bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Data-Driven Optimal Scheduling of Power System
Authors: Luo Jianxun , Zhang Wei , Wang Hui , Wei Wenmiao , He Jinpeng
Published: March 2023

The uncertainty of output makes it difficult to effectively solve the economic security dispatching problem of the power grid when a high proportion of renewable energy generating units are integrated into the power grid. Based on the proximal policy optimization (PPO) algorithm, a safe and economical grid scheduling method is designed. First, constraints on the safe and economical operation of renewable energy power systems are defined. Then, the quintuple of Markov decision process is defined under the framework of deep reinforcement learning, and the dispatching optimization problem is transformed into Markov decision process. To solve the problem of low sample data utilization in online reinforcement learning strategies, a PPO optimization algorithm based on the Kullback–Leibler (KL) divergence penalty factor and importance sampling technique is proposed, which transforms on-policy into off-policy and improves sample utilization. Finally, the simulation analysis of the example shows that in a power system with a high proportion of renewable energy generating units connected to the grid, the proposed scheduling strategy can meet the load demand under different load trends. In the dispatch cycle with different renewable energy generation rates, renewable energy can be absorbed to the maximum extent to ensure the safe and economic operation of the grid.
Evolution Law of Wellbore Instability Risk under Fluctuating Pressure
Authors: Zhao Kai , Song Wenjie , Deng Jingen , Tan Qiang , Wang Xiaoyun
Published: March 2023

The bottom hole fluctuating pressure has a large influence on the wellbore instability. To address this problem, firstly, according to the principle of seepage mechanics, we established a calculation model of the change in pore pressure around the wellbore radius under fluctuating pressure; then, through laboratory rock mechanics test and rock damage mechanics theory analysis, the change law of formation strength under the action of static hydration and dynamic damage are determined; finally, based on the theory of rock mechanics in porous media, a quantitative evaluation method for the risk of wellbore instability under fluctuating pressure is established and the changing pattern of wellbore instability risk is analyzed. The results show that the pore pressure around the well shows a trend of fluctuation increase under fluctuating pressure, and there is a certain lag in the fluctuation of pore pressure inside the formation; the longer the muddy shale is immersed in drilling fluid, the greater the reduction in strength; the reduction is greater in the early stage of immersion, and the reduction in strength in water-based drilling fluid is greater than that in oil-based drilling fluid. At the beginning of the pressure cycle, the formation damage variable and compressive strength gradually increase and decrease with the increase of the pressure cycle number; after several cycles, the magnitude of change gradually decreases with the increase of the cycle number. When the bottom hole pressure fluctuates at a certain period, the greater the fluctuation, the shorter the period of wellbore stability; when the bottom hole pressure fluctuates at a certain range, the smaller the fluctuation period, the faster the borehole enters the high-risk period, while the shortest period of wellbore stability occurs when the fluctuation period is smallest; and when the wave cycle is in the middle, the wellbore stability period is the longest.
Evaluation of the Influence of the Load Resistance on Power and Efficiency in the Square and Circular Periodic WPT Systems
Authors: Stankiewicz Jacek Maciej
Published: March 2023

We are currently seeing an increasing number of devices that support wireless power transfer (WPT) technology. In order to avoid early prototyping and carry out a series of experimental analyses, it was possible to use numerical methods at the design stage to estimate the potential power transfer and efficiency of the system. The purpose of this study is to present a method of analysis for a periodic wireless power transfer system, using periodically arranged planar coils with field and circuit models. A three-dimensional numerical model of a multi-segment charging system with periodic boundary conditions was solved with the finite element method (FEM). An equivalent circuit model of the periodic WPT system was proposed, and the required lumped parameters were obtained using analytical formulas. Mathematical formulas were supplemented with the analysis of several geometric variants, taking into account different sizes of transmitting and receiving coils, as well as different numbers of turns. Both proposed methods of analysis allowed for the determination of load resistance values at which the variants of WPT systems considered in the research had maximum efficiency. The ranges of load resistance values in which the efficiency of the system exceeded 50% were indicated. The results obtained are very helpful in the proper selection of the load resistance, without the need for multiple tests and their resulting multiple measurements. The results also showed that the proposed circuit model was able to achieve similar accuracy as the numerical model, and the complexity of the model and analysis was significantly reduced. The obtained results will allow the design of WPT systems with appropriate selections of load resistance to achieve maximum efficiency.
A Mathematical Model for Home Appliances in a DC Home Nanogrid
Authors: Cordova-Fajardo Miguel , Tututi Eduardo S.
Published: March 2023

A mathematical model for nonlinear loads, that contains, in its design, a switching power supply is presented. The model was tested in home appliances operating in a Direct Current Home Nanogrid (DCHN). Compact Fluorescent Lamps (CFLs) and LED lamps were used as nonlinear loads to study, through the model, the experimental results in the profile of ripple in voltage and current of the lamps. The profile of ripples, due to the home appliances, could be explained by the model, even in the simultaneous operation of two loads. Additionally, the effect of decreasing the ripple amplitude when an induction stove in standby mode was incorporated with the DCHN was analyzed.
A Model for Determining Fuzzy Evaluations of Partial Indicators of Availability for High-Capacity Continuous Systems at Coal Open Pits Using a Neuro-Fuzzy Inference System
Authors: Gomilanovic Miljan , Tanasijevic Milos , Stepanovic Sasa , Miletic Filip
Published: March 2023

This paper presents a model for determining fuzzy evaluations of partial indicators of the availability of continuous systems at coal open pits using a neuro-fuzzy inference system. The system itself is a combination of fuzzy logic and artificial neural networks. The system availability is divided into partial indicators. By combining the fuzzy logic and artificial neural networks, a model is obtained that has the ability to learn and uses expert judgment for that learning. This paper deals with the ECC system (bucket wheel excavator-conveyor-crushing plant) of the open pit Drmno-Kostolac, which operates within the Electric Power Company of Serbia. The advantage of a model of this type is that it does not rely on the historical experiences of experts and usual predicted values for the fuzzy evaluation of partial indicators, which are based on the assumption that similar systems affect availability in a similar way. The fuzzy evaluation of partial indicators is based on historical data for the specific system for which the model was created. As such, it can more accurately predict continuous systems availability on the basis of expert evaluations in the appropriate time period. Another advantage of this model is that the availability is estimated on a quarterly basis, which gives a more accurate view because it uses a smaller time period with more similar characteristics and, thus, includes certain external influences which are related to the quarterly meteorological conditions.
Comparative Evaluation of Common-Ground Converters for Dual-Purpose Application
Authors: Hemmati Shahsavar Tala , Rahimpour Saeed , Vosoughi Kurdkandi Naser , Fesenko Artem , Matiushkin Oleksandr , Husev Oleksandr , Vinnikov Dmitri
Published: March 2023

The focus of this paper is to provide a comparative analysis of various common-ground converters that serve as dual-purpose power electronic interfaces. These interfaces are designed to be used in both DC and single-phase AC grids, utilizing the same terminals for both modes of operation. The idea lies in the utilization of the same semiconductors in the DC-DC and DC-AC configurations, resulting in minimal redundancy. Particular attention is focused on the comparative evaluation approach. A novel Flying Inductor (FI)-based converter was selected for experimental verification. The design example and experimental prototype of a dual-purpose DC-DC/AC power electronic converter is capable of providing 2 kVA of power in AC mode and 4 kW in DC mode. The experimental results indicate that the converter can operate in both AC and DC grids according to their respective modes. The conclusion of the study highlights the potential applications and main benefits of this technology.
Fatigue Assessment of Carbon Fiber-Reinforced Polyurethane with Regard to Crack Initiation and Propagation
Authors: Gerdes Lars , Franck Pascal , Richle Stefan , Barandun Gion A. , Walther Frank
Published: March 2023

Due to their lightweight potential, the use of fiber-reinforced polymers is the current standard for many technical fields of application. Especially, the automotive and aerospace sectors are to be emphasized. This entails a sophisticated knowledge regarding the material properties, since the safety standards applied in these fields are of high importance. To ensure the safety of the components, a detailed mechanical material characterization is indispensable. The aim of this work was to investigate different influencing factors on the fatigue behavior of carbon fiber-reinforced polyurethane, which is to be certified for aviation applications. Tensile tests provided a basic understanding of the material properties, which appeared to be affected by the specimen width, varied from 3 to 25 mm, by up to 30%. Subsequently, the influence of the cutting direction was investigated in the course of the fatigue tests. Thus, the fatigue strength of longitudinally cut specimens was found to be higher than that of transversely cut specimens by 6%. By means of specific measurement technologies, the material responses were associated with crack initiation and propagation during the fatigue lifetime. The material properties, such as the thermoelastic effect, could be examined during the fatigue tests. Furthermore, turning points in the courses of the characteristic values of the material and correlations with local phenomena were identified.
Determining the Weightage of Visual Aesthetic Variables for Permanent Urban Forest Reserves Based on the Converging Approach
Authors: Mundher Riyadh , Abu Bakar Shamsul , Aziz Azlizam , Maulan Suhardi , Mohd Yusof Mohd Johari , Al-Sharaa Ammar , Gao Hangyu
Published: March 2023

Permanent urban forest reserves are aesthetic assets within cities. Consequently, their aesthetic quality must be continuously preserved and visually assessed. Even though numerous studies have utilized multiple variables to characterize visual aesthetics, they have lacked information on the importance and weightage of each variable, making it very challenging to assess this. Therefore, this study aimed to determine the relative weightage of the visual aesthetic variables for permanent urban forest reserves in Malaysia. We used a converging approach assessment method to determine the ranked preferences for the visual aesthetic variables of permanent urban forest reserves by selecting multiple variables based on public preferences and expert survey assessments of these. In addition, we utilized the converging approach results as a guide for the analytic hierarchy process in order to determine the weights of the visual aesthetic variables. We identified 14 variables, derived from six main variables, as multiple visual aesthetic variables for permanent urban forest reserves based on the content of photos taken by 12 public participants. The expert survey confirmed the validity of the classification of the variables and the importance of their linear sequencing. It was revealed that the greatest weight normalization (W = 10) was achieved from the variables “openness with city view”, “uniqueness of water with natural elements”, and “openness with water view”, while the least weight normalization (W = 1) was obtained from the variables “legibility with natural path”, “uniqueness with man-made elements”, and “uniqueness with natural elements”. Our findings provide a foundation for assessing the visual aesthetic quality of permanent urban forest reserves.
Evaluation of DNA Methylation-Based Age-Prediction Models from Saliva and Buccal Swab Samples Using Pyrosequencing Data
Authors: Poussard Alexandre , Curci Jean-Yves , Siatka Christian , Hermitte Francis , Pussiau Amaury , Singla-Sanchez Hélène , Hubac Sylvain
Published: March 2023

In forensic genetics, the identification of an individual is often carried out by comparing unknown DNA profiles obtained in a case against databases or references. When no match is found, investigators need new tools in order to obtain additional leads. The latest technical advances now make it possible to predict externally visible characteristics. With this objective, predicting the age of an individual through DNA methylation analysis remains one of the last challenges. The prediction models have to account for the specific constraints of this field, including tissue specificity and DNA availability (i.e., low DNA amounts or low-quality DNA). Jung and colleagues have recently produced models from blood, saliva and buccal cells by using a single base extension sequencing method. With the goal of evaluating these models in our own analytical conditions, saliva and buccal cell samples from 115 French individuals between the ages of 0 and 88 years old were collected and analyzed. After having determined the optimal analysis conditions, including the DNA quantity for bisulfite conversion (75 ng), some differences were highlighted in the measured methylation rates between the two studies. Despite these discrepancies, the prediction performance levels remain very similar, our study showing mean absolute errors of 3.5 years, 3.9 years and 3.2 years, respectively, for the saliva, buccal swab and multitissue model, with limitations observed for the oldest and youngest individuals. Furthermore, we propose the use of a prediction interval with an error dispersion and correct prediction rate at ±5 years and ±10 years, respectively.
A Novel Three-Dimensional Fractal Model for the Normal Contact Stiffness of Mechanical Interface Based on Axisymmetric Cosinusoidal Asperity
Authors: Wang Weikun , An Qi , Suo Shuangfu , Meng Guoying , Yu Yibo , Bai Yuzhu
Published: March 2023

A novel three-dimensional fractal model for normal contact stiffness is proposed in this paper. First of all, a hypothetical surface based on axisymmetric cosinusoidal asperity is established. Then, based on the hypothetical surface, the analytical expressions for the contact stiffness and contact load are derived by combining the three-dimensional fractal theory with the contact mechanics theory. In addition, the simulation results of the presented model and the Pan model are compared with the experimental results. The comparison results show that the maximum relative error of the Pan model is 29.58%, while the maximum relative error of the presented model is 4.35%. Ultimately, the influence of different fractal parameters on contact stiffness is discussed. Under the same contact load, the normal contact stiffness first increases and then decreases with the increase of the fractal dimension D, while the normal contact stiffness monotonically decreases with the increase of scale coefficient G. The results are explained from the perspective of the shape of the asperity. This study provides a novel model for the calculation of normal contact stiffness, which provides a model basis for the study of contact properties for the mechanical interface.
On Reservoir Computing Approach for Digital Image Encryption and Forecasting of Hyperchaotic Finance Model
Authors: Elsonbaty Amr , Elsadany A. A. , Adel Waleed
Published: March 2023

Forecasting the dynamical behaviors of nonlinear systems over long time intervals represents a great challenge for scientists and has become a very active area of research. The employment of the well-known artificial recurrent neural networks (RNNs)-based models requires a high computational cost, and they usually maintain adequate accuracy for complicated dynamics over short intervals only. In this work, an efficient reservoir-computing (RC) approach is presented to predict the time evolution of the complicated dynamics of a fractional order hyperchaotic finance model. Compared with the well-known deep learning techniques, the suggested RC-based forecasting model is faster, more accurate for long-time prediction, and has a smaller execution time. Numerical schemes for fractional order systems are generally time-consuming. The second goal of the present study is to introduce a faster, more efficient, and simpler simulator to the fractional order chaotic/hyperchaotic systems. The RC model is utilized in a proposed RC-based digital image encryption scheme. Security analysis is carried out to verify the performance of the proposed encryption scheme against different types of statistical, KPA, brute-force, CCA, and differential attacks.
T-Cell Receptor Repertoire Characteristics Associated with Prognostic Significance in High-Grade Serous Ovarian Carcinoma
Authors: Kim Ju-Won , Kim Sewha , Yang So-Yun , Joung Je-Gun , Hwang Sohyun
Published: March 2023

High-grade serous ovarian carcinoma (HGSOC) is a fatal gynecological malignancy. Somatic recombination occurring during T-cell receptor (TCR) development results in TCR diversity, and the TCR repertoire, thus produced, is associated with immune response. This study analyzed the difference in the TCR repertoire and their prognostic significance in 51 patients with HGSOC. The patient’s clinical characteristics, gene expression pattern, TCR clonotypes, and degree of tumor-infiltrating leukocytes (TILs) were analyzed, and the patients were divided into groups depending on their recurrence pattern, tumor-infiltrating leukocyte (TIL) score, and homologous recombinant repair pathway deficiency (HRD)-associated mutations. The TCR repertoire was low in patients with recurrence and showed the expansion of eight TCR segments. Interestingly, a few genes correlated with the TCRs also showed a difference in expression according to the prognosis. Among them, seven genes were related to immune responses and KIAA1199 was up-regulated in ovarian cancer. Our study shows that the differences in the TCR repertoire in patients with ovarian cancer and their associated immune pathways could affect the prognosis of HGSOC.
Toward a Plausible Methodology to Assess Rock Slope Instabilities at a Regional Scale
Authors: Sotiriadis Dimitris , Klimis Nikolaos , Koutsoupaki Elisavet Isavela , Petala Eleni , Valkaniotis Sotiris , Taftsoglou Maria , Margaris Vasileios , Dokas Ioannis
Published: March 2023

Slope failures along road cuts and highways, occurring due to heavy rainfalls or earthquakes, pose significant threats to people, vehicles, and emergency plans. In the present study, a methodology to assess the stability of rock slopes at a regional scale is proposed using a kinematic analysis and a probabilistic limit equilibrium analysis for plane sliding and wedge failure modes. The workflow adopted is described through its implementation along the main road network of the island of Thasos, located in northern Greece. On-site investigations and measurements along the island’s road network formed the basis of the present study. The results of the kinematic analysis showed that the joint sets, which were identified during the on-site investigations, formed critical intersections that could lead to wedge and plane sliding failures. The on-site measurements and the results of the kinematic analysis were utilized to perform limit equilibrium back-analyses at sites of identified failures due to the water pressure effects to probabilistically estimate the material strength properties of the joints. Subsequently, numerous limit equilibrium analyses were executed within a Monte Carlo simulation framework to produce representative fragility curves of rock slopes against plane sliding and wedge failures along the main road network, due to earthquake loading and water pressures.
Information Technology Undergraduate Students’ Intercultural Value Orientations and Their Beliefs about the Influence of Such Orientations on Teamwork Interactions
Authors: Bahrami Parsia , Kim Yeji , Jaiswal Aparajita , Patel Devang , Aggrawal Sakhi , Magana Alejandra J.
Published: March 2023

Companies and their executives are concluding that to accomplish their complex tasks and all-encompassing missions and goals, they must step outside the traditional realms of teamwork and partnership and engage in cross-cultural and multinational alliances. One of the principal areas affecting teamwork today, especially in diverse workplaces, is the variety of cultural value orientations that the members relate to. To better prepare students for joining global enterprises, it is necessary to understand their cultural orientations and how those may influence their teamwork interactions. This study used a mixed methods design to characterize computer and information technology undergraduate students’ cultural orientations and their cultural awareness in the context of teamwork experiences. The data for the study was collected in the form of a reflection assignment that was implemented during the first week of classes as a way to promote students’ cultural awareness and how that may play out in their teamwork interactions. The reflection assignment had two parts: (i) a survey and (ii) reflection questions. The study used descriptive statistics and t-tests to analyze the survey (quantitative data), and thematic analysis was conducted to analyze the reflection questions (qualitative data). Our analysis of the quantitative data revealed that students identified the following core values they are Individualism, Equality, Monochronic, Meritocracy, Informality, Personal Efficacy, and Directness, and these values resonated with most of the students in class. Corresponding qualitative themes that emerged regarding students’ beliefs of how those values may play out in their teamwork experience were (a) Treating everyone equally and understanding others, (b) Increasing temporal Awareness, (c) Enacting effective communication, (d) Monitoring the progress of team members and (e) Establishing rules and boundaries.
Recent Reflections on the Sociology of Archaeology: Introduction
Authors: Claassen Cheryl
Published: March 2023

Nothing in the past 60 years has nullified the impact of the social positioning of archaeologists and the discipline in the creation of archaeological knowledge [...]
Families with Mentally Ill Parents and Their Partners: Overlaps in Psychiatric Symptoms and Symptom Coping
Authors: Wiegand-Grefe Silke , Warkentin Hannah , Adema Bonnie , Daubmann Anne , Kilian Reinhold , Winter Sibylle M. , Lambert Martin , Wegscheider Karl , Busmann Mareike
Published: March 2023

Partners in families with a mentally ill parent often experience psychiatric symptoms themselves. Recent studies indicate that there might be overlaps in disorder-specific symptom areas between partners and spouses. This study aimed at examining associations in psychiatric symptoms and symptom coping in partners in families with a mentally ill parent, e.g., having a psychiatric diagnosis according to the International Classification of Diseases (ICD-10). Furthermore, a moderation of the psychiatric symptoms of the parent with a mental illness on the association in symptom coping was assumed. Families with at least one parent with a mental illness were recruited into the longitudinal “Children of Mentally Ill Parents” (CHIMPS) trial at seven clinical centers in Germany and Switzerland. In total, 139 families were included in the current study. Psychiatric symptoms were assessed using the Brief Symptom Inventory (BSI), Clinical Global Impression scale (CGI), Global Assessment of Functioning (GAF), and Patient Health Questionnaire (PHQ), while symptom coping strategies were measured using the Freiburger Fragebogen zur Krankheitsverarbeitung (FKV). Regression analyses have indicated an association in psychiatric symptoms between mentally ill parents and their partners concerning psychosocial functioning, somatic, and stress-related symptoms. Additionally, one symptom coping strategy of the partners was predicted by the same strategy of the parent with a mental illness. The results emphasize the importance of screening and providing support to parents burdened by the mental disorder of their partners, especially regarding the children in these partnerships.
A Proposed New Model to Explain the Role of Low Dose Non-DNA Targeted Radiation Exposure in Chronic Fatigue and Immune Dysfunction Syndrome
Authors: Cocchetto Alan , Seymour Colin , Mothersill Carmel
Published: March 2023

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) is considered to be a multidimensional illness whose etiology is unknown. However, reports from Chernobyl, as well as those from the United States, have revealed an association between radiation exposure and the development of CFIDS. As such, we present an expanded model using a systems biology approach to explain the etiology of CFIDS as it relates to this cohort of patients. This paper proposes an integrated model with ionizing radiation as a suggested trigger for CFIDS mediated through UVA induction and biophoton generation inside the body resulting from radiation-induced bystander effects (RIBE). Evidence in support of this approach has been organized into a systems view linking CFIDS illness markers with the initiating events, in this case, low-dose radiation exposure. This results in the formation of reactive oxygen species (ROS) as well as important immunologic and other downstream effects. Furthermore, the model implicates melanoma and subsequent hematopoietic dysregulation in this underlying process. Through the identification of this association with melanoma, clinical medicine, including dermatology, hematology, and oncology, can now begin to apply its expansive knowledge base to provide new treatment options for an illness that has had few effective treatments.
Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors
Authors: Scandiffio Rosaria , Bonzano Sara , Cottone Erika , Shrestha Sujata , Bossi Simone , De Marchis Silvia , Maffei Massimo E. , Bovolin Patrizia
Published: March 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease; however, no specific pharmacological therapy has yet been approved for this condition. Plant-derived extracts can be an important source for the development of new drugs. The aim of this study was to investigate the effects of (E)-β-caryophyllene (BCP), a phytocannabinoid recently found to be beneficial against metabolic diseases, on HepG2 steatotic hepatocytes. Using a fluorescence-based lipid quantification assay and GC-MS analysis, we show that BCP is able to decrease lipid accumulation in steatotic conditions and to change the typical steatotic lipid profile by primarily reducing saturated fatty acids. By employing specific antagonists, we demonstrate that BCP action is mediated by multiple receptors: CB2 cannabinoid receptor, peroxisome proliferator-activated receptor α (PPARα) and γ (PPARγ). Interestingly, BCP was able to counteract the increase in CB2 and the reduction in PPARα receptor expression observed in steatotic conditions. Moreover, through immunofluorescence and confocal microscopy, we demonstrate that CB2 receptors are mainly intracellularly localized and that BCP is internalized in HepG2 cells with a maximum peak at 2 h, suggesting a direct interaction with intracellular receptors. The results obtained with BCP in normal and steatotic hepatocytes encourage future applications in the treatment of NAFLD.
Intestinal Carnitine Status and Fatty Acid Oxidation in Response to Clofibrate and Medium-Chain Triglyceride Supplementation in Newborn Pigs
Authors: Pike Brandon , Zhao Jinan , Hicks Julie A. , Wang Feng , Hagen Rachel , Liu Hsiao-Ching , Odle Jack , Lin Xi
Published: March 2023

To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in carnitine status and intestinal fatty acid oxidation in neonates, a total of 72 suckled newborn piglets were assigned into 8 dietary treatments following a 2 (±0.35% clofibrate) × 4 (diets with: succinate+glycerol (Succ), tri-valerate (TC5), tri-hexanoate (TC6), or tri-2-methylpentanoate (TMPA)) factorial design. All pigs received experimental milk diets with isocaloric energy for 5 days. Carnitine statuses were evaluated, and fatty acid oxidation was measured in vitro using [1-14C]-palmitic acid (1 mM) as a substrate in absence or presence of L659699 (1.6 µM), iodoacetamide (50 µM), and carnitine (1 mM). Clofibrate increased concentrations of free (41%) and/or acyl-carnitine (44% and 15%) in liver and plasma but had no effects in the intestine. The effects on carnitine status were associated with the expression of genes involved in carnitine biosynthesis, absorption, and transportation. TC5 and TMPA stimulated the increased fatty acid oxidation rate induced by clofibrate, while TC6 had no effect on the increased fatty acid oxidation induced by clofibrate (p > 0.05). These results suggest that dietary clofibrate improved carnitine status and increased fatty acid oxidation. Propionyl-CoA, generated from TC5 and TMPA, could stimulate the increased fatty acid oxidation rate induced by clofibrate as anaplerotic carbon sources.
MPEP Attenuates Intrahepatic Fat Accumulation in Obese Mice
Authors: Ferrigno Andrea , Cagna Marta , Bosco Oriana , Trucchi Michelangelo , Berardo Clarissa , Nicoletti Ferdinando , Vairetti Mariapia , Di Pasqua Laura G.
Published: March 2023

The blockade of metabotropic glutamate receptor type 5 (mGluR5) was previously found to reduce fat accumulation in HEPG2 cells. Here, we evaluated the effects of mGluR5 blockade in a mouse model of steatosis. Male ob/ob mice fed a high-fat diet were treated with MPEP or vehicle. After 7 weeks, liver biopsies were collected, and nuclei were isolated from fresh tissue. Lipid droplet area and collagen deposition were evaluated on tissue slices; total lipids, lipid peroxidation, and ROS were evaluated on tissue homogenates; PPARα, SREBP-1, mTOR, and NF-κB were assayed on isolated nuclei by Western Blot. Target genes of the above-mentioned factors were assayed by RT-PCR. Reduced steatosis and hepatocyte ballooning were observed in the MPEP group with respect to the vehicle group. Concomitantly, increased nuclear PPARα and reduced nuclear SREBP-1 levels were observed in the MPEP group. Similar trends were obtained in target genes of PPARα and SREBP-1, Acox1 and Acc1, respectively. MPEP administration also reduced oxidative stress and NF-κB activation, probably via NF-κB inhibition. Levels of common markers of inflammation (Il-6, Il1β and Tnf-α) and oxidative stress (Nrf2) were significantly reduced. mTOR, as well as collagen deposition, were unchanged. Concluding, MPEP, a selective mGluR5 negative allosteric modulator, reduces both fat accumulation and oxidative stress in a 7-week murine model of steatosis. Although underlying mechanisms need to be further investigated, this is the first in vivo study showing the beneficial effects of MPEP in a murine model of steatosis.
Comparative Efficacy of Intra-Articular Injection, Physical Therapy, and Combined Treatments on Pain, Function, and Sarcopenia Indices in Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Liao Chun-De , Chen Hung-Chou , Huang Mao-Hua , Liou Tsan-Hon , Lin Che-Li , Huang Shih-Wei
Published: March 2023

Knee osteoarthritis (KOA) is associated with a high risk of sarcopenia. Both intra-articular injections (IAIs) and physical therapy (PT) exert benefits in KOA. This network meta-analysis (NMA) study aimed to identify comparative efficacy among the combined treatments (IAI+PT) in patients with KOA. Seven electronic databases were systematically searched from inception until January 2023 for randomized controlled trials (RCTs) reporting the effects of IAI+PT vs. IAI or PT alone in patients with KOA. All RCTs which had treatment arms of IAI agents (autologous conditioned serum, botulinum neurotoxin type A, corticosteroids, dextrose prolotherapy (DxTP), hyaluronic acid, mesenchymal stem cells (MSC), ozone, platelet-rich plasma, plasma rich in growth factor, and stromal vascular fraction of adipose tissue) in combination with PT (exercise therapy, physical agent modalities (electrotherapy, shockwave therapy, thermal therapy), and physical activity training) were included in this NMA. A control arm receiving placebo IAI or usual care, without any other IAI or PT, was used as the reference group. The selected RCTs were analyzed through a frequentist method of NMA. The main outcomes included pain, global function (GF), and walking capability (WC). Meta-regression analyses were performed to explore potential moderators of the treatment efficacy. We included 80 RCTs (6934 patients) for analyses. Among the ten identified IAI+PT regimens, DxTP plus PT was the most optimal treatment for pain reduction (standard mean difference (SMD) = −2.54) and global function restoration (SMD = 2.28), whereas MSC plus PT was the most effective for enhancing WC recovery (SMD = 2.54). More severe KOA was associated with greater changes in pain (β = −2.52) and WC (β = 2.16) scores. Combined IAI+PT treatments afford more benefits than do their corresponding monotherapies in patients with KOA; however, treatment efficacy is moderated by disease severity.
Insights into Canine Infertility: Apoptosis in Chronic Asymptomatic Orchitis
Authors: Morawietz Judith , Körber Hanna , Packeiser Eva-Maria , Beineke Andreas , Goericke-Pesch Sandra
Published: March 2023

Chronic asymptomatic orchitis (CAO) is a common cause of acquired non-obstructive azoospermia in dogs. To understand the impact and mode of action of apoptosis, we investigated TUNEL, Bax, Bcl-2, Fas/Fas ligand, and caspase 3/8/9 in testicular biopsies of CAO-affected dogs and compared the results to undisturbed spermatogenesis in healthy males (CG). TUNEL+ cells were significantly increased in CAO, correlating with the disturbance of spermatogenesis. Bcl-2, Bax (p < 0.01 each), caspase 9 (p < 0.05), Fas, caspase 8 (p < 0.01 each), and caspase 3 (p < 0.05) were significantly increased at the mRNA level, whereas FasL expression was downregulated. Cleaved caspase 3 staining was sporadic in CAO but not in CG. Sertoli cells, some peritubular (CAO/CG) and interstitial immune cells (CAO) stained Bcl-2+, with significantly more immunopositive cells in both compartments in CAO compared to CG. Bcl-2 and CD20 co-expressing B lymphocytes were encountered interstitially and in CAO occasionally also found intratubally, underlining their contribution to the maintenance of CAO. Our results support the crucial role of the intrinsic and extrinsic apoptotic pathways in the pathophysiology of canine CAO. Autoprotective Bcl-2 expression in Sertoli cells and B lymphocytes seems to be functional, however, thereby also maintaining and promoting the disease by immune cell activation.
Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury
Authors: Zhou Qingyu , Quirk James D. , Hu Ying , Yan Huimin , Gaut Joseph P. , Pham Christine T. N. , Wickline Samuel A. , Pan Hua
Published: March 2023

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10–20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury.
Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology
Authors: Kluivers Kirsten B. , Lince Sabrina L. , Ruiz-Zapata Alejandra M. , Post Wilke M. , Cartwright Rufus , Kerkhof Manon H. , Widomska Joanna , De Witte Ward , Pecanka Jakub , Kiemeney Lambertus A. , Vermeulen Sita H. , Goeman Jelle J. , Allen-Brady Kristina , Oosterwijk Egbert , Poelmans Geert
Published: March 2023

Pelvic organ prolapse (POP) represents a major health care burden in women, but its underlying pathophysiological mechanisms have not been elucidated. We first used a case-control design to perform an exome chip study in 526 women with POP and 960 control women to identify single nucleotide variants (SNVs) associated with the disease. We then integrated the functional interactions between the POP candidate proteins derived from the exome chip study and other POP candidate molecules into a molecular landscape. We found significant associations between POP and SNVs in 54 genes. The proteins encoded by 26 of these genes fit into the molecular landscape, together with 43 other POP candidate molecules. The POP landscape is located in and around epithelial cells and fibroblasts of the urogenital tract and harbors four interacting biological processes—epithelial-mesenchymal transition, immune response, modulation of the extracellular matrix, and fibroblast function—that are regulated by sex hormones and TGFB1. Our findings were corroborated by enrichment analyses of differential gene expression data from an independent POP cohort. Lastly, based on the landscape and using vaginal fibroblasts from women with POP, we predicted and showed that metformin alters gene expression in these fibroblasts in a beneficial direction. In conclusion, our integrated molecular landscape of POP provides insights into the biological processes underlying the disease and clues towards novel treatments.
Hericium erinaceus Promotes Anti-Inflammatory Effects and Regulation of Metabolites in an Animal Model of Cerebellar Ataxia
Authors: Chau Sze Chun , Chong Pit Shan , Jin Hongkai , Tsui Ka Chun , Khairuddin Sharafuddin , Tse Anna Chung Kwan , Lew Sze Yuen , Tipoe George Lim , Lee Chi Wai , Fung Man-Lung , Wong Kah Hui , Lim Lee Wei
Published: March 2023

Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.
Circulating Pulmonary-Originated Epithelial Biomarkers for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis
Authors: Lin Huishu , Liu Qisijing , Zhao Lei , Liu Ziquan , Cui Huanhuan , Li Penghui , Fan Haojun , Guo Liqiong
Published: March 2023

Previous studies have found several biomarkers for acute respiratory distress syndrome (ARDS), but the accuracy of most biomarkers is still in doubt due to the occurrence of other comorbidities. In this systematic review and meta-analysis, we aimed to explore ideal ARDS biomarkers which can reflect pathophysiology features precisely and better identify at-risk patients and predict mortality. Web of Science, PubMed, Embase, OVID, and the Cochrane Library were systematically searched for studies assessing the reliability of pulmonary-originated epithelial proteins in ARDS. A total of 32 studies appeared eligible for meta-analysis, including 2654 ARDS/ALI patients in this study. In the at-risk patients’ identification group, the highest pooled effect size was observed in Krebs von den Lungren-6 (KL-6) (SMD: 1.17 [95% CI: 0.55, 1.79]), followed by club cell proteins 16 (CC16) (SMD: 0.74 [95% CI: 0.01, 1.46]), and surfactant proteins-D (SP-D) (SMD: 0.71 [95% CI: 0.57, 0.84]). For the mortality prediction group, CC16 exhibited the largest effect size with SMD of 0.92 (95% CI: 0.42, 1.43). Meanwhile, the summary receiver operating characteristic (SROC) of CC16 for ARDS diagnosis reached an AUC of 0.80 (95% CI: 0.76, 0.83). In conclusion, this study provides a ranking system for pulmonary-originated epithelial biomarkers according to their association with distinguishing at-risk patients and predicting mortality. In addition, the study provides evidence for the advantage of biomarkers over traditional diagnostic criteria. The performance of biomarkers may help to clinically improve the ARDS diagnosis and mortality prediction.
Inhibitory Effects of Thermolysis Transformation Products of Rotenone on Nitric Oxide Production
Authors: Jeong Gyeong Han , Lee Hanui , Lee Seung Sik , Chung Byung Yeoup , Bai Hyoung-Woo , Kim Tae Hoon
Published: March 2023

Rotenone, isolated from Derris, Lonchocarpus, and Tephrosia from the family Fabaceae, has been shown to have a variety of biological properties and is used in various agricultural industries as a potent biopesticide. However, recent reports have demonstrated that rotenone has the potential to cause several adverse effects such as a neurodegenerative disease. This study aimed to induce thermolysis of the biopesticide rotenone and enhance the functionality of the degraded products. Rotenone (1) was degraded after autoclaving for 12 h, and the thermolytic reactants showed enhanced anti-inflammatory capacity against nitric oxide (NO) production. The structures of the newly modified products were spectroscopically determined. The thermal reaction products included various isoflavonoid derivatives 2–6, whose structures were characterized as being produced via chemical reactions in rotenone at the C-12 positions. Among the degraded products, (−)-tubaic acid (6) exhibited significantly improved anti-inflammatory effects compared to the original rotenone. Quantitative LC-MS analysis of the major thermolysis products generated in Derris extract containing rotenone was performed using isolate 2–5 purified from autoclaved rotenone. These results suggest that the thermal transformation of rotenone can improve the functionality of anti-inflammatory agents.
Platelets and Cardioprotection: The Role of Nitric Oxide and Carbon Oxide
Authors: Russo Isabella , Barale Cristina , Melchionda Elena , Penna Claudia , Pagliaro Pasquale
Published: March 2023

Nitric oxide (NO) and carbon monoxide (CO) represent a pair of biologically active gases with an increasingly well-defined range of effects on circulating platelets. These gases interact with platelets and cells in the vessels and heart and exert fundamentally similar biological effects, albeit through different mechanisms and with some peculiarity. Within the cardiovascular system, for example, the gases are predominantly vasodilators and exert antiaggregatory effects, and are protective against damage in myocardial ischemia-reperfusion injury. Indeed, NO is an important vasodilator acting on vascular smooth muscle and is able to inhibit platelet activation. NO reacts with superoxide anion (O2(−•)) to form peroxynitrite (ONOO(−)), a nitrosating agent capable of inducing oxidative/nitrative signaling and stress both at cardiovascular, platelet, and plasma levels. CO reduces platelet reactivity, therefore it is an anticoagulant, but it also has some cardioprotective and procoagulant properties. This review article summarizes current knowledge on the platelets and roles of gas mediators (NO, and CO) in cardioprotection. In particular, we aim to examine the link and interactions between platelets, NO, and CO and cardioprotective pathways.
Macroporous Epoxy-Based Monoliths Functionalized with Anti-CD63 Nanobodies for Effective Isolation of Extracellular Vesicles in Urine
Authors: Neumair Julia , D’Ercole Claudia , De March Matteo , Elsner Martin , Seidel Michael , de Marco Ario
Published: March 2023

Extracellular vesicles (EVs) have enormous potential for the implementation of liquid biopsy and as effective drug delivery means, but the fulfilment of these expectations requires overcoming at least two bottlenecks relative to their purification, namely the finalization of reliable and affordable protocols for: (i) EV sub-population selective isolation and (ii) the scalability of their production/isolation from complex biological fluids. In this work, we demonstrated that these objectives can be achieved by a conceptually new affinity chromatography platform composed of a macroporous epoxy monolith matrix functionalized with anti-CD63 nanobodies with afflux of samples and buffers regulated through a pump. Such a system successfully captured and released integral EVs from urine samples and showed negligible unspecific binding for circulating proteins. Additionally, size discrimination of eluted EVs was achieved by different elution approaches (competitive versus pH-dependent). The physical characteristics of monolith material and the inexpensive production of recombinant nanobodies make scaling-up the capture unit feasible and affordable. Additionally, the availability of nanobodies for further specific EV biomarkers will allow for the preparation of monolithic affinity filters selective for different EV subclasses.