bluuebunny/crossref_metadata_2025 huggingface dataset:
The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds
Authors: Roy Tithi , Boateng Samuel T. , Uddin Mohammad B. , Banang-Mbeumi Sergette , Yadav Rajesh K. , Bock Chelsea R. , Folahan Joy T. , Siwe-Noundou Xavier , Walker Anthony L. , King Judy A. , Buerger Claudia , Huang Shile , Chamcheu Jean Christopher
Published: June 2023

The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, and vitiligo, and is associated with poor treatment outcomes. Improved comprehension of the consequences of the dysregulated PI3K/Akt/mTOR pathway in patients with inflammatory dermatoses has resulted in the development of novel therapeutic approaches. Nonetheless, more studies are necessary to validate the regulatory role of this pathway and to create more effective preventive and treatment methods for a wide range of inflammatory skin diseases. Several studies have revealed that certain natural products and synthetic compounds can obstruct the expression/activity of PI3K/Akt/mTOR, underscoring their potential in managing common and persistent skin inflammatory disorders. This review summarizes recent advances in understanding the role of the activated PI3K/Akt/mTOR pathway and associated components in immune-mediated inflammatory dermatoses and discusses the potential of bioactive natural products, synthetic scaffolds, and biologic agents in their prevention and treatment. However, further research is necessary to validate the regulatory role of this pathway and develop more effective therapies for inflammatory skin disorders.
p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
Authors: Qi Xiao-Mei , Chen Guan
Published: June 2023

p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and in pathogenesis of cancer, diabetes, and Alzheimer’s disease, indicating its potential as a therapeutic target. p38γphosphorylates at least 19 substrates through which p38γ activity is further modified to regulate life-important cellular processes such as proliferation, differentiation, cell death, and transformation, thereby impacting biological outcomes of p38γ-driven pathogenesis. P38γ signaling is characterized by its unique reciprocal regulation with its specific phosphatase PTPH1 and by its direct binding to promoter DNAs, leading to transcriptional activation of targets including cancer-like stem cell drivers. This paper will review recent findings about p38γ inflammation and metabolic signaling in physiology and diseases. Moreover, we will discuss the progress in the development of p38γ-specific pharmacological inhibitors for therapeutic intervention in disease prevention and treatment by targeting the p38γ signaling network.
Generation of Hybrid Lead Halide CH3NH3PbI3-xClx Perovskite Crystals via Convective Self-Assembly
Authors: Petrovai Ioan , Todor-Boer Otto , Vulpoi Adriana , David Leontin , Botiz Ioan
Published: June 2023

In this study, we have employed a film deposition technique based on convective forces acting at the triple air–solution–substrate contact line to tune the rate of solvent evaporation and, thus, to exert control over the morphology of the resulting mixed lead halide perovskite CH3NH3PbI3-xClx films. By varying the speed of film deposition while processing at two different temperatures, perovskite crystals of various shapes and dimensions were generated upon the crystallization of the initial perovskite precursor ink. More precisely, longer than half a millimeter 3D needle-like perovskite crystals exhibiting sharp edges co-existing with large cross-like 3D perovskite crystals could only be obtained upon the slow deposition of films at a low sample processing temperature of 17 °C, i.e., under conditions of low solvent evaporation rate. On the contrary, the utilization of higher film deposition speeds and/or processing temperatures led to smaller 3D needle-like or quasi-2D rectangular perovskite crystals that often appeared interconnected and coalesced. Moreover, as it was revealed by the photoluminescence measurements, the emission intensity of perovskite crystals was larger and dominated by a shorter wavelength peak, as compared to the uncrystallized material that emitted much less light, but at a longer wavelength.
Did the COVID-19 Pandemic Disproportionately Affect the Most Socioeconomically Vulnerable Areas of Brazil?
Authors: dos Santos Alves Jonatha C. , Ribeiro Caíque J. N. , Lima Shirley V. M. A. , Morato Gabriel S. , Andrade Lucas A. , Santos Márcio B. , Lopes de Sousa Álvaro F. , Nogales Crespo Katya A. , Araújo Damião da C. , dos Santos Allan D.
Published: June 2023

Objective: To analyze the spatial pattern of the incidence of COVID-19 in association with social determinants of health (SDH) in the Northeast Region of Brazil during the first year of the pandemic. Methods: We conducted an ecological analytical study that included notifications made between 27 March 2020 and 27 March 2021. The data analysis used two global regression models: the ordinary least squares (OLS) and spatial lag model and the geographically weighted multiscale regression model (GWMSR). Results: We observed that the Gini index, illiteracy rate, percentages of people living below the poverty line, people in households who were vulnerable to poverty, and dependent elderly people are predictors of a higher incidence of COVID-19 in Northeast Brazil. Conclusions: Results of this study may contribute to generating new hypotheses for studies focusing on the syndemic process and for the formulation of intersectoral public policies targeting the population at greatest vulnerability to minimize the impact of the disease.
The Impact of the Intuitionistic Fuzzy Entropy-Based Weights on the Results of Subjective Quality of Life Measurement Using Intuitionistic Fuzzy Synthetic Measure
Authors: Roszkowska Ewa , Filipowicz-Chomko Marzena , Kusterka-Jefmańska Marta , Jefmański Bartłomiej
Published: June 2023

In this paper, an extended Intuitionistic Fuzzy Synthetic Measure (IFSM) with intuitionistic fuzzy (IF) entropy-based weights is presented. This method can be implemented in a ranking problem where the assessments of the criteria are expressed in the form of intuitionistic fuzzy values and the information about the importance criteria is unknown. One example of such a problem is measuring the subjective quality of life in cities. We join the debate on the determination of weights for the analysis of the quality of life problem using multi-criteria methods. To handle this problem, four different IF entropy-based weight methods were applied. Their performances were compared and analyzed based on the questionnaires from the survey concerning the quality of life in European cities. The studies show very similar weighting systems obtained by different IF entropy-based approaches, resulting in almost the same city rankings acquired through IFSM by using those weights. The differences in rankings obtained through the IFSM measure (and only by one position) concern the six cities included in the analysis. Our results support the assumption of the equal importance of the criteria in measuring this complex phenomenon.
Distributed Intelligence in Autonomous PEM Fuel Cell Control
Authors: Rubio Abel , Agila Wilton , González Leandro , Aviles-Cedeno Jonathan
Published: June 2023

A combination of perceptive and deliberative processes is necessary to ensure the efficient and autonomous control of proton exchange membrane fuel cells (PEMFCs) under optimal humidification conditions. These processes enable monitoring and control tasks across various application scenarios and operating conditions. Consequently, it becomes crucial to adjust parameter values corresponding to different states of the PEMFC during its operation. In this context, this work presents the design and development of an architecture for the control and management of a PEMFC with a maximum power output of 500 [W] based on intelligent agents operating under optimal conditions (membrane humidification). The proposed architecture integrates perception and action algorithms that leverage sensory and contextual information using heuristic algorithms. It adopts a hierarchical structure with distinct layers, each featuring varying time windows and levels of abstraction. Notably, this architecture demonstrates its effectiveness in achieving the desired energy efficiency objective, as evidenced by successful validation tests conducted with different electrical power values delivered by the fuel cell, encompassing three distinct operating states (dry, normal, and flooded). An exemplary application of this scheme is the dynamic control of the humidification of the polymeric membrane, which further highlights the capabilities of this architecture.
Compensation of the Current Imbalance of an Interleaved DC–DC Buck Converter, Sensorless Online Solution Based on Offline Fuzzy Identification and Post-Linearization
Authors: Baždarić Robert , Ćelić Jasmin , Vončina Danjel
Published: June 2023

This paper presents a new approach to compensate for the current imbalance of an interleaved DC–DC buck converter (IBC), in which the current sensors are not involved in the operation of the converter when it is connected to an invariable load. The current sensors are only used during the offline identification process that builds the universal fuzzy model of the converter’s steady states. Model building involves an upstream identification phase, followed by further dimensionality reduction of the model and error minimization. The method presented here discusses the mathematical complexity of the analytical modelling of hybrid systems and opposes it with a complexity-reduced identification by learning from data. An offline rendered model of the stable and steady states of the IBC is used as a mapping of the required inverter output current to n-fold asymmetric duty cycles, which are distributed among the IBC phases to allow arbitrarily accurate load sharing. The mapping is carried out in the mathematically normalized space of variables or in the physical sense RMS values, achieving the desired robustness in a noisy environment and stability. The final and canonical feedback control is built from the standard and optimized PI controller, which is compensated by the identified IBC model correction. The only measured feedback of the whole controller is the output voltage. Even when applied to the simulation model (physical MATLAB platform) of a two-phase IBC with the built-in system asymmetry, the presented methodology is also applicable to the n-phase IBC without loss of generality.
The Necessity and Feasibility of Hydrogen Storage for Large-Scale, Long-Term Energy Storage in the New Power System in China
Authors: Yan Huaguang , Zhang Wenda , Kang Jiandong , Yuan Tiejiang
Published: June 2023

In the process of building a new power system with new energy sources as the mainstay, wind power and photovoltaic energy enter the multiplication stage with randomness and uncertainty, and the foundation and support role of large-scale long-time energy storage is highlighted. Considering the advantages of hydrogen energy storage in large-scale, cross-seasonal and cross-regional aspects, the necessity, feasibility and economy of hydrogen energy participation in long-time energy storage under the new power system are discussed. Firstly, power supply and demand production simulations were carried out based on the characteristics of new energy generation in China. When the penetration of new energy sources in the new power system reaches 45%, long-term energy storage becomes an essential regulation tool. Secondly, by comparing the storage duration, storage scale and application scenarios of various energy storage technologies, it was determined that hydrogen storage is the most preferable choice to participate in large-scale and long-term energy storage. Three long-time hydrogen storage methods are screened out from numerous hydrogen storage technologies, including salt-cavern hydrogen storage, natural gas blending and solid-state hydrogen storage. Finally, by analyzing the development status and economy of the above three types of hydrogen storage technologies, and based on the geographical characteristics and resource endowment of China, it is pointed out that China will form a hydrogen storage system of “solid state hydrogen storage above ground and salt cavern storage underground” in the future.
An Alternative Method for Estimation of Stand-Level Biomass for Three Conifer Species in Northeast China
Authors: Xin Shidong , Shahzad Muhammad Khurram , Mahardika Surya Bagus , Wang Weifang , Jiang Lichun
Published: June 2023

Accurate large-scale biomass prediction is crucial for assessing forest carbon storage and dynamics. It can also inform sustainable forest management practices and climate change mitigation efforts. However, stand-level biomass models are still scarce worldwide. Our study aims to introduce the generalized additive model (GAM) as a convenient and efficient approach for forest biomass estimation. Data from 311 sample plots of three conifer species in northeastern China were used to evaluate the performance of the GAM model and compare it with traditional nonlinear seemingly unrelated regression (NSUR) models in predicting stand biomass, including total, aboveground, and component biomass. The results indicated that the goodness of fit of GAM was better than that of NSUR in two model systems. In the majority of cases, the scatter plots and prediction performance revealed that the stand total and component biomass models utilizing GAM outperformed those based on NSUR. Disregarding heteroscedasticity and requiring fewer statistical assumptions provide additional support for the replacement of NSUR-based models with GAM-based models. This study implies that the GAM approach has greater potential for developing a system of stand biomass models.
Experimental Study of Surface Roughness of Pine Wood by High-Speed Milling
Authors: Yang Chunmei , Ma Yaqiang , Liu Tongbin , Ding Yucheng , Qu Wen
Published: June 2023

The surface roughness of wood has a great influence on its performance and is a very important indicator in processing and manufacturing. In this paper, we use the central composite design experiment (CCD experiment) and artificial neural network (ANN) model to study the changing pattern of surface roughness during the high-speed milling process of pine wood. In the CCD experiments, the spindle speed, feed speed, and depth of cut are used as the influencing factors, and the surface roughness is used as the index to analyze the variation law and fit the surface roughness parameter equation. By measuring the chip size in each group in the CCD experiment, the ANN model is used to predict the surface roughness under this machining parameter by measuring the chip size in each test group. The experimental results showed that the mean error of the surface roughness prediction values in the CCD experiment (12.2%) was larger than that of the ANN model (7.8%), and the mean squared error (MSE) of the ANN model was 0.025, the mean absolute percentage error(MAPE) was 0.01, and the coefficient of determination R2 was 0.95. Compared with the CCD experiment, the ANN model had a higher prediction accuracy. The results of this paper can provide some guidance for the prediction of surface roughness during wood processing.
Extractable Compounds in a Birch Tree—Variations in Composition and Yield Potentials
Authors: Janzen Philipp , Zimmer Katrin , Appelt Jörn
Published: June 2023

Extractives from silver birch (Betula pendula) can play an important role in the future bioeconomy by delivering the feedstock, for instance, for antioxidative applications. It is, therefore, inevitable to gain knowledge of the distribution of extractive content and composition in the different tissues of the tree for estimating the potential volumes of valuable extractable compounds. This study examines the extractable compound distribution of different tree tissues such as outer and inner bark and wood, respectively, considering the original height of the stem and comparing the yields after Soxhlet and accelerated solvent extraction (ASE). Eleven parts of the model tree (seven stem discs and four branches) were separated into primary tissues and extracted with a ternary solvent system. The investigated extraction methods resulted in a comparable performance regarding yields and the composition of the extractives. The extractives were divided into single compounds such as betulin, lupeol, γ-sitosterol, and lupeone and substance groups such as carbohydrates, terpenes, aromatics, and other groups. The distribution of single substances and substance groups depends on the location and function of the examined tissues. Furthermore, the evidence for the correlation of a single substance’s location and original tree height is stronger for lupeol than for betulin. Primary betulin sources of the calculated betulin output are the outer bark of the stem and the branches. By using small branches, further potential for the extraction of betulin can be utilized. A model calculation of the betulin content in the current birch tree revealed a significant potential of 23 kg of betulin available as a valuable chemical resource after by-product utilization.
Molecular Characterization and Functional Analysis of GPCR Gene Bx-srh-1 in Pinewood Nematode (Bursaphelenchus xylophilus)
Authors: Cao Yefan , Wang Xizhuo , Wang Laifa , Wang Xiang , Yuan Yanzhi , Cheng Xiangchen , Lv Chunhe
Published: June 2023

Bursaphelenchus xylophilus, also known as the pine wood nematode (PWD), which causes pine wilt disease (PWD), is one of the most devastating diseases affecting pine forests globally. G protein-coupled receptors (GPCRs) are crucial in many biological processes and serve as privileged points of communication between cells and the surrounding environment. α-pinene has been found to play a crucial role in combating the infection, colonization, and early stages of pathogenesis caused by B. xylophilus. In this study, we investigated the molecular characteristics and biological functions of the GPCR gene Bx-srh-1 in B. xylophilus. Fluorescence in situ hybridization (FISH) was performed to determine the spatial expression patterns of Bx-srh-1 in B. xylophilus. The results indicated that Bx-srh-1 is expressed in the intestine and subcutaneous tissues of J2 and J3 juveniles and in the spicules of adult males and vulvae of adult females. RNA interference (RNAi) was used to analyze Bx-srh-1 gene function, and we examined the expression patterns of Bx-srh-1 in B. xylophilus under α-pinene stress. The RNA interference indicated that Bx-srh-1 was involved in the reproductive ability and pathogenicity of B. xylophilus; the expression levels of Bx-srh-1 significantly increased after the exposure to α-pinene for 12 h, and they peaked at 48 h. Silencing Bx-srh-1 may therefore lead to a reduction in B. xylophilus reproduction and pathogenicity. These results demonstrate that Bx-srh-1 is related to the feeding behavior, reproduction, pathogenicity, and resistance to α-pinene process of B. xylophilus.
Genotype–Environment Interaction and Horizontal and Vertical Distributions of Heartwood for Acacia melanoxylon R.Br
Authors: Zhang Ruping , Zeng Bingshan , Chen Tianxiao , Hu Bing
Published: June 2023

Acacia melanoxylon (blackwood) is a valuable wood with excellent-quality heartwood extensively utilized worldwide. The main aim of this study was to confirm the horizontal and vertical variation and provide estimated values of genetic gains and clonal repeatabilities for improving the breeding program of A. melanoxylon. Six blackwood clones at 10 years old were analyzed in Heyuan and Baise cities in China. Stem trunk analysis was conducted for sample trees to explore the differences between heartwood and sapwood. The heartwood radius (HR), heartwood area (HA), and heartwood volume (HV) in heartwood properties decreased as the tree height (H) in growth traits increased, and the HV = 1.2502 DBH (diameter at breast height)1.7009 model can accurately estimate the heartwood volume. Furthermore, G × E analysis showed that the heritabilities of the eleven indices, including DBH, DGH (diameter at ground height), H, HR, SW (sapwood width), BT (bark thickness), HA, SA (sapwood area), HV, HRP (heartwood radius percentage), HAP (heartwood area percentage), and HVP (heartwood volume percentage) were between 0.94 and 0.99, and repeatabilities of the eleven indices were between 0.74 and 0.90. Clonal repeatability of DBH (0.88), DGH (0.88), and H (0.90) in growth traits and HR (0.90), HVP (0.90), and HV (0.88) in heartwood properties were slightly higher than for SA (0.74), SW (0.75), HAP (0.75), HRP (0.75), and HVP (0.75). These data also implied that the growth characteristics of heartwood and sapwood of blackwood clones were less affected by the environment and had substantial heritability.
Genetic Diversity and Population Structure of a Longan Germplasm in Thailand Revealed by Genotyping-By-Sequencing (GBS)
Authors: Riangwong Kanamon , Saensuk Chatree , Pitaloka Mutiara K. , Dumhai Reajina , Ruanjaichon Vinitchan , Toojinda Theerayut , Wanchana Samart , Arikit Siwaret
Published: June 2023

Longan (Dimocarpus longan Lour.) is grown commercially in many countries, including China, Thailand, the Philippines, Malaysia, Vietnam, India, Australia, and Hawaii. Thailand is the second largest producer and largest exporter of longan in the world. Currently, there is limited information on the genetic background, population structure, and genetic relationships among longan cultivars in Thailand. In this study, a total of 50 longan accessions from a community-based germplasm collection in Thailand were analyzed using 10,619 SNPs from genotyping-by-sequencing (GBS). Based on the results of STRUCTURE analysis, 43 accessions were classified into 4 subpopulations, and the other 7 accessions were found to contain admixed genotypes. Based on UPGMA clustering analysis and PCoA analysis, the longan accessions could be divided into six major groups consistent with those identified by STRUCTURE. A relatively high degree of genetic variation was observed among the longan accessions, as quantified by the expected heterozygosity (He = 0.308). AMOVA results showed that 74% and 26% of the total variation occurred between and within populations, respectively. Obvious genetic differentiation between populations (FST = 0.25) was observed. The results of this study are useful for managing longan germplasm and may facilitate the genetic improvement of longan.
Development of Responsive Nanoparticles for Cancer Therapy
Authors: Puiggalí Jordi
Published: June 2023

Great efforts are focused on the development of safe nano-carriers for the treatment of cancer in order to overcome some of the typical limitations of conventional therapies [...]
Harnessing the Potential of Non-Apoptotic Cell Death Processes in the Treatment of Drug-Resistant Melanoma
Authors: Dong Linyinxue , Vargas Ceeane Paul Dagoc , Tian Xuechen , Chu Xiayu , Yin Chenqi , Wong Aloysius , Yang Yixin
Published: June 2023

Melanoma is a highly malignant skin cancer that is known for its resistance to treatments. In recent years, there has been significant progress in the study of non-apoptotic cell death, such as pyroptosis, ferroptosis, necroptosis, and cuproptosis. This review provides an overview of the mechanisms and signaling pathways involved in non-apoptotic cell death in melanoma. This article explores the interplay between various forms of cell death, including pyroptosis, necroptosis, ferroptosis, and cuproptosis, as well as apoptosis and autophagy. Importantly, we discuss how these non-apoptotic cell deaths could be targeted as a promising therapeutic strategy for the treatment of drug-resistant melanoma. This review provides a comprehensive overview of non-apoptotic processes and gathers recent experimental evidence that will guide future research and eventually the creation of treatment strategies to combat drug resistance in melanoma.
Thermodynamic Behavior of (2-Propanol + 1,8-Cineole) Mixtures: Isothermal Vapor–Liquid Equilibria, Densities, Enthalpies of Mixing, and Modeling
Authors: Gimeno Beatriz , Martinez Santiago , Mainar Ana M. , Urieta Jose S. , Perez Pascual
Published: June 2023

Vapor pressures and other thermodynamic properties of liquids, such as density and enthalpy of mixtures, are the key parameters in chemical engineering for designing new process units, and are also essential for understanding the physical chemistry, macroscopic and molecular behavior of fluid systems. In this work, vapor pressures between 278.15 and 323.15 K, densities and enthalpies of mixtures between 288.15 and 318.15 K for the binary mixture (2-propanol + 1,8-cineole) have been measured. From the vapor pressure data, activity coefficients and excess Gibbs energies were calculated via the Barker’s method and the Wilson equation. Excess molar volumes and excess molar enthalpies were also obtained from the density and calorimetric measurements. Thermodynamic consistency test between excess molar Gibbs energies and excess molar enthalpies has been carried out using the Gibbs–Helmholtz equation. Robinson–Mathias, and Peng–Robinson–Stryjek–Vera together with volume translation of Peneloux equations of state (EoS) are considered, as well as the statistical associating fluid theory that offers a molecular vision quite suitable for systems having highly non-spherical or associated molecules. Of these three models, the first two fit the experimental vapor pressure results quite adequately; in contrast, only the last one approaches the volumetric behavior of the system. A brief comparison of the thermodynamic excess molar functions for binary mixtures of short-chain alcohol + 1,8-cineole (cyclic ether), or +di-n-propylether (lineal ether) is also included.
Cholesterol, Amyloid Beta, Fructose, and LPS Influence ROS and ATP Concentrations and the Phagocytic Capacity of HMC3 Human Microglia Cell Line
Authors: Muñoz Herrera Oscar M. , Hong Brian V. , Ruiz Mendiola Ulises , Maezawa Izumi , Jin Lee-Way , Lebrilla Carlito B. , Harvey Danielle J. , Zivkovic Angela M.
Published: June 2023

Research has found that genes specific to microglia are among the strongest risk factors for Alzheimer’s disease (AD) and that microglia are critically involved in the etiology of AD. Thus, microglia are an important therapeutic target for novel approaches to the treatment of AD. High-throughput in vitro models to screen molecules for their effectiveness in reversing the pathogenic, pro-inflammatory microglia phenotype are needed. In this study, we used a multi-stimulant approach to test the usefulness of the human microglia cell 3 (HMC3) cell line, immortalized from a human fetal brain-derived primary microglia culture, in duplicating critical aspects of the dysfunctional microglia phenotype. HMC3 microglia were treated with cholesterol (Chol), amyloid beta oligomers (AβO), lipopolysaccharide (LPS), and fructose individually and in combination. HMC3 microglia demonstrated changes in morphology consistent with activation when treated with the combination of Chol + AβO + fructose + LPS. Multiple treatments increased the cellular content of Chol and cholesteryl esters (CE), but only the combination treatment of Chol + AβO + fructose + LPS increased mitochondrial Chol content. Microglia treated with combinations containing Chol + AβO had lower apolipoprotein E (ApoE) secretion, with the combination of Chol + AβO + fructose + LPS having the strongest effect. Combination treatment with Chol + AβO + fructose + LPS also induced APOE and TNF-α expression, reduced ATP production, increased reactive oxygen species (ROS) concentration, and reduced phagocytosis events. These findings suggest that HMC3 microglia treated with the combination of Chol + AβO + fructose + LPS may be a useful high-throughput screening model amenable to testing on 96-well plates to test potential therapeutics to improve microglial function in the context of AD.
Novel Molecular Vehicle-Based Approach for Cardiac Cell Transplantation Leads to Rapid Electromechanical Graft–Host Coupling
Authors: Aitova Aleria , Scherbina Serafima , Berezhnoy Andrey , Slotvitsky Mikhail , Tsvelaya Valeriya , Sergeeva Tatyana , Turchaninova Elena , Rybkina Elizaveta , Bakumenko Sergey , Sidorov Ilya , Popov Mikhail A. , Dontsov Vladislav , Agafonov Evgeniy G. , Efimov Anton E. , Agapov Igor , Zybin Dmitriy , Shumakov Dmitriy , Agladze Konstantin
Published: June 2023

Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.
Improvements in Systemic Therapies for Advanced Malignant Mesothelioma
Authors: Deiana Chiara , Fabbri Francesca , Tavolari Simona , Palloni Andrea , Brandi Giovanni
Published: June 2023

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs. Furthermore, we focused on promising treatments under investigation, such as immunotherapy with targets different from anti-PD-1/PD-L1 inhibitors, vaccines, target therapies, and metabolism-based strategies.
Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation
Authors: Hajdú István , Végh Barbara M. , Szilágyi András , Závodszky Péter
Published: June 2023

The amyloidogenic processing of APP depends on two events: its phosphorylation by ROCK2 (at Thr654) and the phosphorylation of the APP-cleaving enzyme BACE1 (at Ser498). However, the mechanisms and structural details of APP-ROCK2 and BACE1-ROCK2 binding are unknown. Using direct physical methods in combination with an in silico approach, we found that BACE1 binds into the substrate-binding groove of ROCK2 with a low affinity (Kd = 18 µM), while no binding of APP to ROCK2 alone could be detected. On the other hand, a strong association (Kd = 3.5 nM) of APP to the weak ROCK2-BACE1 complex was observed, although no stable ternary complex was detected, i.e., BACE1 was displaced by APP. We constructed a sequential functional model: (1) BACE1 weakly binds to ROCK2 and induces an allosteric conformational change in ROCK2; (2) APP strongly binds to the ROCK2-BACE1 complex, and BACE1 is released; and (3) ROCK2 phosphorylates APP at Thr654 (leading to a longer stay in the early endosome during APP processing). Direct fluorescence titration experiments showed that the APP646–664 or APP665–695 fragments did not bind separately to the ROCK2-BACE1 complex. Based on these observations, we conclude that two binding sites are involved in the ROCK2-APP interaction: (1) the substrate-binding groove, where the APP646–664 sequence containing Thr654 sits and (2) the allosteric binding site, where the APP665–695 sequence binds. These results open the way to attack the allosteric site to prevent APP phosphorylation at Thr654 by ROCK2 without inhibiting the activity of ROCK2 towards its other substrates.
Application of IRI Visualization to Terahertz Vibrational Spectroscopy of Hydroxybenzoic Acid Isomers
Authors: Tu Shan , Zhang Wentao , Tang Yuan , Li Yuanpeng , Hu Junhui
Published: June 2023

The characteristic absorption spectra of three positional isomers of hydroxybenzoic acid are measured using a terahertz time-domain spectroscopy system (THz-TDS) in the 0.6–2.0 THz region at room temperature. Significant differences in their terahertz spectra are discovered, which indicates that THz-TDS is an effective means to identify positional isomers. In order to simulate their spectra, the seven molecular clusters of 2-, 3-, and 4-hydroxybenzoic acid (2-, 3-, and 4-HA) are calculated using the DFT-D3 method. Additionally, the potential energy distribution (PED) method is used to analyze their vibration modes. The analysis indicates that the vibration modes of 2-HA are mainly out-of-plane angle bending and bond angle bend in plane. The vibration modes of 3-HA are mainly bond length stretch and dihedral angle torsion. The vibration modes of 4-HA are mainly bond angle bend in plane and dihedral angle torsion. Interaction region indicator (IRI) analysis is used to visualize the location and type of intermolecular interactions in 2-, 3-, and 4-HA crystals. The results show that the weak interaction type of 2-, 3-, and 4-HA is dominated by van der Waals (vdW) interaction. Therefore, we can confirm that terahertz spectroscopy detection technology can be used as an effective means to identify structural isomers and detect the intermolecular interactions in these crystals. In addition, it can explain the absorption mechanism of terahertz waves interacting with matter.
Biochemical Recurrence in Prostate Cancer Is Associated with the Composition of Lactobacillus: Microbiome Analysis of Prostatic Tissue
Authors: Kim Jae Heon , Seo Hoonhee , Kim Sukyung , Ul-Haq Asad , Rahim Md Abdur , Jo Sujin , Song Ho-Yeon , Song Yun Seob
Published: June 2023

Many human pathologies, such as malignancy, are linked with specific bacteria and changes in the constituents of the microbiome. In order to examine the association between an imbalance of bacteria and prostate carcinoma, a comparison of the microbiomes present in patients with biochemical recurrence (BCR) or NO BCR (NBCR) was performed. Additionally, 16S rRNA-based next-generation sequencing was applied to identify the bacterial profiles within these tumors in terms of the bacteria and operational genes present. The percentage average taxonomic composition between the taxa indicated no difference between BCR and NBCR. In addition, alpha and beta diversity indices presented no distinction between the cohorts in any statistical method. However, taxonomic biomarker discovery indicated a relatively higher population of Lactobacillus in the NBCR group, and this finding was supported by PCR data. Along with that, differences in the operational activity of the bacterial genes were also determined. It is proposed that the biochemical recurrence was linked to the quantity of Lactobacillus present. The aim of this study was to investigate the microbiome involved in prostate carcinoma and the potential association between them.
Concomitant Use of Antiplatelet Agents and Proton-Pump Inhibitors Increases the Risk of Adverse Cardiovascular Events: A Nationwide Population-Based Cohort Study Using Balanced Operational Definitions
Authors: Yang Hee Gyu , Kim Dong-Kyu
Published: June 2023

Antiplatelet agents are commonly used in combination with proton-pump inhibitors (PPIs) in patients with acute coronary syndrome who are at risk of gastrointestinal hemorrhage. However, studies have reported that PPIs can alter the pharmacokinetics of antiplatelet agents and result in adverse cardiovascular events. We enrolled 311 patients who received antiplatelet therapy with PPIs for >30 days and 1244 matched controls following a 1:4 propensity score matching during the index period. Patients were followed up until death, myocardial infarction, coronary revascularization, or the end of the follow-up period. Patients who used antiplatelet therapy with PPIs were found to be at higher risk of mortality than the controls (adjusted hazard ratio (HR): 1.77; 95% confidence interval (CI): 1.30–2.40). The adjusted HR for patients who used antiplatelet agents with PPIs developing myocardial infarction and coronary revascularization events was 3.52 (95% CI: 1.34–9.22) and 4.74 (95% CI: 2.03–11.05), respectively. Additionally, middle-aged patients or those within 3 years of concomitant use showed a higher risk of myocardial infarction and coronary revascularization. Our findings suggest that antiplatelet therapy combined with PPIs has a higher mortality risk in patients with gastrointestinal bleeding and is associated with an increased risk of myocardial infarction and coronary revascularization.
Charge Transfer and Charge Trapping Processes in Ca- or Al-Co-doped Lu2SiO5 and Lu2Si2O7 Scintillators Activated by Pr3+ or Ce3+ Ions
Authors: Laguta Valentyn , Havlak Lubomir , Babin Vladimir , Barta Jan , Pejchal Jan , Nikl Martin
Published: June 2023

Lutetium oxyorthosilicate Lu2SiO5 (LSO) and pyrosilicate Lu2Si2O7 (LPS) activated by Ce3+ or Pr3+ are known to be effective and fast scintillation materials for the detection of X-rays and γ-rays. Their performances can be further improved by co-doping with aliovalent ions. Herein, we investigate the Ce3+(Pr3+) → Ce4+(Pr4+) conversion and the formation of lattice defects stimulated by co-doping with Ca2+ and Al3+ in LSO and LPS powders prepared by the solid-state reaction process. The materials were studied by electron paramagnetic resonance (EPR), radioluminescence spectroscopy, and thermally stimulated luminescence (TSL), and scintillation decays were measured. EPR measurements of both LSO:Ce and LPS:Ce showed effective Ce3+ → Ce4+ conversions stimulated by Ca2+ co-doping, while the effect of Al3+ co-doping was less effective. In Pr-doped LSO and LPS, a similar Pr3+ → Pr4+ conversion was not detected by EPR, suggesting that the charge compensation of Al3+ and Ca2+ ions is realized via other impurities and/or lattice defects. X-ray irradiation of LPS creates hole centers attributed to a hole trapped in an oxygen ion in the neighborhood of Al3+ and Ca2+. These hole centers contribute to an intense TSL glow peak at 450–470 K. In contrast to LPS, only weak TSL peaks are detected in LSO and no hole centers are visible via EPR. The scintillation decay curves of both LSO and LPS show a bi-exponential decay with fast and slow component decay times of 10–13 ns and 30–36 ns, respectively. The decay time of the fast component shows a small (6–8%) decrease due to co-doping.
Lead-Free Halide Double Perovskite for High-Performance Photodetectors: Progress and Perspective
Authors: Li Xiaoyan , Shi Junzhe , Chen Jianjun , Tan Zuojun , Lei Hongwei
Published: June 2023

Lead halide perovskite has become a promising candidate for high-performance photodetectors (PDs) due to its attractive optical and electrical properties, such as high optical absorption coefficient, high carrier mobility, and long carrier diffusion length. However, the presence of highly toxic lead in these devices has limited their practical applications and even hindered their progress toward commercialization. Therefore, the scientific community has been committed to searching for low-toxic and stable perovskite-type alternative materials. Lead-free double perovskite, which is still in the preliminary stage of exploration, has achieved inspiring results in recent years. In this review, we mainly focus on two types of lead-free double perovskite based on different Pb substitution strategies, including A2M(I)M(III)X6 and A2M(IV)X6. We review the research progress and prospects of lead-free double perovskite photodetectors in the past three years. More importantly, from the perspective of optimizing the inherent defects in materials and improving device performance, we propose some feasible pathways and make an encouraging perspective for the future development of lead-free double perovskite photodetectors.
High-Temperature Corrosion Behavior of Selected HVOF-Sprayed Super-Alloy Based Coatings in Aggressive Environment at 800 °C
Authors: Česánek Zdeněk , Lencová Kateřina , Schubert Jan , Antoš Jakub , Mušálek Radek , Lukáč František , Palán Marek , Vostřák Marek , Houdková Šárka
Published: June 2023

This study is focused on the high-temperature corrosion evaluation of selected thermally sprayed coatings. NiCoCrAlYHfSi, NiCoCrAlY, NiCoCrAlTaReY, and CoCrAlYTaCSi coatings were sprayed on the base material 1.4923. This material is used as a cost-efficient construction material for components of power equipment. All evaluated coatings were sprayed using HP/HVOF (High-Pressure/High-Velocity Oxygen Fuel) technology. High-temperature corrosion testing was performed in a molten salt environment typical for coal-fired boilers. All coatings were exposed to the environment of 75% Na2SO4 and 25% NaCl at the temperature of 800 °C under cyclic conditions. Each cycle consisted of 1 h heating in a silicon carbide tube furnace followed by 20 min of cooling. The weight change measurement was performed after each cycle to establish the corrosion kinetics. Optical microscopy (OM), scanning electron microscopy (SEM), and elemental analysis (EDS) were used to analyze the corrosion mechanism. The CoCrAlYTaCSi coating showed the best corrosion resistance of all the evaluated coatings, followed by NiCoCrAlTaReY and NiCoCrAlY. All the evaluated coatings performed better in this environment than the reference P91 and H800 steels.
Influence of Surface Roughness on the Properties of Nitrided Layer on 42CrMo4 Steel
Authors: Moneta Marcin , Stodolny Jerzy , Michalkiewicz Beata , Wróbel Rafał Jan
Published: June 2023

A crucial factor of a nitriding process of treated parts is surface roughness. Eight samples of 42CrMo4 steel were used to investigate the parameter represented by Ra. In the study, the innovative combined microhardness profiles were used to present results within the compound zone and diffusion layer. Therefore, two loads were applied in the compound zone, 5 gf, and diffusion layer, 500 gf. Observation with SEM and chemical analysis of the investigated samples showed a correlation between microstructure, nitrogen concentration and microhardness of the compound zone. XRD diffraction was used to identify the phase composition. Moreover, the X-ray photoelectron spectroscopy technique was also applied in the study. No distinct correlations between compound zone morphology and the Ra parameter were observed. The thickness value of the structure was constant and fluctuated around 20 µm in the vast majority of the examined cases. However, analysis of the results revealed a dependence between the Ra parameter and diffusion layer thickness. The values of this parameter varied in the range of 356–394 µm depending on the Ra parameter. A distinct nitrided layer was observed on the polished sample.
Point-of-Care Ultrasound: A Multimodal Tool for the Management of Sepsis in the Emergency Department
Authors: Polyzogopoulou Effie , Velliou Maria , Verras Christos , Ventoulis Ioannis , Parissis John , Osterwalder Joseph , Hoffmann Beatrice
Published: June 2023

Sepsis and septic shock are life-threatening emergencies associated with increased morbidity and mortality. Hence, early diagnosis and management of both conditions is of paramount importance. Point-of-care ultrasound (POCUS) is a cost-effective and safe imaging modality performed at the bedside, which has rapidly emerged as an excellent multimodal tool and has been gradually incorporated as an adjunct to physical examination in order to facilitate evaluation, diagnosis and management. In sepsis, POCUS can assist in the evaluation of undifferentiated sepsis, while, in cases of shock, it can contribute to the differential diagnosis of other types of shock, thus facilitating the decision-making process. Other potential benefits of POCUS include prompt identification and control of the source of infection, as well as close haemodynamic and treatment monitoring. The aim of this review is to determine and highlight the role of POCUS in the evaluation, diagnosis, treatment and monitoring of the septic patient. Future research should focus on developing and implementing a well-defined algorithmic approach for the POCUS-guided management of sepsis in the emergency department setting given its unequivocal utility as a multimodal tool for the overall evaluation and management of the septic patient.
Atlantic Salmon Gill Epithelial Cell Line (ASG-10) as a Suitable Model for Xenobiotic Biotransformation
Authors: Ivanova Lada , Fæste Christiane Kruse , Solhaug Anita
Published: June 2023

Fish are exposed to xenobiotics in the water. Uptake occurs mainly through the gills, which function as an exchange point with the environment. The gills’ ability to detoxify harmful compounds by biotransformation is an essential protection mechanism. The enormous numbers of waterborne xenobiotics requiring ecotoxicological assessment makes it necessary to replace in vivo fish studies with predictive in vitro models. Here, we have characterized the metabolic capacity of the ASG-10 gill epithelial cell line from Atlantic salmon. Inducible CYP1A expression was confirmed by enzymatic assays and immunoblotting. The activities of important cytochrome P450 (CYP) and uridine 5’-diphospho-glucuronosyltransferase (UGT) enzymes were established using specific substrates and metabolite analysis by liquid chromatography (LC) triple quadrupole mass spectrometry (TQMS). Metabolism of the fish anesthetic benzocaine (BZ) in ASG-10 confirmed esterase and acetyl transferase activities through the production of N-acetylbenzocaine (AcBZ), p-aminobenzoic acid (PABA) and p-acetaminobenzoic acid (AcPABA). Moreover, we were able to determine hydroxylamine benzocaine (BZOH), benzocaine glucuronide (BZGlcA) and hydroxylamine benzocaine glucuronide (BZ(O)GlcA) by LC high-resolution tandem mass spectrometry (HRMS/MS) fragment pattern analysis for the first time. Comparison to metabolite profiles in hepatic fractions, and in plasma of BZ-euthanized salmon, confirmed the suitability of the ASG-10 cell line for investigating biotransformation in gills.