperatures from 125 to 800 °C to obtain CeO2. It was shown that, at an annealing temperature of 650 °C, single-phase CeO2 nanopowders with an average particle size in the range of 10–20 nm can be obtained. The study of acid-base properties showed that with an increase in the calcination temperature from 500 to 650 °C, the concentration of active centers with pKa 9.4 and 6.4 sharply increases. An analysis of the acid-base properties of CeO2-Ag nanocomposites showed that with an increase in the silver concentration, the concentration of centers with pKa 4.1 decreases, and the number of active centers with pKa 7.4 increases. In a model experiment on dye photodegradation, it was shown that the resulting CeO2 and CeO2-Ag nanopowders have photocatalytic activity. CeO2-Ag nanocomposites, regardless of the silver concentration, demonstrated better photocatalytic activity than pure nanosized CeO2.
Update on Mycochemical Profile and Selected Biological Activities of Genus Schizophyllum Fr. 1815
Authors: Mišković Jovana , Rašeta Milena , Krsmanović Nenad , Karaman Maja
Published: March 2023

The aim of this systematic review was to investigate new research on the antioxidant, anti-acetylcholine, antimicrobial, and antitumor activity of genus Schizophyllum, as well as to describe the mycochemical profiles. A summary was made on the published studies in the five-year period from 2017 to 2022, with the focus on the most investigated species of this genus, S. commune. Data were obtained through various scientific online databases, including Google Scholar, Semantic Scholar, PubMed, Science Direct, Elsevier, and Wiley Online Library using specific keywords. Out of 918 records published between 2017 and 2022, a total of 44 peer-reviewed studies were included in qualitative synthesis. Most examined compounds were glucans isolated from the submerged cultivation of S. commune, even though many studies reported proteins, phenolics, and some other secondary metabolites such as flavonoids, saponins, steroids, tannins, triterpenoids, etc. Schizophyllan (SPG), one of the most studied β-glucans isolated from S. commune, has been utilized in clinical trials to treat patients receiving anticancer therapy as an immunopotentiator. Considering the enormous biopotential of genus Schizophyllum, specifically S. commune and S. radiatum, additional attention should be paid to identify the biomolecules more accurately and focus on their antitumor and anti-acetylcholinesterase properties, since they proved to have great prospects in the pharmaceutical and nutraceutical industries.
Heterologous 1,3-Propanediol Production Using Different Recombinant Clostridium beijerinckii DSM 6423 Strains
Authors: Schoch Teresa , Baur Tina , Kunz Johanna , Stöferle Sophia , Dürre Peter
Published: March 2023

1,3-propanediol (1,3-PDO) is a valuable basic chemical, especially in the polymer industry to produce polytrimethylene terephthalate. Unfortunately, the production of 1,3-PDO mainly depends on petroleum products as precursors. Furthermore, the chemical routes have significant disadvantages, such as environmental issues. An alternative is the biobased fermentation of 1,3-PDO from cheap glycerol. Clostridium beijerinckii DSM 6423 was originally reported to produce 1,3-PDO. However, this could not be confirmed, and a genome analysis revealed the loss of an essential gene. Thus, 1,3-PDO production was genetically reinstalled. Genes for 1,3-PDO production from Clostridium pasteurianum DSM 525 and Clostridium beijerinckii DSM 15410 (formerly Clostridium diolis) were introduced into C. beijerinckii DSM 6423 to enable 1,3-PDO production from glycerol. 1,3-PDO production by recombinant C. beijerinckii strains were investigated under different growth conditions. 1,3-PDO production was only observed for C. beijerinckii [pMTL83251_Ppta-ack_1,3-PDO.diolis], which harbors the genes of C. beijerinckii DSM 15410. By buffering the growth medium, production could be increased by 74%. Furthermore, the effect of four different promoters was analyzed. The use of the constitutive thlA promoter from Clostridium acetobutylicum led to a 167% increase in 1,3-PDO production compared to the initial recombinant approach.
Genomic Analysis of the Deep-Sea Bacterium Shewanella sp. MTB7 Reveals Backgrounds Related to Its Deep-Sea Environment Adaptation
Authors: Li Sicong , Wang Jiahua , Liu Jie , Zhang Hongcai , Bao Tianqiang , Sun Chengwen , Fang Jiasong , Cao Junwei
Published: March 2023

Shewanella species are widely distributed in various environments, especially deep-sea sediments, due to their remarkable ability to utilize multiple electron receptors and versatile metabolic capabilities. In this study, a novel facultatively anaerobic, psychrophilic, and piezotolerant bacterium, Shewanella sp. MTB7, was isolated from the Mariana Trench at a depth of 5900 m. Here, we report its complete genome sequence and adaptation strategies for survival in deep-sea environments. MTB7 contains what is currently the third-largest genome among all isolated Shewanella strains and shows higher coding density than neighboring strains. Metabolically, MTB7 is predicted to utilize various carbon and nitrogen sources. D-amino acid utilization and HGT-derived purine-degrading genes could contribute to its oligotrophic adaptation. For respiration, the cytochrome o ubiquinol oxidase genes cyoABCDE, typically expressed at high oxygen concentrations, are missing. Conversely, a series of anaerobic respiratory genes are employed, including fumarate reductase, polysulfide reductase, trimethylamine-N-oxide reductase, crotonobetaine reductase, and Mtr subunits. The glycine reductase genes and the triplication of dimethyl sulfoxide reductase genes absent in neighboring strains could also help MTB7 survive in low-oxygen environments. Many genes encoding cold-shock proteins, glycine betaine transporters and biosynthetic enzymes, and reactive oxygen species-scavenging proteins could contribute to its low-temperature adaptation. The genomic analysis of MTB7 will deepen our understanding of microbial adaptation strategies in deep-sea environments.
Study on the Characteristics of Damaged Sandstone in the Longshan Grottoes Using Water Chemistry and Freeze–Thaw Cycling
Authors: Sun Bo , Li Xingyue , Cui Kai , Peng Ningbo , Hong Jie , Chen Rui , Jia Chen
Published: March 2023

Sandstone from the Longshan Grottoes in Taiyuan, China, was the research object of this paper. The sandstone samples were soaked in distilled water, Na2SO4 solution, and NaCl solution and subjected to freeze–thaw testing. Sandstone specimens were treated with 0, 5, 10, 15, 20, 25, and 30 freeze–thaw cycles. The mass ratio, P-wave velocity, surface hardness, uniaxial compressive strength, and other physical-mechanical features of rock samples were measured after different numbers of cycles. The results of mercury injection, scanning electron microscopy, and X-ray diffraction were combined to explore the damage mechanisms and characteristics of the rock samples under the combined action of chemicals and freeze–thaw cycles. It was found that the damage degree of sandstone increased logarithmically with the number of cycles, with Na2SO4 solution causing the most damage. Damage variables D of the samples soaked in distilled water, Na2SO4 solution, and NaCl solution after 30 freeze–thaw cycles were 3.89%, 6.51%, and 4.74%, respectively. The difference in damage between the solutions is caused by the combination of frost heave, dissolution, and salt crystallization, and the damage process generally occurs from the inside and the outside and is manifested as an increase in the number of macropores and the appearance of new pores. Freezing–thawing and salt action are important causes of the powdering and detachment of sandstone in the Longshan Grottoes.