bluuebunny/crossref_metadata_2025 huggingface dataset:
Mulberry Component Kuwanon C Exerts Potent Therapeutic Efficacy In Vitro against COVID-19 by Blocking the SARS-CoV-2 Spike S1 RBD:ACE2 Receptor Interaction
Authors: Kim Young Soo , Kwon Eun-Bin , Kim Buyun , Chung Hwan-Suck , Choi Garam , Kim Yeoun-Hee , Choi Jang-Gi
Published: October 2022

There has been an immense effort by global pharmaceutical companies to develop anti-COVID-19 drugs, including small molecule-based RNA replication inhibitors via drug repositioning and antibody-based spike protein blockers related to cell entry by SARS-CoV-2. However, several limitations to their clinical use have emerged in addition to a lack of progress in the development of small molecule-based cell entry inhibitors from natural products. In this study, we tested the effectiveness of kuwanon C (KC), which has mainly been researched using in silico docking simulation and can serve as an effective building block for developing anti-COVID-19 drugs, in blocking the spike S1 RBD:ACE2 receptor interaction. KC is a natural product derived from Morus alba L., commonly known as mulberry, which has known antiviral efficacy. Molecular interaction studies using competitive ELISA and the BLItz system revealed that KC targets both the spike S1 RBD and the ACE2 receptor, successfully disrupting their interaction, as supported by the in silico docking simulation. Furthermore, we established a mechanism of action by observing how KC prevents the infection of SARS-CoV-2 spike pseudotyped virus in ACE2/TPRSS2-overexpressing HEK293T cells. Finally, we demonstrated that KC inhibits clinical isolates of SARS-CoV-2 in Vero cells. Future combinations of small molecule-based cell entry inhibitors, such as KC, with the currently prescribed RNA replication inhibitors are anticipated to significantly enhance the efficacy of COVID-19 therapies.
Antimicrobial and Photoantimicrobial Activities of Chitosan/CNPPV Nanocomposites
Authors: Facchinatto William M. , Araujo Leandro O. , Moraes Tiago B. , Abelha Thais F. , Lima Thalita H. N. , Santos Danilo M. dos , Campana-Filho Sérgio P. , Colnago Luiz A. , Caires Anderson R. L.
Published: October 2022

Multidrug-resistant bacteria represent a global health and economic burden that urgently calls for new technologies to combat bacterial antimicrobial resistance. Here, we developed novel nanocomposites (NCPs) based on chitosan that display different degrees of acetylation (DAs), and conjugated polymer cyano-substituted poly(p-phenylene vinylene) (CNPPV) as an alternative approach to inactivate Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Chitosan’s structure was confirmed through FT-Raman spectroscopy. Bactericidal and photobactericidal activities of NCPs were tested under dark and blue-light irradiation conditions, respectively. Hydrodynamic size and aqueous stability were determined by DLS, zeta potential (ZP) and time-domain NMR. TEM micrographs of NCPs were obtained, and their capacity of generating reactive oxygen species (ROS) under blue illumination was also characterized. Meaningful variations on ZP and relaxation time T2 confirmed successful physical attachment of chitosan/CNPPV. All NCPs exhibited a similar and shrunken spherical shape according to TEM. A lower DA is responsible for driving higher bactericidal performance alongside the synergistic effect from CNPPV, lower nanosized distribution profile and higher positive charged surface. ROS production was proportionally found in NCPs with and without CNPPV by decreasing the DA, leading to a remarkable photobactericidal effect under blue-light irradiation. Overall, our findings indicate that chitosan/CNPPV NCPs may constitute a valuable asset for the development of innovative strategies for inactivation and/or photoinactivation of bacteria.
Identification and Investigation of the Genetic Variations and Candidate Genes Responsible for Seed Weight via GWAS in Paper Mulberry
Authors: Hu Yanmin , Peng Xianjun , Shen Shihua
Published: October 2022

Seeds directly determine the survival and population size of woody plants, but the genetic basis of seed weight in woody plants remain poorly explored. To identify genetic variations and candidate genes responsible for seed weight in natural woody populations, we investigated the hundred-seed weight of 198 paper mulberry individuals from different areas. Our results showed that the hundred-seed weight of paper mulberry was significantly associated with the bioclimatic variables of sampling sites, which increased from south to north along the latitudinal-temperature gradient. Using 2,414,978 high-quality SNPs from re-sequencing data, the genome-wide association analysis of the hundred-seed weight was performed under three models, which identified 148, 19 and 12 associated genes, respectively. Among them, 25 candidate genes were directly hit by the significant SNPs, including the WRKY transcription factor, fatty acid desaturase, F-box protein, etc. Most importantly, we identified three crucial genetic variations in the coding regions of candidate genes (Bp02g2123, Bp01g3291 and Bp10g1642), and significant differences in the hundred-seed weight were detected among the individuals carrying different genotypes. Further analysis revealed that Bp02g2123 encoding a fatty acid desaturase (FAD) might be a key factor affecting the seed weight and local climate adaptation of woody plants. Furthermore, the genome-wide investigation and expression analysis of FAD genes were performed, and the results suggested that BpFADs widely expressed in various tissues and responded to multiple phytohormone and stress treatments. Overall, our study identifies valuable genetic variations and candidate genes, and provides a better understanding of the genetic basis of seed weight in woody plants.
Annexin A2 Improves the Osteogenic Differentiation of Mesenchymal Stem Cells Exposed to High-Glucose Conditions through Lessening the Senescence
Authors: Klabklai Parin , Phetfong Jitrada , Tangporncharoen Rattanawan , Isarankura-Na-Ayudhya Chartchalerm , Tawonsawatruk Tulyapruek , Supokawej Aungkura
Published: October 2022

Osteoporosis is frequently found in chronic diabetic patients, and it results in an increased risk of bone fractures occurring. The underlying mechanism of osteoporosis in diabetic patients is still largely unknown. Annexin A2 (ANXA2), a family of calcium-binding proteins, has been reported to be involved in many biological process including bone remodeling. This study aimed to investigate the role of ANXA2 in mesenchymal stem cells (MSCs) during in vitro osteoinduction under high-glucose concentrations. Osteogenic gene expression, calcium deposition, and cellular senescence were determined. The high-glucose conditions reduced the osteogenic differentiation potential of the MSCs along with the lower expression of ANXA2. Moreover, the high-glucose conditions increased the cellular senescence of the MSCs as determined by senescence-associated β-galactosidase staining and the expression of p16, p21, and p53 genes. The addition of recombinant ANXA2 could recover the glucose-induced deterioration of the osteogenic differentiation of the MSCs and ameliorate the glucose-induced cellular senescence of the MSCs. A Western blot analysis revealed an increase in p53 and phosphorylated p53 (Ser 15), which was decreased by recombinant ANXA2 in MSC osteoblastic differentiation under high-glucose conditions. Our study suggested that the alteration of ANXA2 in high-glucose conditions may be one of the plausible factors in the deterioration of bones in diabetic patients by triggering cellular senescence.
Reactive Centre Loop Mutagenesis of SerpinB3 to Target TMPRSS2 and Furin: Inhibition of SARS-CoV-2 Cell Entry and Replication
Authors: Singh Saravjeet , O’Reilly Sophie , Gewaid Hossam , Bowie Andrew G. , Gautier Virginie , Worrall D. Margaret
Published: October 2022

The SARS-CoV-2 virus can utilize host cell proteases to facilitate cell entry, whereby the Spike (S) protein is cleaved at two specific sites to enable membrane fusion. Furin, transmembrane protease serine 2 (TMPRSS2), and cathepsin L (CatL) are the major proteases implicated, and are thus targets for anti-viral therapy. The human serpin (serine protease inhibitor) alpha-1 antitrypsin (A1AT) shows inhibitory activity for TMPRSS2, and has previously been found to suppress cell infection with SARS-CoV-2. Here, we have generated modified serpin inhibitors with increased specificity for these cellular proteases. Using SerpinB3 (SCCA-1), a cross-class inhibitor of CatL, as a scaffold, we have designed and produced reactive centre loop (RCL) variants to more specifically target both furin and TMPRSS2. Two further variants were generated by substituting the RCL P7–P1 with the spike protein S1/S2 cleavage site from either SARS-CoV-2 alpha or delta (P681R) sequences. Altered inhibitory specificity of purified recombinant proteins was verified in protease assays, with attenuated CatL inhibition and gain of furin or TMPRSS2 inhibition, as predicted, and modified serpins were shown to block S protein cleavage in vitro. Furthermore, the serpin variants were able to inhibit S-pseudoparticle entry into A549-ACE2-TMPRSS2 cells and suppress SARS-CoV-2 replication in Vero E6 cells expressing TMPRSS2. The construct designed to inhibit TMPRSS2 (B3-TMP) was most potent. It was more effective than A1AT for TMPRSS2 enzyme inhibition (with an eighteen-fold improvement in the second order inhibition rate constant) and for blocking SARS-CoV-2 viral replication. These findings advance the potential for serpin RCL mutagenesis to generate new inhibitors, and may lead to novel anti-viral biological molecules.
Advances in the Management of Central Nervous System Metastases from Breast Cancer
Authors: Avila Jorge , Leone José Pablo
Published: October 2022

Central nervous system (CNS) metastases are common in breast cancer (BC) patients and are particularly relevant as new treatments for BC are prolonging survival. Here, we review advances in the treatment of CNS metastases from BC, including radiotherapy, systemic therapies, and the evolving role of immunotherapy. The use of radiotherapy and chemotherapy is the cornerstone of treatment for CNS metastases. However, new targeted therapies have recently been developed, including anti-HER2 agents and antibody–drug conjugates that have presented promising results for the treatment of these patients.
Antifungal Effect of Nanoparticles against COVID-19 Linked Black Fungus: A Perspective on Biomedical Applications
Authors: Gurunathan Sangiliyandi , Lee Ah Reum , Kim Jin Hoi
Published: October 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that has caused a ‘coronavirus disease 2019’ (COVID-19) pandemic in multiple waves, which threatens human health and public safety. During this pandemic, some patients with COVID-19 acquired secondary infections, such as mucormycosis, also known as black fungus disease. Mucormycosis is a serious, acute, and deadly fungal infection caused by Mucorales-related fungal species, and it spreads rapidly. Hence, prompt diagnosis and treatment are necessary to avoid high mortality and morbidity rates. Major risk factors for this disease include uncontrolled diabetes mellitus and immunosuppression that can also facilitate increases in mucormycosis infections. The extensive use of steroids to prevent the worsening of COVID-19 can lead to black fungus infection. Generally, antifungal agents dedicated to medical applications must be biocompatible, non-toxic, easily soluble, efficient, and hypoallergenic. They should also provide long-term protection against fungal growth. COVID-19-related black fungus infection causes a severe increase in fatalities. Therefore, there is a strong need for the development of novel and efficient antimicrobial agents. Recently, nanoparticle-containing products available in the market have been used as antimicrobial agents to prevent bacterial growth, but little is known about their efficacy with respect to preventing fungal growth, especially black fungus. The present review focuses on the effect of various types of metal nanoparticles, specifically those containing silver, zinc oxide, gold, copper, titanium, magnetic, iron, and carbon, on the growth of various types of fungi. We particularly focused on how these nanoparticles can impact the growth of black fungus. We also discussed black fungus co-infection in the context of the global COVID-19 outbreak, and management and guidelines to help control COVID-19-associated black fungus infection. Finally, this review aimed to elucidate the relationship between COVID-19 and mucormycosis.
MnHR4 Functions during Molting of Macrobrachium nipponense by Regulating 20E Synthesis and Mediating 20E Signaling
Authors: Yuan Huwei , Zhang Wenyi , Qiao Hui , Jin Shubo , Jiang Sufei , Xiong Yiwei , Gong Yongsheng , Fu Hongtuo
Published: October 2022

HR4, a member of the nuclear receptor family, has been extensively studied in insect molting and development, but reports on crustaceans are still lacking. In the current study, the MnHR4 gene was identified in Macrobrachium nipponense. To further improve the molting molecular mechanism of M. nipponense, this study investigated whether MnHR4 functions during the molting process of M. nipponense. The domain, phylogenetic relationship and 3D structure of MnHR4 were analyzed by bioinformatics. Quantitative real-time PCR (qRT-PCR) analysis showed that MnHR4 was highly expressed in the ovary. In different embryo stages, the highest mRNA expression was observed in the cleavage stage (CS). At different individual stages, the mRNA expression of MnHR4 reached its peak on the fifteenth day after hatching (L15). The in vivo injection of 20-hydroxyecdysone (20E) can effectively promote the expression of the MnHR4 gene, and the silencing of the MnHR4 gene increased the content of 20E in M. nipponense. The regulatory role of MnHR4 in 20E synthesis and 20E signaling was further investigated by RNAi. Finally, the function of the MnHR4 gene in the molting process of M. nipponense was studied by counting the molting frequency. After knocking down MnHR4, the molting frequency of M. nipponense decreased significantly. It was proved that MnHR4 plays a pivotal role in the molting process of M. nipponense.
Deodorized Garlic Decreases Oxidative Stress Caused by Lipopolysaccharide in Rat Heart through Hydrogen Sulfide: Preliminary Findings
Authors: Pérez-Torres Israel , Manzano-Pech Linaloe , Guarner-Lans Verónica , Soto María Elena , Castrejón-Téllez Vicente , Márquez-Velasco Ricardo , Vargas-González Álvaro , Martínez-Memije Raúl , Del Valle-Mondragón Leonardo , Díaz-Juárez Julieta Anabell , Sánchez-Aguilar María , Torres-Narváez Juan Carlos
Published: October 2022

Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.
SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation
Authors: Xie Qipeng , Hua Xiaohui , Huang Chao , Liao Xin , Tian Zhongxian , Xu Jiheng , Zhao Yunping , Jiang Guosong , Huang Haishan , Huang Chuanshu
Published: October 2022

SOX2, a member of the SRY-related HMG-box (SOX) family, is abnormally expressed in many tumors and associated with cancer stem cell-like properties. Previous reports have shown that SOX2 is a biomarker for cancer stem cells in human bladder cancer (BC), and our most recent study has indicated that the inhibition of SOX2 by anticancer compound ChlA-F attenuates human BC cell invasion. We now investigated the mechanisms through which SOX2 promotes the invasive ability of BC cells. Our studies revealed that SOX2 promoted SKP2 transcription and increased SKP2-accelerated Sp1 protein degradation. As Sp1 is a transcriptionally regulated gene, HUR transcription was thereby attenuated, and, in the absence of HUR, FOXO1 mRNA was degraded fast, which promoted BC cell invasion. In addition, SOX2 promoted BC invasion through the upregulation of nucleolin transcription, which resulted in increased MMP2 mRNA stability and expression. Collectively, our findings show that SOX2 promotes BC invasion through both SKP2-Sp1-HUR-FOXO1 and nucleolin-MMP2 dual axes.
Individual Variabilities in Adipose Stem Cell Proliferation, Gene Expression and Responses to Lipopolysaccharide Stimulation
Authors: Yasmeen Rumana , Pham Quynhchi , Fukagawa Naomi K. , Wang Thomas T. Y.
Published: October 2022

Adipose stem cells (ASCs) are reported to play a role in normal physiology as well as in inflammation and disease. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASCs from different donors. Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASCs with or without bacterial lipopolysaccharide (LPS), marker gene mRNAs for proliferation, steroid hormones, and xenobiotic and immune pathways were determined using RT-PCR, and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. ASCs from both donors expressed androgen receptors but not estrogen receptors. ASC2 had a 2-fold higher proliferation rate and a 6-fold higher level of proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited significantly greater fold induction of TNF-α and CCL2 by LPS compared to ASC1. TNF-α and GM-CSF protein levels were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media. Our findings suggest that inter-individual variability and/or possible sex differences exist in ASCs, which may serve as a key determinant to inflammatory responses of ASCs.
Physiological and Transcriptomic Analyses Reveal the Effects of Elevated Root-Zone CO2 on the Metabolism of Sugars and Starch in the Roots of Oriental Melon Seedlings
Authors: Gao Lijia , Wang Wanxin , Xu Chuanqiang , Han Xintong , Li Yanan , Liu Yiling , Qi Hongyan
Published: October 2022

Root-zone CO2 is a major factor that affects crop growth, development, nutrient uptake, and metabolism. Oriental melon is affected by root-zone gases during growth, the microstructure, sugar and starch contents, enzymatic activities related to sugar and starch metabolism, and gene expression in the roots of oriental melon seedlings were investigated under three root-zone CO2 concentrations (CK: 0.2%, T1: 0.4%, T2: 1.1%). Elevated root-zone CO2 altered the cellular microstructure, accelerated the accumulation and release of starch grains, disrupted organelle formation, and accelerated root senescence. The sugar and starch contents and metabolic activity in the roots increased within a short duration following treatment. Compared to the control, 232 and 1492 differentially expressed genes (DEGs) were identified on the 6th day of treatment in T1 and T2 plants, respectively. The DEGs were enriched in three metabolic pathways. The majority of genes related to sucrose and starch hydrolysis were upregulated, while the genes related to sucrose metabolism were downregulated. The study revealed that oriental melon seedlings adapt to elevated root-zone CO2 stress by adjusting sugar and starch metabolism at the transcriptome level and provides new insights into the molecular mechanism underlying the response to elevated root-zone CO2 stress.
Role of Tunneling Nanotubes in the Nervous System
Authors: Tarasiuk Olga , Scuteri Arianna
Published: October 2022

Cellular communication and the transfer of information from one cell to another is crucial for cell viability and homeostasis. During the last decade, tunneling nanotubes (TNTs) have attracted scientific attention, not only as a means of direct intercellular communication, but also as a possible system to transport biological cargo between distant cells. Peculiar TNT characteristics make them both able to increase cellular survival capacities, as well as a potential target of neurodegenerative disease progression. Despite TNT formation having been documented in a number of cell types, the exact mechanisms triggering their formation are still not completely known. In this review, we will summarize and highlight those studies focusing on TNT formation in the nervous system, as well as their role in neurodegenerative diseases. Moreover, we aim to stress some possible mechanisms and important proteins probably involved in TNT formation in the nervous system.
Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting
Authors: Yeo Natalie Jia Ying , Wazny Vanessa , Nguyen Nhi Le Uyen , Ng Chun-Yi , Wu Kan Xing , Fan Qiao , Cheung Chui Ming Gemmy , Cheung Christine
Published: October 2022

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.
Evaluation of Proteomic and Lipidomic Changes in Aeromonas-Infected Trout Kidney Tissue with the Use of FT-IR Spectroscopy and MALDI Mass Spectrometry Imaging
Authors: Matys Joanna , Turska-Szewczuk Anna , Gieroba Barbara , Kurzylewska Maria , Pękala-Safińska Agnieszka , Sroka-Bartnicka Anna
Published: October 2022

Aeromonas species are opportunistic bacteria causing a vast spectrum of human diseases, including skin and soft tissue infections, meningitis, endocarditis, peritonitis, gastroenteritis, and finally hemorrhagic septicemia. The aim of our research was to indicate the molecular alterations in proteins and lipids profiles resulting from Aeromonas sobria and A. salmonicida subsp. salmonicida infection in trout kidney tissue samples. We successfully applied FT-IR (Fourier transform infrared) spectroscopy and MALDI-MSI (matrix-assisted laser desorption/ionization mass spectrometry imaging) to monitor changes in the structure and compositions of lipids, secondary conformation of proteins, and provide useful information concerning disease progression. Our findings indicate that the following spectral bands’ absorbance ratios (spectral biomarkers) can be used to discriminate healthy tissue from pathologically altered tissue, for example, lipids (CH2/CH3), amide I/amide II, amide I/CH2 and amide I/CH3. Spectral data obtained from 10 single measurements of each specimen indicate numerous abnormalities concerning proteins, lipids, and phospholipids induced by Aeromonas infection, suggesting significant disruption of the cell membranes. Moreover, the increase in the content of lysolipids such as lysophosphosphatidylcholine was observed. The results of this study suggest the application of both methods MALDI-MSI and FT-IR as accurate methods for profiling biomolecules and identifying biochemical changes in kidney tissue during the progression of Aeromonas infection.
Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells
Authors: Scalia Alessandro , Kindt Nadège , Trelcat Anne , Nachtergael Amandine , Duez Pierre , Journé Fabrice , Carlier Stéphane
Published: October 2022

Cardiovascular diseases (CVD) and cancers are the two main causes of death worldwide. The initiation and progression of atherosclerosis is, in large part, caused by oxidized low-density lipoproteins (oxLDL); interestingly, oxLDL may also play a role in cancer cell metabolism and migration. As oxLDL are generally obtained by tedious ultracentrifugation procedures, “home-made” oxLDL were obtained by (i) applying a purification kit to isolate LDL and VLDL from human plasma; (ii) isolating LDL from VLDL by gel permeation chromatography (GPC); and (iii) oxidating LDL through CuSO4 incubation. On three HPV-positive head and neck cancer cells (HNCC) (93VU-147T, UM-SCC47, and UPCI-SCC154), cell migration was assessed using Boyden chambers, the Wnt/ß-catenin pathway was analyzed by Western Blotting, and the expression of two oxLDL receptors, LOX-1 and CD36, in response to oxLDL exposure, was analysed by immunofluorescence. Our data indicate: (a) a non-significant difference between reference and “home-made” oxLDL; (b) a decreased migration, parallel to an inhibition of the ß-catenin pathway; and (c) an increase of CD36 and LOX-1 expression in all HNCC. In conclusion, we successfully produced oxLDL. Our results demonstrate a decrease in HNCC migration after oxLDL exposure, and an increased expression of LOX-1 and CD36 associated with lipid uptake.
Genome-Wide Identification of the AGC Protein Kinase Gene Family Related to Photosynthesis in Rice (Oryza sativa)
Authors: Jiang Yifei , Liu Xuhui , Zhou Mingao , Yang Jian , Ke Simin , Li Yangsheng
Published: October 2022

The cAMP-dependent protein kinase A, cGMP-dependent protein kinase G and phospholipid-dependent protein kinase C (AGC) perform various functions in plants, involving growth, immunity, apoptosis and stress response. AGC gene family is well described in Arabidopsis, however, limited information is provided about AGC genes in rice, an important cereal crop. This research studied the AGC gene family in the AA genome species: Oryza sativa ssp. japonica, Oryza sativa ssp. indica, Oryza nivara, Oryza rufipogon, Oryza glaberrima, Oryza meridionalis, Oryza barthii, Oryza glumaepatula and Oryza longistaminata were searched and classified into six subfamilies, and it was found that these species have similar numbers of members. The analysis of gene duplication and selection pressure indicated that the AGC gene family expanded mainly by segmental or whole genome duplication (WGD), with purifying selection during the long evolutionary period. RNA-seq analysis revealed that OsAGCs of subfamily V were specifically highly expressed in leaves, and the expression patterns of these genes were compared with that of photosynthesis-related genes using qRT-PCR, discovered that OsAGC9, OsAGC20, and OsAGC22 might participate in photosynthesis. These results provide an informative perspective for exploring the evolutionary of AGC gene family and its practical application in rice.
Graphene Quantum Dots Modified Upconversion Nanoparticles for Photodynamic Therapy
Authors: Li Yuting , Wang Yufei , Shang Hong , Wu Jing
Published: October 2022

Photodynamic therapy (PDT), as a novel technique, has been extensively employed in cancer treatment by utilizing reactive oxygen species (ROS) to kill malignant cells. However, most photosensitizers (PSs) are short of ROS yield and affect the therapeutic effect of PDT. Thus, there is a substantial demand for the development of novel PSs for PDT to advance its clinical translation. In this study, we put forward a new strategy for PS synthesis via modifying graphene quantum dots (GQDs) on the surface of rare-earth elements doped upconversion nanoparticles (UCNPs) to produce UCNPs@GQDs with core-shell structure. This new type of PSs combined the merits of UCNPs and GQDs and produced ROS efficiently under near-infrared light excitation to trigger the PDT process. UCNPs@GQDs exhibited high biocompatibility and obvious concentration-dependent PDT efficiency, shedding light on nanomaterials-based PDT development.
Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy
Authors: Sokolova Tatiana V. , Zabrodskaya Yulia M. , Litovchenko Anastasia V. , Paramonova Natalia M. , Kasumov Vugar R. , Kravtsova Svetlana V. , Skiteva Ekaterina N. , Sitovskaya Daria A. , Bazhanova Elena D.
Published: October 2022

Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc. (multiplex analysis) were studied. In the present work, ultrastructural and immunohistochemical apoptotic signs were found in neurons and oligodendrocytes in the temporal lobe of DRE patients. Levels of proinflammatory cytokines that play a role in apoptosis (TNF-α, FAS, NF-kB) were increased. The blood concentration of IL-4, IL-7, TNF-α is increased and IL-2 is reduced. Oligodendroglial apoptosis has been shown to play an important role in DRE pathogenesis and to explain demyelination. Thus, a comprehensive analysis of revealed changes in the blood and brain in DRE patients showed the neuroinflammation in the epileptic focus, which was combined with the development of apoptosis of glial cells and neurons. This creates conditions for the development of drug resistance and the epilepsy progression.
Synthesis and Anticancer and Antiviral Activities of C-2′-Branched Arabinonucleosides
Authors: Bege Miklós , Kiss Alexandra , Bereczki Ilona , Hodek Jan , Polyák Lenke , Szemán-Nagy Gábor , Naesens Lieve , Weber Jan , Borbás Anikó
Published: October 2022

d-Arabinofuranosyl-pyrimidine and -purine nucleoside analogues containing alkylthio-, acetylthio- or 1-thiosugar substituents at the C2’ position were prepared from the corresponding 3’,5’-O-silylene acetal-protected nucleoside 2’-exomethylenes by photoinitiated, radical-mediated hydrothiolation reactions. Although the stereochemical outcome of the hydrothiolation depended on the structure of both the thiol and the furanoside aglycone, in general, high d-arabino selectivity was obtained. The cytotoxic effect of the arabinonucleosides was studied on tumorous SCC (mouse squamous cell) and immortalized control HaCaT (human keratinocyte) cell lines by MTT assay. Three pyrimidine nucleosides containing C2’-butylsulfanylmethyl or -acetylthiomethyl groups showed promising cytotoxicity at low micromolar concentrations with good selectivity towards tumor cells. SAR analysis using a methyl β-d-arabinofuranoside reference compound showed that the silyl-protecting group, the nucleobase and the corresponding C2’ substituent are crucial for the cell growth inhibitory activity. The effects of the three most active nucleoside analogues on parameters indicative of cytotoxicity, such as cell size, division time and cell generation time, were investigated by near-infrared live cell imaging, which showed that the 2’-acetylthiomethyluridine derivative induced the most significant functional and morphological changes. Some nucleoside analogues also exerted anti-SARS-CoV-2 and/or anti-HCoV-229E activity with low micromolar EC50 values; however, the antiviral activity was always accompanied by significant cytotoxicity.
Comprehensive Comparative Analysis and Development of Molecular Markers for Dianthus Species Based on Complete Chloroplast Genome Sequences
Authors: Lin Shengnan , Liu Jianyi , He Xingqun , Wang Jie , Wang Zehao , Zhang Xiaoni , Bao Manzhu , Fu Xiaopeng
Published: October 2022

Dianthus spp. is a genus with high economic and ornamental value in the Caryophyllaceae, which include the famous fresh-cut carnation and the traditional Chinese herbal medicine, D. superbus. Despite the Dianthus species being seen everywhere in our daily lives, its genome information and phylogenetic relationships remain elusive. Thus, we performed the assembly and annotation of chloroplast genomes for 12 individuals from seven Dianthus species. On this basis, we carried out the first comprehensive and systematic analysis of the chloroplast genome sequence characteristics and the phylogenetic evolution of Dianthus. The chloroplast genome of 12 Dianthus individuals ranged from 149,192 bp to 149,800 bp, containing 124 to 126 functional genes. Sequence repetition analysis showed the number of simple sequence repeats (SSRs) ranged from 75 to 80, tandem repeats ranged from 23 to 41, and pair-dispersed repeats ranged from 28 to 43. Next, we calculated the synonymous nucleotide substitution rates (Ks) of all 76 protein coding genes to obtain the evolution rate of these coding genes in Dianthus species; rpl22 showed the highest Ks (0.0471), which suggested that it evolved the swiftest. By reconstructing the phylogenetic relationships within Dianthus and other species of Caryophyllales, 16 Dianthus individuals (12 individuals reported in this study and four individuals downloaded from NCBI) were divided into two strongly supported sister clades (Clade A and Clade B). The Clade A contained five species, namely D. caryophyllus, D. barbatus, D. gratianopolitanus, and two cultivars (‘HY’ and ‘WC’). The Clade B included four species, in which D. superbus was a sister branch with D. chinensis, D. longicalyx, and F1 ‘87M’ (the hybrid offspring F1 from D. chinensis and ‘HY’). Further, based on sequence divergence analysis and hypervariable region analysis, we selected several regions that had more divergent sequences, to develop DNA markers. Additionally, we found that one DNA marker can be used to differentiate Clade A and Clade B in Dianthus. Taken together, our results provide useful information for our understanding of Dianthus classification and chloroplast genome evolution.
Conservation Genomic Analysis of the Asian Honeybee in China Reveals Climate Factors Underlying Its Population Decline
Authors: Sang Huiling , Li Yancan , Sun Cheng
Published: October 2022

The Asian honeybee, Apis cerana, is one of the most important native pollinators in Asia. Asian honeybees were believed to be under significant decline in China based on a report in 2005. On the contrary, a recent survey revealed that Asian honeybee populations in China are stable and even slightly increased in some regions. Therefore, the declining status of A. cerana populations in China is still unclear. Taking advantage of the abundant, publicly available genomic data for Asian honeybees in China, we employed conservation genomics methods to understand if Asian honeybee populations in China are declining and what the underlying climate factors are. We reconstructed the changes of effective population size (Ne) within the recent past for 6 population groups of Asian honeybees and found out that only one of them (population in Bomi, Tibet) showed a consistently declining Ne from the last 100 generations to 25 generations. Selective sweep analysis suggests that genes related to the tolerance of low temperatures and strong ultraviolet radiation are under selection in the declining population, indicating that these two climate factors most likely underlie the decline of BM populations during the recent past. Our study provides insights into the dynamic changes of Asian honeybee populations in China and identifies climate factors that underlie its population decline, which is valuable for the conservation of this important pollinator.
Biological Parameters, Phenology and Temperature Requirements of Halyomorpha halys (Hemiptera: Pentatomidae) in the Sub-Mediterranean Climate of Western Slovenia
Authors: Rot Mojca , Maistrello Lara , Costi Elena , Trdan Stanislav
Published: October 2022

In the last decade, the invasive brown marmorated stink bug Halyomorpha halys, native to East Asia, has become one of the most serious pests for agricultural crops worldwide. First detected in Europe (in Switzerland), the insect is now widely found across the European continent and many Eurasian countries. Since its first appearance in Slovenia in 2017 it has caused considerable damage to fruit and vegetable production. Understanding the biology and behavior in the local environmental conditions is of key importance for an effective pest management. Knowledge of the voltinism of the species is crucial to anticipate critical phases of pest development and for adapting control measures that target the vulnerable life stages of the pest. A 3-year study (2019–2021) of H. halys biological parameters was performed outdoors in Nova Gorica (western Slovenia), confirming that in the sub-Mediterranean climate this pest has two overlapping generations per year. The net reproductive rates observed in the studied period indicate growing populations. The highest population growth was recorded in 2019, when the net reproductive rate of increase (R0) reached 14.84 for the summer generation and 5.64 for the overwintering generation. These findings match the current situation in Slovenia, where increasing populations of H. halys and severe crop damage have been observed since 2019.
CBCT Evaluation of Sticky Bone in Horizontal Ridge Augmentation with and without Collagen Membrane—A Randomized Parallel Arm Clinical Trial
Authors: Tony Jane Belinda , Parthasarathy Harinath , Tadepalli Anupama , Ponnaiyan Deepa , Alamoudi Ahmed , Kamil Mona Awad , Alzahrani Khalid J. , Alsharif Khalaf F. , Halawani Ibrahim F. , Alnfiai Mrim M. , Ramachandran Lakshmi , Balaji Thodur Madapusi , Patil Shankargouda
Published: October 2022

Guided bone regeneration (GBR) is a reliable technique used to treat ridge deficiencies prior or during implant placement. Injectable-platelet rich fibrin (i-PRF) laced with a bone substitute (sticky bone) has heralded the way for advancing the outcomes of bone regeneration. This study evaluated the efficacy of sticky bone in horizontal ridge augmentation with and without collagen membrane. A total of 20 partially edentulous patients (Group-I n = 10; Group-II n = 10) that indicated GBR were included, and the surgical procedure was carried out. In Group-I, the sticky bone and collagen membrane were placed in ridge-deficient sites and Group-II received only sticky bone. At the end of 6 months, 20 patients (Group-I (n = 10); Group-II (n = 10)) completed the follow-up period. A CBCT examination was performed to assess changes in the horizontal ridge width (HRW) and vertical bone height (VBH). A statistically significant increase in HRW (p < 0.05) was observed in both groups with mean gains of 1.35 mm, 1.55 mm, and 1.93 mm at three levels (crest, 3 mm, and 6 mm) in Group-I and 2.7 mm, 2.8 mm, and 2.6 mm at three levels in Group-II. The intergroup comparison revealed statistical significance (p < 0.05) with respect to HRW and KTW (Keratinised tissue width) gains of 0.775 at the 6-month follow-up. Sticky-bone (Xenogenic-bone graft + i-PRF) served as a promising biomaterial in achieving better horizontal bone width gain.
Application of Fuzzy Delphi-AHP-TOPSIS for Selecting an International Crew Change Center in Taiwan
Authors: Ho Tien-Chun , Lee Hsuan-Shih
Published: October 2022

The COVID-19 crisis has brought disruption to the global economy and to international passenger and cargo transportation, and the unprecedented crew change crisis remains an issue for governments around the world to address. The selection of a port for international crew changes is a major decision for a country, and this port selection can be considered as a multi-criteria decision-making (MCDM) issue. As with other facility-siting issues, the issue of selecting a port for international crew changes requires consideration of several criteria relative to cargo transshipment, and since this process involves uncertainty, fuzzy logic must be incorporated into the process to obtain more accurate results. This study proceeds from the standpoint of shipping companies and ship management companies, conducting a survey questionnaire on carriers calling at Taiwan ports using cargo structure, transit costs, transit time, environmental factors, geographic location, infrastructure, and crew safety certification facilities. Fuzzy Delphi and FAHP are used to obtain the subjective opinions of carriers and FTOPSIS is used to explore and prioritize the objective opinions of carriers on international crew change ports. This is then used to construct an evaluation model of the key factors influencing the selection of an international crew change location for the development of Taiwanese ports. The results of the study showed that the hinterland industry economy was the main key factor and Kaohsiung container terminal 5 was the most suitable place for crew replacement.
Assessing the Various Antagonistic Mechanisms of Trichoderma Strains against the Brown Root Rot Pathogen Pyrrhoderma noxium Infecting Heritage Fig Trees
Authors: Panchalingam Harrchun , Powell Daniel , Adra Cherrihan , Foster Keith , Tomlin Russell , Quigley Bonnie L. , Nyari Sharon , Hayes R. Andrew , Shapcott Alison , Kurtböke D. İpek
Published: October 2022

A wide range of phytopathogenic fungi exist causing various plant diseases, which can lead to devastating economic, environmental, and social impacts on a global scale. One such fungus is Pyrrhoderma noxium, causing brown root rot disease in over 200 plant species of a variety of life forms mostly in the tropical and subtropical regions of the globe. The aim of this study was to discover the antagonistic abilities of two Trichoderma strains (#5001 and #5029) found to be closely related to Trichoderma reesei against P. noxium. The mycoparasitic mechanism of these Trichoderma strains against P. noxium involved coiling around the hyphae of the pathogen and producing appressorium like structures. Furthermore, a gene expression study identified an induced expression of the biological control activity associated genes in Trichoderma strains during the interaction with the pathogen. In addition, volatile and diffusible antifungal compounds produced by the Trichoderma strains were also effective in inhibiting the growth of the pathogen. The ability to produce Indole-3-acetic acid (IAA), siderophores and the volatile compounds related to plant growth promotion were also identified as added benefits to the performance of these Trichoderma strains as biological control agents. Overall, these results show promise for the possibility of using the Trichoderma strains as potential biological control agents to protect P. noxium infected trees as well as preventing new infections.
Investigation of the Surface Roughness and Surface Uniformity of a Hybrid Sandwich Structure after Machining
Authors: Doluk Elżbieta , Rudawska Anna , Miturska-Barańska Izabela
Published: October 2022

The parameters of surface roughness Ra, Rz and Rmax as well as surface topography Sa, Sz, Sp and Sv of the two-layer sandwich structure composed of an AW-2024 T3 aluminum alloy (Al) and a carbon-fiber-reinforced polymer (CFRP) were measured to determine an impact of the machining configuration (arrangement of the materials forming a sandwich structure) and the type of tool (presence of the tool coating) on the quality of the surface obtained through circumferential milling. The measurements revealed that milling produced different values of surface roughness for the aluminum alloy and the CFRP composite with values of 2D and 3D surface roughness being higher for the composite layer. The highest value of Ra of 1.10 µm was obtained for the surface of the CFRP composite using the CFRP/Al configuration and a TiAlN-coated tool. The highest values of the Rz (6.51 µm) and Rmax (8.85 µm) surface roughness parameters were also obtained for the composite layer using the same machining configuration and type of tool.
Surface Modification of Biomass with Di-(2-Ethylhexyl)phosphoric Acid and Its Use for Vanadium Adsorption
Authors: Yu Zhekun , Fan Yong , Liu Tao , Zhang Yimin , Hu Pengcheng
Published: October 2022

The method of carbonizing biomass using di-(2-Ethylhexyl) phosphoric acid and tributyl phosphate impregnation (SICB) was studied in this research. SICB combines the benefits of an extractant and an ion exchange resin. The adsorption and desorption properties of vanadium were investigated, and the adsorption mechanism was analyzed. The results showed that the carrier was first prepared at a temperature of 1073.15 K using sawdust as a biomass substitute and then cooled to room temperature. The best adsorption performance was obtained by impregnating the carriers with di-(2-Ethylhexyl) phosphoric acid and tributyl phosphate for 60 min. The vanadium adsorption rate of 98.12% was achieved using the biomass at an initial V(IV) solution concentration of 1.1 g/L, a pH value of 1.6, and a solid-to-liquid ratio of 1:20 g·mL for 24 h. Using 25 wt.% sulfuric acid solution as desorbent, the desorption rate of vanadium was as high as 98.36%. The analysis showed that the adsorption of vanadium by SICB was chemisorption, and the adsorption process was more consistent with the proposed second-order kinetic equation. Therefore, SICB has high selectivity and high saturation capacity because of the mesopores and micropores produced by carbonization.
Performance of Capsules in Self-Healing Cementitious Material
Authors: Reda Mouna A. , Chidiac Samir E.
Published: October 2022

Encapsulation is a very promising technique that is being explored to enhance the autonomous self-healing of cementitious materials. However, its success requires the survival of self-healing capsules during mixing and placing conditions, while still trigger the release of a healing agent upon concrete cracking. A review of the literature revealed discontinuities and inconsistencies in the design and performance evaluation of self-healing cementitious material. A finite element model was developed to study the compatibility requirements for the capsule and the cementing material properties while the cement undergoes volume change due to hydration and/or drying. The FE results have provided insights into the observed inconsistencies and the importance of having capsules’ mechanical and geometrical properties compatible with the cementitious matrix.