bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators
Authors: Antonyová Veronika , Tatar Ameneh , Brogyányi Tereza , Kejík Zdeněk , Kaplánek Robert , Vellieux Fréderic , Abramenko Nikita , Sinica Alla , Hajduch Jan , Novotný Petr , Masters Bettie Sue , Martásek Pavel , Jakubek Milan
Published: September 2022

Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2–6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC50 = 1.33 μM), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2–6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson’s correlation coefficient of 0.92.
Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer
Authors: Skurikhin Evgenii G. , Ermakova Natalia , Zhukova Mariia , Pershina Olga , Pan Edgar , Pakhomova Angelina , Kogai Lena , Goldberg Victor , Simolina Elena , Skurikhina Victoria , Widera Darius , Kubatiev Aslan , Morozov Sergey G. , Kushlinskii Nikolai , Dygai Alexander
Published: September 2022

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH+, CD87+CD276+, and EGF+Axl+) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3+CD8+ T-lymphocytes (rTcells) in relation to naive CD3+CD8+ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G’s blood CSCs. Reprogramming of CD3+CD8+ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient’s G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.
Synthesis, Molecular Docking, In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway
Authors: Zapevalova Maria V. , Shchegravina Ekaterina S. , Fonareva Irina P. , Salnikova Diana I. , Sorokin Danila V. , Scherbakov Alexander M. , Maleev Alexander A. , Ignatov Stanislav K. , Grishin Ivan D. , Kuimov Alexander N. , Konovalova Maryia V. , Svirshchevskaya Elena V. , Fedorov Alexey Yu.
Published: September 2022

A (series) range of potential dimorpholinoquinazoline-based inhibitors of the PI3K/Akt/mTOR cascade was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in the low and sub-micromolar range. Compound 7c with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins. Compound 7c inhibited the phosphorylation of Akt, mTOR, and S6K at 125–250 nM. It also triggered PARP1 cleavage, ROS production, and cell death via several mechanisms. Inhibition of PI3Kα was observed at a concentration of 7b 50 µM and of 7c 500 µM and higher, that can indicate minority PI3Kα as a target among other kinases in the titled cascade for 7c. In vivo studies demonstrated an inhibition of tumor growth in the colorectal tumor model. According to the docking studies, the replacement of the triazine core in gedatolisib (8) by a quinazoline fragment, and incorporation of a (hetero)aromatic unit connected with the carbamide group via a flexible spacer, can result in more selective inhibition of the PI3Kα isoform.
Effects of Various Disinfection Methods on the Material Properties of Silicone Dental Impressions of Different Types and Viscosities
Authors: Wezgowiec Joanna , Paradowska-Stolarz Anna , Malysa Andrzej , Orzeszek Sylwia , Seweryn Piotr , Wieckiewicz Mieszko
Published: September 2022

There is an ongoing search for novel disinfection techniques that are not only effective, cheap, and convenient, but that also do not have adverse effects on the properties of dental impressions. We compared the effects of various methods (UVC, gaseous ozone, commercial solution, and spray) on the dimensional change, tensile strength, and hardness of silicone impressions. Moreover, as a secondary aim, we performed a statistical comparison of the properties of nondisinfected addition (Panasil Putty Soft, Panasil monophase Medium, Panasil initial contact Light) and condensation silicones (Zetaplus Putty and Oranwash L), as well as a comparison of materials of various viscosities (putty, medium-bodied, and light-bodied). Our results revealed that addition silicones had higher dimensional stability, tensile strength, and Shore A hardness compared to condensation silicones. Both traditional (immersion and spraying) and alternative methods of disinfection (UVC and ozone) had no significant impact on the tensile properties and dimensional stability of the studied silicones; however, they significantly affected the hardness, particularly of Oranwash L. Our study demonstrated that, similarly to standard liquid disinfectants, both UVC and ozone do not strongly affect the material properties of most silicones. However, before recommendation, their usefulness for each individual material should be thoroughly evaluated.
Successful Derivation of Hepatoblasts, Cholangiocytes and Hepatocytes from Simian Induced Pluripotent Stem Cells
Authors: Luce Eleanor , Steichen Clara , Abed Soumeya , Weber Anne , Leboulch Philippe , Maouche-Chrétien Leila , Dubart-Kupperschmitt Anne
Published: September 2022

The use of primary cells in human liver therapy is limited by a lack of cells. Induced pluripotent stem cells (iPSCs) represent an alternative to primary cells as they are infinitely expandable and can be differentiated into different liver cell types. The aim of our work was to demonstrate that simian iPSCs (siPSCs) could be used as a new source of liver cells to be used as a large animal model for preclinical studies. We first differentiated siPSCs into a homogenous population of hepatoblasts (siHBs). We then separately differentiated them into hepatocytes (siHeps) and cholangiocytes (siChols) expressing respective specific markers and displaying epithelial polarity. Moreover, we showed that polarized siChols can self-organize into 3D structures. These results should facilitate the deciphering of liver development and open the way to exploring co-culture systems that could be assessed during preclinical studies, including in autologous monkey donors, for regenerative medicine purposes.
Evaluation of Synaptic and Axonal Dysfunction Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment Based on CSF and Bioinformatic Analysis
Authors: Dulewicz Maciej , Kulczyńska-Przybik Agnieszka , Borawska Renata , Słowik Agnieszka , Mroczko Barbara
Published: September 2022

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets.
Intercontinental Gut Microbiome Variances in IBD
Authors: Mayorga Luis , Serrano-Gómez Gerard , Xie Zixuan , Borruel Natalia , Manichanh Chaysavanh
Published: September 2022

The development of biomarkers for inflammatory bowel disease (IBD) diagnosis would be relevant in a generalized context. However, intercontinental investigation on these microbial biomarkers remains scarce. We examined taxonomic microbiome variations in IBD using published DNA shotgun metagenomic data. For this purpose, we used sequenced data from our previous Spanish Crohn’s disease (CD) and ulcerative colitis (UC) cohort, downloaded sequence data from a Chinese CD cohort, and downloaded taxonomic and functional profiling tables from a USA CD and UC cohort. At the global level, geographical location and disease phenotype were the main explanatory covariates of microbiome variations. In healthy controls (HC) and UC, geography turned out to be the most important factor, while disease intestinal location was the most important one in CD. Disease severity correlated with lower alpha-diversity in UC but not in CD. Across geography, alpha-diversity was significantly different independently of health status, except for CD. Despite recruitment from different countries and with different disease severity scores, CD patients may harbor a very similar microbial taxonomic profile. Our study pointed out that geographic location, disease activity status, and other environmental factors are important contributing factors in microbiota changes in IBD. We therefore strongly recommend taking these factors into consideration for future IBD studies to obtain globally valid and reproducible biomarkers.
Integrated Physiological, Transcriptomic, and Metabolomic Analyses of the Response of Peach to Nitrogen Levels during Different Growth Stages
Authors: Zhang Yu , Guo Jiying , Ren Fei , Jiang Quan , Zhou Xin , Zhao Jianbo , Liu Xin
Published: September 2022

This study performed physiological, transcriptome, and metabolite analyses of peach fruit under different nitrogen (N) conditions at different growth stages. Nitrogen management directly affected the yield, fruit quality, and metabolites of peach in different growth stages. Different fertilizing time influenced yield and leaf N concentration. RNA-Seq was used to analyze the influence of N levels at the fruit pit hardening (PH) and fruit expansion (FE) stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed differentially expressed genes (DEGs) related to carbon and nitrogen metabolite processes. Metabolome analysis shows that applying different nitrogen fertilizers at different growth stages of peach mainly affected metabolites related to carbon and amino acids. This research provides insight into the metabolic processes underlying different N responses during different growth stages and provides a foundation to improve the efficiency of N use in peach.
From AKI to CKD: Maladaptive Repair and the Underlying Mechanisms
Authors: Wang Zhiwen , Zhang Chun
Published: September 2022

Acute kidney injury (AKI) is defined as a pathological condition in which the glomerular filtration rate decreases rapidly over a short period of time, resulting in changes in the physiological function and tissue structure of the kidney. An increasing amount of evidence indicates that there is an inseparable relationship between acute kidney injury and chronic kidney disease (CKD). With the progress in research in this area, researchers have found that the recovery of AKI may also result in the occurrence of CKD due to its own maladaptation and other potential mechanisms, which involve endothelial cell injury, inflammatory reactions, progression to fibrosis and other pathways that promote the progress of the disease. Based on these findings, this review summarizes the occurrence and potential mechanisms of maladaptive repair in the progression of AKI to CKD and explores possible treatment strategies in this process so as to provide a reference for the inhibition of the progression of AKI to CKD.
Induced Resistance Combined with RNA Interference Attenuates the Counteradaptation of the Western Flower Thrips
Authors: Zhang Tao , Liu Li , Jia Yulian , Zhi Junrui , Yue Wenbo , Li Dingyin , Zeng Guang
Published: September 2022

The western flower thrips, Frankliniella occidentalis Pergande, is an invasive pest that damages agricultural and horticultural crops. The induction of plant defenses and RNA interference (RNAi) technology are potent pest control strategies. This study investigated whether the anti-adaptive ability of F. occidentalis to jasmonic acid (JA)- and methyl jasmonate (MeJA)-induced defenses in kidney bean plants was attenuated after glutathione S-transferase (GST) gene knockdown. The expression of four GSTs in thrips fed JA- and MeJA-induced leaves was analyzed, and FoGSTd1 and FoGSTs1 were upregulated. Exogenous JA- and MeJA-induced defenses led to increases in defensive secondary metabolites (tannins, alkaloids, total phenols, flavonoids, and lignin) in leaves. Metabolome analysis indicated that the JA-induced treatment of leaves led to significant upregulation of defensive metabolites. The activity of GSTs increased in second-instar thrips larvae fed JA- and MeJA-induced leaves. Co-silencing with RNAi simultaneously knocked down FoGSTd1 and FoGSTs1 transcripts and GST activity, and the area damaged by second-instar larvae feeding on JA- and MeJA-induced leaves decreased by 62.22% and 55.24%, respectively. The pupation rate of second-instar larvae also decreased by 39.68% and 39.89%, respectively. Thus, RNAi downregulation of FoGSTd1 and FoGSTs1 reduced the anti-adaptive ability of F. occidentalis to JA- or MeJA-induced defenses in kidney bean plants.
CpMAX1a, a Cytochrome P450 Monooxygenase Gene of Chimonanthus praecox Regulates Shoot Branching in Arabidopsis
Authors: Zhang Haiyuan , Hua Run , Wang Xia , Wu Huafeng , Ou Hua , Lu Xin , Huang Yan , Liu Daofeng , Sui Shunzhao
Published: September 2022

Strigolactones (SLs) are a class of important hormones in the regulation of plant branching. In the model plant Arabidopsis, AtMAX1 encodes a cytochrome P450 protein and is a crucial gene in the strigolactone synthesis pathway. Yet, the regulatory mechanism of MAX1 in the shoot branching of wintersweet (Chimonanthus praecox) remains unclear. Here we identified and isolated three MAX1 homologous genes, namely CpMAX1a, CpMAX1b, and CpMAX1c. Quantitative real-time PCR (qRT-PCR) revealed the expression of CpMAX1a in all tissues, being highest in leaves, whereas CpMAX1b was only expressed in stems, while CpMAX1c was expressed in both roots and stem tips. However, CpMAX1a’s expression decreased significantly after decapitation; hence, we verified its gene function. CpMAX1a was located in Arabidopsis chloroplasts. Overexpressing CpMAX1a restored the phenotype of the branching mutant max1–3, and reduced the rosette branch number, but resulted in no significant phenotypic differences from the wild type. Additionally, expression of AtBRC1 was significantly upregulated in transgenic lines, indicating that the CpMAX1a gene has a function similar to the homologous gene of Arabidopsis. In conclusion, our study shows that CpMAX1a plays a conserved role in regulating the branch development of wintersweet. This work provides a molecular and theoretical basis for better understanding the branch development of wintersweet.
Participation of the Serotonergic System and Brain-Derived Neurotrophic Factor in the Antidepressant-like Effect of Flavonoids
Authors: German-Ponciano León Jesús , Rosas-Sánchez Gilberto Uriel , Cueto-Escobedo Jonathan , Fernández-Demeneghi Rafael , Guillén-Ruiz Gabriel , Soria-Fregozo César , Herrera-Huerta Emma Virginia , Rodríguez-Landa Juan Francisco
Published: September 2022

Depressive disorders are among the most disabling diseases experienced around the world, and their incidence has significantly increased over the last few decades due to multiple environmental, social, and biological factors. The search for new pharmacological alternatives to treat depression is a global priority. In preclinical research, molecules obtained from plants, such as flavonoids, have shown promising antidepressant-like properties through several mechanisms of action that have not been fully elucidated, including crossing of the blood brain barrier (BBB). This review will focus on discussing the main findings related to the participation of the serotonergic system and brain-derived neurotrophic factor (BDNF) on the antidepressant-like effect of some flavonoids reported by behavioral, neurochemical, and molecular studies. In this sense, evidence shows that depressive individuals have low levels of serotonin and BDNF, while flavonoids can reverse it. Finally, the elucidation of the mechanism used by flavonoids to modulate serotonin and BDNF will contribute to our understanding of the neurobiological bases underlying the antidepressant-like effects produced by these natural compounds.
Identification of a Gene Panel Predictive of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy Employing Transcriptomic and Functional Validation
Authors: Vishnubalaji Radhakrishnan , Abdel-Razeq Hikmat , Gehani Salahddin , Albagha Omar M. E. , Alajez Nehad M.
Published: September 2022

Triple-negative breast cancer (TNBC) patients exhibiting pathological complete response (pCR) have better clinical outcomes compared to those with residual disease (RD). Therefore, robust biomarkers that can predict pCR may help with triage and resource prioritization in patients with TNBC. Herein, we identified a gene panel predictive of RD and pCR in TNBC from the discovery (n = 90) treatment-naive tumor transcriptomic data. Eight RD-derived genes were identified as TNBC-essential genes, which were highly predicative of overall survival (OS) and relapse-free survival (RFS) in an additional cohort of basal breast cancer (n = 442). Mechanistically, targeted depletion of the eight genes reduced the proliferation potential of TNBC cell models, while most remarkable effects were for combined SLC39A7, TIMM13, BANF1, and MVD knockdown in conjunction with doxorubicin. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and receiver operating characteristic curve (ROC) analyses revealed significant predictive power for the identified gene panels with an area under the curve (AUC) of 0.75 for the validation cohort (n = 50) to discriminate RD from pCR. Protein–Protein Interaction (PPI) network analysis of the pCR-derived gene signature identified an 87-immune gene signature highly predictive of pCR, which correlated with better OS, RFS, and distant-metastasis-free survival (DMFS) in an independent cohort of basal and, to a lesser extent, HER2+ breast cancer. Our data have identified gene signatures predicative of RD and pCR in TNBC with potential clinical implications.
Screening and Characterization of Shark-Derived VNARs against SARS-CoV-2 Spike RBD Protein
Authors: Chen Yu-Lei , Lin Jin-Jin , Ma Huan , Zhong Ning , Xie Xin-Xin , Yang Yunru , Zheng Peiyi , Zhang Ling-Jing , Jin Tengchuan , Cao Min-Jie
Published: September 2022

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the major target for antibody therapeutics. Shark-derived variable domains of new antigen receptors (VNARs) are the smallest antibody fragments with flexible paratopes that can recognize protein motifs inaccessible to classical antibodies. This study reported four VNARs binders (JM-2, JM-5, JM-17, and JM-18) isolated from Chiloscyllium plagiosum immunized with SARS-CoV-2 RBD. Biolayer interferometry showed that the VNARs bound to the RBD with an affinity KD ranging from 38.5 to 2720 nM, and their Fc fusions had over ten times improved affinity. Gel filtration chromatography revealed that JM-2-Fc, JM-5-Fc, and JM-18-Fc could form stable complexes with RBD in solution. In addition, five bi-paratopic VNARs, named JM-2-5, JM-2-17, JM-2-18, JM-5-18, and JM-17-18, were constructed by fusing two VNARs targeting distinct RBD epitopes based on epitope grouping results. All these bi-paratopic VNARs except for JM-5-18 showed higher RBD binding affinities than its component VNARs, and their Fc fusions exhibited further enhanced binding affinities, with JM-2-5-Fc, JM-2-17-Fc, JM-2-18-Fc, and JM-5-18-Fc having KD values lower than 1 pM. Among these Fc fusions of bi-paratopic VNARs, JM-2-5-Fc, JM-2-17-Fc, and JM-2-18-Fc could block the angiotensin-converting enzyme 2 (ACE2) binding to the RBD of SARS-CoV-2 wildtype, Delta, Omicron, and SARS-CoV, with inhibition rates of 48.9~84.3%. Therefore, these high-affinity VNAR binders showed promise as detectors and therapeutics of COVID-19.
Steroidogenic Effects of Salinity Change on the Hypothalamus–Pituitary–Gonad (HPG) Axis of Male Chinese Sea Bass (Lateolabrax maculatus)
Authors: Fang Zhenru , Li Xujian , Wang Yapeng , Lu Wei , Hou Juncheng , Cheng Jie
Published: September 2022

As lower vertebrates, teleost species could be affected by dynamic aquatic environments and may respond to environmental changes through the hypothalamus–pituitary–gonad (HPG) axis to ensure their normal growth and sexual development. Chinese sea bass (Lateolabrax maculatus), euryhaline marine teleosts, have an extraordinary ability to deal with a wide range of salinity changes, whereas the salinity decrease during their sex-maturation season may interfere with the HPG axis and affect their steroid hormone metabolism, resulting in abnormal reproductive functioning. To this end, in this study, 40 HPG axis genes in the L. maculatus genome were systematically characterized and their copy numbers, phylogenies, gene structures, and expression patterns were investigated, revealing the conservation of the HPG axis among teleost lineages. In addition, freshwater acclimation was carried out with maturing male L. maculatus, and their serum cortisol and 11-ketotestosterone (11-KT) levels were both increased significantly after the salinity change, while their testes were found to be partially degraded. After salinity reduction, the expression of genes involved in cortisol and 11-KT synthesis (cyp17a, hsd3b1, cyp21a, cyp11c, hsd11b2, and hsd17b3) showed generally upregulated expression in the head kidneys and testes, respectively. Moreover, cyp11c and hsd11b2 were involved in the synthesis and metabolism of both cortisol and 11-KT, and after salinity change their putative interaction may contribute to steroid hormone homeostasis. Our results proved the effects of salinity change on the HPG axis and steroidogenic pathway in L. maculatus and revealed the gene interactions involved in the regulation of steroid hormone levels. The coordinated interaction of steroidogenic genes provides comprehensive insights into steroidogenic pathway regulation, as well as sexual development, in teleost species.
Comparative Transcriptome Analysis and Genetic Methods Revealed the Biocontrol Mechanism of Paenibacilluspolymyxa NSY50 against Tomato Fusarium Wilt
Authors: Du Nanshan , Guo Hui , Fu Ruike , Dong Xiaoxing , Xue Dongqi , Piao Fengzhi
Published: September 2022

Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol) is a common disease that affects tomatoes, which can cause the whole plant to wilt and seriously reduce the production of tomatoes in greenhouses. In this study, the morphological indexes, photosynthetic performance and incidence rate of NSY50 under Fol infection were evaluated. It was found that NSY50 could improve the growth of tomato seedlings and significantly reduce the incidence rate of Fusarium wilt. However, the molecular mechanism of NSY50 that induces resistance to Fusarium wilt is still unclear. We used transcriptomic methods to analyze NSY50-induced resistance to Fol in tomatoes. The results showed that plant defense related genes, such as PR and PAL, were highly expressed in tomato seedlings pretreated with NSY50. At the same time, photosynthetic efficiency, sucrose metabolism, alkaloid biosynthesis and terpene biosynthesis were significantly improved, which played a positive role in reducing the damage caused by Fol infection and enhancing the disease tolerance of seedlings. Through transgenic validation, we identified an important tomato NAC transcription factor, SlNAP1, which was preliminarily confirmed to be effective in relieving the detrimental symptoms induced by Fol. Our findings reveal that P. polymyxa NSY50 is an effective plant-growth-promoting rhizosphere bacterium and also a biocontrol agent of soil-borne diseases, which can significantly improve the resistance of tomato to Fusarium wilt.
A Novel Approach of SWATH-Based Metabolomics Analysis Using the Human Metabolome Database Spectral Library
Authors: Shikshaky Hassan , Ahmed Eman Abdelnaby , Anwar Ali Mostafa , Osama Aya , Ezzeldin Shahd , Nasr Antony , Mahgoub Sebaey , Magdeldin Sameh
Published: September 2022

Metabolomics is a potential approach to paving new avenues for clinical diagnosis, molecular medicine, and therapeutic drug monitoring and development. The conventional metabolomics analysis pipeline depends on the data-independent acquisition (DIA) technique. Although powerful, it still suffers from stochastic, non-reproducible ion selection across samples. Despite the presence of different metabolomics workbenches, metabolite identification remains a tedious and time-consuming task. Consequently, sequential windowed acquisition of all theoretical MS (SWATH) acquisition has attracted much attention to overcome this limitation. This article aims to develop a novel SWATH platform for data analysis with a generation of an accurate mass spectral library for metabolite identification using SWATH acquisition. The workflow was validated using inclusion/exclusion compound lists. The false-positive identification was 3.4% from the non-endogenous drugs with 96.6% specificity. The workflow has proven to overcome background noise despite the complexity of the SWATH sample. From the Human Metabolome Database (HMDB), 1282 compounds were tested in various biological samples to demonstrate the feasibility of the workflow. The current study identified 377 compounds in positive and 303 in negative modes with 392 unique non-redundant metabolites. Finally, a free software tool, SASA, was developed to analyze SWATH-acquired samples using the proposed pipeline.
Identifying Soybean Pod Borer (Leguminivora glycinivorella) Resistance QTLs and the Mechanism of Induced Defense Using Linkage Mapping and RNA-Seq Analysis
Authors: Chen Liangyu , Song Baixing , Yu Cheng , Zhang Jun , Zhang Jian , Bi Rui , Li Xueying , Ren Xiaobo , Zhu Yanyu , Yao Dan , Song Yang , Yang Songnan , Zhao Rengui
Published: September 2022

The soybean pod borer (Leguminivora glycinivorella) (SPB) is a major cause of soybean (Glycine max L.) yield losses in northeast Asia, thus it is desirable to elucidate the resistance mechanisms involved in soybean response to the SPB. However, few studies have mapped SPB-resistant quantitative trait loci (QTLs) and deciphered the response mechanism in soybean. Here, we selected two soybean varieties, JY93 (SPB-resistant) and K6 (SPB-sensitive), to construct F2 and F2:3 populations for QTL mapping and collected pod shells before and after SPB larvae chewed on the two parents to perform RNA-Seq, which can identify stable QTLs and explore the response mechanism of soybean to the SPB. The results show that four QTLs underlying SPB damage to seeds were detected on chromosomes 4, 9, 13, and 15. Among them, qESP-9-1 was scanned in all environments, hence it can be considered a stable QTL. All QTLs explained 0.79 to 6.09% of the phenotypic variation. Meanwhile, 2298 and 3509 DEGs were identified for JY93 and K6, respectively, after the SPB attack, and most of these genes were upregulated. Gene Ontology enrichment results indicated that the SPB-induced and differently expressed genes in both parents are involved in biological processes such as wound response, signal transduction, immune response, and phytohormone pathways. Interestingly, secondary metabolic processes such as flavonoid synthesis were only significantly enriched in the upregulated genes of JY93 after SPB chewing compared with K6. Finally, we identified 18 candidate genes related to soybean pod borer resistance through the integration of QTL mapping and RNA-Seq analysis. Seven of these genes had similar expression patterns to the mapping parents in four additional soybean germplasm after feeding by the SPB. These results provide additional knowledge of the early response and induced defense mechanisms against the SPB in soybean, which could help in breeding SPB-resistant soybean accessions.
Ayka, a Novel Curtobacterium Bacteriophage, Provides Protection against Soybean Bacterial Wilt and Tan Spot
Authors: Tarakanov Rashit I. , Lukianova Anna A. , Evseev Peter V. , Pilik Roksana I. , Tokmakova Anna D. , Kulikov Eugene E. , Toshchakov Stepan V. , Ignatov Alexander N. , Dzhalilov Fevzi S.-U. , Miroshnikov Konstantin A.
Published: September 2022

Diseases caused by the Gram-positive bacterium Curtobacteriumflaccumfaciens pv. flaccumfaciens (Cff) inflict substantial economic losses in soybean cultivation. Use of specific bacterial viruses (bacteriophages) for treatment of seeds and plants to prevent the development of bacterial infections is a promising approach for bioprotection in agriculture. Phage control has been successfully tested for a number of staple crops. However, this approach has never been applied to treat bacterial diseases of legumes caused by Cff, and no specific bacteriophages have been known to date. This paper presents detailed characteristics of the first lytic bacteriophage infecting this pathogen. Phage Ayka, related to φ29-like (Salasmaviridae) viruses, but representing a new subfamily, was shown to control the development of bacterial wilt and tan spot in vitro and in greenhouse plants.
Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates
Authors: Li Mu , Chen Qingyang , Zhang Yuan-Wei
Published: September 2022

Conformational changes are fundamental events in the transport mechanism. The serotonin transporter (SERT) catalyzes reuptake of the neurotransmitter serotonin after its release by serotonergic neurons and is the molecular target for antidepressant drugs and psychostimulants. Despite significant progress in characterizing the structure–function relationship of SERT, its conformational mechanism has not been fully understood. We present here a cell-based method for determining conformational changes in SERT with its fluorescent substrates by fluorescence imaging analysis. This method fluorometrically measures accessibility of strategically positioned cysteine residues in the substrate permeation pathway to calculate the rate constants of reactivity with MTS reagents in live or permeabilized cells. We validated this method by investigating ligand and ion-induced conformational changes in both the extracellular and cytoplasmic pathways of SERT. Furthermore, we applied this method for examining the influence of Cl− binding and vilazodone inhibition on SERT conformation. Our results showed that Cl− ion, in the presence of Na+, facilitates the conformational conversion from outward to inward open states, and that vilazodone binding stabilizes SERT in an outward open and inward-closed conformation. The present work provided insights into the conformational mechanism of SERT and also indicated that the cell-based fluorometric method is robust, straightforward to perform, and potentially applicable to any monoamine transporters in exploring the transport mechanism and mechanism of action of therapeutic agents for the treatment of several psychiatric disorders.
The Relationship of Tumor Microbiome and Oral Bacteria and Intestinal Dysbiosis in Canine Mammary Tumor
Authors: Zheng Hui-Hua , Du Chong-Tao , Yu Chao , Tang Xin-Yue , Huang Rong-Lei , Zhang Yu-Zhu , Gao Wei , Xie Guang-Hong
Published: September 2022

Canine mammary tumor (CMT) is the most common tumor in dogs, with 50% of malignant cases, and lacks an effective therapeutic schedule, hence its early diagnosis is of great importance to achieve a good prognosis. Microbiota is believed to play important roles in systemic diseases, including cancers. In this study, 91 tumors, 21 oral and fecal samples in total were collected from dogs with CMTs, and 31 oral and 21 fecal samples from healthy dogs were collected as control. The intratumoral, oral and gut bacterial community of dogs with CMTs and healthy dogs was profiled by 16S rRNA high-throughput sequencing and bioinformatic methods. The predominant intratumoral microbes were Ralstonia, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Pseudomonas, unidentified_Chloroplast and Bacteroides at the genus level. In addition, our findings demonstrated striking changes in the composition of the oral and gut bacterium community in the dogs suffered from CMTs compared to the healthy dogs, with a significant increase of Bacteroides which also was the significant microbial biomarker in the oral and gut bacterium community. It showed that the Bacteroides was shared in the intratumoral, oral and intestinal bacterial microbiomes, confirming that microbiota might travel from the mouth to the intestine and finally to the distant mammary tumor tissue. This study provides a new microbiological idea for the treatment of canine mammary tumors, and also provides a theoretical basis for the study of human breast cancer.
Innovative Fragility-Based Method for Failure Mechanisms and Damage Extension Analysis of Bridges
Authors: Minnucci Lucia , Scozzese Fabrizio , Carbonari Sandro , Gara Fabrizio , Dall’Asta Andrea
Published: September 2022

The seismic assessment of existing bridges is of the utmost importance to characterise the main structural deficiencies, estimate the risk, prioritise retrofit interventions, or estimate losses and repair costs in case of earthquakes. The above tasks require information on the damage mechanisms likely to occur as well as on the damage extent over the structure. Such types of information are generally not provided by classical fragility analysis, which is mainly focused on the evaluation of the global performance of the bridge. In this paper, a systematic probabilistic methodology for the evaluation of bridge fragility is proposed. The methodology aims at offering insight into the failure mechanisms most likely to occur and the evolution and extent of damage within the bridge structure. First, a mathematical description of the proposed analysis methods is given, then an application to a realistic case study—a reinforced concrete multi-span simply supported deck link-slab bridge—is provided to illustrate the applicability of the tool. A nonlinear 3D finite element model is developed, and a multiple-stripe (nonlinear dynamic) analysis is performed by using a stochastic bidirectional seismic input. The results highlight the suitability of the proposed methodology to reveal the main structural deficiencies, the relations among different failure mechanisms (involving piers, bearings, abutments, etc.), and the expected damage extent.
Structural Control and Electrical Behavior of Thermally Reduced Graphene Oxide Samples Assisted with Malonic Acid and Phosphorus Pentoxide
Authors: Aukstakojyte Ruta , Gaidukevic Justina , Niaura Gediminas , Skapas Martynas , Bukauskas Virginijus , Barkauskas Jurgis
Published: September 2022

We present a detailed study of the structural and electrical changes occurring in two graphene oxide (GO) samples during thermal reduction in the presence of malonic acid (MA) (5 and 10 wt%) and P2O5 additives. The morphology and de-oxidation efficiency of reduced GO (rGO) samples are characterized by Fourier transform infrared, X-ray photoelectron, energy-dispersive X-ray, Raman spectroscopies, transmission electron and scanning electron microscopies, X-ray diffraction (XRD), and electrical conductivity measurements. Results show that MA and P2O5 additives are responsible for the recovery of π-conjugation in rGO as the XRD pattern presents peaks corresponding to (002) graphitic-lattice planes, suggesting the formation of the sp2-like carbon structure. Raman spectra show disorders in graphene sheets. Elemental analysis shows that the proposed reduction method in the presence of additives also suggests the simultaneous insertion of phosphorus with a relatively high content (0.3–2.3 at%) in rGO. Electrical conductivity measurements show that higher amounts of additives used in the GO reduction more effectively improve electron mobility in rGO samples, as they possess the highest electrical conductivity. Moreover, the relatively high conductivity at low bulk density indicates that prepared rGO samples could be applied as metal-free and non-expensive carbon-based electrodes for supercapacitors and (bio)sensors.
Preparation, Microstructural Characterization and Photocatalysis Tests of V5+-Doped TiO2/WO3 Nanocomposites Supported on Electrospun Membranes
Authors: Pereira Michel F. G. , Nascimento Mayane M. , Cardoso Pedro Henrique N. , Oliveira Carlos Yure B. , Tavares Ginetton F. , Araújo Evando S.
Published: September 2022

Metal oxide nanocomposites (MON) have gained significant attention in the literature for the possibility of improving the optical and electronic properties of the hybrid material, compared to its pristine constituent oxides. These superior properties have been observed for TiO2 — based MON, which exhibit improved structural stability and photoactivity in environmental decontamination processes. In addition, the use of polymer membrane-supported MON is preferable to prevent further aggregation of particles, increase the surface area of the semiconductor in contact with the contaminant, and enable material reuse without considerable efficiency loss. In this work, V5+-doped TiO2/WO3 MON nanostructures were prepared by the sintering process at 500 °C and supported in electrospun fiber membranes for application as photocatalyst devices. Microstructural characterization of the samples was performed by XRD, SEM, EDS, Raman, and DSC techniques. The reflectance spectra showed that the bandgap of the MON was progressively decreased (3.20 to 2.11 eV) with the V5+ ions doping level increase. The fiber-supported MON showed photoactivity for rhodamine B dye degradation using visible light. In addition, the highest photodegradation efficiency was noted for the systems with 5 wt% vanadium oxide dispersed in the fibers (92% dye degradation in 120 min of exposure to the light source), with recyclability of the composite material for use in new photocatalysis cycles. The best results are directly related to the microstructure, lower bandgap and aggregation of metal oxide nanocomposite in the electrospun membrane, compared to the support-free MON.
Field and Cage Studies Show No Effects of Exposure to Flonicamid on Honey Bees at Field-Relevant Concentrations
Authors: Meikle William G. , Weiss Milagra
Published: September 2022

The extent to which insecticides harm non-target beneficial insects is controversial. The effects of long-term exposure on honey bees to sublethal concentrations of flonicamid, a pyridinecarboxamide compound used as a systemic insecticide against sucking insects, were examined in a field study and two cage studies. The field study involved the continuous weight, temperature, and CO2 monitoring of 18 honey bee colonies, 6 of which were exposed over six weeks to 50 ppb flonicamid in sugar syrup, 6 exposed to 250 ppb flonicamid in syrup, and 6 exposed to unadulterated syrup (control). Treatments were derived from concentrations observed in honey samples in a published study. No effects were observed on foraging activity, hive weight gain, thermoregulation, or average CO2 concentrations. However, Varroa mite infestations may have also contributed to experimental variability. The two cage studies, in which cages (200 newly-emerged bees in each) were exposed to the same flonicamid concentrations as the field study and kept in a variable-temperature incubator, likewise did not show any experiment-wide effects on survivorship, thermoregulation, or syrup consumption. These results suggest that field applications of flonicamid that result in concentrations as high as 250 ppb in honey may be largely safe for honey bees.
Insights into the Use of Eco-Friendly Synergists in Resistance Management of Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)
Authors: Kaleem Ullah Rana Muhammad , Gökçe Ayhan , Bakhsh Allah , Salim Muhammad , Wu Hai Yan , Naqqash Muhammad Nadir
Published: September 2022

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is the most notorious insect pest of potato globally. Injudicious use of insecticides for management of this pest has resulted in resistance to all major groups of insecticides along with many human, animal health, and environmental concerns. Additionally, the input cost of insecticide development/discovery is markedly increasing because each year thousands of chemicals are produced and tested for their insecticidal properties, requiring billions of dollars. For the management of resistance in insect pests, synergists can play a pivotal role by reducing the application dose of most insecticides. These eco-friendly synergists can be classified into two types: plant-based synergists and RNAi-based synergists. The use of plant-based and RNAi-based synergists in resistance management of insect pests can give promising results with lesser environmental side effects. This review summarizes the resistance status of CPB and discusses the potential advantage of plant-based and RNAi-based synergists for CPB resistance management. It will motivate researchers to further investigate the techniques of using plant- and RNAi-based synergists in combination with insecticides.
Host and Seasonal Effects on the Abundance of Bean Leaf Beetles (Ootheca spp.) (Coleoptera: Chrysomelidae) in Northern Uganda
Authors: Lutaakome Moses , Kyamanywa Samuel , Paparu Pamela , Olaboro Samuel , Halerimana Charles , Nkalubo Stanley Tamusange , Otim Michael Hilary
Published: September 2022

Bean leaf beetles (BLBs) (Ootheca spp.) are serious legume pests in Uganda and sub-Saharan Africa, but their ecology is not well understood. We planted host plants, viz., common bean, cowpea, and soybean, in an experiment in the hotspot areas of Arua and Lira districts in Northern Uganda in order to assess their influence on the density of adults and immature stages of BLBs in different seasons. Overall, the number of adults, larvae, and pupae were higher in cowpea than common bean and soybean plots. The number of adults were highest in cowpea (29.5 adults/15 plants) in Arua during the long rainy season (2018A). The number of adults did not differ significantly during short rains (season B) in 2017 and 2018. Similarly, in Lira district, the highest number of adult BLBs was in cowpea (4.6 beetles) compared to the common bean (2.7 beetles) and soybean plots, with a peak at four weeks after planting (WAP). During 2018A, larvae of BLBs first appeared at five WAP and seven WAP and peaked at 13 WAP and 11 WAP in Arua and Lira, respectively. The pupae were present in the soil after the harvesting of crops during 2018A, but peaked at seven WAP and eight WAP in 2018B season in Arua and Lira, respectively. The occurrence of below-ground adults in 2018B followed the peak abundance of pupae, although this was delayed until six WAP in Arua compared to Lira. We conclude that cowpea is the most preferred by adults and larvae compared to common bean and soybean. Similarly, the first rain season (2018A) attracted higher abundance and damage than the second rain season. Management of the BLBs should thus take into consideration avoidance of host crop rotation and dealing with the below-ground stages.
Contactless Blood Pressure Estimation System Using a Computer Vision System
Authors: Al-Naji Ali , Fakhri Ahmed Bashar , Mahmood Mustafa F. , Chahl Javaan
Published: September 2022

Blood pressure (BP) is one of the most common vital signs related to cardiovascular diseases. BP is traditionally measured by mercury, aneroid, or digital sphygmomanometers; however, these approaches are restrictive, inconvenient, and need a pressure cuff to be attached directly to the patient. Therefore, it is clinically important to develop an innovative system that can accurately measure BP without the need for any direct physical contact with the people. This work aims to create a new computer vision system that remotely measures BP using a digital camera without a pressure cuff. The proposed BP system extracts the optical properties of photoplethysmographic signals in two regions in the forehead captured by a digital camera and calculates BP based on specific formulas. The experiments were performed on 25 human participants with different skin tones and repeated at different times under ambient light conditions. Compared to the systolic/diastolic BP readings obtained from a commercial digital sphygmomanometer, the proposed BP system achieves an accuracy of 94.6% with a root mean square error (RMSE) of 9.2 mmHg for systolic BP readings and an accuracy of 95.4% with an RMSE of 7.6 mmHg for diastolic BP readings. Thus, the proposed BP system has the potential of being a promising tool in the upcoming generation of BP monitoring systems.