bluuebunny/crossref_metadata_2025 huggingface dataset:
Kritik Analitik Düşünmeye Tuzak Kuran İki Sinsi Kardeş; Ruminasyon Ve Endişe
Authors: Karatepe Hasan Turan
Published: May 2022

Son 20 yılda psikopatoloji araştırmalarının temel kavramları haline gelen ruminasyon ve endişe, tekrarlayıcı düşünme stillerinin daha yüksek bir şemsiye tanımının alt biçimleri olarak düşünülebilir. Birçok psikiyatrik yakınmanın ortaya çıkmasında ve devam etmesinde etkili bir mekanizma olduğu gösterilmiştir. Tekrarlayan düşünme stilleri sadece psikopatoloji durumlarında önemli rol oynamakla kalmaz, aynı zamanda günlük hayatımızı zorlayıcı bir şekilde yaşamamıza neden olur. Ruminasyon, geçmişte karşılaşılan bir konu/durum/olay hakkında sık sık, istem dışı ve araya girerek düşünme durumunu ifade eder. Farklı kuramcıların farklı psikopatolojik durumları merkeze alarak tanımladıkları kavramın genel özelliği araya girici, kontrol edilemez, tersine çevrilebilir ve tekrarlanabilir olmasıdır. Kişiyi tekrar eden bu iki düşünce biçimine yönlendiren en önemli faktör, bir problem çözme durumudur. Kişi, içinde yaşamak istemediği/olmak istemediği bir durumda olduğunu fark ettiğinde, bu durumun geçmişteki bağlantılarını ve bu duruma neden olan faktörleri gözden geçirmek için derin derin düşünebilir. bu durumu besleyen geçmişte yaşanmıştır. Kaygı, hem afete hazırlanmak hem de karşılaşılacak olumsuzluklara karşı önlemleri güçlendirmek için yaşanan zorluğun/zorlamanın veya olumsuzlukların gelecekteki yansımalarını görmeye çalışmak için girişilen bir süreç olarak ortaya çıkabilir. Bir problemi çözme motivasyonu, ruminasyon ve endişenin ana parçasıdır. Bu nedenlerle, tekrarlayan düşünme stillerinin eleştirel analitik düşünmeye (CAT) eşlik etmesi ve süreci etkilemesi kuvvetle muhtemeldir. Problemi iyi ve doğru anlamak, mümkün olduğunca fazla araştırma ve araştırma yapmak, gerekli bilgileri toplamak ve nihai çözümü uygulamak gibi aşamaları olan KADın ruminasyon ve endişe de kalite ve verimliliğini olumsuz etkileyecektir.
Zâhide-Sûfiye Kadınların Tasavvuf Tarihindeki Yeri ve Önemi
Authors: ALTUNKAYA Mevhibe
Published: May 2022

Temel İslam Bilimlerinde kadın araştırmaları konusu, oldukça yenidir. İslâm’ın ilk döneminde aktif bir şekilde sahada olan kadınlar, sonraki yüzyıllarda geriye itilmişlerdir. Bunun hem erkeklere hem de kadınlara bakan iki yönü vardır. Tasavvuf tarihinde de kadınlar etkili bir konuma ve öneme sahiplerdi. Hadice, Aişe, Ümmü Seleme, Fatıma, Zeynep, Rabia gibi zâhide sahabiyye ve tabiiyye kadınlar mescid-i Nebevî’nin müdavimiydiler. Tezkirelerde makamından söz edilen başkaca birçok kadın âlime, fakihe,aârife vardır. Ancak zühd döneminden sonra fakiheler ve zâhidelerden söz eden metinler giderek azalmaktadır. Bu dönemde sûfî müellif Sülemî gibi istisnalar dışında kadın âlime ve ârifelerden söz eden yazar neredeyse yoktur. Tezkireler, menakıbnâmeler dışında âlime/ârife kadınların söz ve kerametlerinden (üstünlüklerinden) bahseden başkaca eserler günümüze ulaşmamıştır. Gözler, kadınların varlığına adeta yumulmuş gibidir. Ciltler dolusu fıkıh, kelam, hadis, tefsir kitapları yazıp bir tek kadın müfessir veya kadın sûfiyeden bahsetmeyen eserler İslam’ın zühd asrından sonraki dönemlere aittir. Halbuki İslam tarihinde gerilere gidildikçe kadınların daha aktif ve etkin olduklarını görmekteyiz. Örneğin Zünnûn-i Mısrî, Şâm’da altı beyitte sûfîlerin özelliğini sayan Fâtıma-i Nişâbûrî’ye hayran kaldığını belirtmiştir. Sülemî yüzlerce kadın sûfiyenin biyografisini vermiştir. Muhammed el-Kelâbâzî, tasavvufa dair meşhur kitabını, yine bir kadın sûfîyenin sözleriyle sonlandırmıştır.
Understanding Role of DNA Repair and Cytochrome p-450 Gene Polymorphisms in Cervical Cancer Patient Treated With Concomitant Chemoradiation
Authors: Abbas Mohammad , Kushwaha Vandana Singh , Srivastava Kirti , Banerjee Monisha
Published: May 2022

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT).

Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0).

Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively).

Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.
Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19
Authors: Russo Constanza , Raiden Silvina , Algieri Silvia , De Carli Norberto , Davenport Carolina , Sarli Mariam , Bruera María José , Seery Vanesa , Sananez Inés , Simaz Nancy , Bayle Carola , Nivela Valeria , Ferrero Fernando , Geffner Jorge , Arruvito Lourdes
Published: May 2022

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.
Serum miRNA Profile in Diabetic Patients With Ischemic Heart Disease as a Promising Non-Invasive Biomarker
Authors: Bielska Agnieszka , Niemira Magdalena , Bauer Witold , Sidorkiewicz Iwona , Szałkowska Anna , Skwarska Anna , Raczkowska Justyna , Ostrowski Damian , Gugała Kamil , Dobrzycki Sławomir , Krętowski Adam
Published: May 2022

The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlight an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived micro RNAs (miRNAs) may serve as potential biomarkers for early IHD diagnosis and support the identification of diabetic individuals with a predisposition to undergo IHD. We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter technology platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Gene Ontology (GO) analysis was used to identify the biological function and signalling pathways associated with miRNA target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and Cytotoscape tool. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Real-time quantitative polymerase chain reaction (qRT-PCR) was used for nCounter platform data validation. Our data showed that six miRNAs (miR-615-3p, miR-3147, miR-1224-5p, miR-5196-3p, miR-6732-3p, and miR-548b-3p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. Further analysis indicated that 489 putative target genes mainly affected the endothelin-1 signalling pathway, glucocorticoid biosynthesis, and apelin cardiomyocyte signalling pathway. All tested miRNAs showed high diagnostic value (AUC = 0.779 - 0.877). Taken together, our research suggests that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.
The Role of Quality of Governance in Reducing Pollution in Romania: An ARDL and Nonparametric Bayesian Approach
Authors: Simionescu Mihaela , Neagu Olimpia , Gavurova Beata
Published: May 2022

Achieving global sustainability and greener growth goals poses a challenge for all countries, especially the developing ones. The quality of institutional framework of a country and its effectiveness determines the level of environmental control and sustainability. Since pollution reduction is an objective for European environmental policies, Romania should achieve this goal taking into account the quality of governance. In this study, the impact of Worldwide Governance Indicators on greenhouse gas emissions is assessed for Romania during 1996–2019 using autoregressive distributed lag models. The results indicate that control of corruption, political stability, and regulatory quality reduced pollution in the long-run, while voice and accountability contributed to the growth of greenhouse gas emissions. Renewable energy consumption did not reduce pollution in the short- and long-run during 1996–2019, while the analysis made for 2007–2019 suggested the significant contribution of renewable energy consumption in reducing pollution. The analysis based on Bayesian ridge regressions after Romania joined the European Union indicated that control of corruption and political stability reduced the level of pollution. Policy implications of these results are widely discussed.
How Multiple Interaction Types Affect Disease Spread and Dilution in Ecological Networks
Authors: Su Min , Jiang Zhengjun , Hui Cang
Published: May 2022

Ecological communities are composed of different functional guilds that are engaging in multiple types of biotic interactions. We explore how ecological networks fare when confronting infectious diseases according to density-dependent (DD) and frequency-dependent (FD) transmission modes. Our model shows that network compositions can dictate both disease spreading and the relationship between disease and community diversity (including species richness and Shannon’s diversity) as depicted in the dilution effect. The disease becomes more prevalent within communities harboring more mutualistic interactions, generating a positive relationship between disease prevalence and community diversity (i.e., an amplification effect). By contrast, in communities with a fixed proportion of mutualistic interactions, higher diversity from the balance of competition and predation can impede disease prevalence (i.e., the dilution effect). Within-species disease prevalence increases linearly with a species’ degree centrality. These patterns of disease transmission and the diversity-disease relationship hold for both transmission modes. Our analyses highlight the complex effects of interaction compositions in ecological networks on infectious disease dynamics and further advance the debate on the dilution effect of host diversity on disease prevalence.
Molecular Genetics and Pathogenesis of the Floating Harbor Syndrome: Case Report of Long-Term Growth Hormone Treatment and a Literature Review
Authors: Turkunova Mariia E. , Barbitoff Yury A. , Serebryakova Elena A. , Polev Dmitrii E. , Berseneva Olga S. , Bashnina Elena B. , Baranov Vladislav S. , Glotov Oleg S. , Glotov Andrey S.
Published: May 2022

Introduction: Floating Harbor syndrome (FHS) is an extremely rare disorder, with slightly more than a hundred cases reported worldwide. FHS is caused by heterozygous mutations in the SRCAP gene; however, little is known about the pathogenesis of FHS or the effectiveness of its treatment.

Methods: Whole-exome sequencing (WES) was performed for the definitive molecular diagnosis of the disease. Identified variants were validated using Sanger sequencing. In addition, systematic literature and public data on genetic variation in SRCAP and the effects of growth hormone (GH) treatment was conducted.

Results: We herein report the first case of FHS in the Russian Federation. The male proband presented with most of the typical phenotypic features of FHS, including short stature, skeletal and facial features, delayed growth and bone age, high pitched voice, and intellectual impairment. The proband also had partial growth hormone deficiency. We report the history of treatment of the proband with GH, which resulted in modest improvement in growth prior to puberty. WES revealed a pathogenic c.7466C>G (p.Ser2489*) mutation in the last exon of the FHS-linked SRCAP gene. A systematic literature review and analysis of available genetic variation datasets highlighted an unusual distribution of pathogenic variants in SRCAP and confirmed the lack of pathogenicity for variants outside of exons 33 and 34. Finally, we suggested a new model of FHS pathogenesis which provides possible basis for the dominant negative nature of FHS-causing mutations and explains limited effects of GH treatment in FHS.

Conclusion: Our findings expand the number of reported FHS cases and provide new insights into disease genetics and the efficiency of GH therapy for FHS patients.
Innovative in Silico Approaches for Characterization of Genes and Proteins
Authors: Bhat Gh. Rasool , Sethi Itty , Rah Bilal , Kumar Rakesh , Afroze Dil
Published: May 2022

Bioinformatics is an amalgamation of biology, mathematics and computer science. It is a science which gathers the information from biology in terms of molecules and applies the informatic techniques to the gathered information for understanding and organizing the data in a useful manner. With the help of bioinformatics, the experimental data generated is stored in several databases available online like nucleotide database, protein databases, GENBANK and others. The data stored in these databases is used as reference for experimental evaluation and validation. Till now several online tools have been developed to analyze the genomic, transcriptomic, proteomics, epigenomics and metabolomics data. Some of them include Human Splicing Finder (HSF), Exonic Splicing Enhancer Mutation taster, and others. A number of SNPs are observed in the non-coding, intronic regions and play a role in the regulation of genes, which may or may not directly impose an effect on the protein expression. Many mutations are thought to influence the splicing mechanism by affecting the existing splice sites or creating a new sites. To predict the effect of mutation (SNP) on splicing mechanism/signal, HSF was developed. Thus, the tool is helpful in predicting the effect of mutations on splicing signals and can provide data even for better understanding of the intronic mutations that can be further validated experimentally. Additionally, rapid advancement in proteomics have steered researchers to organize the study of protein structure, function, relationships, and dynamics in space and time. Thus the effective integration of all of these technological interventions will eventually lead to steering up of next-generation systems biology, which will provide valuable biological insights in the field of research, diagnostic, therapeutic and development of personalized medicine.
Gene Regulatory Identification Based on the Novel Hybrid Time-Delayed Method
Authors: Bao Wenzheng , Lin Xiao , Yang Bin , Chen Baitong
Published: May 2022

Gene regulatory network (GRN) inference with biology data is a difficult and serious issue in the field of system biology. In order to detect the direct associations of GRN more accurately, a novel two-step GRN inference technique based on the time-delayed correlation coefficient (TDCC) and time-delayed complex-valued S-system model (TDCVSS) is proposed. First, a TDCC algorithm is utilized to construct an initial network. Second, a TDCVSS model is utilized to prune the network topology in order to delete false-positive regulatory relationships for each target gene. The complex-valued restricted additive tree and complex-valued differential evolution are proposed to approximate the optimal TDCVSS model. Finally, the overall network could be inferred by integrating the regulations of all target genes. Two real gene expression datasets from E. coli and S. cerevisiae gene networks are utilized to evaluate the performances of our proposed two-step GRN inference algorithm. The results demonstrated that the proposed algorithm could infer GRN more correct than classical methods and time-delayed methods.
Context-Aware Phylogenetic Trees for Phylogeny-Based Taxonomy Visualization
Authors: Kaya Gizem , Ezekannagha Chisom , Heider Dominik , Hattab Georges
Published: May 2022

Sustained efforts in next-generation sequencing technologies are changing the field of taxonomy. The increase in the number of resolved genomes has made the traditional taxonomy of species antiquated. With phylogeny-based methods, taxonomies are being updated and refined. Although such methods bridge the gap between phylogeny and taxonomy, phylogeny-based taxonomy currently lacks interactive visualization approaches. Motivated by enriching and increasing the consistency of evolutionary and taxonomic studies alike, we propose Context-Aware Phylogenetic Trees (CAPT) as an interactive web tool to support users in exploration- and validation-based tasks. To complement phylogenetic information with phylogeny-based taxonomy, we offer linking two interactive visualizations which compose two simultaneous views: the phylogenetic tree view and the taxonomic icicle view. Thanks to its space-filling properties, the icicle visualization follows the intuition behind taxonomies where different hierarchical rankings with equal number of child elements can be represented with same-sized rectangular areas. In other words, it provides partitions of different sizes depending on the number of elements they contain. The icicle view integrates seven taxonomic rankings: domain, phylum, class, order, family, genus, and species. CAPT enriches the clades in the phylogenetic tree view with context from the genomic data and supports interactive techniques such as linking and brushing to highlight correspondence between the two views. Four different use cases, extracted from the Genome Taxonomy DataBase, were employed to create four scenarios using our approach. CAPT was successfully used to explore the phylogenetic trees as well as the taxonomic data by providing context and using the interaction techniques. This tool is essential to increase the accuracy of categorization of newly identified species and validate updated taxonomies. The source code and data are freely available athttps://github.com/ghattab/CAPT.
Comparative Genomic-Based Study of Reproduction-Related Genes in Three Fruit Fly Species
Authors: Wu Yinggu , Lian Yuyang , Peng Sihua , Wang Aqiang , Yang Heming , Li Jinlei , Yang Shuyan , Zhou Shihao
Published: May 2022

Zeugodacus cucurbitae (Coquillett), Bactrocera dorsalis (Hendel), and Ceratitis capitata (Wiedemann) are important pests of fruit and vegetable crops and are difficult to control because of their rapid reproduction rate and egg production. To investigate the key genes regulating reproduction in three fruit fly species, we selected genomic information of three fruit fly species, screened specific genes and single-copy homolog genes, and performed KEGG and GO enrichment analysis on specific genes and single-copy homolog genes of the strong positive select (SP); the results showed that Z. cucurbitae (Coquillett), B. dorsalis (Hendel), and C. capitata (Wiedemann) had seven, 11, and one Vitellogenin-related genes, respectively; Z. cucurbitae (Coquillett) had 84 specific genes enriched in immune system-related pathways; B. dorsalis (Hendel) had 1,121 specific genes enriched in signaling pathways related to cell growth and differentiation; C. capitata (Wiedemann) had 42 specific genes enriched in the degradation and metabolism pathways of exogenous organisms; Z. cucurbitae (Coquillett) may have a stronger immune system; B. dorsalis (Hendel) has a faster developmental and reproductive rate; and C. capitata (Wiedemann) has a higher detoxification capacity. Only one SP single-copy homolog gene (gene name: very long-chain specific acyl-CoA dehydrogenase, mitochondrial) is enriched in the fatty acid metabolic pathway in both Z. cucurbitae (Coquillett) and B. dorsalis (Hendel) as well as in Z. cucurbitae (Coquillett) and C. capitata (Wiedemann). This study provides a molecular basis for studying the reproductive mechanisms of three fruit fly species and provides a scientific basis for developing effective control strategies for fruit flies.
Intracellular Lipid Accumulation Drives the Differentiation of Decidual Polymorphonuclear Myeloid-Derived Suppressor Cells via Arachidonic Acid Metabolism
Authors: Wang Qiaohong , Zhang Xinyang , Li Congcong , Xiong Miao , Bai Wenxin , Sun Si , Chen Chao , Zhang Xiaoxin , Li Mingyang , Zhao Aimin
Published: May 2022

Decidual polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are essential to immune tolerance during pregnancy. A reduction in the number of these cells is associated with unexplained recurrent pregnancy loss (URPL). In our previous study, we reported that PMN-MDSCs are a group of mature neutrophils that are activated by the decidua microenvironment. In the present study, we show that the decidua microenvironment induces substantial lipid accumulation in neutrophils during their differentiation to PMN-MDSCs. Lower levels of lipid accumulation are detected in PMN-MDSCs from URPL patients, and the amount of lipid in the PMN-MDSCs is positively correlated with the proportion of PMN-MDSCs. Next, we demonstrate that decidua-derived IL6 with the presence of arachidonic acid upregulates fatty acid-binding protein 5 (FABP5) via the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Fy -60ABP5 then continuously stimulates intracellular lipid accumulation. Increased intracellular lipid accumulation mediates arachidonic acid metabolism, a pathway that is significantly activated by the induction of the decidua microenvironment, to stimulate the synthesis of prostaglandin E2 (PGE2) and finally induce the differentiation of PMN-MDSCs. To summarize, decidua-derived IL6 facilitates the differentiation of PMN-MDSCs from neutrophils via the pSTAT3/FABP5/PGE2 pathway. Defects in the process may result in impaired differentiation and dysfunction of PMN-MDSCs in URPL. These findings enhance our understanding of the physiological mechanisms of immune tolerance in pregnancy and provide therapeutic options for URPL.
Neuroinflammation in Parkinson’s Disease – Putative Pathomechanisms and Targets for Disease-Modification
Authors: Grotemeyer Alexander , McFleder Rhonda Leah , Wu Jingjing , Wischhusen Jörg , Ip Chi Wang
Published: May 2022

Parkinson’s disease (PD) is a progressive and debilitating chronic disease that affects more than six million people worldwide, with rising prevalence. The hallmarks of PD are motor deficits, the spreading of pathological α-synuclein clusters in the central nervous system, and neuroinflammatory processes. PD is treated symptomatically, as no causally-acting drug or procedure has been successfully established for clinical use. Various pathways contributing to dopaminergic neuron loss in PD have been investigated and described to interact with the innate and adaptive immune system. We discuss the possible contribution of interconnected pathways related to the immune response, focusing on the pathophysiology and neurodegeneration of PD. In addition, we provide an overview of clinical trials targeting neuroinflammation in PD.
Puerarin: A Potential Therapeutic for SARS-CoV-2 and Hantavirus Co-Infection
Authors: Liang Weizheng , Li Xiushen , Wang Hao , Nie Kechao , Meng Qingxue , He Junli , Zheng Chunfu
Published: May 2022

Patients with Hantavirus-caused epidemic hemorrhagic fever (EHF) are at risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is currently no validated EHF/SARS-CoV-2 strategy. Several studies have recently shown Puerarin, a natural product, has potent antiviral properties. The goal of present study was to determine the mechanism of puerarin in patients with EHF/COVID-19. We use network pharmacology and bioinformatics to investigate the possible pharmacological targets, bioactivities, and molecular mechanisms of puerarin in the treatment of patients with EHF/SARS-CoV-2. The study investigated the pathogenesis of COVID-19 and EHF and the signaling pathway impacted by puerarin. 68 common genes linked to puerarin and EHF/SARS-CoV-2 were discovered during the investigation. By using protein-protein interaction (PPI) network, we identified RELA, JUN, NF-B1, NF-B2, and FOS as potential therapeutic targets. The bioactivity and signaling pathways of puerarin have also been demonstrated in the treatment of EHF and COVID-19. According to present study, puerarin could reduce excessive immune responses and inflammation through the NF-B, TNF, and HIF-1 signaling pathways. This study explored the potential therapeutic targets and mechanisms of Puerarin in the treatment of EHF/COVID-19.
Soluble P2X7 Receptor Is Elevated in the Plasma of COVID-19 Patients and Correlates With Disease Severity
Authors: García-Villalba Julio , Hurtado-Navarro Laura , Peñín-Franch Alejandro , Molina-López Cristina , Martínez-Alarcón Laura , Angosto-Bazarra Diego , Baroja-Mazo Alberto , Pelegrin Pablo
Published: May 2022

Inflammation is a tightly coordinated response against bacterial and viral infections, triggered by the production of pro-inflammatory cytokines. SARS-CoV-2 infection induces COVID-19 disease, characterized by an inflammatory response mediated through the activation of the NLRP3 inflammasome, which results in the production of IL-1β and IL-18 along with pyroptotic cell death. The NLRP3 inflammasome could be also activated by sterile danger signals such as extracellular ATP triggering the purinergic P2X7 receptor. Severe inflammation in the lungs of SARS-CoV-2-infected individuals is associated with pneumonia, hypoxia and acute respiratory distress syndrome, these being the causes of death associated with COVID-19. Both the P2X7 receptor and NLRP3 have been considered as potential pharmacological targets for treating inflammation in COVID-19. However, there is no experimental evidence of the involvement of the P2X7 receptor during COVID-19 disease. In the present study, we determined the concentration of different cytokines and the P2X7 receptor in the plasma of COVID-19 patients and found that along with the increase in IL-6, IL-18 and the IL-1 receptor antagonist in the plasma of COVID-19 patients, there was also an increase in the purinergic P2X7 receptor. The increase in COVID-19 severity and C-reactive protein concentration positively correlated with increased concentration of the P2X7 receptor in the plasma, but not with the IL-18 cytokine. The P2X7 receptor was found in the supernatant of human peripheral blood mononuclear cells after inflammasome activation. Therefore, our data suggest that determining the levels of the P2X7 receptor in the plasma could be a novel biomarker of COVID-19 severity.
Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus
Authors: Liu Yaling , Tao Xinyu , Tao Jinhui
Published: May 2022

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ dysfunction resulting from the production of multiple autoantibodies and adaptive immune system abnormalities involving T and B lymphocytes. In recent years, inflammasomes have been recognized as an important component of innate immunity and have attracted increasing attention because of their pathogenic role in SLE. In short, inflammasomes regulate the abnormal differentiation of immune cells, modulate pathogenic autoantibodies, and participate in organ damage. However, due to the clinical heterogeneity of SLE, the pathogenic roles of inflammasomes are variable, and thus, the efficacy of inflammasome-targeting therapies is uncertain. To provide a foundation for the development of such therapeutic strategies, in this paper, we review the role of different inflammasomes in the pathogenesis of SLE and their correlation with clinical phenotypes and propose some corresponding treatment strategies.
Highly Efficient Biotransformation of Phenolic Glycosides Using a Recombinant β-Glucosidase From White Rot Fungus Trametes trogii
Authors: Qu Yuan , Luo Yuan , Yang Xulei , Zhang Yu , Yang En , Xu Huini , He Yingying , Chagan Irbis , Yan JinPing
Published: May 2022

Phenolic glycosides are the important bioactive molecules, and their bioavailability can be influenced by enzyme hydrolysis, such as β-glucosidases (EC3.2.1.21) and other glycosyl hydrolases (GHs). Wood rotting fungi possess a superfamily of GHs, but little attention has been paid to the GHs and their potential applications in biotransformation of phenolic glycosides. In this study, two GH3 gene family members of Trametes trogii S0301, mainly expressed in the carbon sources conversion stage were cloned, and TtBgl3 coded by T_trogii_12914 showed β-glucosidase activity toward 4-nitrophenyl β-D-glucopyranoside (pNPG). The recombinant TtBgl3 preferred an intermediately neutral optimum pH with >80% of the maximum activity at pH 5.0–7.0 and was stable at a wide range of pH (5.0–10.0). Phenolic glycosides transformation experiments showed that TtBgl3 was a dual-activity enzyme with both activities of aryl-β-D-glucosidase and β-glucuronidase, and could hydrolyze the β-glucoside/glucuronide bond of phenolic glycosides. Under optimized conditions, the recombinant TtBgl3 had much higher transformation efficiency toward the β-glucoside bond of gastrodin, esculin and daidzin than β-glucuronide bond of baicalin, with the transformation rate of 100 and 50%, respectively. Our homology modeling, molecular docking, and mutational analysis demonstrated that His85 and Lys467 in the acceptor-binding pocket of TtBgl3 were the potential active sites. The point mutation of His85 and Lys467 leads to the significantly impaired catalytic activity toward pNPG and also the weak transformation efficiency toward gastrodin. These findings provide insights for the identification of novel GH3 β-glucosidases from T. trogii and other wood-rotting fungi. Furthermore, TtBgl3 might be applied as green and efficient biological catalysts in the deglycosylation of diverse phenolics to produce bioactive glycosides for drug discovery in the future.
Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites
Authors: Wu Zhengjie , Xu Qiaomai , Gu Silan , Chen Yunbo , Lv Longxian , Zheng Beiwen , Wang Qiangqiang , Wang Kaicen , Wang Shuting , Xia Jiafeng , Yang Liya , Bian Xiaoyuan , Jiang Xianwan , Zheng Lisi , Li Lanjuan
Published: May 2022

Clostridioides difficile is a common cause of nosocomial infection. Antibiotic-induced dysbiosis in the intestinal microbiota is a core cause of C. difficile infection (CDI). Akkermansia muciniphila plays an active role in maintaining gastrointestinal balance and might offer the protective effects on CDI as probiotics. Here, we investigated the effects and mechanisms of A. muciniphila on CDI. C57BL/6 mice (n = 29) were administered A. muciniphila MucT (3 × 109 CFUs, 0.2 mL) or phosphate-buffered saline (PBS) by oral gavage for 2 weeks. Mice were pretreated with an antibiotic cocktail and subsequently challenged with the C. difficile strain VPI 10463. A. muciniphila treatment prevented weight loss in mice and reduced the histological injury of the colon. And it also alleviated inflammation and improved the barrier function of the intestine. The administration effects of A. muciniphila may be associated with an increase in short-chain fatty acid production and the maintenance of bile acids’ steady-state. Our results provide evidence that administration of A. muciniphila to CDI mice, with an imbalance in the microbial community structure, lead to a decrease in abundance of members of the Enterobacteriaceae and Enterococcaceae. In short, A. muciniphila shows a potential anti-CDI role by modulating gut microbiota and the metabolome.
High-Frequency Detection of fosA3 and blaCTX–M–55 Genes in Escherichia coli From Longitudinal Monitoring in Broiler Chicken Farms
Authors: Menck-Costa Maísa Fabiana , Baptista Ana Angelita Sampaio , Gazal Luiz Eduardo de Souza , Justino Larissa , Sanches Matheus Silva , de Souza Marielen , Nishio Erick Kenji , Queiroz dos Santos Beatriz , Cruz Victor Dellevedove , Berbert João Vitor Monteiro , Gonçalves Bruna Carolina , Andrade Galdino , Vespero Eliana Carolina , Nakazato Gerson , Kobayashi Renata Katsuko Takayama
Published: May 2022

Considering the worrying emergence of multidrug resistance, including in animal husbandry and especially in food-producing animals, the need to detect antimicrobial resistance strains in poultry environments is relevant, mainly considering a One Health approach. Thus, this study aimed to conduct longitudinal monitoring of antimicrobial resistance in broiler chicken farms, with an emphasis on evaluating the frequency of resistance to fosfomycin and β-lactams. Escherichia coli was isolated from broiler chicken farms (cloacal swabs, meconium, poultry feed, water, poultry litter, and Alphitobius diaperinus) in northern Paraná from 2019 to 2020 during three periods: the first period (1st days of life), the second period (20th to 25th days of life), and third period (40th to 42nd days of life). Antibiogram tests and the detection of phenotypic extended-spectrum β-lactamase (ESBL) were performed, and they were confirmed by seaching for genes from the blaCTX–M group. The other resistance genes searched were mcr-1 and fosA3. Some ESBL blaCTX–M–1 group strains were selected for ESBL identification by sequencing and enterobacterial repetitive intergenic consensus-polymerase chain reaction analysis. To determine the transferability of the blaCTX–M–1– and fosA3-carrying plasmids, strains were subjected to conjugation experiments. A total of 507 E. coli were analyzed: 360 from cloacal swabs, 24 from meconium samples, 3 from poultry feed samples, 18 from water samples, 69 from poultry litter samples, and 33 from A. diaperinus samples. Among the strain isolate, 80% (406/507) were multidrug-resistant (MDR), and 51% (260/507) were ESBL-positive, with the blaCTX–M–1 group being the most frequent. For the fosA3 gene, 68% (344/507) of the strains isolated were positive, deserves to be highlighted E. coli isolated from day-old chickens (OR 6.34, CI 2.34–17.17), when compared with strains isolated from other origins (poultry litter, A. diaperinus, water, and poultry feed). This work alerts us to the high frequency of the fosA3 gene correlated with the CTX-M-1 group (OR 3.57, CI 95% 2.7–4.72, p < 0.05), especially the blaCTX–M–55 gene, in broiler chickens. This profile was observed mainly in day-old chicken, with a high percentage of E. coli that were MDR. The findings emphasize the importance of conducting longitudinal monitoring to detect the primary risk points during poultry production.
Comparative Genomics of Lactiplantibacillus plantarum: Insights Into Probiotic Markers in Strains Isolated From the Human Gastrointestinal Tract and Fermented Foods
Authors: Garcia-Gonzalez Natalia , Bottacini Francesca , van Sinderen Douwe , Gahan Cormac G. M. , Corsetti Aldo
Published: May 2022

Lactiplantibacillus (Lpb.) plantarum is a versatile species commonly found in a wide variety of ecological niches including dairy products and vegetables, while it may also occur as a natural inhabitant of the human gastrointestinal tract. Although Lpb. plantarum strains have been suggested to exert beneficial properties on their host, the precise mechanisms underlying these microbe–host interactions are still obscure. In this context, the genome-scale in silico analysis of putative probiotic bacteria represents a bottom–up approach to identify probiotic biomarkers, predict desirable functional properties, and identify potentially detrimental antibiotic resistance genes. In this study, we characterized the bacterial genomes of three Lpb. plantarum strains isolated from three distinct environments [strain IMC513 (from the human GIT), C904 (from table olives), and LT52 (from raw-milk cheese)]. A whole-genome sequencing was performed combining Illumina short reads with Oxford Nanopore long reads. The phylogenomic analyses suggested the highest relatedness between IMC513 and C904 strains which were both clade 4 strains, with LT52 positioned within clade 5 within the Lpb. plantarum species. The comparative genome analysis performed across several Lpb. plantarum representatives highlighted the genes involved in the key metabolic pathways as well as those encoding potential probiotic features in these new isolates. In particular, our strains varied significantly in genes encoding exopolysaccharide biosynthesis and in contrast to strains IMC513 and C904, the LT52 strain does not encode a Mannose-binding adhesion protein. The LT52 strain is also deficient in genes encoding complete pentose phosphate and the Embden–Meyerhof pathways. Finally, analyses using the CARD and ResFinder databases revealed that none of the strains encode known antibiotic resistance loci. Ultimately, the results provide better insights into the probiotic potential and safety of these three strains and indicate avenues for further mechanistic studies using these isolates.
Variations in Concentration and Carbon Isotope Composition of Methanotroph Biomarkers in Sedge Peatlands Along the Altitude Gradient in the Changbai Mountain, China
Authors: Zhao Meiling , Wang Ming , Zhao Yantong , Jiang Ming , Wang Guodong
Published: May 2022

Northern peatlands are one of the largest natural sources of atmospheric methane globally. As the only biological sink of methane, different groups of methanotrophs use different carbon sources. However, the variations in microbial biomass and metabolism of different methanotrophic groups in peatlands along the altitude gradient are uncertain. We measured the concentrations and metabolic characteristics of type I (16:1ω7c and 16:1ω5c) and type II (18:1ω7c) methanotroph biomarkers using biomarkers and stable isotopes in eight Carex peatlands along an altitude gradient from 300 to 1,500 m in the Changbai Mountain, China. We found that the trends with altitude in concentrations of the type I and type II methanotroph biomarkers were different. The dominating microbial group changed from type I to type II methanotroph with increasing altitude. The concentrations of type I and type II methanotroph biomarkers were significantly affected by the total phosphorus, total nitrogen, and dissolved organic carbon, respectively. The δ13C values of type II methanotroph biomarkers changed significantly along the altitude gradient, and they were more depleted than type II methanotroph biomarkers, which indicates the difference in carbon source preference between type I and type II methanotrophs. This study highlights the difference in the concentration and carbon source utilization of type I and type II methanotrophic groups along the altitude gradient, and enhances our understanding of the metabolic process of methane mediated by methanotrophs and its impact on carbon-sink function in northern peatlands.
Interleaved Pro/Anti-saccade Behavior Across the Lifespan
Authors: Yep Rachel , Smorenburg Matthew L. , Riek Heidi C. , Calancie Olivia G. , Kirkpatrick Ryan H. , Perkins Julia E. , Huang Jeff , Coe Brian C. , Brien Donald C. , Munoz Douglas P.
Published: May 2022

The capacity for inhibitory control is an important cognitive process that undergoes dynamic changes over the course of the lifespan. Robust characterization of this trajectory, considering age continuously and using flexible modeling techniques, is critical to advance our understanding of the neural mechanisms that differ in healthy aging and neurological disease. The interleaved pro/anti-saccade task (IPAST), in which pro- and anti-saccade trials are randomly interleaved within a block, provides a simple and sensitive means of assessing the neural circuitry underlying inhibitory control. We utilized IPAST data collected from a large cross-sectional cohort of normative participants (n = 604, 5–93 years of age), standardized pre-processing protocols, generalized additive modeling, and change point analysis to investigate the effect of age on saccade behavior and identify significant periods of change throughout the lifespan. Maturation of IPAST measures occurred throughout adolescence, while subsequent decline began as early as the mid-20s and continued into old age. Considering pro-saccade correct responses and anti-saccade direction errors made at express (short) and regular (long) latencies was crucial in differentiating developmental and aging processes. We additionally characterized the effect of age on voluntary override time, a novel measure describing the time at which voluntary processes begin to overcome automated processes on anti-saccade trials. Drawing on converging animal neurophysiology, human neuroimaging, and computational modeling literature, we propose potential frontal-parietal and frontal-striatal mechanisms that may mediate the behavioral changes revealed in our analysis. We liken the models presented here to “cognitive growth curves” which have important implications for improved detection of neurological disease states that emerge during vulnerable windows of developing and aging.
The Effects of Aerobic Exercise Training on Cerebrovascular and Cognitive Function in Sedentary, Obese, Older Adults
Authors: Bliss Edward S. , Wong Rachel H. X. , Howe Peter R. C. , Mills Dean E.
Published: May 2022

Cerebrovascular function and cognition decline with age and are further exacerbated by obesity and physical inactivity. This decline may be offset by aerobic exercise training (AT). We investigated the effects of 16 weeks AT on cerebrovascular and cognitive function in sedentary, obese, older adults. Twenty-eight participants were randomly allocated to AT or a control group. Before and after the intervention, transcranial Doppler ultrasonography was used to measure the cerebrovascular responsiveness (CVR) to physiological (hypercapnia, 5% carbon dioxide) and cognitive stimuli. AT increased the CVR to hypercapnia (98.5 ± 38.4% vs. 58.0 ± 42.0%, P = 0.021), CVR to cognitive stimuli (25.9 ± 6.1% vs. 16.4 ± 5.4%, P < 0.001) and total composite cognitive score (111 ± 14 vs. 104 ± 14, P = 0.004) compared with the control group. A very strong relationship was observed between the number of exercise sessions completed and CVR to cognitive stimuli (r = 0.878, P < 0.001), but not for CVR to hypercapnia (r = 0.246, P = 0.397) or total composite cognitive score (r = 0.213, P = 0.465). Cerebrovascular function and cognition improved following 16 weeks of AT and a dose-response relationship exists between the amount of exercise sessions performed and CVR to cognitive stimuli.
Medial Temporal Atrophy Contributes to Cognitive Impairment in Cerebral Small Vessel Disease
Authors: Sun Wenshan , Huang Lili , Cheng Yue , Qin Ruomeng , Xu Hengheng , Shao Pengfei , Ma Junyi , Yao Zhelv , Shi Lin , Xu Yun
Published: May 2022

Background

The role of brain atrophy in cognitive decline related to cerebral small vessel disease (CSVD) remains unclear. This study used AccuBrain™ to identify major CSVD-related brain changes and verified the relationship between brain atrophy and different cognition domains in CSVD patients.

Methods

All enrolled 242 CSVD patients and 76 healthy participants underwent magnetic resonance imaging examinations and detailed neuropsychological scale assessments were collected at the same time. The AccuBrain™ technology was applied to fully automated image segmentation, measurement, and calculation of the acquired imaging results to obtain the volumes of different brain partitions and the volume of WMH for quantitative analysis. Correlation analyses were used to estimate the relationship between MRI features and different cognitive domains. Multifactor linear regression models were performed to analyze independent predictors of MTA and cognitive decline.

Results

CSVD patients exhibited multiple gray matter nucleus volume decreases in the basal ganglia regions and brain lobes, including the temporal lobe (P = 0.019), especially in the medial temporal lobe (p < 0.001), parietal lobe (p = 0.013), and cingulate lobe (p = 0.036) compare to HC. The volume of PWMH was an independent predictor of MTA for CSVD patients. Both medial temporal atrophy (MTA) and PWMH were associated with cognition impairment in CSVD-CI patients. MTA mediated the effect of PWMH on executive function in CSVD-CI patients.

Conclusions

Our results showed that MTA was related to cognition impairment in CSVD patients, which might become a potential imaging marker for CSVD-CI.
Glymphatic System Dysfunction: A Novel Mediator of Sleep Disorders and Headaches
Authors: Yi Ting , Gao Ping , Zhu Tianmin , Yin Haiyan , Jin Shuoguo
Published: May 2022

Sleep contributes to the maintenance of overall health and well-being. There are a growing number of patients who have headache disorders that are significantly affected by poor sleep. This is a paradoxical relationship, whereby sleep deprivation or excess sleep leads to a worsening of headaches, yet sleep onset also alleviates ongoing headache pain. Currently, the mechanism of action remains controversial and poorly understood. The glymphatic system is a newly discovered perivascular network that encompasses the whole brain and is responsible for removing toxic proteins and waste metabolites from the brain as well as replenishing nutrition and energy. Recent studies have suggested that glymphatic dysfunction is a common underlying etiology of sleep disorders and headache pain. This study reviews the current literature on the relationship between the glymphatic system, sleep, and headaches, discusses their roles, and proposes acupuncture as a non-invasive way to focus on the glymphatic function to improve sleep quality and alleviate headache pain.