bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and Simulation of Space-Based LM-APD 3D Imaging
Authors: Wang Shuai , Quan Lin , Zhang Jie , Liu Lei , Cong Dianwei , Sun Guangde , Li Ling , Wang Kunpeng
Published: May 2023

The linear mode avalanche photodiode (LM-APD) array has the capability of real-time 3D imaging for moving targets, which is a promising 3D imaging means in space. The main system parameters of the LM-APD array 3D imaging system, the characteristics of the space target itself, and the relative positional relationship between them will affect the 3D imaging results at the same time, and there is a need for an appropriate simulation method to describe the space target point cloud acquired by the LM-APD array 3D imaging system under different conditions. We propose a simulation method for the 3D imaging of space targets with LM-APD arrays, which takes the characteristics of the space targets and the relative position into consideration, and build a link from the laser to the receiving system to simulate the echo waveform of each pixel in the LM-APD array. The experiment results under different conditions show that the proposed simulation method can accurately describe the imaging results of the LM-APD array 3D imaging system for space targets with different shapes, materials, and motion states, which providing theoretical and data support for the design of LM-APD array 3D imaging systems.
An Efficient Strategy for Catastrophic Forgetting Reduction in Incremental Learning
Authors: Doan Huong-Giang , Luong Hong-Quan , Ha Thi-Oanh , Pham Thi Thanh Thuy
Published: May 2023

Deep neural networks (DNNs) have made outstanding achievements in a wide variety of domains. For deep learning tasks, large enough datasets are required for training efficient DNN models. However, big datasets are not always available, and they are costly to build. Therefore, balanced solutions for DNN model efficiency and training data size have caught the attention of researchers recently. Transfer learning techniques are the most common for this. In transfer learning, a DNN model is pre-trained on a large enough dataset and then applied to a new task with modest data. This fine-tuning process yields another challenge, named catastrophic forgetting. However, it can be reduced using a reasonable strategy for data argumentation in incremental learning. In this paper, we propose an efficient solution for the random selection of samples from the old task to be incrementally stored for learning a sequence of new tasks. In addition, a loss combination strategy is also proposed for optimizing incremental learning. The proposed solutions are evaluated on standard datasets with two scenarios of incremental fine-tuning: (1) New Class (NC) dataset; (2) New Class and new Instance (NCI) dataset. The experimental results show that our proposed solution achieves outstanding results compared with other SOTA rehearsal methods, as well as traditional fine-tuning solutions, ranging from 1% to 16% in recognition accuracy.
Preheating Analysis of Semi-Coke in a Circulating Fluidized Bed and Its Kinetic Characteristics
Authors: Zhang Jiahang , Zhu Jianguo , Liu Jingzhang
Published: May 2023

Semi-coke has difficulties with stable ignition and high-efficiency combustion due to its low volatile content. Preheating in a circulating fluidized bed before combustion offers a novel method for the improvement of fuel properties. During preheating, the semi-coke was converted to preheated fuel composed of coal gas and preheated char. When increasing the preheating temperature, the ratio of CO/CO2 in the coal gas significantly increased, while the ratio of CH4/CO2 remained almost unchanged. After preheating, the release ratios for different species from the semi-coke followed the order C >H > N > S. Thermogravimetric analysis was used to evaluate the kinetic characteristics. We found that the ignition and burnout temperatures of the preheated char decreased compared to those of the semi-coke, and the reaction rate constant for the preheated char increased by 20 times. Three models were used to predict the variations in the conversion ratio with time, and the modified volumetric reaction model showed good agreement with the experiment. This investigation provides support for better developing preheating combustion technology in the future.
Theoretical Analysis of Integrated Community Energy Systems (ICES) Considering Integrated Demand Response (IDR): A Review of the System Modelling and Optimization
Authors: Kong Dezhou , Jing Jianru , Gu Tingyue , Wei Xuanyue , Sa Xingning , Yang Yimin , Zhang Zhiang
Published: May 2023

The transition of the energy model dominated by centralized fossil energy use and the emergence of the Energy Internet and the Integrated Community Energy System (ICES) has gained attention. ICES involved the connection of electricity, heat, gas, and other kinds of energy, and was a significant form of the targeted transformation of conventional single energy networks. Within this system, the traditional demand response (DR) was transformed into an integrated demand response (IDR) in which all energy consumers could participate. The purpose of this study is to discuss the important technologies and models along with assessment and optimization strategies for the implementation of ICES and IDR, based on an extensive literature review. The analysis results show the “IDR + ICES” ecosystem proved to hold great potential for achieving renewable energy penetration, energy efficiency, and climate change control goals, while there are still many limitations in the coordination and reliability of the model and the design of the market mechanism. To conclude, the challenges and opportunities that ICES and IDR face were summarized, and future avenues for research are outlined.
A Review on Multilevel Converters for Efficient Integration of Battery Systems in Stationary Applications
Authors: Rauf Abdul Mannan , Abdel-Monem Mohamed , Geury Thomas , Hegazy Omar
Published: May 2023

Recently, multilevel converters (MLCs) have gained significant attention for stationary applications, including static compensators, industrial drives, and utility-grid interfaces for renewable energy sources. Compared to two-level voltage-source inverters (VSI) MLCs feature high-quality AC voltage with reduced harmonic content despite the lower switching frequency of the semiconductor devices. On the DC side, MLCs can integrate multiple isolated/non-isolated battery modules instead of a single battery pack. This helps to keep the system in service in case of a malfunction of one or more battery modules, as well as active balancing among the modules, a feature not possible with two-level VSI. In general, MLCs can be classified into two types: (i) two-port MLCs, which provide a single interface to connect with the battery pack, and (ii) multiport MLCs, which provide multiple interfaces to allow connection at the module or cell level. The classical topologies of both MLC types (e.g., neutral point clamped, flying capacitor, cascaded bridge) face limitations due to the high switch count. Consequently, many hybrid and reduced-switch topologies are reported in the literature. This paper presents a critical overview of both classical and recently reported MLC topologies and offers a better insight of MLC operation for grid-connected and standalone applications. In addition, the analysis thoroughly assesses various high-level control and modulation strategies while considering active balancing among the battery modules. Other salient features such as balancing speed during offtake/grid-injection mode and fault-ride-through capability are also incorporated. In conclusion, the key findings are summarized for a better understanding of the present and future integration of battery systems in stationary applications.
New Concept of Forest Medicine
Authors: Li Qing
Published: May 2023

Forest bathing was proposed in Japan in 1982 for the purpose of reducing stress and health management, and research on the health promotion and disease prevention effects of forest bathing began in Japan in 2004. Since then, the author’s research team has published many papers and, in 2012, established Forest Medicine as a new preventive medicine. Imagine a new medical science that could let you know how to be more active, more relaxed, healthier, and happier, with reduced stress and a reduced risk of lifestyle-related diseases. This new medical science is Forest Medicine. Forest Medicine studies the effects of forest environments on human health and is a new interdisciplinary science that belongs to the categories of environmental and preventive medicine. On the other hand, more than 10 years have passed since then, and a lot of evidence has been obtained and many articles regarding Forest Medicine have been published. Therefore, in this review, the author proposes a new concept of Forest Medicine, based on the new evidence and published papers, with the psycho-neuro-endocrino-immune network in mind.
Microbiological Characterization of Protected Designation of Origin Serra da Estrela Cheese
Authors: Rocha Rui , Couto Nélson , Pinto Ricardo Pereira , Vaz-Velho Manuela , Fernandes Paulo , Santos Joana
Published: May 2023

Serra da Estrela is the oldest and most recognizable traditional protected designation of origin (PDO) cheese from Portugal. It has been extensively studied over the years, but the latest microbial characterization is 20 years old. Hence, this work aimed to perform an updated characterization of Serra da Estrela PDO cheeses and raw materials. Our analysis showed that lactic acid bacteria content on Serra da Estrela cheeses exceeded 8.8 log CFUsg−1, in all analyzed samples, with lactococci, lactobacilli and Leuconostoc spp. predominating over enterococci strains. Moreover, lactococci and lactobacilli abundance increased across the production season, while enterococci dropped considerably in late manufactures. Lastly, Leuconostoc spp. content remained unchanged in all analyzed periods. A correspondence analysis showed that L. paracasei, L. lactis, E. durans, E. faecium and L. mesenteroides are transversal in Serra da Estrela cheese manufacturing and were closely associated with milk, curd and cheese matrices. Additionally, L. casei, L. plantarum and L. curvatus were specifically associated with cheese matrices, possibly active during ripening and contributing for the development of these cheeses’ organoleptic characteristics.
Genome-Wide Investigation and Functional Analysis Reveal That CsKCS3 and CsKCS18 Are Required for Tea Cuticle Wax Formation
Authors: Mo Lilai , Yao Xinzhuan , Tang Hu , Li Yan , Jiao Yujie , He Yumei , Jiang Yihe , Tian Shiyu , Lu Litang
Published: May 2023

Cuticular wax is a complex mixture of very long-chain fatty acids (VLCFAs) and their derivatives that constitute a natural barrier against biotic and abiotic stresses on the aerial surface of terrestrial plants. In tea plants, leaf cuticular wax also contributes to the unique flavor and quality of tea products. However, the mechanism of wax formation in tea cuticles is still unclear. The cuticular wax content of 108 germplasms (Niaowang species) was investigated in this study. The transcriptome analysis of germplasms with high, medium, and low cuticular wax content revealed that the expression levels of CsKCS3 and CsKCS18 were strongly associated with the high content of cuticular wax in leaves. Hence, silencing CsKCS3 and CsKCS18 using virus-induced gene silencing (VIGS) inhibited the synthesis of cuticular wax and caffeine in tea leaves, indicating that expression of these genes is necessary for the synthesis of cuticular wax in tea leaves. The findings contribute to a better understanding of the molecular mechanism of cuticular wax formation in tea leaves. The study also revealed new candidate target genes for further improving tea quality and flavor and cultivating high-stress-resistant tea germplasms.
The Effect of Superficial Oregano Essential Oil Application on the Quality of Modified Atmosphere-Packed Pork Loin
Authors: Zduńczyk Weronika , Tkacz Katarzyna , Modzelewska-Kapituła Monika
Published: May 2023

During meat storage, changes in the meat colour occur, making it less intensive and red. The present study was aimed at investigating the effect of oregano EO applied directly on the surface of fresh pork on its quality, with a special emphasis on the colour. In the study, an oregano essential oil in concentrations of 0.5% and 1.0% (v/v) was used on the surface of pork loins (1.5% v/w) packed in a modified atmosphere during 15-d storage at 4 °C. The application of oregano EO in the concentration of 1.0% increased lightness and hue and decreased redness compared to the control, whereas the concentration of 0.5% did not affect the pork colour. EO did not affect pH, free water content, purge and cooking losses, cooked meat juiciness and tenderness; however, it gave the meat a distinctive herbal aroma and taste. The antimicrobial effect of 1% EO was noted only on the 15th day. Therefore, the application of oregano essential oil is not recommended to protect the colour of raw pork nor to prolong its shelf-life; however, it might be used to obtain a new product with a specific herbal aroma and taste, with modifications in water-holding capacity of the meat.
Multiscale Structural Insight into Dairy Products and Plant-Based Alternatives by Scattering and Imaging Techniques
Authors: Heiden-Hecht Theresia , Wu Baohu , Appavou Marie-Sousai , Förster Stephan , Frielinghaus Henrich , Holderer Olaf
Published: May 2023

Dairy products and plant-based alternatives have a large range of structural features from atomic to macroscopic length scales. Scattering techniques with neutrons and X-rays provide a unique view into this fascinating world of interfaces and networks provided by, e.g., proteins and lipids. Combining these scattering techniques with a microscopic view into the emulsion and gel systems with environmental scanning electron microscopy (ESEM) assists in a thorough understanding of such systems. Different dairy products, such as milk, or plant-based alternatives, such as milk-imitating drinks, and their derived or even fermented products, including cheese and yogurt, are characterized in terms of their structure on nanometer- to micrometer-length scales. For dairy products, the identified structural features are milk fat globules, casein micelles, CCP nanoclusters, and milk fat crystals. With increasing dry matter content in dairy products, milk fat crystals are identified, whereas casein micelles are non-detectable due to the protein gel network in all types of cheese. For the more inhomogeneous plant-based alternatives, fat crystals, starch structures, and potentially protein structures are identified. These results may function as a base for improving the understanding of dairy products and plant-based alternatives, and may lead to enhanced plant-based alternatives in terms of structure and, thus, sensory aspects such as mouthfeel and texture.
Bacterial and Fungal Communities Are Specifically Modulated by the Cocoa Bean Fermentation Method
Authors: Ghisolfi Rebecca , Bandini Francesca , Vaccari Filippo , Bellotti Gabriele , Bortolini Cristian , Patrone Vania , Puglisi Edoardo , Morelli Lorenzo
Published: May 2023

Cocoa bean fermentation is carried out in different production areas following various methods. This study aimed to assess how the bacterial and fungal communities were affected by box, ground or jute fermentation methods, using high-throughput sequencing (HTS) of phylogenetic amplicons. Moreover, an evaluation of the preferable fermentation method was carried out based on the microbial dynamics observed. Box fermentation resulted in higher bacterial species diversity, while beans processed on the ground had a wider fungal community. Lactobacillus fermentum and Pichia kudriavzevii were observed in all three fermentation methods studied. Moreover, Acetobacter tropicalis dominated box fermentation and Pseudomonas fluorescens abounded in ground-fermented samples. Hanseniaspora opuntiae was the most important yeast in jute and box, while Saccharomyces cerevisiae prevailed in the box and ground fermentation. PICRUST analysis was performed to identify potential interesting pathways. In conclusion, there were noticeable differences between the three different fermentation methods. Due to its limited microbial diversity and the presence of microorganisms that guarantee good fermentation, the box method was found to be preferable. Moreover, the present study allowed us to thoroughly explore the microbiota of differently treated cocoa beans and to better understand the technological processes useful to obtain a standardized end-product.
New Variant of Hermite–Hadamard, Fejér and Pachpatte-Type Inequality and Its Refinements Pertaining to Fractional Integral Operator
Authors: Tariq Muhammad , Ntouyas Sotiris K. , Shaikh Asif Ali
Published: May 2023

In order to show novel generalizations of mathematical inequality, fractional integral operators are frequently used. Fractional operators are used to simulate a broad range of scientific as well as engineering phenomena such as elasticity, viscous fluid, fracture mechanics, continuous population, equilibrium, visco-elastic deformation, heat conduction problems, and others. In this manuscript, we introduce some novel notions of generalized preinvexity, namely the (m,tgs)-type s-preinvex function, Godunova–Levin (s,m)-preinvex of the 1st and 2nd kind, and a prequasi m-invex. Furthermore, we explore a new variant of the Hermite–Hadamard (H–H), Fejér, and Pachpatte-type inequality via a generalized fractional integral operator, namely, a non-conformable fractional integral operator (NCFIO). In addition, we explore new equalities. With the help of these equalities, we examine and present several extensions of H–H and Fejér-type inequalities involving a newly introduced concept via NCFIO. Finally, we explore some special means as applications in the aspects of NCFIO. The results and the unique situations offered by this research are novel and significant improvements over previously published findings.
Loneliness before and after COVID-19: Sense of Coherence and Hope as Coping Mechanisms
Authors: Einav Michal , Margalit Malka
Published: May 2023

The COVID-19 pandemic posed a major threat to public health, with long-lasting consequences for the daily habits and practices of people around the world. The combination of hazardous health conditions and extensive changes to people’s daily routines due to lockdowns, social restrictions, and employment uncertainty have led to mental health challenges, reduced levels of subjective wellbeing, and increased maladaptive behaviors and emotional distress. Nevertheless, some studies have reported increased adaptive functioning and resilience after the pandemic, suggesting a more complex pattern of effects. The goals of the current study were to explore the role of two coping variables, sense of coherence and hope, in people’s emotional wellbeing and adaptation in dealing with loneliness before and after such a stressful period. In a cross-sectional study, 974 Israeli participants (sample 1: 540 participants before the pandemic; sample 2: 434 participants after the pandemic restrictions) answered online questionnaires about their loneliness, hope and sense of coherence levels before and after the pandemic. While the two groups did not differ in their levels of hope, the participants in the group before COVID-19 reported lower levels of loneliness and sense of coherence. However, the results also indicated that although the COVID-19 pandemic was related to increased levels of loneliness, the participants’ sense of coherence mediated this increase and their levels of hope moderated it. The theoretical contribution of these findings is discussed, as well as interventional implications and future directions.
Yarrowia lipolytica as a Platform for Punicic Acid Production
Authors: Urbanikova Veronika , Park Young-Kyoung , Krajciova Daniela , Tachekort Mehdi , Certik Milan , Grigoras Ioana , Holic Roman , Nicaud Jean-Marc , Gajdos Peter
Published: May 2023

Punicic acid (PuA) is a polyunsaturated fatty acid with significant medical, biological, and nutraceutical properties. The primary source of punicic acid is the pomegranate seed oil obtained from fruits of trees that are mainly cultivated in subtropical and tropical climates. To establish sustainable production of PuA, various recombinant microorganisms and plants have been explored as platforms with limited efficiencies. In this study, the oleaginous yeast Yarrowia lipolytica was employed as a host for PuA production. First, growth and lipid accumulation of Y. lipolytica were evaluated in medium supplemented with pomegranate seed oil, resulting in the accumulation of lipids up to 31.2%, consisting of 22% PuA esterified in the fraction of glycerolipids. In addition, lipid-engineered Y. lipolytica strains, transformed with the bifunctional fatty acid conjugase/desaturase from Punica granatum (PgFADX), showed the ability to accumulate PuA de novo. PuA was detected in both polar and neutral lipid fractions, especially in phosphatidylcholine and triacylglycerols. Promoter optimization for PgFADX expression resulted in improved accumulation of PuA from 0.9 to 1.8 mg/g of dry cell weight. The best-producing strain expressing PgFADX under the control of a strong erythritol-inducible promoter produced 36.6 mg/L PuA. These results demonstrate that the yeast Y. lipolytica is a promising host for PuA production.
Derivation of Human Corneal Keratocytes from ReLEx SMILE Lenticules for Cell Therapy and Tissue Engineering
Authors: Surovtseva Maria A. , Kim Irina I. , Bondarenko Natalia A. , Lykov Alexander P. , Krasner Kristina Yu. , Chepeleva Elena V. , Bgatova Nataliya P. , Trunov Alexander N. , Chernykh Valery V. , Poveshchenko Olga V.
Published: May 2023

Fibroblasts isolated and expanded from ReLEx SMILE lenticules can be a source of human keratocytes. Since corneal keratocytes are quiescent cells, it is difficult to expand them in vitro in suitable numbers for clinical and experimental use. In the present study, this problem was solved by isolating and growing corneal fibroblasts (CFs) with a high proliferative potential and their reversion to keratocytes in a selective serum-free medium. Fibroblasts reversed into keratocytes (rCFs) had a dendritic morphology and ultrastructural signs of activation of protein synthesis and metabolism. The cultivation of CFs in a medium with 10% FCS and their reversion into keratocytes was not accompanied by the induction of myofibroblasts. After reversion, the cells spontaneously formed spheroids and expressed keratocan and lumican markers, but not mesenchymal ones. The rCFs had low proliferative and migratory activity, and their conditioned medium contained a low level of VEGF. CF reversion was not accompanied by a change with the levels of IGF-1, TNF-alpha, SDF-1a, and sICAM-1. In the present study, it has been demonstrated that fibroblasts from ReLEx SMILE lenticules reverse into keratocytes in serum-free KGM, maintaining the morphology and functional properties of primary keratocytes. These keratocytes have a potential for tissue engineering and cell therapy of various corneal pathologies.
The Sts Proteins: Modulators of Host Immunity
Authors: Zaman Anika , French Jarrod B. , Carpino Nick
Published: May 2023

The suppressor of TCR signaling (Sts) proteins, Sts-1 and Sts-2, are a pair of closely related signaling molecules that belong to the histidine phosphatase (HP) family of enzymes by virtue of an evolutionarily conserved C-terminal phosphatase domain. HPs derive their name from a conserved histidine that is important for catalytic activity and the current evidence indicates that the Sts HP domain plays a critical functional role. Sts-1HP has been shown to possess a readily measurable protein tyrosine phosphatase activity that regulates a number of important tyrosine-kinase-mediated signaling pathways. The in vitro catalytic activity of Sts-2HP is significantly lower than that of Sts-1HP, and its signaling role is less characterized. The highly conserved unique structure of the Sts proteins, in which additional domains, including one that exhibits a novel phosphodiesterase activity, are juxtaposed together with the phosphatase domain, suggesting that Sts-1 and -2 occupy a specialized intracellular signaling niche. To date, the analysis of Sts function has centered predominately around the role of Sts-1 and -2 in regulating host immunity and other responses associated with cells of hematopoietic origin. This includes their negative regulatory role in T cells, platelets, mast cells and other cell types, as well as their less defined roles in regulating host responses to microbial infection. Regarding the latter, the use of a mouse model lacking Sts expression has been used to demonstrate that Sts contributes non-redundantly to the regulation of host immunity toward a fungal pathogen (C. albicans) and a Gram-negative bacterial pathogen (F. tularensis). In particular, Sts-/- animals demonstrate significant resistance to lethal infections of both pathogens, a phenotype that is correlated with some heightened anti-microbial responses of phagocytes derived from mutant mice. Altogether, the past several years have seen steady progress in our understanding of Sts biology.
Genome-Wide Identification and Comparative Analysis of RALF Gene Family in Legume and Non-Legume Species
Authors: Jia Yancui , Li Youguo
Published: May 2023

Rapid alkalinization factor (RALF) are small secreted peptide hormones that can induce rapid alkalinization in a medium. They act as signaling molecules in plants, playing a critical role in plant development and growth, especially in plant immunity. Although the function of RALF peptides has been comprehensively analyzed, the evolutionary mechanism of RALFs in symbiosis has not been studied. In this study, 41, 24, 17 and 12 RALFs were identified in Arabidopsis, soybean, Lotus and Medicago, respectively. A comparative analysis including the molecular characteristics and conserved motifs suggested that the RALF pre-peptides in soybean represented a higher value of isoelectric point and more conservative motifs/residues composition than other species. All 94 RALFs were divided into two clades according to the phylogenetic analysis. Chromosome distribution and synteny analysis suggested that the expansion of the RALF gene family in Arabidopsis mainly depended on tandem duplication, while segment duplication played a dominant role in legume species. The expression levels of most RALFs in soybean were significantly affected by the treatment of rhizobia. Seven GmRALFs are potentially involved in the release of rhizobia in the cortex cells. Overall, our research provides novel insights into the understanding of the role of the RALF gene family in nodule symbiosis.
The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO)
Authors: Tullo Maria Giulia , Cerulli Irelli Emanuele , Caramia Francesca , Tessari Gianmarco , Di Bonaventura Carlo , Turchetta Rosaria , Giallonardo Anna Teresa , Palumbo Giovanna , Bianchi Simona , Atturo Francesca , Nebbioso Marcella , Mancini Patrizia , Guariglia Cecilia , Giona Fiorina
Published: May 2023

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient’s initial classification.
Potential Benefits of Epidermal Growth Factor for Inhibiting Muscle Degrative Markers in Rats with Alcoholic Liver Damage
Authors: Xiao Qian , Chen Yi-Hsiu , Chen Ya-Ling , Chien Yu-Shan , Hsieh Li-Hsuan , Shirakawa Hitoshi , Yang Suh-Ching
Published: May 2023

This study investigated the beneficial effects of epidermal growth factor (EGF) on muscle loss in rats with chronic ethanol feeding. Six-week-old male Wistar rats were fed either a control liquid diet without EGF (C group, n = 12) or EGF (EGF-C group, n = 18) for two weeks. From the 3rd to 8th week, the C group was divided into two groups. One was continually fed with a control liquid diet (C group), and the other one was fed with an ethanol-containing liquid diet (E group); moreover, the EGF-C group was divided into three groups, such as the AEGF-C (continually fed with the same diet), PEGF-E (fed with the ethanol-containing liquid diet without EGF), and AEGF-E (fed with the ethanol-containing liquid diet with EGF). As a result, the E group had significantly higher plasma ALT and AST, endotoxin, ammonia, and interleukin 1b (IL-1b) levels, along with liver injuries, such as hepatic fatty changes and inflammatory cell infiltration. However, plasma endotoxin and IL-1b levels were significantly decreased in the PEGF-E and AEGF-E groups. In addition, the protein level of muscular myostatin and the mRNA levels of forkhead box transcription factors (FOXO), muscle RING-finger protein-1 (MURF-1) and atorgin-1 was increased considerably in the E group but inhibited in the PEGF-E and AEGF-E groups. According to the principal coordinate analysis findings, the gut microbiota composition differed between the control and ethanol liquid diet groups. In conclusion, although there was no noticeable improvement in muscle loss, EGF supplementation inhibited muscular protein degradation in rats fed with an ethanol-containing liquid diet for six weeks. The mechanisms might be related to endotoxin translocation inhibition, microbiota composition alteration as well as the amelioration of liver injury. However, the reproducibility of the results must be confirmed in future studies.
Mitochondrial Transfer as a Novel Therapeutic Approach in Disease Diagnosis and Treatment
Authors: Clemente-Suárez Vicente Javier , Martín-Rodríguez Alexandra , Yáñez-Sepúlveda Rodrigo , Tornero-Aguilera José Francisco
Published: May 2023

Mitochondrial dysfunction is a hallmark of numerous diseases, including neurodegenerative disorders, metabolic disorders, and cancer. Mitochondrial transfer, the transfer of mitochondria from one cell to another, has recently emerged as a potential therapeutic approach for restoring mitochondrial function in diseased cells. In this review, we summarize the current understanding of mitochondrial transfer, including its mechanisms, potential therapeutic applications, and impact on cell death pathways. We also discuss the future directions and challenges in the field of mitochondrial transfer as a novel therapeutic approach in disease diagnosis and treatment.
Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants
Authors: Bader Werner , Steinacher Claudia , Fischer Hannes Thomas , Glueckert Rudolf , Schmutzhard Joachim , Schrott-Fischer Anneliese
Published: May 2023

Globally, over the next few decades, more than 2.5 billion people will suffer from hearing impairment, including profound hearing loss, and millions could potentially benefit from a cochlea implant. To date, several studies have focused on tissue trauma caused by cochlea implantation. The direct immune reaction in the inner ear after an implantation has not been well studied. Recently, therapeutic hypothermia has been found to positively influence the inflammatory reaction caused by electrode insertion trauma. The present study aimed to evaluate the hypothermic effect on the structure, numbers, function and reactivity of macrophages and microglial cells. Therefore, the distribution and activated forms of macrophages in the cochlea were evaluated in an electrode insertion trauma cochlea culture model in normothermic and mild hypothermic conditions. In 10-day-old mouse cochleae, artificial electrode insertion trauma was inflicted, and then they were cultured for 24 h at 37 °C and 32 °C. The influence of mild hypothermia on macrophages was evaluated using immunostaining of cryosections using antibodies against IBA1, F4/80, CD45 and CD163. A clear influence of mild hypothermia on the distribution of activated and non-activated forms of macrophages and monocytes in the inner ear was observed. Furthermore, these cells were located in the mesenchymal tissue in and around the cochlea, and the activated forms were found in and around the spiral ganglion tissue at 37 °C. Our findings suggest that mild hypothermic treatment has a beneficial effect on immune system activation after electrode insertion trauma.
Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?
Authors: Witte Katrin , Schneider-Burrus Sylke , Salinas Gabriela , Mössner Rotraut , Ghoreschi Kamran , Wolk Kerstin , Sabat Robert
Published: May 2023

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4+ memory T (Thmem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Thmem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Thmem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Thmem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Thmem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Thmem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Thmem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.
A Novel Ageladine A Derivative Acts as a STAT3 Inhibitor and Exhibits Potential Antitumor Effects
Authors: He Na , Li Li , Li Rui , Zhang Si-Qi , Wu Li-Hong , Guan Xian , Zhang Qian-Yue , Jiang Tao , Yang Jin-Bo
Published: May 2023

The Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway controls multiple biological processes, including cell survival, proliferation, and differentiation. Abnormally activated STAT3 signaling promotes tumor cell growth, proliferation, and survival, as well as tumor invasion, angiogenesis, and immunosuppression. Hence, JAK/STAT3 signaling has been considered a promising target for antitumor therapy. In this study, a number of ageladine A derivative compounds were synthesized. The most effective of these was found to be compound 25. Our results indicated that compound 25 had the greatest inhibitory effect on the STAT3 luciferase gene reporter. Molecular docking results showed that compound 25 could dock into the STAT3 SH2 structural domain. Western blot assays demonstrated that compound 25 selectively inhibited the phosphorylation of STAT3 on the Tyr705 residue, thereby reducing STAT3 downstream gene expression without affecting the expression of the upstream proteins, p-STAT1 and p-STAT5. Compound 25 also suppressed the proliferation and migration of A549 and DU145 cells. Finally, in vivo research revealed that 10 mg/kg of compound 25 effectively inhibited the growth of A549 xenograft tumors with persistent STAT3 activation without causing significant weight loss. These results clearly indicate that compound 25 could be a potential antitumor agent by inhibiting STAT3 activation.
Step-by-Step Regeneration of Tentacles after Injury in Anemonia viridis—Morphological and Structural Cell Analyses
Authors: La Corte Claudia , Baranzini Nicolò , Dara Mariano , Bon Camilla , Grimaldi Annalisa , Parisi Maria Giovanna , Zizzo Maria Grazia , Cammarata Matteo
Published: May 2023

Benthic marine invertebrates, such as corals, are often subjected to injury caused by several sources. Here, the differences and characteristics in injured and health tissues in terms of cellular components are shown through a histological investigation of the soft coral Anemonia viridis at 0 h, 6 h, 24 h, and 7 days after injury caused by tentacle amputation. In addition, a new tool was used for the first time in invertebrates, positron emission tomography, in order to investigate the events that occur during regeneration within a longer time period (0 h, 24 h, and 14 days after the tentacles were cut). Higher integrated density values were measured through a densitometric analysis in sections stained with Fontana–Masson at 24 h after the tentacles were cut. This suggests an increase in melanin-like containing cells and a subsequent increase in fibroblast-like cells differentiated by amoebocytes that converge to the lesion site in the early stages of inflammation and regeneration. This work provides, for the first time, an elucidation of the events that occur during wound-healing and regeneration in basal metazoan, focusing on the characterisation of immune cells and their role. Our results indicate that Mediterranean anthozoan proves to be a valuable model for studying regeneration. Many events highlighted in this research occur in different phyla, suggesting that they are highly conserved.
Antiviral Therapy of COVID-19
Authors: Gudima Georgii , Kofiadi Ilya , Shilovskiy Igor , Kudlay Dmitry , Khaitov Musa
Published: May 2023

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.
The Pollen Donor Affects Seed Development, Taste, and Flavor Quality in ‘Hayward’ Kiwifruit
Authors: Chai Yanan , Hong Weijin , Liu Hang , Shi Xia , Liu Yanfei , Liu Zhande
Published: May 2023

To investigate how different species or ploidy level of pollen donors affects the fruit quality of kiwifruit, flowers of ‘Hayward’ kiwifruit (a hexaploid Actinidia deliciosa cultivar, 6x) were hand-pollinated with pollen from ten different male donors. Kiwifruit plants pollinated with four distant species—M7 (2x, A. kolomikta), M8 (4x, A. arguta), M9 (4x, A. melanandra), and M10 (2x, A. eriantha)—had a low fruit-setting rate and therefore were not investigated further. Of the other six treatments, kiwifruit plants pollinated with M4 (4x, A. chinensis), M5 (6x, A. deliciosa) M6 (6x, A. deliciosa) had a larger fruit size and weight than those pollinated with M1 (2x, A. chinensis) and M2 (2x, A. chinensis). However, pollination with M1 (2x) and M2 (2x) resulted in seedless fruits, having few small and aborted seeds. Notably, these seedless fruits had higher fructose, glucose, and total sugar and lower citric acid content. This resulted in a higher sugar to acid ratio compared to fruits from plants pollinated with M3 (4x, A. chinensis), M4 (4x), M5 (6x), and M6 (6x). Most volatile compounds increased in the M1 (2x)- and M2 (2x)-pollinated fruit. A combination of principal component analysis (PCA), electronic tongue, and electronic nose suggested that the different pollen donors significantly affected the kiwifruit’s overall taste and volatiles. Specifically, two diploid donors had the most positive contribution. This was in agreement with the findings from the sensory evaluation. In conclusion, the present study showed that the pollen donor affected the seed development, taste, and flavor quality of ‘Hayward’ kiwifruit. This provides useful information for improving the fruit quality and breeding of seedless kiwifruit.
The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis
Authors: Shaker Baraah Tariq , Ismail Asmaa Anwar , Salih Rawan , Hadj Kacem Hassen , Rahmani Mohamed , Struman Ingrid , Bajou Khalid
Published: May 2023

The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.
Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need
Authors: Pretelli Giulia , Spagnolo Calogera Claudia , Ciappina Giuliana , Santarpia Mariacarmela , Pasello Giulia
Published: May 2023

The majority of epidermal growth factor receptor (EGFR) mutations (85–90%) are exon 19 deletions and L858R point mutations of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10–15% of EGFR mutations). The predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions, and exon 20 S768I. This group shows a heterogeneous prevalence, partly due to different testing methods and to the presence of compound mutations, which in some cases can lead to shorter overall survival and different sensitivity to different TKIs compared to simple mutations. Additionally, EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain, and the data of EGFR-TKIs efficacy are based on few prospective and some retrospective series. Newer investigational agents are still under study, and there are no other approved specific treatments targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remains an unmet medical need. The objective of this review is to evaluate existing data on the outcomes, epidemiology, and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.
Pilot Program of Newborn Screening for 5q Spinal Muscular Atrophy in the Russian Federation
Authors: Mikhalchuk Kristina , Shchagina Olga , Chukhrova Alena , Zabnenkova Viktoria , Chausova Polina , Ryadninskaya Nina , Vlodavets Dmitry , Kutsev Sergei I. , Polyakov Alexander
Published: May 2023

5q spinal muscular atrophy (5q SMA) is one of the most common autosomal recessive disorders in the Russian Federation. The first medication to treat 5q SMA was registered in the Russian Federation for treatment of all 5q SMA types in 2019, and the last of the three currently available in December 2021. We launched the pilot newborn screening (NBS) program for 5q SMA in Moscow, the Russian Federation, starting in 2019. During the pilot program, 23,405 neonates were tested for the deletion of exon 7 of the SMN1 gene, the most common cause of 5q SMA. We used the SALSA® MC002 SMA Newborn Screen Kit (MRC Holland) to specifically detect homozygous deletions of SMN1 exon 7. We used the restriction fragment length polymorphism (RFLP) approach to validate detected homozygous deletions and the SALSA MLPA Probemix P060 SMA Carrier Kit (MRC Holland) to determine the SMN2 exon 7 copy number to prescribe gene therapy for 5q SMA. Three newborns with a homozygous deletion of the SMN1 gene were detected. The calculated birth prevalence of 1:7801 appears to be similar to the results in other European countries. The children did not show any signs of respiratory involvement or bulbar weakness immediately after birth. Until now, no 5q SMA case missed by NBS has been detected.