bluuebunny/crossref_metadata_2025 huggingface dataset:
EjFAD8 Enhances the Low-Temperature Tolerance of Loquat by Desaturation of Sulfoquinovosyl Diacylglycerol (SQDG)
Authors: Xu Xun , Yang Hao , Suo Xiaodong , Liu Mingxiu , Jing Danlong , Zhang Yin , Dang Jiangbo , Wu Di , He Qiao , Xia Yan , Wang Shuming , Liang Guolu , Guo Qigao
Published: April 2023

Loquat (Eriobotrya japonica Lindl.) is an evergreen fruit tree of Chinese origin, and its autumn–winter flowering and fruiting growth habit means that its fruit development is susceptible to low-temperature stress. In a previous study, the triploid loquat (B431 × GZ23) has been identified with high photosynthetic efficiency and strong resistance under low-temperature stress. Analysis of transcriptomic and lipidomic data revealed that the fatty acid desaturase gene EjFAD8 was closely associated with low temperatures. Phenotypic observations and measurements of physiological indicators in Arabidopsis showed that overexpressing-EjFAD8 transgenic plants were significantly more tolerant to low temperatures compared to the wild-type. Heterologous overexpression of EjFAD8 enhanced some lipid metabolism genes in Arabidopsis, and the unsaturation of lipids was increased, especially for SQDG (16:0/18:1; 16:0/18:3), thereby improving the cold tolerance of transgenic lines. The expression of ICE-CBF-COR genes were further analyzed so that the relationship between fatty acid desaturase and the ICE-CBF-COR pathway can be clarified. These results revealed the important role of EjFAD8 under low-temperature stress in triploid loquat, the increase expression of FAD8 in loquat under low temperatures lead to desaturation of fatty acids. On the one hand, overexpression of EjFAD8 in Arabidopsis increased the expression of ICE-CBF-COR genes in response to low temperatures. On the other hand, upregulation of EjFAD8 at low temperatures increased fatty acid desaturation of SQDG to maintain the stability of photosynthesis under low temperatures. This study not only indicates that the EjFAD8 gene plays an important role in loquat under low temperatures, but also provides a theoretical basis for future molecular breeding of loquat for cold resistance.
Vibrational Spectroscopy as a Tool for Bioanalytical and Biomonitoring Studies
Authors: Pirutin Sergey K. , Jia Shunchao , Yusipovich Alexander I. , Shank Mikhail A. , Parshina Evgeniia Yu. , Rubin Andrey B.
Published: April 2023

The review briefly describes various types of infrared (IR) and Raman spectroscopy methods. At the beginning of the review, the basic concepts of biological methods of environmental monitoring, namely bioanalytical and biomonitoring methods, are briefly considered. The main part of the review describes the basic principles and concepts of vibration spectroscopy and microspectrophotometry, in particular IR spectroscopy, mid- and near-IR spectroscopy, IR microspectroscopy, Raman spectroscopy, resonance Raman spectroscopy, Surface-enhanced Raman spectroscopy, and Raman microscopy. Examples of the use of various methods of vibration spectroscopy for the study of biological samples, especially in the context of environmental monitoring, are given. Based on the described results, the authors conclude that the near-IR spectroscopy-based methods are the most convenient for environmental studies, and the relevance of the use of IR and Raman spectroscopy in environmental monitoring will increase with time.
Reversal of Pulmonary Fibrosis: Human Umbilical Mesenchymal Stem Cells from Wharton’s Jelly versus Human-Adipose-Derived Mesenchymal Stem Cells
Authors: Chu Kuo-An , Yeh Chang-Ching , Hsu Chun-Hsiang , Hsu Chien-Wei , Kuo Fu-Hsien , Tsai Pei-Jiun , Fu Yu-Show
Published: April 2023

Pulmonary fibrosis (PF) is a progressive, non-reversible illness with various etiologies. Currently, effective treatments for fibrotic lungs are still lacking. Here, we compared the effectiveness of transplantation of human mesenchymal stem cells from umbilical cord Wharton’s jelly (HUMSCs) versus those from adipose tissue (ADMSCs) in reversing pulmonary fibrosis in rats. Bleomycin 5 mg was intratracheally injected to establish a severe, stable, single left lung animal model with PF. On Day 21 post-BLM administration, one single transplantation of 2.5 × 107 HUMSCs or ADMSCs was performed. Lung function examination of Injury and Injury+ADMSCs rats displayed significantly decreased blood oxygen saturation and increased respiratory rates, while Injury+HUMSCs rats showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Reduced cell number in the bronchoalveolar lavage and lower myofibroblast activation appeared in the rats transplanted with either ADMSCs or HUMSCS than that in the Injury group. However, ADMSC transplantation stimulated more adipogenesis. Furthermore, matrix-metallopeptidase-9 over-expression for collagen degradation, and the elevation of Toll-like receptor-4 expression for alveolar regeneration were observed only in the Injury+HUMSCs. In comparison with the transplantation of ADMSCs, transplantation of HUMSCs exhibited a much more effective therapeutic effect on PF, with significantly better results in alveolar volume and lung function.
Genome-Wide Identification and Analysis of Stress Response of Trehalose-6-Phosphate Synthase and Trehalose-6-Phosphate Phosphatase Genes in Quinoa
Authors: Wang Xiaoting , Wang Mingyu , Huang Yongshun , Zhu Peng , Qian Guangtao , Zhang Yiming , Liu Yuqi , Zhou Jingwen , Li Lixin
Published: April 2023

Saline-alkali stress seriously affects the yield and quality of crops, threatening food security and ecological security. Improving saline-alkali land and increasing effective cultivated land are conducive to sustainable agricultural development. Trehalose, a nonreducing disaccharide, is closely related to plant growth and development and stress response. Trehalose 6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) are key enzymes catalyzing trehalose biosynthesis. To elucidate the effects of long-term saline-alkali stress on trehalose synthesis and metabolism, we conducted an integrated transcriptome and metabolome analysis. As a result, 13 TPS and 11 TPP genes were identified in quinoa (Chenopodium quinoa Willd.) and were named CqTPS1-13 and CqTPP1-11 according to the order of their Gene IDs. Through phylogenetic analysis, the CqTPS family is divided into two classes, and the CqTPP family is divided into three classes. Analyses of physicochemical properties, gene structures, conservative domains and motifs in the proteins, and cis-regulatory elements, as well as evolutionary relationships, indicate that the TPS and TPP family characteristics are highly conserved in quinoa. Transcriptome and metabolome analyses of the sucrose and starch metabolism pathway in leaves undergoing saline-alkali stress indicate that CqTPP and Class II CqTPS genes are involved in the stress response. Moreover, the accumulation of some metabolites and the expression of many regulatory genes in the trehalose biosynthesis pathway changed significantly, suggesting the metabolic process is important for the saline-alkali stress response in quinoa.
Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model
Authors: Watanabe Masaki , Shishido Koya , Kanehira Nao , Hiura Koki , Nakano Kenta , Okamura Tadashi , Ando Ryo , Sasaki Hayato , Sasaki Nobuya
Published: April 2023

Most mitochondrial diseases are hereditary and highly heterogeneous. Cattle born with the V79L mutation in the isoleucyl-tRNA synthetase 1 (IARS1) protein exhibit weak calf syndrome. Recent human genomic studies about pediatric mitochondrial diseases also identified mutations in the IARS1 gene. Although severe prenatal-onset growth retardation and infantile hepatopathy have been reported in such patients, the relationship between IARS mutations and the symptoms is unknown. In this study, we generated hypomorphic IARS1V79L mutant mice to develop an animal model of IARS mutation-related disorders. We found that compared to wild-type mice, IARSV79L mutant mice showed a significant increase in hepatic triglyceride and serum ornithine carbamoyltransferase levels, indicating that IARS1V79L mice suffer from mitochondrial hepatopathy. In addition, siRNA knockdown of the IARS1 gene decreased mitochondrial membrane potential and increased reactive oxygen species in the hepatocarcinoma-derived cell line HepG2. Furthermore, proteomic analysis revealed decreased levels of the mitochondrial function-associated protein NME4 (mitochondrial nucleoside diphosphate kinase). Concisely, our mutant mice model can be used to study IARS mutation-related disorders.
Endothelial Injury Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation: Angiopetin-2 as a Novel Predictor of the Outcome and the Role of Functional Autoantibodies against Angiotensin II Type 1 and Endothelin A Receptor
Authors: Vythoulkas Dionysios , Lazana Ioanna , Kroupis Christos , Gavriilaki Eleni , Konstantellos Ioannis , Bousiou Zoi , Chondropoulos Spiros , Griniezaki Marianna , Vardi Anna , Gkirkas Konstantinos , Karagiannidou Aggeliki , Batsis Ioannis , Stamouli Maria , Sakellari Ioanna , Tsirigotis Panagiotis
Published: April 2023

Transplant-associated thrombotic microangiopathy (TMA) occurs in a significant percentage of patients after allogeneic stem cell transplantation (allo-SCT) and is associated with significant morbidity and mortality. The aim of the present study was to examine the association of serum angiopoetin-2 (Ang2) levels and the presence of antibodies against angiotensin II type 1 (AT1R) and ndothelin A Recreptor (ETAR) with the outcome of patients with TMA and/or graft-versus-host disease (GVHD) after allo-SCT. Analysis of our data showed that elevated serum Ang2 levels at the time of TMA diagnosis are significantly associated with increased non-relapse mortality and decreased overall survival. To our knowledge, this is the first study demonstrating an association between raised Ang2 levels and poor outcomes in patients with TMA. Antibodies against AT1R (AT1R-Abs) and ETAR (ETAR-Abs) were detected in 27% and 23% of the patients, respectively, but there was no association between the presence of autoantibodies and the outcome of patients with TMA. However, a significant finding was the strong positive correlation between the presence of AT1R-Abs with the occurrence of chronic fibrotic GVHD, such as scleroderma and cryptogenic organizing pneumonia, raising the possibility of the contribution of autoantibodies in the pathogenesis of fibrotic GVHD manifestations.
How Can We Prevent Mother-to-Child Transmission of HTLV-1?
Authors: Itabashi Kazuo , Miyazawa Tokuo , Uchimaru Kaoru
Published: April 2023

The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a “silent disease” has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells; however, it is also responsible for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Most patients develop ATL as a result of HTLV-1 mother-to-child transmission. The primary route of mother-to-child transmission is through the mother’s milk. In the absence of effective drug therapy, total artificial nutrition such as exclusive formula feeding is a reliable means of preventing mother-to-child transmission after birth, except for a small percentage of prenatal infections. A recent study found that the rate of mother-to-child transmission with short-term breastfeeding (within 90 days) did not exceed that of total artificial nutrition. Because these preventive measures are in exchange for the benefits of breastfeeding, clinical applications of antiretroviral drugs and immunotherapy with vaccines and neutralizing antibodies are urgently needed.
Immunogenicity and Safety of Adjuvanted Recombinant Zoster Vaccine in Rheumatoid Arthritis Patients on Anti-Cellular Biologic Agents or JAK Inhibitors: A Prospective Observational Study
Authors: Venerito Vincenzo , Stefanizzi Pasquale , Cantarini Luca , Lavista Marlea , Galeone Maria Grazia , Di Lorenzo Antonio , Iannone Florenzo , Tafuri Silvio , Lopalco Giuseppe
Published: April 2023

Rheumatoid arthritis (RA) patients on JAK inhibitors (JAKi) have an increased HZ risk compared to those on biologic DMARDs (bDMARDs). Recently, the Adjuvanted Recombinant Zoster Vaccine (RZV) became available worldwide, showing good effectiveness in patients with inflammatory arthritis. Nevertheless, direct evidence of the immunogenicity of such a vaccine in those on JAKi or anti-cellular bDMARDs is still lacking. This prospective study aimed to assess RZV immunogenicity and safety in RA patients receiving JAKi or anti-cellular bDMARDs that are known to lead to impaired immune response. Patients with classified RA according to ACR/EULAR 2010 criteria on different JAKi or anti-cellular biologics (namely, abatacept and rituximab) followed at the RA clinic of our tertiary center were prospectively observed. Patients received two shots of the RZV. Treatments were not discontinued. At the first and second shots, and one month after the second shot, from all patients with RA, a sample was collected and RZV immunogenicity was assessed and compared between the treatment groups and healthy controls (HCs) receiving RZV for routine vaccination. We also kept track of disease activity at different follow-up times. Fifty-two consecutive RA patients, 44 females (84.61%), with an average age (±SD) of 57.46 ± 11.64 years and mean disease duration of 80.80 ± 73.06 months, underwent complete RZV vaccination between February and June 2022 at our center. At the time of the second shot (1-month follow-up from baseline), anti-VZV IgG titer increased significantly in both groups with similar magnitude (bDMARDs: 2258.76 ± 897.07 mIU/mL; JAKi: 2059.19 ± 876.62 mIU/mL, p < 0.001 for both from baseline). At one-month follow-up from the second shot, anti-VZV IgG titers remained stable in the bDMARDs group (2347.46 ± 975.47) and increased significantly in the JAKi group (2582.65 ± 821.59 mIU/mL, p = 0.03); still, no difference was observed between groups comparing IgG levels at this follow-up time. No RA flare was recorded. No significant difference was shown among treatment groups and HCs. RZV immunogenicity is not impaired in RA patients on JAKi or anti-cellular bDMARDs. A single shot of RZV can lead to an anti-VZV immune response similar to HCs without discontinuing DMARDs.
Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer’s Disease
Authors: Lopes Cátia R. , Silva Joana S. , Santos Joana , Rodrigues Matilde S. , Madeira Daniela , Oliveira Andreia , Moreira-de-Sá Ana , Lourenço Vanessa S. , Gonçalves Francisco Q. , Silva Henrique B. , Simões Ana Patrícia , Rolo Anabela P. , Canas Paula M. , Tomé Ângelo R. , Palmeira Carlos M. , Lopes João Pedro , Cunha Rodrigo A. , Agostinho Paula , Ferreira Samira G.
Published: April 2023

Alzheimer’s disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.
Study of Lipophilicity and ADME Properties of 1,9-Diazaphenothiazines with Anticancer Action
Authors: Morak-Młodawska Beata , Jeleń Małgorzata , Martula Emilia , Korlacki Rafał
Published: April 2023

Lipophilicity is one of the key properties of a potential drug that determines the solubility, the ability to penetrate through cell barriers, and transport to the molecular target. It affects pharmacokinetic processes such as adsorption, distribution, metabolism, excretion (ADME). The 10-substituted 1,9-diazaphenothiazines show promising if not impressive in vitro anticancer potential, which is associated with the activation of the mitochondrial apoptosis pathway connected with to induction BAX, forming a channel in MOMP and releasing cytochrome c for the activation of caspases 9 and 3. In this publication, the lipophilicity of previously obtained 1,9-diazaphenothiazines was determined theoretically using various computer programs and experimentally using reverse-phase thin-layer chromatography (RP-TLC) and a standard curve. The study presents other physicochemical, pharmacokinetic, and toxicological properties affecting the bioavailability of the test compounds. ADME analysis was determined in silico using the SwissADME server. Molecular targets studies were identified in silico using the SwissTargetPrediction server. Lipinski’s rule of five, Ghose’s, and Veber’s rules were checked for the tested compounds, confirming their bioavailability.
The Pathogenesis of Diabetes
Authors: Guo Huiqin , Wu Haili , Li Zhuoyu
Published: April 2023

Diabetes is the most common metabolic disorder, with an extremely serious effect on health systems worldwide. It has become a severe, chronic, non-communicable disease after cardio-cerebrovascular diseases. Currently, 90% of diabetic patients suffer from type 2 diabetes. Hyperglycemia is the main hallmark of diabetes. The function of pancreatic cells gradually declines before the onset of clinical hyperglycemia. Understanding the molecular processes involved in the development of diabetes can provide clinical care with much-needed updates. This review provides the current global state of diabetes, the mechanisms involved in glucose homeostasis and diabetic insulin resistance, and the long-chain non-coding RNA (lncRNA) associated with diabetes.
New Perspectives of Multiplex Mass Spectrometry Blood Protein Quantification on Microsamples in Biological Monitoring of Elderly Patients
Authors: Vialaret Jérôme , Vignon Margaux , Badiou Stéphanie , Baptista Gregory , Fichter Laura , Dupuy Anne-Marie , Maceski Aleksandra Maleska , Fayolle Martin , Brousse Mehdi , Cristol Jean-Paul , Jeandel Claude , Hirtz Christophe , Lehmann Sylvain
Published: April 2023

Blood microsampling combined with large panels of clinically relevant tests are of major interest for the development of home sampling and predictive medicine. The aim of the study was to demonstrate the practicality and medical utility of microsamples quantification using mass spectrometry (MS) in a clinical setting by comparing two types of microsamples for multiplex MS protein detection. In a clinical trial based on elderly population, we compared 2 µL of plasma to dried blood spot (DBS) with a clinical quantitative multiplex MS approach. The analysis of the microsamples allowed the quantification of 62 proteins with satisfactory analytical performances. A total of 48 proteins were significantly correlated between microsampling plasma and DBS (p < 0.0001). The quantification of 62 blood proteins allowed us to stratify patients according to their pathophysiological status. Apolipoproteins D and E were the best biomarker link to IADL (instrumental activities of daily living) score in microsampling plasma as well as in DBS. It is, thus, possible to detect multiple blood proteins from micro-samples in compliance with clinical requirements and this allows, for example, to monitor the nutritional or inflammatory status of patients. The implementation of this type of analysis opens new perspectives in the field of diagnosis, monitoring and risk assessment for personalized medicine approaches.
Optimization of Monobenzone-Induced Vitiligo Mouse Model by the Addition of Chronic Stress
Authors: Dong Jing , Lai Yifan , Zhang Xiaofeng , Yue Yunyun , Zhong Hui , Shang Jing
Published: April 2023

Vitiligo is a common primary, limited or generalized skin depigmentation disorder. Its pathogenesis is complex, multifactorial and unclear. For this reason, few animal models can simulate the onset of vitiligo, and studies of drug interventions are limited. Studies have found that there may be a pathophysiological connection between mental factors and the development of vitiligo. At present, the construction methods of the vitiligo model mainly include chemical induction and autoimmune induction against melanocytes. Mental factors are not taken into account in existing models. Therefore, in this study, mental inducement was added to the monobenzone (MBEH)-induced vitiligo model. We determined that chronic unpredictable mild stress (CUMS) inhibited the melanogenesis of skin. MBEH inhibited melanin production without affecting the behavioral state of mice, but mice in the MBEH combined with CUMS (MC) group were depressed and demonstrated increased depigmentation of the skin. Further analysis of metabolic differences showed that all three models altered the metabolic profile of the skin. In summary, we successfully constructed a vitiligo mouse model induced by MBEH combined with CUMS, which may be better used in the evaluation and study of vitiligo drugs.
Genome-Wide Identification and Transcriptome-Based Expression Profile of Cuticular Protein Genes in Antheraea pernyi
Authors: Fu Xin , Chen Miaomiao , Xia Runxi , Li Xinyu , Li Qun , Li Yuping , Cao Huiying , Liu Yanqun
Published: April 2023

Antheraea pernyi is one of the most famous edible and silk-producing wild silkworms of Saturniidae. Structural cuticular proteins (CPs) are the primary component of insect cuticle. In this paper, the CPs in the genome of A. pernyi were identified and compared with those of the lepidopteran model species Bombyx mori, and expression patterns were analyzed based on the transcriptomic data from the larval epidermis/integument (epidermis in the following) and some non-epidermis tissues/organs of two silkworm species. A total of 217 CPs was identified in the A. pernyi genome, a comparable number to B. mori (236 CPs), with CPLCP and CPG families being the main contribution to the number difference between two silkworm species. We found more RR-2 genes expressed in the larval epidermis of fifth instar of A. pernyi than B. mori, but less RR-2 genes expressed in the prothoracic gland of A. pernyi than B. mori, which suggests that the hardness difference in the larval epidermis and prothoracic gland between the two species may be caused by the number of RR-2 genes expressed. We also revealed that, in B. mori, the number of CP genes expressed in the corpus allatum and prothoracic gland of fifth instar was higher than that in the larval epidermis. Our work provided an overall framework for functional research into the CP genes of Saturniidae.
Early Steps towards Hearing: Placodes and Sensory Development
Authors: Zine Azel , Fritzsch Bernd
Published: April 2023

Sensorineural hearing loss is the most prevalent sensory deficit in humans. Most cases of hearing loss are due to the degeneration of key structures of the sensory pathway in the cochlea, such as the sensory hair cells, the primary auditory neurons, and their synaptic connection to the hair cells. Different cell-based strategies to replace damaged inner ear neurosensory tissue aiming at the restoration of regeneration or functional recovery are currently the subject of intensive research. Most of these cell-based treatment approaches require experimental in vitro models that rely on a fine understanding of the earliest morphogenetic steps that underlie the in vivo development of the inner ear since its initial induction from a common otic–epibranchial territory. This knowledge will be applied to various proposed experimental cell replacement strategies to either address the feasibility or identify novel therapeutic options for sensorineural hearing loss. In this review, we describe how ear and epibranchial placode development can be recapitulated by focusing on the cellular transformations that occur as the inner ear is converted from a thickening of the surface ectoderm next to the hindbrain known as the otic placode to an otocyst embedded in the head mesenchyme. Finally, we will highlight otic and epibranchial placode development and morphogenetic events towards progenitors of the inner ear and their neurosensory cell derivatives.
Correction: Liu et al. Exogenous H2S Attenuates Hypertension by Regulating Renin Exocytosis under Hyperglycaemic and Hyperlipidaemic Conditions. Int. J. Mol. Sci. 2023, 24, 1690
Authors: Liu Ning , Li Mingyu , Liu Siyuan , Kang Jiaxin , Chen Lingxue , Huang Jiayi , Wang Yan , Chen He , Zhang Weihua
Published: April 2023

In the original publication [...]
Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial Progenitor Cells and Function
Authors: Hsu Chien-Yi , Huang Chun-Yao , Shih Chun-Ming , Lin Yi-Wen , Huang Po-Hsun , Lin Shing-Jong , Liu Chen-Wei , Lin Cheng-Yen , Lin Feng-Yen
Published: April 2023

Tumor necrosis factor superfamily 14 (TNFSF14) is also known as the LT-related inducible ligand (LIGHT). It can bind to the herpesvirus invasion mediator and lymphotoxin-β receptor to perform its biological activity. LIGHT has multiple physiological functions, including strengthening the synthesis of nitric oxide, reactive oxygen species, and cytokines. LIGHT also stimulates angiogenesis in tumors and induces the synthesis of high endothelial venules; degrades the extracellular matrix in thoracic aortic dissection, and induces the expression of interleukin-8, cyclooxygenase-2, and cell adhesion molecules in endothelial cells. While LIGHT induces tissue inflammation, its effects on angiogenesis after tissue ischemia are unclear. Thus, we analyzed these effects in the current study. In this study, the animal model of hind limb ischemia surgery in C57BL/6 mice was performed. Doppler ultrasound, immunohistochemical staining, and Western blotting were employed to analyze the situation of angiogenesis. In addition, human endothelial progenitor cells (EPCs) were used for in vitro studies to analyze the possible mechanisms. The results in the animal study showed that LIGHT injection inhibited angiogenesis in ischemic limbs. For the in vitro studies, LIGHT inhibited the expression of integrins and E-selectin; decreased migration and tube formation capabilities, mitochondrial respiration, and succinate dehydrogenase activity; and promoted senescence in EPCs. Western blotting revealed that the impairment of EPC function by LIGHT may be due to its effects on the proper functioning of the intracellular Akt signaling pathway, endothelial nitrite oxide synthase (eNOS), and mitochondrial respiration. In conclusion, LIGHT inhibits angiogenesis after tissue ischemia. This may be related to the clamped EPC function.
RFRP-3 Influences Apoptosis and Steroidogenesis of Yak Cumulus Cells and Compromises Oocyte Meiotic Maturation and Subsequent Developmental Competence
Authors: Xiong Xianrong , Hu Yulei , Pan Bangting , Zhu Yanjin , Fei Xixi , Yang Qinhui , Xie Yumian , Xiong Yan , Lan Daoliang , Fu Wei , Li Jian
Published: April 2023

RF amide-related peptide 3 (RFRP-3), a mammalian ortholog of gonadotropin-inhibitory hormone (GnIH), is identified to be a novel inhibitory endogenous neurohormonal peptide that regulates mammalian reproduction by binding with specific G protein-coupled receptors (GPRs) in various species. Herein, our objectives were to explore the biological functions of exogenous RFRP-3 on the apoptosis and steroidogenesis of yak cumulus cells (CCs) and the developmental potential of yak oocytes. The spatiotemporal expression pattern and localization of GnIH/RFRP-3 and its receptor GPR147 were determined in follicles and CCs. The effects of RFRP-3 on the proliferation and apoptosis of yak CCs were initially estimated by EdU assay and TUNEL staining. We confirmed that high-dose (10−6 mol/L) RFRP-3 suppressed viability and increased the apoptotic rates, implying that RFRP-3 could repress proliferation and induce apoptosis. Subsequently, the concentrations of E2 and P4 were significantly lower with 10−6 mol/L RFRP-3 treatment than that of the control counterparts, which indicated that the steroidogenesis of CCs was impaired after RFRP-3 treatment. Compared with the control group, 10−6 mol/L RFRP-3 treatment decreased the maturation of yak oocytes efficiently and subsequent developmental potential. We sought to explore the potential mechanism of RFRP-3-induced apoptosis and steroidogenesis, so we observed the levels of apoptotic regulatory factors and hormone synthesis-related factors in yak CCs after RFRP-3 treatment. Our results indicated that RFRP-3 dose-dependently elevated the expression of apoptosis markers (Caspase and Bax), whereas the expression levels of steroidogenesis-related factors (LHR, StAR, 3β-HSD) were downregulated in a dose-dependent manner. However, all these effects were moderated by cotreatment with inhibitory RF9 of GPR147. These results demonstrated that RFRP-3 adjusted the expression of apoptotic and steroidogenic regulatory factors to induce apoptosis of CCs, probably through binding with its receptor GPR147, as well as compromised oocyte maturation and developmental potential. This research revealed the expression profiles of GnIH/RFRP-3 and GPR147 in yak CCs and supported a conserved inhibitory action on oocyte developmental competence.
Molecular Recognition of Methacryllysine and Crotonyllysine by the AF9 YEATS Domain
Authors: Bilgin Nurgül , Moesgaard Laust , Rahman Mohammad M. , Türkmen Vildan A. , Kongsted Jacob , Mecinović Jasmin
Published: April 2023

Histone lysine methacrylation and crotonylation are epigenetic marks that play important roles in human gene regulation. Here, we explore the molecular recognition of histone H3 peptides possessing methacryllysine and crotonyllysine at positions 18 and 9 (H3K18 and H3K9) by the AF9 YEATS domain. Our binding studies demonstrate that the AF9 YEATS domain displays a higher binding affinity for histones possessing crotonyllysine than the isomeric methacryllysine, indicating that AF9 YEATS distinguishes between the two regioisomers. Molecular dynamics simulations reveal that the crotonyllysine/methacryllysine-mediated desolvation of the AF9 YEATS domain provides an important contribution to the recognition of both epigenetic marks. These results provide important knowledge for the development of AF9 YEATS inhibitors, an area of biomedical interest.
Graph Neural Networks and Open-Government Data to Forecast Traffic Flow
Authors: Brimos Petros , Karamanou Areti , Kalampokis Evangelos , Tarabanis Konstantinos
Published: April 2023

Traffic forecasting has been an important area of research for several decades, with significant implications for urban traffic planning, management, and control. In recent years, deep-learning models, such as graph neural networks (GNN), have shown great promise in traffic forecasting due to their ability to capture complex spatio–temporal dependencies within traffic networks. Additionally, public authorities around the world have started providing real-time traffic data as open-government data (OGD). This large volume of dynamic and high-value data can open new avenues for creating innovative algorithms, services, and applications. In this paper, we investigate the use of traffic OGD with advanced deep-learning algorithms. Specifically, we deploy two GNN models—the Temporal Graph Convolutional Network and Diffusion Convolutional Recurrent Neural Network—to predict traffic flow based on real-time traffic OGD. Our evaluation of the forecasting models shows that both GNN models outperform the two baseline models—Historical Average and Autoregressive Integrated Moving Average—in terms of prediction performance. We anticipate that the exploitation of OGD in deep-learning scenarios will contribute to the development of more robust and reliable traffic-forecasting algorithms, as well as provide innovative and efficient public services for citizens and businesses.
Optimal Load Redistribution in Distribution Systems Using a Mixed-Integer Convex Model Based on Electrical Momentum
Authors: Bohórquez-Álvarez Daniela Patricia , Niño-Perdomo Karen Dayanna , Montoya Oscar Danilo
Published: April 2023

This paper addresses the problem concerning the efficient minimization of power losses in asymmetric distribution grids from the perspective of convex optimization. This research’s main objective is to propose an approximation optimization model to reduce the total power losses in a three-phase network using the concept of electrical momentum. To obtain a mixed-integer convex formulation, the voltage variables at each node are relaxed by assuming them to be equal to those at the substation bus. With this assumption, the power balance constraints are reduced to flow restrictions, allowing us to formulate a set of linear rules. The objective function is formulated as a strictly convex objective function by applying the concept of average electrical momentum, by representing the current flows in distribution lines as the active and reactive power variables. To solve the relaxed MIQC model, the GAMS software (Version 28.1.2) and its CPLEX, SBB, and XPRESS solvers are used. In order to validate the effectiveness of load redistribution in power loss minimization, the initial and final grid configurations are tested with the triangular-based power flow method for asymmetric distribution networks. Numerical results show that the proposed mixed-integer model allows for reductions of 24.34%, 18.64%, and 4.14% for the 8-, 15-, and 25-node test feeders, respectively, in comparison with the benchmark case. The sine–cosine algorithm and the black hole optimization method are also used for comparison, demonstrating the efficiency of the MIQC approach in minimizing the expected grid power losses for three-phase unbalanced networks.
Enhanced Readability of Electrical Network Complex Emergency Modes Provided by Data Compression Methods
Authors: Kulikov Aleksandr , Ilyushin Pavel , Loskutov Anton
Published: April 2023

Current microprocessor-based relay protection and automation (RPA) devices supported by IEC 61850 provide access to a large amount of information on the protected or controlled electric power facility in real time. The issue of using such information (Big Data) in order to improve the parameters of technical modification of intelligent electronic devices at digital substations remains unaddressed. Prerequisites arise for designing modern power systems with relay protection devices of a new generation based on new information algorithms. In particular, it is expedient to develop multi-parameter protections using more than one information parameter: modules of current, voltage, derivatives thereof, phase angles, active and reactive resistances, etc. An information approach based on multiple modeling and statistical processing of modeling results is also promising. This article explores the issues of enhanced sensitivity of multi-parameter relay protection using long-range redundancy protection as an example. Transition to “generalized features” is proposed in order to simplify multi-parameter protection and reduction in the computational load on the RPA device. Out of a large number of analyzed indicators (currents, voltages, their derivatives, resistances, increments of currents, angles between current and voltage, etc.), we specify the most informative by using the method of “data compression”. The transition to generalized features simplifies the parameterization of settings, and the process of making a decision by the relay protection device is reduced to obtaining a generalized feature and comparing it with a dimensionless setting in relative terms. For the formation of generalized information features, two mathematical methods are studied: the method of principal components and Fisher’s linear discriminant.
Structure Learning and Hyperparameter Optimization Using an Automated Machine Learning (AutoML) Pipeline
Authors: Filippou Konstantinos , Aifantis George , Papakostas George A. , Tsekouras George E.
Published: April 2023

In this paper, we built an automated machine learning (AutoML) pipeline for structure-based learning and hyperparameter optimization purposes. The pipeline consists of three main automated stages. The first carries out the collection and preprocessing of the dataset from the Kaggle database through the Kaggle API. The second utilizes the Keras-Bayesian optimization tuning library to perform hyperparameter optimization. The third focuses on the training process of the machine learning (ML) model using the hyperparameter values estimated in the previous stage, and its evaluation is performed on the testing data by implementing the Neptune AI. The main technologies used to develop a stable and reusable machine learning pipeline are the popular Git version control system, the Google cloud virtual machine, the Jenkins server, the Docker containerization technology, and the Ngrok reverse proxy tool. The latter can securely publish the local Jenkins address as public through the internet. As such, some parts of the proposed pipeline are taken from the thematic area of machine learning operations (MLOps), resulting in a hybrid software scheme. The machine learning model was used to evaluate the pipeline, which is a multilayer perceptron (MLP) that combines typical dense, as well as polynomial, layers. The simulation results show that the proposed pipeline exhibits a reliable and accurate performance while managing to boost the network’s performance in classification tasks.
Architecture and Data Knowledge of the Regional Data Center for Intelligent Agriculture
Authors: Doychev Emil , Terziyski Atanas , Tenev Stoyan , Stoyanova-Doycheva Asya , Ivanova Vanya , Atanasova Pepa
Published: April 2023

The main task of the National Research Program “Smart crop production”, supported by the Ministry of Education and Science of Bulgaria and approved by the Council of Ministers, is the development of a regional data center to facilitate the work of farmers. The regional data center is part of the implementation of a smart crop production environment called ZEMEL which provides personal assistants supporting the work of farmers. The environment provides intelligent services for crop analysis and prevention and assists farmers in performing basic tasks related to crop production. The objective of the proposed article is to present the implementation of the architecture, infrastructure, and data architecture of a regional data center in the Plovdiv region. In order to clearly present the results of this work, which are the architectural and physical implementations of a regional data center and the storage of dynamic data and background knowledge, a methodology consisting of several steps is followed: the system infrastructure of the data center and the data architecture are discussed; one of the local pieces of infrastructure, implemented in the Institute of Plant Genetic Resources (IPGR) in the town of Sadovo in the Plovdiv region, is presented in detail, including the different types of sensors and their connection to the data center in wheat cultivation; the data repositories are discussed where dynamic data and background knowledge are stored. The paper pays special attention to background knowledge developed as ontologies for winter wheat cultivation. The results are summarized by drawing some conclusions and recommendations for the design of the local infrastructure of the center and the stored data to improve its performance.
Novel Approach for a Controlled Delivery of Essential Oils during Long-Term Maize Storage: Clove Bud and Pennyroyal Oils Efficacy to Control Sitophilus zeamais, Reducing Grain Damage and Post-Harvest Losses
Authors: Sousa Pedro A. S. , Neto Joana , Barbosa Joana V. , Peres Joana , Magro Ana , Barros Graça , Sousa José M. , Magalhães Fernão D. , Mexia António , Aguiar Ana A. R. M. , Bastos Margarida M. S. M.
Published: April 2023

Maize grains represent a significant contribution for assuring food safety all over the globe. Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae), also known as the maize weevil, is one of the most destructive pests in stored maize, causing qualitative and quantitative losses. To control S. zeamais populations in maize storage sites, synthetical chemical insecticides are applied. However, these are often used wastefully, have environmental implications, and can induce the development of resistant populations. In this work, the insecticidal and grain protecting efficacy of an innovative macro-capsule delivery device, loaded with essential oils from Clove bud and Pennyroyal, as well as their combined solutions, was tested against naturally S. zeamais-infested maize grains. The blend of both compounds incorporated in a controlled release device reduced losses by more than 45% over a long storage period of twenty weeks, diminishing the survivability of maize weevils by over 90%. The usage of the blend at a concentration of 370 μL⋅Lair−1 with an antioxidant showed the best results, however, by halving the concentration (185 μL⋅Lair−1), a significant control of S. zeamais populations was still achieved.
The Interaction of Slaughtering, Drying, and Defatting Methods Differently Affects Oxidative Quality of the Fat from Black Soldier Fly (Hermetia illucens) Larvae
Authors: Hurtado-Ribeira Raúl , Hernández Diego Martín , Villanueva-Bermejo David , García-Risco Mónica R. , Hernández M. Dolores , Vázquez Luis , Fornari Tiziana , Martin Diana
Published: April 2023

The interrelation effect of slaughtering, drying, and defatting methods of BSFL on the oxidative quality of the derived fat was studied. Blanching and freezing were compared as slaughtering methods, followed by oven or freeze-drying for drying and mechanical pressing or SFE for defatting. The oxidative state and stability of the extracted fat and defatted meals were monitored immediately after their production, using peroxide value (PV) and Rancimat test, and over 24 weeks of storage. Slaughtering and drying methods had an independent effect on PV, with freezing and freeze-drying being the best methods. Mechanical pressing and SFE were comparable and superior to conventional hexane defatting. Interactions were observed between slaughtering and defatting, drying and defatting, and between all three factors. Generally, freeze-drying combined with any of the slaughtering and defatting methods resulted in the lowest PVs, with mechanical pressing being preferred. Freeze-drying plus mechanical pressing also produced the most stable fats during storage according to the evolution of PV, while the combination of blanching and SFE produced the least stable. A significant correlation was found between the PV at 24 weeks and the antioxidant activity of the fats. Contrary to storage assays, in accelerated Rancimat assays, freeze-dried samples were the least stable, which was partially attributed to the significant correlation with the acid values of the samples. Defatted meals followed a similar pattern to the extracted fat, except for worse oxidation for SFE defatting. Therefore, the different processing methods of slaughtering, drying, and defatting of BSFL differently affect lipid oxidation, with interactions between such successive steps.
Association between Sex-Related ALOX5 Gene Polymorphisms and Lung Atopy Risk
Authors: Mirra Davida , Esposito Renata , Spaziano Giuseppe , Rafaniello Concetta , Iovino Pasquale , Cione Erika , Gallelli Luca , D’Agostino Bruno
Published: April 2023

Atopy is an exaggerated IgE-mediated immune response to foreign antigens in which metabolic abnormalities of the leukotrienes (LTs) pathway play a crucial role. Recent studies have described sex as a key variable in LT biosynthesis, partly explaining why treatment with anti-LT drugs in atopic subjects leads to better control of symptoms in women. In addition, variability in LT production is often associated with single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase (ALOX5) gene, which encodes the leukotriene-synthesizing enzyme machinery, 5-lipoxygenase (5-LO). This study aimed to investigate whether two SNPs of ALOX5 are implicated in sex differences in allergic diseases in a prospective cohort of 150 age- and sex-matched atopic and healthy subjects. Rs2029253 and rs2115819 were genotyped using allele-specific RT-PCR, and serum levels of 5-LO and LTB4 were measured by ELISA. Both polymorphisms are significantly more common in women than in men, and their influences on LT production vary as a function of sex, leading to a decrease in men’s and an increase in women’s serum levels of 5-LO and LTB4. These data represent a new resource for understanding sex-related differences in lung inflammatory diseases, partly explaining why women are more likely to develop allergic disorders than men.