bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision and Accuracy of Pulse Propagation Velocity Measurement in Power Cables
Authors: Kiitam Ivar , Shafiq Muhammad , Choudhary Maninder , Parker Martin , Palu Ivo , Taklaja Paul
Published: March 2023

The partial discharge (PD) measurement is an important method used in determining the condition of medium- and high-voltage cable insulation. Considering the propagation velocity of PD signals in power cables is necessary for determining the location of PD defects. However, the determination of velocity is not straightforward due to propagation-related attenuation and dispersion, which distorts the PD pulse waveform. This introduces a degree of uncertainty into the pulse velocity as well as the PD source locations determined based on that velocity, which is usually considered to be of constant value in PD analysis. This paper investigates the accuracy of the pulse propagation velocity measurement in power cables. Tests were performed on a medium voltage power cable in a laboratory setting using two sets of PD-specific measurement equipment: a high-frequency current transformer (HFCT) and an IEC 60270-compliant conventional measurement system. The propagation velocities and their statistical variability were determined using both devices to assess the uncertainty of the propagation velocity measurement. The results indicate that the measured velocity is slightly higher in the case of the HFCT and that the 50% peak threshold value should be used rather than the peak value of PD sensor response waveforms to increase the precision of velocity measurements.
Numerical and Parametric Study on Open-Type Ceiling Radiant Cooling Panel with Curved and Segmented Structure
Authors: Ye Minzhi , Serageldin Ahmed A. , Nagano Katsunori
Published: March 2023

A suspended open-type ceiling radiant cooling panel (CRCP) has been proposed recently. The main challenge is improving its cooling performance to overcome limitations for extensive use. Therefore, this study aims to optimize the design of CRCPs with curved and segmented structure to enhance heat transfer. A three-dimensional CFD model was developed to investigate the cooling capacity and heat transfer coefficient of the CRCPs installed inside a single enclosed room. Panel structure was determined based on four dependent parameters: the panel curvature width (L, m), the panel curvature radius (r, m), the void distance (d, m) between each panel or panel segment, and the panel coverage area (Ac, m2). The panel surface area (As, m2) and the ratio of panel curvature width to radius (L/r) were also examined. A total of 35 designs were compared under 7 different cooling load conditions, and 245 cases were carried out. The results show that the nominal cooling capacity and heat transfer coefficient rise with increasing curvature radius and decreasing curvature width. The void distance plays the most crucial role in influencing cooling performance. It is possible to simultaneously improve cooling performance, achieve uniform temperature distribution, and reduce the number of panels through structure optimization.
Research on Object Detection of Overhead Transmission Lines Based on Optimized YOLOv5s
Authors: Gu Juping , Hu Junjie , Jiang Ling , Wang Zixu , Zhang Xinsong , Xu Yiming , Zhu Jianhong , Fang Lurui
Published: March 2023

Object detection of overhead transmission lines is a solution for promoting inspection efficiency for power companies. However, aerial images contain many complex backgrounds and small objects, and traditional algorithms are incompetent in the identification of details of power transmission lines accurately. To address this problem, this paper develops an object detection method based on optimized You Only Look Once v5-small (YOLOv5s). This method is designed to be engineering-friendly, with the objective of maximal detection accuracy and computation simplicity. Firstly, to improve the detecting accuracy of small objects, a larger scale detection layer and jump connections are added to the network. Secondly, a self-attention mechanism is adopted to merge the feature relationships between spatial and channel dimensions, which could suppress the interference of complex backgrounds and boost the salience of objects. In addition, a small object enhanced Complete Intersection over Union (CIoU) is put forward as the loss function of the bounding box regression. This loss function could increase the derived loss for small objects automatically, thereby improving the detection of small objects. Furthermore, based on the scaling factors of batch-normalization layers, a pruning method is adopted to reduce the parameters and achieve a lightweight method. Finally, case studies are fulfilled by comparing the proposed method with classic YOLOv5s, which demonstrate that the detection accuracy is increased by 4%, the model size is reduced by 58%, and the detection speed is raised by 3.3%.
Numerical Study of the Erosion Distribution of Sulfur-Containing Particulate Gas in 90-Degree Gathering Elbow
Authors: Zhu Runhua , Ren Hongming , Fang Qiang , Ren Yang , Jiang Dong , Liu Yongliang , Liu Shudong , Li Chengyong , Tang Danni
Published: March 2023

The phenomenon of pipeline erosion dominated by sulfur particles has become a key research target for sulfur-containing gas-gathering pipelines. Gas-solid two-phase flow of sulfur-containing gases is simulated with a coupled CFD-DPM model in this paper. The Realizable k-ε turbulence model was used to determine the changes in the complex flow field and the Euler-Lagrange method was used to describe the specific trajectory of sulfur particles in the complex flow field. The main erosion trace distribution and the effect of secondary flow effects at the elbow were analyzed and the erosion distribution pattern was investigated for different curvature ratios, particle sizes, and pipe diameters. The results show that the formation of erosion along the tip of the V-shaped erosion trace on the outlet sidewall of the elbow may be related to secondary flow effects. The increase of the curvature ratio RD reduces the erosion intensity of the maximum erosion area, but subsequent increase will result in new secondary erosion trace near the outlet of the elbow and reach the maximum when RD = 8. Variations in particle size will have a significant effect on the extent of the erosion distribution, causing the main erosion distribution of the elbow to vary between 48.2° and 84.2°, while variations in pipeline diameter will have a lesser effect. The Stokes number can also be reduced by controlling the variation in particle size and pipe diameter to alter the force profile on the particles and reduce the erosion effect.
Impact of Matrix Species and Mass Spectrometry on Matrix Effects in Multi-Residue Pesticide Analysis Based on QuEChERS-LC-MS
Authors: Zhang Shuang , He Zhiyong , Zeng Maomao , Chen Jie
Published: March 2023

With the popularity of multi-residue pesticide analysis based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) cleanup and liquid chromatography–mass spectrometry (LC-MS), matching optimal matrix-matched calibration protocols and LC-MS conditions to reduce matrix effects (MEs) has become a crucial task for analysts in their routines. However, dozens to hundreds of pesticide analytes in a single run generate increasingly multi-dimensional ME data, requiring appropriate tools to handle these data sets. Therefore, we established an ME analysis strategy by drawing on analytical thinking and tools from metabolomics analysis. Using this, matrix species-induced and mass spectrometry-induced systematic ME variations were distinguished, and pesticides contributed to the variations were scanned out. A simultaneous weakening of MEs on 24 pesticides in 32 different matrices was achieved using the time-of-flight-mass spectrometry (TOF-MS) scan under the information-dependent acquisition (IDA) mode of high-resolution mass spectrometry (HR-MS), compared to multiple reaction monitoring (MRM) scanning by tandem mass spectrometry (MS/MS). Bay leaf, ginger, rosemary, Amomum tsao-ko, Sichuan pepper, cilantro, Houttuynia cordata, and garlic sprout showed enhanced signal suppression in the MRM scan for 105 differential MRM transitions for 42 pesticides and in IDA mode for 33 pesticides, respectively. This study revealed the interference of matrix species and mass spectrometry on MEs and provided a novel strategy for ME analysis.
Optimization of Extrusion Treatments, Quality Assessments, and Kinetics Degradation of Enzyme Activities during Storage of Rice Bran
Authors: Rashid Muhammad Tayyab , Liu Kunlun , Han Simeng , Jatoi Mushtaq Ahmed , Sarpong Frederick
Published: March 2023

Over the years, extrusion has been a multi-step thermal technique that has proven to be the most effective process to stabilize rice bran (RB). This study aimed to investigate the effects of extrusion treatment and temperature (15, 25, and 40 °C) on the storage stability, lipid oxidation, peroxidase, and peroxide values, free fatty acids, fatty acid composition, and protein variations of RB over 60 days. The study offers novel insights into the changes in RB’s protein and amino acid compositions during extrusion and storage, which has not been extensively explored in prior research. After extrusion processing, peroxidase activity (POD) and lipase activity (LPS) were significantly reduced. However, peroxide value (PV), free fatty acids (FFA), and malondialdehyde content (MDA) observed a significantly increased by 0.64 mEqO2/kg, 8.3 mg/100 g, and 0.0005 μmol/L respectively. The storage stability of RB after extrusion shows that the POD, LPS, FFA, PV, and MDA were positively correlated with storage duration and temperature. The oleic acid/linoleic acid ratio in processed RB by extrusion had no significant changes during storage. The total and essential/non-essential amino acid ratios showed a downward trend of 5.26% and 8.76%, respectively. The first-order kinetics was the best-fitting model to describe the enzymatic inactivation and degradation of extruded RB during storage. The extrusion treatment did not affect the crude protein and the essential subunits of protein. Overall, the optimized extrusion procedure exhibited promising results in stabilizing the RB.
Study of the Possibility of Using Sol–Gel Technology to Obtain Magnetic Nanoparticles Based on Transition Metal Ferrites
Authors: Shabelskaya Nina , Sulima Sergey , Sulima Elena , Medennikov Oleg , Kulikova Marina , Kolesnikova Tatyana , Sushkova Svetlana
Published: March 2023

The article presents results for the magnetic nanoparticles sol–gel method synthesis of cobalt (II) ferrite and organic–inorganic composite materials based on it. The obtained materials were characterized using X-ray phase analysis, scanning and transmission electron microscopy, Scherrer, Brunauer–Emmett–Teller (BET) methods. A composite materials formation mechanism is proposed, which includes a gelation stage where transition element cation chelate complexes react with citric acid and subsequently decompose under heating. The fundamental possibility of obtaining an organo–inorganic composite material based on cobalt (II) ferrite and an organic carrier using the presented method has been proved. Composite materials formation is established to lead to a significant (5–9 times) increase in the sample surface area. Materials with a developed surface are formed: the surface area measured by the BET method is 83–143 m2/g. The resulting composite materials have sufficient magnetic properties to be mobile in a magnetic field. Consequently, wide possibilities for polyfunctional materials synthesis open up for various applications in medicine.
A Scoping Review with Bibliometric Analysis of Para-Rowing: State of the Art and Future Directions
Authors: Puce Luca , Biz Carlo , Trompetto Carlo , Marinelli Lucio , Currà Antonio , Cavaggioni Luca , Formica Matteo , Vecchi Vittorio , Cerchiaro Maria Chiara , Trabelsi Khaled , Bragazzi Nicola Luigi , Ruggieri Pietro
Published: March 2023

Para-rowing is a format of rowing practiced by people with different types of disabilities, thanks to adapted equipment set-ups and regulations. Para-rowing made its debut recently at the 2008 Paralympic Games. According to the mandate of the “International Paralympic Committee”, para-rowers should be enabled to pursue sporting excellence. Therefore, rigorous research is needed in terms of well-designed, high-quality studies. To the best of our knowledge, there are no systematic appraisals of the body of scholarly evidence in the field of para-rowing. As such, a scoping review enhanced by bibliometric analyses was carried out to provide a comprehensive synthesis of knowledge related to para-rowing for the perusal of practitioners and athletes. By mining eighteen major databases, 17 studies were retained in the present review. The included studies were found to focus on a range of aspects involving health, the etiology of injuries (n = 5), psychological and physiological responses (n = 5), performance, biomechanical analysis (n = 4), and new analytical approaches for kinematic assessments and predictions of mechanical outputs in para-rowers (n = 3). The scholarly community on para-rowing consists of 78 researchers, 16 (20.51%) of whom are highly interconnected. The most prolific author was Smoljanović T., from Croatia, with three items/documents. In total, 93.6% of scholars have authored one single document. Topological features indicated a highly fragmented and dispersed, poorly connected community characterized by a high number of clusters and a low strength of connections. In terms of publication years, the first scholarly article dates back to 2008, with four articles (23.5%) published in the current year, showing an increasing interest in this para-sports discipline. Finally, gaps in current research on para-rowing were identified in terms of overlooked topics, including sports nutrition, doping, and psychological aspects in para-rowers other than those with visual impairment.
Association between Secondhand Smoke and Allergic Diseases in Korean Adolescents: Cross-Sectional Analysis of the 2019 KYRBS
Authors: Choi Mi-Jin , Park Jong , Kim So-Yeong
Published: March 2023

This study aimed to determine whether secondhand smoking (SHS) in adolescents is associated with allergic diseases. Data from the 2019 Korea Youth Risk Behavior Survey were used (N = 37,848 Korean adolescents: 19,114 boys and 18,734 girls). This study assessed SHS exposure using questionnaire data, which included information, such as exposure to SHS and allergic diseases. Multiple logistic regression analysis was used to estimate the association between exposure to SHS and allergic diseases. The results showed that exposure to SHS in schools and public places, exposure for 1–3 days (OR = 1.158, 95% CI, 1.077–1.246), 4–6 days (OR = 1.308, 95% CI, 1.190–1.438), and everyday (OR = 1.306, 95% CI, 1.187–1.437), and exposure in one, two, or three places were significantly associated with allergic diseases (one OR = 1.226, 95% CI, 1.169–1.128, two OR = 1.289, 95% CI, 1.222–1.360 and three OR = 1.282, 95% CI, 1.177–1.395). The present results show that exposure to SHS occurs in various places and at various frequencies, and it is associated with allergic diseases in Korean adolescents.
A Comprehensive Investigation into the Crystallology, Molecule, and Quantum Chemistry Properties of Two New Hydrous Long-Chain Dibasic Ammonium Salts CnH2n+8N2O6 (n = 35 and 37)
Authors: Ke Zengbo , Fan Xinhui , Di Youying , Chen Fengying , Han Xi , Yang Ke , Li Bing
Published: March 2023

Through the salification reaction of carboxylation, successful attachment of the long-chain alkanoic acid to the two ends of 1,3-propanediamine was realized, which enabled the doubling of the long-chain alkanoic acid carbon chain. Hydrous 1,3-propanediamine dihexadecanoate (abbreviated as 3C16) and 1,3-propanediamine diheptadecanoate (abbreviated as 3C17) were synthesized afterward, and their crystal structures were characterized by the X-ray single crystal diffraction technique. By analyzing their molecular and crystal structure, their composition, spatial structure, and coordination mode were determined. Two water molecules played important roles in stabilizing the framework of both compounds. Hirshfeld surface analysis revealed the intermolecular interactions between the two molecules. The 3D energy framework map presented the intermolecular interactions more intuitively and digitally, in which dispersion energy plays a dominant role. DFT calculations were performed to analyze the frontier molecular orbitals (HOMO–LUMO). The energy difference between the HOMO–LUMO is 0.2858 eV and 0.2855 eV for 3C16 and 3C17, respectively. DOS diagrams further confirmed the distribution of the frontier molecular orbitals of 3C16 and 3C17. The charge distributions in the compounds were visualized using a molecular electrostatic potential (ESP) surface. ESP maps indicated that the electrophilic sites are localized around the oxygen atom. The crystallographic data and parameters of quantum chemical calculation in this paper will provide data and theoretical support for the development and application of such materials.
Generation of a Triple-Shuttling Vector and the Application in Plant Plus-Strand RNA Virus Infectious cDNA Clone Construction
Authors: Feng Chenwei , Guo Xiao , Gu Tianxiao , Hua Yanhong , Zhuang Xinjian , Zhang Kun
Published: March 2023

Infectious cloning of plant viruses is a powerful tool for studying the reverse genetic manipulation of viral genes in virus–host plant interactions, contributing to a deeper understanding of the life history and pathogenesis of viruses. Yet, most of the infectious clones of RNA virus constructed in E. coli are unstable and toxic. Therefore, we modified the binary vector pCass4-Rz and constructed the ternary shuttle vector pCA4Y. The pCA4Y vector has a higher copy number in the E. coli than the conventional pCB301 vector, can obtain a high concentration of plasmid, and is economical and practical, so it is suitable for the construction of plant virus infectious clones in basic laboratories. The constructed vector can be directly extracted from yeast and transformed into Agrobacterium tumefaciens to avoid toxicity in E. coli. Taking advantage of the pCA4Y vector, we established a detailed large and multiple DNA HR-based cloning method in yeast using endogenous recombinase. We successfully constructed the Agrobacterium-based infectious cDNA clone of ReMV. This study provides a new choice for the construction of infectious viral clones.
Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea
Authors: Meliante Piero Giuseppe , Zoccali Federica , Cascone Francesca , Di Stefano Vanessa , Greco Antonio , de Vincentiis Marco , Petrella Carla , Fiore Marco , Minni Antonio , Barbato Christian
Published: March 2023

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions.
Preparation and Characterization of Poly(vinyl Acetate-co-2-hydroxyethyl Methacrylate) and In Vitro Application as Contact Lens for Acyclovir Delivery
Authors: Alqahtani Saad Mohammed , Al Khulaifi Rana Salem , Alassaf Mohammed , Saeed Waseem Sharaf , Bedja Idriss , Aldarwesh Amal , Aljubailah Abeer , Semlali Abdelhabib , Aouak Taieb
Published: March 2023

A series of poly(vinyl acetate-co-2-hydroxyethylmethacrylate)/acyclovir drug carrier systems (HEMAVAC) containing different acyclovir contents was prepared through bulk free radical polymerization of 2-hydroxyethyl methacrylate with vinyl acetate (VAc) in presence of acyclovir (ACVR) as the drug using a LED lamp in presence of camphorquinone as the photoinitiator. The structure of the drug carrier system was confirmed by FTIR and 1HNMR analysis, and the uniform dispersion of the drug particles in the carrier was proved by DSC and XRD analysis. The study of the physico-chemical properties of the prepared materials, such as the transparency, swelling capacity, wettability and optical refraction, was carried out by UV–visible analysis, a swelling test and measurement of the contact angle and the refractive index, respectively. The elastic modulus and the yield strength of the wet prepared materials were examined by dynamic mechanical analysis. The cytotoxicity of the prepared materials and cell adhesion on these systems were studied by LDH assay and the MTT test, respectively. The results obtained were comparable to those of standard lenses with a transparency of 76.90–89.51%, a swelling capacity of 42.23–81.80% by weight, a wettability of 75.95–89.04°, a refractive index of 1.4301–1.4526 and a modulus of elasticity of 0.67–1.50 MPa, depending on the ACVR content. It was also shown that these materials exhibit no significant cytotoxicity; on the other hand, they show significant cell adhesion. The in vitro dynamic release of ACVR in water revealed that the HEMAVAC drug carrier can consistently deliver uniformly adequate amounts of ACVR (5.04–36 wt%) over a long period (7 days) in two steps. It was also found that the solubility of ACVR obtained from the release process was improved by 1.4 times that obtained by direct solubility of the drug in powder form at the same temperature.
RPflex: A Coarse-Grained Network Model for RNA Pocket Flexibility Study
Authors: Zhuo Chen , Zeng Chengwei , Yang Rui , Liu Haoquan , Zhao Yunjie
Published: March 2023

RNA regulates various biological processes, such as gene regulation, RNA splicing, and intracellular signal transduction. RNA’s conformational dynamics play crucial roles in performing its diverse functions. Thus, it is essential to explore the flexibility characteristics of RNA, especially pocket flexibility. Here, we propose a computational approach, RPflex, to analyze pocket flexibility using the coarse-grained network model. We first clustered 3154 pockets into 297 groups by similarity calculation based on the coarse-grained lattice model. Then, we introduced the flexibility score to quantify the flexibility by global pocket features. The results show strong correlations between the flexibility scores and root-mean-square fluctuation (RMSF) values, with Pearson correlation coefficients of 0.60, 0.76, and 0.53 in Testing Sets I–III. Considering both flexibility score and network calculations, the Pearson correlation coefficient was increased to 0.71 in flexible pockets on Testing Set IV. The network calculations reveal that the long-range interaction changes contributed most to flexibility. In addition, the hydrogen bonds in the base–base interactions greatly stabilize the RNA structure, while backbone interactions determine RNA folding. The computational analysis of pocket flexibility could facilitate RNA engineering for biological or medical applications.
Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells
Authors: Leow Damien Meng-Kiat , Cheah Irwin Kee-Mun , Fong Zachary Wei-Jie , Halliwell Barry , Ong Wei-Yi
Published: March 2023

Recent findings have suggested that the natural compound ergothioneine (ET), which is synthesised by certain fungi and bacteria, has considerable cytoprotective potential. We previously demonstrated the anti-inflammatory effects of ET on 7-ketocholesterol (7KC)-induced endothelial injury in human blood-brain barrier endothelial cells (hCMEC/D3). 7KC is an oxidised form of cholesterol present in atheromatous plaques and the sera of patients with hypercholesterolaemia and diabetes mellitus. The aim of this study was to elucidate the protective effect of ET on 7KC-induced mitochondrial damage. Exposure of human brain endothelial cells to 7KC led to a loss of cell viability, together with an increase in intracellular free calcium levels, increased cellular and mitochondrial reactive oxygen species, a decrease in mitochondrial membrane potential, reductions in ATP levels, and increases in mRNA expression of TFAM, Nrf2, IL-1β, IL-6 and IL-8. These effects were significantly decreased by ET. Protective effects of ET were diminished when endothelial cells were coincubated with verapamil hydrochloride (VHCL), a nonspecific inhibitor of the ET transporter OCTN1 (SLC22A4). This outcome demonstrates that ET-mediated protection against 7KC-induced mitochondrial damage occurred intracellularly and not through direct interaction with 7KC. OCTN1 mRNA expression itself was significantly increased in endothelial cells after 7KC treatment, consistent with the notion that stress and injury may increase ET uptake. Our results indicate that ET can protect against 7KC-induced mitochondrial injury in brain endothelial cells.
Role of Adhesion G Protein-Coupled Receptors in Immune Dysfunction and Disorder
Authors: Tseng Wen-Yi , Stacey Martin , Lin Hsi-Hsien
Published: March 2023

Disorders of the immune system, including immunodeficiency, immuno-malignancy, and (auto)inflammatory, autoimmune, and allergic diseases, have a great impact on a host’s health. Cellular communication mediated through cell surface receptors, among different cell types and between cell and microenvironment, plays a critical role in immune responses. Selective members of the adhesion G protein-coupled receptor (aGPCR) family are expressed differentially in diverse immune cell types and have been implicated recently in unique immune dysfunctions and disorders in part due to their dual cell adhesion and signaling roles. Here, we discuss the molecular and functional characteristics of distinctive immune aGPCRs and their physiopathological roles in the immune system.
Interaction of Laurusides 1 and 2 with the 3C-like Protease (Mpro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study
Authors: Autiero Ida , Roviello Giovanni N.
Published: March 2023

Laurus nobilis (bay laurel) is a natural source of biological compounds, and some of its extracts and phytocompounds are also endowed with antiviral activity toward the family of the severe acute respiratory syndrome (SARS)-associated β-coronaviruses. Some glycosidic laurel compounds such as laurusides were proposed as inhibitors of important protein targets of SARS-CoV-2, which clearly recalls their potential as anti-COVID-19 drugs. Due to the frequent genomic variations of the β-coronaviruses and the consequent importance of evaluating a new drug candidate with respect to the variants of the target β-coronavirus, we decided to investigate at an atomistic level the molecular interactions of the potential laurel-derived drugs laurusides 1 and 2 (L01 and L02, respectively) toward a well-conserved and crucial target, the 3C-like protease (Mpro), using the enzymes of both the wild-type of SARS-CoV-2 and of the more recent Omicron variant. Thus, we performed molecular dynamic (MD) simulations of laurusides—SARS-CoV-2 protease complexes to deepen the knowledge on the stability of the interaction and compare the effects of the targeting among the two genomic variants. We found that the Omicron mutation does not significantly impact the lauruside binding and that L02 connects more stably with respect to L01 in the complexes from both variants, even though both compounds prevalently interact within the same binding pocket. Although purely in silico, the current study highlights the potential role of bay laurel phytocompounds in the antiviral and specifically anti-coronavirus research and shows their potential binding toward Mpro, corroborating the important commitment of bay laurel as functional food and disclosing novel scenarios of lauruside-based antiviral therapies.
Combining Three Tyrosine Kinase Inhibitors: Drug Monitoring Is the Key
Authors: Thomas Quentin Dominique , Firmin Nelly , Mbatchi Litaty , Evrard Alexandre , Quantin Xavier , Leenhardt Fanny
Published: March 2023

A combination of tyrosine kinase inhibitors (TKIs) is likely to be a therapeutic option for numerous oncological situations due to high frequency of oncogenic addiction and progress in precision oncology. Non-small cell lung cancer (NSCLC) represents a subtype of tumors for which oncogenic drivers are frequently involved. To the best of our knowledge, we report the first case of a patient treated with three different TKIs. Osimertinib and crizotinib were administered concurrently for an epidermal growth factor receptor (EGFR)-mutated NSCLC developing a MET amplification as a resistance mechanism to osimertinib. Simultaneously, imatinib was administered for a metastatic gastrointestinal stromal tumor. The progression-free survival was 7 months for both tumors with this tritherapy. The use of therapeutic drug monitoring to assess plasma concentrations of each TKI was a powerful tool to manage the toxicity profile of this combination (creatine phosphokinase elevation) while preserving an optimal exposure to each TKI and treatment efficacy. We observed an imatinib over-exposition related to crizotinib introduction, probably explained by drug–drug interaction mediated by crizotinib enzymatic inhibition on cytochrome P-450 3A4. Posology adjustment due to therapeutic drug monitoring was probably involved in the good survival outcome of the patient. This tool should be used more routinely for patients treated by TKIs to prevent co-treatment interactions and, in particular, for patients receiving TKI combinations to obtain optimal therapeutic exposure and efficacy while reducing possible side-effects.
Current and Future Therapeutical Options in Alport Syndrome
Authors: Reiterová Jana , Tesař Vladimír
Published: March 2023

Alport syndrome (AS) is a hereditary kidney disease caused by pathogenic variants in COL4A3 and COL4A4 genes with autosomal recessive or autosomal dominant transmission or in the COL4A5 gene with X-linked inheritance. Digenic inheritance was also described. Clinically it is associated with microscopic hematuria, followed by proteinuria and chronic renal insufficiency with end-stage renal disease in young adults. Nowadays, there is no curative treatment available. The inhibitors of RAS (renin-angiotensin system) since childhood slow the progression of the disease. Sodium-glucose cotransporter-2 inhibitors seem to be promising drugs from DAPA-CKD (dapagliflozin–chronic kidney disease) study, but only a limited number of patients with Alport syndrome was included. Endothelin type A receptor and angiotensin II type 1 receptor combined inhibitors, and lipid-lowering agents are used in ongoing studies in patients with AS and focal segmental glomerulosclerosis (FSGS). Hydroxychloroquine in AS is studied in a clinical trial in China. Molecular genetic diagnosis of AS is crucial not only for prognosis prediction but also for future therapeutic options. Different types of mutations will require various types of gene, RNA, or protein therapy to improve the function, the of final protein product.
Progress on the Effects of Microplastics on Aquatic Crustaceans: A Review
Authors: Zhang Siyi , Wu Haodi , Hou Jing
Published: March 2023

It is impossible to overlook the effects of microplastics on aquatic life as they continuously accumulate in aquatic environments. Aquatic crustaceans, as both predator and prey, play an important role in the food web and energy transmission. It is of great practical significance to pay attention to the toxic effects of microplastics on aquatic crustaceans. This review finds that most studies have shown that microplastics negatively affect the life history, behaviors and physiological functions of aquatic crustaceans under experimental conditions. The effects of microplastics of different sizes, shapes or types on aquatic crustaceans are different. Generally, smaller microplastics have more negative effects on aquatic crustaceans. Irregular microplastics have more negative effects on aquatic crustaceans than regular microplastics. When microplastics co-exist with other contaminants, they have a greater negative impact on aquatic crustaceans than single contaminants. This review contributes to rapidly understanding the effects of microplastics on aquatic crustaceans, providing a basic framework for the ecological threat of microplastics to aquatic crustaceans.
Acute ACAT1/SOAT1 Blockade Increases MAM Cholesterol and Strengthens ER-Mitochondria Connectivity
Authors: Harned Taylor C. , Stan Radu V. , Cao Ze , Chakrabarti Rajarshi , Higgs Henry N. , Chang Catherine C. Y. , Chang Ta Yuan
Published: March 2023

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer’s disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain unknown. Here, using biochemical fractionation techniques, we observe cholesterol accumulation at the MAM which leads to ACAT1/SOAT1 enrichment in this domain. MAM proteomics data suggests that ACAT1/SOAT1 inhibition strengthens the ER-mitochondria connection. Confocal and electron microscopy confirms that ACAT1/SOAT1 inhibition increases the number of ER-mitochondria contact sites and strengthens this connection by shortening the distance between these two organelles. This work demonstrates how directly manipulating local cholesterol levels at the MAM can alter inter-organellar contact sites and suggests that cholesterol buildup at the MAM is the impetus behind the therapeutic benefits of ACAT1/SOAT1 inhibition.
A Comprehensive Ab Initio Study of Halogenated A···U and G···C Base Pair Geometries and Energies
Authors: Gomila Rosa M. , Frontera Antonio , Bauzá Antonio
Published: March 2023

Unraveling the binding preferences involved in the formation of a supramolecular complex is key to properly understand molecular recognition and aggregation phenomena, which are of pivotal importance to biology. The halogenation of nucleic acids has been routinely carried out for decades to assist in their X-ray diffraction analysis. The incorporation of a halogen atom on a DNA/RNA base not only affected its electronic distribution, but also expanded the noncovalent interactions toolbox beyond the classical hydrogen bond (HB) by incorporating the halogen bond (HalB). In this regard, an inspection of the Protein Data Bank (PDB) revealed 187 structures involving halogenated nucleic acids (either unbound or bound to a protein) where at least 1 base pair (BP) exhibited halogenation. Herein, we were interested in disclosing the strength and binding preferences of halogenated A···U and G···C BPs, which are predominant in halogenated nucleic acids. To achieve that, computations at the RI-MP2/def2-TZVP level of theory together with state of the art theoretical modeling tools (including the computation of molecular electrostatic potential (MEP) surfaces, the quantum theory of “Atoms in Molecules” (QTAIM) and the non-covalent interactions plot (NCIplot) analyses) allowed for the characterization of the HB and HalB complexes studied herein.
Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients
Authors: Höhn Lukas , Hußler Wilhelm , Richter Anni , Smalla Karl-Heinz , Birkl-Toeglhofer Anna-Maria , Birkl Christoph , Vielhaber Stefan , Leber Stefan L. , Gundelfinger Eckart D. , Haybaeck Johannes , Schreiber Stefanie , Seidenbecher Constanze I.
Published: March 2023

The brain’s extracellular matrix (ECM) is assumed to undergo rearrangements in Alzheimer’s disease (AD). Here, we investigated changes of key components of the hyaluronan-based ECM in independent samples of post-mortem brains (N = 19), cerebrospinal fluids (CSF; N = 70), and RNAseq data (N = 107; from The Aging, Dementia and TBI Study) of AD patients and non-demented controls. Group comparisons and correlation analyses of major ECM components in soluble and synaptosomal fractions from frontal, temporal cortex, and hippocampus of control, low-grade, and high-grade AD brains revealed a reduction in brevican in temporal cortex soluble and frontal cortex synaptosomal fractions in AD. In contrast, neurocan, aggrecan and the link protein HAPLN1 were up-regulated in soluble cortical fractions. In comparison, RNAseq data showed no correlation between aggrecan and brevican expression levels and Braak or CERAD stages, but for hippocampal expression of HAPLN1, neurocan and the brevican-interaction partner tenascin-R negative correlations with Braak stages were detected. CSF levels of brevican and neurocan in patients positively correlated with age, total tau, p-Tau, neurofilament-L and Aβ1-40. Negative correlations were detected with the Aβ ratio and the IgG index. Altogether, our study reveals spatially segregated molecular rearrangements of the ECM in AD brains at RNA or protein levels, which may contribute to the pathogenic process.
The Essential Oil of Citrus lumia Risso and Poit. ‘Pyriformis’ Shows Promising Antioxidant, Anti-Inflammatory, and Neuromodulatory Effects
Authors: Smeriglio Antonella , Alloisio Susanna , Barbieri Raffaella , Ingegneri Mariarosaria , Malaspina Paola , Burlando Bruno , Cornara Laura , Trombetta Domenico
Published: March 2023

Citrus lumia Risso and Poit. ‘Pyriformis’ are horticultural varieties of Citrus lumia Risso. The fruit is very fragrant and pear-shaped, with a bitter juice, a floral flavor, and a very thick rind. The flavedo shows enlarged (0.74 × 1.16 mm), spherical and ellipsoidal secretory cavities containing the essential oil (EO), visible using light microscopy, and more evident using scanning electron microscopy. The GC-FID and GC-MS analyses of the EO showed a phytochemical profile characterized by the predominance of D-limonene (93.67%). The EO showed interesting antioxidant and anti-inflammatory activities (IC50 0.07–2.06 mg/mL), as evaluated by the in vitro cell-free enzymatic and non-enzymatic assays. To evaluate the effect on the neuronal functional activity, the embryonic cortical neuronal networks grown on multi-electrode array chips were exposed to non-cytotoxic concentrations of the EO (5–200 µg/mL). The spontaneous neuronal activity was recorded and the mean firing rate, mean burst rate, percentage of spikes in a burst, mean burst durations and inter-spike intervals within a burst parameter were calculated. The EO induced strong and concentration-dependent neuroinhibitory effects, with IC50 ranging between 11.4–31.1 µg/mL. Furthermore, it showed an acetylcholinesterase inhibitory activity (IC50 0.19 mg/mL), which is promising for controlling some of the key symptoms of neurodegenerative diseases such as memory and cognitive concerns.
Anticancer and Targeting Activity of Phytopharmaceutical Structural Analogs of a Natural Peptide from Trichoderma longibrachiatum and Related Peptide-Decorated Gold Nanoparticles
Authors: Moret Francesca , Menilli Luca , Milani Celeste , Di Cintio Giorgia , Dalla Torre Chiara , Amendola Vincenzo , De Zotti Marta
Published: March 2023

In the large field of bioactive peptides, peptaibols represent a unique class of compounds. They are membrane-active peptides, produced by fungi of the genus Trichoderma and known to elicit plant defenses. Among the short-length peptaibols, trichogin GA IV is nonhemolytic, proteolysis-resistant, antibacterial, and cytotoxic. Several trichogin analogs are endowed with potent activity against phytopathogens, thus representing a sustainable alternative to copper for plant protection. In this work, we tested the activity of trichogin analogs against a breast cancer cell line and a normal cell line of the same derivation. Lys-containing trichogins showed an IC50 below 12 µM, a peptide concentration not significantly affecting the viability of normal cells. Two analogs were found to be membrane-active but noncytotoxic. They were anchored to gold nanoparticles (GNPs) and further investigated for their ability to act as targeting agents. GNP uptake by cancer cells increased with peptide decoration, while it decreased in the corresponding normal epithelial cells. This work highlights the promising biological properties of peptaibol analogs in the field of cancer therapy either as cytotoxic molecules or as active targeting agents in drug delivery.
Quercetin Reprograms Immunometabolism of Macrophages via the SIRT1/PGC-1α Signaling Pathway to Ameliorate Lipopolysaccharide-Induced Oxidative Damage
Authors: Peng Jing , Yang Zhen , Li Hao , Hao Baocheng , Cui Dongan , Shang Ruofeng , Lv Yanan , Liu Yu , Pu Wanxia , Zhang Hongjuan , He Jiongjie , Wang Xuehong , Wang Shengyi
Published: March 2023

The redox system is closely related to changes in cellular metabolism. Regulating immune cell metabolism and preventing abnormal activation by adding antioxidants may become an effective treatment for oxidative stress and inflammation-related diseases. Quercetin is a naturally sourced flavonoid with anti-inflammatory and antioxidant activities. However, whether quercetin can inhibit LPS-induced oxidative stress in inflammatory macrophages by affecting immunometabolism has been rarely reported. Therefore, the present study combined cell biology and molecular biology methods to investigate the antioxidant effect and mechanism of quercetin in LPS-induced inflammatory macrophages at the RNA and protein levels. Firstly, quercetin was found to attenuate the effect of LPS on macrophage proliferation and reduce LPS-induced cell proliferation and pseudopodia formation by inhibiting cell differentiation, as measured by cell activity and proliferation. Subsequently, through the detection of intracellular reactive oxygen species (ROS) levels, mRNA expression of pro-inflammatory factors and antioxidant enzyme activity, it was found that quercetin can improve the antioxidant enzyme activity of inflammatory macrophages and inhibit their ROS production and overexpression of inflammatory factors. In addition, the results of mitochondrial morphology and mitochondrial function assays showed that quercetin could upregulate the mitochondrial membrane potential, ATP production and ATP synthase content decrease induced by LPS, and reverse the mitochondrial morphology damage to a certain extent. Finally, Western blotting analysis demonstrated that quercetin significantly upregulated the protein expressions of SIRT1 and PGC-1α, that were inhibited by LPS. And the inhibitory effects of quercetin on LPS-induced ROS production in macrophages and the protective effects on mitochondrial morphology and membrane potential were significantly decreased by the addition of SIRT1 inhibitors. These results suggested that quercetin reprograms the mitochondria metabolism of macrophages through the SIRT1/PGC-1α signaling pathway, thereby exerting its effect of alleviating LPS-induced oxidative stress damage.
The ENA1 Na+-ATPase Gene Is Regulated by the SPS Sensing Pathway and the Stp1/Stp2 Transcription Factors
Authors: Zekhnini Abdelghani , Albacar Marcel , Casamayor Antonio , Ariño Joaquín
Published: March 2023

The Saccharomyces cerevisiae ENA1 gene, encoding a Na+-ATPase, responds transcriptionally to the alkalinization of the medium by means of a network of signals that involves the Rim101, the Snf1 and PKA kinases, and the calcineurin/Crz1 pathways. We show here that the ENA1 promoter also contains a consensus sequence, located at nt −553/−544, for the Stp1/2 transcription factors, the downstream components of the amino acid sensing SPS pathway. Mutation of this sequence or deletion of either STP1 or STP2 decreases the activity of a reporter containing this region in response to alkalinization as well as to changes in the amino acid composition in the medium. Expression driven from the entire ENA1 promoter was affected with similar potency by the deletion of PTR3, SSY5, or simultaneous deletion of STP1 and STP2 when cells were exposed to alkaline pH or moderate salt stress. However, it was not altered by the deletion of SSY1, encoding the amino acid sensor. In fact, functional mapping of the ENA1 promoter reveals a region spanning from nt −742 to −577 that enhances transcription, specifically in the absence of Ssy1. We also found that the basal and alkaline pH-induced expression from the HXT2, TRX2, and, particularly, SIT1 promoters was notably decreased in an stp1 stp2 deletion mutant, whereas the PHO84 and PHO89 gene reporters were unaffected. Our findings add a further layer of complexity to the regulation of ENA1 and suggest that the SPS pathway might participate in the regulation of a subset of alkali-inducible genes.
The Ah Receptor from Toxicity to Therapeutics: Report from the 5th AHR Meeting at Penn State University, USA, June 2022
Authors: Perdew Gary H. , Esser Charlotte , Snyder Megan , Sherr David H. , van den Bogaard Ellen H. , McGovern Karen , Fernández-Salguero Pedro M. , Coumoul Xavier , Patterson Andrew D.
Published: March 2023

The aryl hydrocarbon receptor (AHR) is a sensor of low-molecular-weight molecule signals that originate from environmental exposures, the microbiome, and host metabolism. Building upon initial studies examining anthropogenic chemical exposures, the list of AHR ligands of microbial, diet, and host metabolism origin continues to grow and has provided important clues as to the function of this enigmatic receptor. The AHR has now been shown to be directly involved in numerous biochemical pathways that influence host homeostasis, chronic disease development, and responses to toxic insults. As this field of study has continued to grow, it has become apparent that the AHR is an important novel target for cancer, metabolic diseases, skin conditions, and autoimmune disease. This meeting attempted to cover the scope of basic and applied research being performed to address possible applications of our basic knowledge of this receptor on therapeutic outcomes.