bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Perforated Concentric Ring Walls Considerably Improves Gas-Liquid Mass Transfer of Shaken Bioreactors
Authors: Hansen Sven , Gumprecht Andreas , Micheel Linda , Hennemann Hans-Georg , Enzmann Franziska , Blümke Wilfried
Published: May 2022

Since their first use in the 1930s, shake flasks have been a widely used bioreactor type for screening and process development due to a number of advantages. However, the limited gas-liquid mass transfer capacities—resulting from practical operation limits regarding shaking frequency and filling volumes—are a major drawback. The common way to increase the gas-liquid mass transfer in shake flasks with the implementation of baffles is generally not recommended as it comes along with several severe disadvantages. Thus, a new design principle for shaken bioreactors that aims for improving the gas-liquid mass transfer without losing the positive characteristics of unbaffled shake flasks is introduced. The flasks consist of cylindrical glass vessels with implemented perforated concentric ring walls. The ring walls improve the gas-liquid mass transfer via the formation of additional liquid films on both of its sides, whereas the perforations allow for mixing between the compartments. Sulfite oxidation experiments revealed over 200% higher maximum oxygen transfer capacities (OTRmax) compared to conventional shake flasks. In batch cultivations of Escherichia coli BL21 in mineral media, unlimited growth until glucose depletion and oxygen transfer rates (OTR) of up to 138 mmol/L/h instead of an oxygen limitation at 57 mmol/L/h as in normal shake flasks under comparable conditions could be achieved. Even overflow metabolism could be prevented due to sufficient oxygen supply without the use of unconventional shaking conditions or oxygen enrichment. Therefore, we believe that the new perforated ring flask principle has a high potential to considerably improve biotechnological screening and process development steps.
Characteristics and Application of Rhodopseudomonas palustris as a Microbial Cell Factory
Authors: Li Meijie , Ning Peng , Sun Yi , Luo Jie , Yang Jianming
Published: May 2022

Rhodopseudomonas palustris, a purple nonsulfur bacterium, is a bacterium with the properties of extraordinary metabolic versatility, carbon source diversity and metabolite diversity. Due to its biodetoxification and biodegradation properties, R. palustris has been traditionally applied in wastewater treatment and bioremediation. R. palustris is rich in various metabolites, contributing to its application in agriculture, aquaculture and livestock breeding as additives. In recent years, R. palustris has been engineered as a microbial cell factory to produce valuable chemicals, especially photofermentation of hydrogen. The outstanding property of R. palustris as a microbial cell factory is its ability to use a diversity of carbon sources. R. palustris is capable of CO2 fixation, contributing to photoautotrophic conversion of CO2 into valuable chemicals. R. palustris can assimilate short-chain organic acids and crude glycerol from industrial and agricultural wastewater. Lignocellulosic biomass hydrolysates can also be degraded by R. palustris. Utilization of these feedstocks can reduce the industry cost and is beneficial for environment. Applications of R. palustris for biopolymers and their building blocks production, and biofuels production are discussed. Afterward, some novel applications in microbial fuel cells, microbial electrosynthesis and photocatalytic synthesis are summarized. The challenges of the application of R. palustris are analyzed, and possible solutions are suggested.
Reconstruction of a Genome-Scale Metabolic Network for Shewanella oneidensis MR-1 and Analysis of its Metabolic Potential for Bioelectrochemical Systems
Authors: Luo Jiahao , Yuan Qianqian , Mao Yufeng , Wei Fan , Zhao Juntao , Yu Wentong , Kong Shutian , Guo Yanmei , Cai Jingyi , Liao Xiaoping , Wang Zhiwen , Ma Hongwu
Published: May 2022

Bioelectrochemical systems (BESs) based on Shewanella oneidensis MR-1 offer great promise for sustainable energy/chemical production, but the low rate of electron generation remains a crucial bottleneck preventing their industrial application. Here, we reconstructed a genome-scale metabolic model of MR-1 to provide a strong theoretical basis for novel BES applications. The model iLJ1162, comprising 1,162 genes, 1,818 metabolites and 2,084 reactions, accurately predicted cellular growth using a variety of substrates with 86.9% agreement with experimental results, which is significantly higher than the previously published models iMR1_799 and iSO783. The simulation of microbial fuel cells indicated that expanding the substrate spectrum of MR-1 to highly reduced feedstocks, such as glucose and glycerol, would be beneficial for electron generation. In addition, 31 metabolic engineering targets were predicted to improve electricity production, three of which have been experimentally demonstrated, while the remainder are potential targets for modification. Two potential electron transfer pathways were identified, which could be new engineering targets for increasing the electricity production capacity of MR-1. Finally, the iLJ1162 model was used to simulate the optimal biosynthetic pathways for six platform chemicals based on the MR-1 chassis in microbial electrosynthesis systems. These results offer guidance for rational design of novel BESs.
Transcriptomic Analysis Provides Insights to Reveal the bmp6 Function Related to the Development of Intermuscular Bones in Zebrafish
Authors: Xu Huan , Tong Guangxiang , Yan Ting , Dong Le , Yang Xiaoxing , Dou Dongyu , Sun Zhipeng , Liu Tianqi , Zheng Xianhu , Yang Jian , Sun Xiaowen , Zhou Yi , Kuang Youyi
Published: May 2022

Intermuscular bones (IBs) are small, hard-boned spicules located in the muscle tissue that mainly exist in the myosepta of lower teleosts, which hurt the edibleness and economic value of fish. The study of the development of IBs is very important for freshwater aquaculture fish, but the molecular mechanism of its formation and the key regulatory genes remain unclear. In this study, we first constructed two types of zebrafish mutants (the mutants losing IBs and the mutants with partial deletion of IBs) by knocking out bmp6. We then carried out a transcriptomic analysis to reveal the role of bmp6 in the developmental mechanism of IBs; we used the caudal musculoskeletal tissues of these mutants and wild-type zebrafish at three development stages (20, 45, and 60 dph) to perform transcriptomic analysis. The results showed that the deficiency of bmp6 upregulated sik1 and activated the TNF-A signaling via the NF-KB pathway, which inhibited the development of osteoblasts and promoted osteoclast formation, thereby inhibiting the formation of IBs. These results provided insights to understand the role of bmp6 in the development of IBs in zebrafish and are useful for selective breeding of IBs in cyprinids.
Epigenetics and Neuroinflammation Associated With Neurodevelopmental Disorders: A Microglial Perspective
Authors: Komada Munekazu , Nishimura Yuhei
Published: May 2022

Neuroinflammation is a cause of neurodevelopmental disorders such as autism spectrum disorders, fetal alcohol syndrome, and cerebral palsy. Converging lines of evidence from basic and clinical sciences suggest that dysregulation of the epigenetic landscape, including DNA methylation and miRNA expression, is associated with neuroinflammation. Genetic and environmental factors can affect the interaction between epigenetics and neuroinflammation, which may cause neurodevelopmental disorders. In this minireview, we focus on neuroinflammation that might be mediated by epigenetic dysregulation in microglia, and compare studies using mammals and zebrafish.
Sequence Determinants of TDP-43 Ribonucleoprotein Condensate Formation and Axonal Transport in Neurons
Authors: Vishal Sonali S. , Wijegunawardana Denethi , Salaikumaran Muthu Raj , Gopal Pallavi P.
Published: May 2022

Mutations in TDP-43, a RNA-binding protein with multiple functions in RNA metabolism, cause amyotrophic lateral sclerosis (ALS), but it is uncertain how defects in RNA biology trigger motor neuron degeneration. TDP-43 is a major constituent of ribonucleoprotein (RNP) granules, phase separated biomolecular condensates that regulate RNA splicing, mRNA transport, and translation. ALS-associated TDP-43 mutations, most of which are found in the low complexity domain, promote aberrant liquid to solid phase transitions and impair the dynamic liquid-like properties and motility of RNP transport granules in neurons. Here, we perform a comparative analysis of ALS-linked mutations and TDP-43 variants in order to identify critical structural elements, aromatic and charged residues that are key determinants of TDP-43 RNP transport and condensate formation in neurons. We find that A315T and Q343R disease-linked mutations and substitutions of aromatic residues within the α-helical domain and LARKS, show the most severe defects in TDP-43 RNP granule transport and impair both anterograde and retrograde motility. F313L and F313-6L/Y substitutions of one or both phenylalanine residues in LARKS suggest the aromatic rings are important for TDP-43 RNP transport. Similarly, W334F/L substitutions of the tryptophan residue in the α-helical domain, impair TDP-43 RNP motility (W334L) or anterograde transport (W334F). We also show that R293A and R293K mutations, which disrupt the only RGG in the LCD, profoundly reduce long-range, directed transport and net velocity of TDP-43 RNP granules. In the disordered regions flanking the α-helical domain, we find that F283Y, F397Y or Y374F substitutions of conserved GF/G and SYS motifs, also impair anterograde and/or retrograde motility, possibly by altering hydrophobicity. Similarly, ALS-linked mutations in disordered regions distant from the α-helical domain also show anterograde transport deficits, consistent with previous findings, but these mutations are less severe than A315T and Q343R. Overall our findings demonstrate that the conserved α-helical domain, phenylalanine residues within LARKS and RGG motif are key determinants of TDP-43 RNP transport, suggesting they may mediate efficient recruitment of motors and adaptor proteins. These results offer a possible mechanism underlying ALS-linked TDP-43 defects in axonal transport and homeostasis.
Recent Publication Trends in Radiotherapy and Male Infertility over Two Decades: A Scientometric Analysis
Authors: Roychoudhury Shubhadeep , Das Anandan , Panner Selvam Manesh Kumar , Chakraborty Saptaparna , Slama Petr , Sikka Suresh C. , Kesari Kavindra Kumar
Published: May 2022

Radiotherapy, a popular cancer management procedure, negatively impacts reproductive health particularly by reducing the fertility potential. The purpose of this study was to analyze the research trend in radiotherapy associated with male infertility over the past 20 years (2000-May 2021). SCOPUS database was used to retrieve relevant scientometric data (publication per year, affiliation, journals, countries, type of document and area of research) for different subgenres of radiotherapy and male infertility. A total of 275 articles were published related to radiotherapy and male infertility, with the United States being the most dominant country in research output in this field. Radiotherapy and male infertility research have shown positive growth over the last two decades. In-depth analysis revealed that publications (n) related to radiotherapy and male infertility research mainly focused its impact on semen parameters (n = 155) and fertility preservation techniques (n = 169). Our scientometric results highlight a limited research focus on the field of radiotherapy and its impact on male reproductive hormones. Furthermore, a significant lack of research was noticed in the area of omics and male reproductive organs linked to radiotherapy. Substantial research is warranted to further decipher the effect of radiotherapy, at molecular level, leading to male infertility.
Treacle Sticks the Nucleolar Responses to DNA Damage Together
Authors: Gál Zita , Nieto Blanca , Boukoura Stavroula , Rasmussen Anna Vestergaard , Larsen Dorthe Helena
Published: May 2022

The importance of chromatin environment for DNA repair has gained increasing recognition in recent years. The nucleolus is the largest sub-compartment within the nucleus: it has distinct biophysical properties, selective protein retention, and houses the specialized ribosomal RNA genes (collectively referred to as rDNA) with a unique chromatin composition. These genes have high transcriptional activity and a repetitive nature, making them susceptible to DNA damage and resulting in the highest frequency of rearrangements across the genome. A distinct DNA damage response (DDR) secures the fidelity of this genomic region, the so-called nucleolar DDR (n-DDR). The composition of the n-DDR reflects the characteristics of nucleolar chromatin with the nucleolar protein Treacle (also referred to as TCOF1) as a central coordinator retaining several well-characterized DDR proteins in the nucleolus. In this review, we bring together data on the structure of Treacle, its known functions in ribosome biogenesis, and its involvement in multiple branches of the n-DDR to discuss their interconnection. Furthermore, we discuss how the functions of Treacle in ribosome biogenesis and in the n-DDR may contribute to Treacher Collins Syndrome, a disease caused by mutations in Treacle. Finally, we outline outstanding questions that need to be addressed for a more comprehensive understanding of Treacle, the n-DDR, and the coordination of ribosome biogenesis and DNA repair.
Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles
Authors: Lin Xiangyu , Zhu Liang , He Jing
Published: May 2022

As one of the main appendages of skin, hair follicles play an important role in the process of skin regeneration. Hair follicle is a tiny organ formed by the interaction between epidermis and dermis, which has complex and fine structure and periodic growth characteristics. The hair growth cycle is divided into three continuous stages, growth (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). And The Morphogenesis and cycle of hair follicles are regulated by a variety of signal pathways. When the signal molecules in the pathways are abnormal, it will affect the development and cycle of hair follicles, which will lead to hair follicle-related diseases.This article will review the structure, development, cycle and molecular regulation of hair follicles, in order to provide new ideas for solving diseases and forming functional hair follicle.
Associations of Blautia Genus With Early-Life Events and Later Phenotype in the NutriHS
Authors: Freitas Renata G. Borges de Oliveira Nascimento , Vasques Ana Carolina J. , Fernandes Gabriel da Rocha , Ribeiro Francieli B. , Solar Isabela , Barbosa Marina G. , Pititto Bianca de Almeida- , Geloneze Bruno , Ferreira Sandra Roberta G.
Published: May 2022

Introduction

Early-life events are associated with the risk of obesity and comorbidities later in life. The gut microbiota—whose composition is influenced by genetics and environmental factors—could be involved. Since the microbiota affects metabolism and fat storage, early-life insults could contribute to the occurrence of obesity driven, in part, by microbiota composition. We examined associations of gut bacteria with early-life events, nutritional status, and body composition in the Nutritionist’s Health Study (NutriHS).

Methods

A cross-sectional study of 114 female participants examining early-life data, body composition, and biological samples was conducted. Fecal microbiota structure was determined targeting the V4 region of the 16S rRNA gene. Principal coordinates analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) were used to test the impact of variables on microbial diversity. Profiles were identified using the Jensen-Shannon divergence matrix and Calinski–Harabasz index. Differential abundance between the categories of exclusive breastfeeding duration and nutritional status was tested using DESeq2.

Results

In the sample [median age 28 years and body mass index (BMI) 24.5 kg/m2], 2 microbiota profiles driven by the Blautia or Prevotella genus were identified. An estimated 9.1% of the variation was explained by the profiles (p < 0.001), 2.1% by nutritional status (p = 0.004), and 1.8% by exclusive breastfeeding (p = 0.012). The proportion of participants with BMI <25 kg/m2 and who were breastfed for at least 6 months was higher in the Blautia profile (p < 0.05).

Conclusion

Findings in a Blautia-driven profile of healthy women reinforce that early-life events play a role in defining gut microbiota composition, confirming the importance of exclusive breastfeeding for infant gut colonization in establishing a protective profile against adiposity-related outcomes in adulthood.
Augmented Enterocyte Damage During Candida albicans and Proteus mirabilis Coinfection
Authors: Niemiec Maria Joanna , Kapitan Mario , Himmel Maximilian , Döll Kristina , Krüger Thomas , Köllner Tobias G. , Auge Isabel , Kage Franziska , Alteri Christopher J. , Mobley Harry L.T. , Monsen Tor , Linde Susanne , Nietzsche Sandor , Kniemeyer Olaf , Brakhage Axel A. , Jacobsen Ilse D.
Published: May 2022

The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen Candida albicans adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast Candida albicans and the Gram-negative bacterium Proteus mirabilis resulting in enhanced host cell damage. This synergistic effect was conserved across different P. mirabilis isolates and occurred also with non-albicans Candida species and C. albicans mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the P. mirabilis hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between Candida and Proteus is induced by contact, but also by soluble factors. Specifically, we identified Candida-mediated glucose consumption and farnesol production as potential triggers for Proteus virulence. In summary, our study demonstrates that coinfection of enterocytes with C. albicans and P. mirabilis can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification via nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.
Ampicillin Treatment of Intracellular Listeria monocytogenes Triggers Formation of Persistent, Drug-Resistant L-Form Cells
Authors: Grosboillot Virginie , Keller Isabelle , Ernst Chantal , Loessner Martin J. , Schuppler Markus
Published: May 2022

Listeria monocytogenes is an opportunistic intracellular pathogen causing an infection termed listeriosis. Despite the low incidence of listeriosis, the high mortality rate in individuals at risk makes this bacterium one of the most dangerous foodborne pathogens. Reports about a relapse of infection after antibiotic treatment suggest that the bacteria may be able to evade antibiotic treatment and persist as a dormant, antibiotic-tolerant subpopulation. In this study, we observed intracellular generation of antibiotic-resistant L-forms of Listeria monocytogenes following Ampicillin treatment of Listeria monocytogenes infected cells. Detection and identification of intracellular Listeria L-forms was performed by a combination of fluorescence in-situ hybridization and confocal laser scanning microscopy. Using micromanipulation, it was possible to isolate single intracellular L-form cells that following transfer into fresh medium gave rise to pure cultures. In conclusion, the results obtained here provide strong evidence that antibiotic treatment of infected host cells can induce the formation of L-forms from intracellular Listeria monocytogenes. Furthermore, our results suggest that intracellular L-forms persist inside host cells and that they represent viable bacteria, which are still able to grow and proliferate.
SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms
Authors: Li Jiaqi , Jia Huimin , Tian Miaomiao , Wu Nijin , Yang Xia , Qi Jianni , Ren Wanhua , Li Feifei , Bian Hongjun
Published: May 2022

As of April 1, 2022, over 468 million COVID-19 cases and over 6 million deaths have been confirmed globally. Unlike the common coronavirus, SARS-CoV-2 has highly contagious and attracted a high level of concern worldwide. Through the analysis of SARS-CoV-2 structural, non-structural, and accessory proteins, we can gain a deeper understanding of structure-function relationships, viral infection mechanisms, and viable strategies for antiviral therapy. Angiotensin-converting enzyme 2 (ACE2) is the first widely acknowledged SARS-CoV-2 receptor, but researches have shown that there are additional co-receptors that can facilitate the entry of SARS-CoV-2 to infect humans. We have performed an in-depth review of published papers, searching for co-receptors or other auxiliary membrane proteins that enhance viral infection, and analyzing pertinent pathogenic mechanisms. The genome, and especially the spike gene, undergoes mutations at an abnormally high frequency during virus replication and/or when it is transmitted from one individual to another. We summarized the main mutant strains currently circulating global, and elaborated the structural feature for increased infectivity and immune evasion of variants. Meanwhile, the principal purpose of the review is to update information on the COVID-19 outbreak. Many countries have novel findings on the early stage of the epidemic, and accruing evidence has rewritten the timeline of the outbreak, triggering new thinking about the origin and spread of COVID-19. It is anticipated that this can provide further insights for future research and global epidemic prevention and control.
Forward Genetics in Apicomplexa Biology: The Host Side of the Story
Authors: Sánchez-Arcila Juan C. , Jensen Kirk D. C.
Published: May 2022

Forward genetic approaches have been widely used in parasitology and have proven their power to reveal the complexities of host-parasite interactions in an unbiased fashion. Many aspects of the parasite’s biology, including the identification of virulence factors, replication determinants, antibiotic resistance genes, and other factors required for parasitic life, have been discovered using such strategies. Forward genetic approaches have also been employed to understand host resistance mechanisms to parasitic infection. Here, we will introduce and review all forward genetic approaches that have been used to identify host factors involved with Apicomplexa infections, which include classical genetic screens and QTL mapping, GWAS, ENU mutagenesis, overexpression, RNAi and CRISPR-Cas9 library screens. Collectively, these screens have improved our understanding of host resistance mechanisms, immune regulation, vaccine and drug designs for Apicomplexa parasites. We will also discuss how recent advances in molecular genetics give present opportunities to further explore host-parasite relationships.
MCC950, a Selective NLRP3 Inhibitor, Attenuates Adverse Cardiac Remodeling Following Heart Failure Through Improving the Cardiometabolic Dysfunction in Obese Mice
Authors: Wang Menglong , Zhao Mengmeng , Yu Junping , Xu Yao , Zhang Jishou , Liu Jianfang , Zheng Zihui , Ye Jing , Wang Zhen , Ye Di , Feng Yongqi , Xu Shuwan , Pan Wei , Wei Cheng , Wan Jun
Published: May 2022

Obesity is often accompanied by hypertension. Although a large number of studies have confirmed that NLRP3 inhibitors can improve cardiac remodeling in mice with a normal diet, it is still unclear whether NLRP3 inhibitors can improve heart failure (HF) induced by pressure overload in obese mice. The purpose of this study was to explore the role of MCC950, a selective NLRP3 inhibitor, on HF in obese mice and its metabolic mechanism. Obese mice induced with a 10-week high-fat diet (HFD) were used in this study. After 4 weeks of HFD, transverse aortic constriction (TAC) surgery was performed to induce a HF model. MCC950 (10 mg/kg, once/day) was injected intraperitoneally from 2 weeks after TAC and continued for 4 weeks. After echocardiography examination, we harvested left ventricle tissues and performed molecular experiments. The results suggest that in obese mice, MCC950 can significantly improve cardiac hypertrophy and fibrosis caused by pressure overload. MCC950 ameliorated cardiac inflammation after TAC surgery and promoted M2 macrophage infiltration in the cardiac tissue. MCC950 not only restored fatty acid uptake and utilization by regulating the expression of CD36 and CPT1β but also reduced glucose uptake and oxidation via regulating the expression of GLUT4 and p-PDH. In addition, MCC950 affected the phosphorylation of AKT and AMPK in obese mice with HF. In summary, MCC950 can alleviate HF induced by pressure overload in obese mice via improving cardiac metabolism, providing a basis for the clinical application of NLRP3 inhibitors in obese patients with HF.
Radiomics and Machine Learning for Detecting Scar Tissue on CT Delayed Enhancement Imaging
Authors: O'Brien Hugh , Williams Michelle C. , Rajani Ronak , Niederer Steven
Published: May 2022

Background

Delayed enhancement CT (CT-DE) has been evaluated as a tool for the detection of myocardial scar and compares well to the gold standard of MRI with late gadolinium enhancement (MRI-LGE). Prior work has established that high performance can be achieved with manual reading; however, few studies have looked at quantitative measures to differentiate scar and healthy myocardium on CT-DE or automated analysis.

Methods

Eighteen patients with clinically indicated MRI-LGE were recruited for CT-DE at multiple 80 and 100 kV post contrast imaging. Left ventricle segmentation was performed on both imaging modalities, along with scar segmentation on MRI-LGE. Segmentations were registered together and scar regions were estimated on CT-DE. 93 radiomic features were calculated and analysed for their ability to differentiate between scarred and non-scarred myocardium regions. Machine learning (ML) classifiers were trained using the strongest set of radiomic features to classify segments containing scar on CT-DE. Features and classifiers were compared across both tube voltages and combined-energy images.

Results

There were 59 and 51 statistically significant features in the 80 and 100 kV images respectively. Combined-energy imaging increased this to 63 with more features having area under the curve (AUC) above 0.9. The 10 highest AUC features for each image were used in the ML classifiers. The 100 kV images produced the best ML classifier, a support vector machine with an AUC of 0.88 (95% CI 0.87–0.90). Comparable performance was achieved with both the 80 kV and combined-energy images.

Conclusions

CT-DE can be quantitatively analyzed using radiomic feature calculations. These features may be suitable for ML classification techniques to prospectively identify AHA segments with performance comparable to previously reported manual reading. Future work on larger CT-DE datasets is warranted to establish optimum imaging parameters and features.
P2Y12 Antagonists in Cardiovascular Disease—Finding the Best Balance Between Preventing Ischemic Events and Causing Bleeding
Authors: Fernando Himawan , McFadyen James D. , Wang Xiaowei , Shaw James , Stub Dion , Peter Karlheinz
Published: May 2022

Dual antiplatelet therapy comprising of aspirin and oral P2Y12 receptor antagonists are an established cornerstone of therapy in acute coronary syndromes and percutaneous coronary intervention. As a result, the platelet P2Y12 receptor remains a key therapeutic target in cardiovascular medicine since pharmacological antagonists were first developed in the 1990’s. With a greater understanding of platelet biology and the role played by the P2Y12 receptor in the amplification of platelet activation and thrombus formation, there has been progressive refinement in the development of P2Y12 receptor antagonists with greater potency and consistency of antiplatelet effect. However, challenges remain in the utilization of these agents particularly in balancing the need for greater protection from ischemic events whilst minimizing the bleeding risk and present a real opportunity for the institution of individualized medicine. Future drug developments will provide clinicians with greater avenues to achieve this.
Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence
Authors: Nopp Stephan , Kraemmer Daniel , Ay Cihan
Published: May 2022

Although anticoagulation therapy has evolved from non-specific drugs (i.e., heparins and vitamin K antagonists) to agents that directly target specific coagulation factors (i.e., direct oral anticoagulants, argatroban, fondaparinux), thrombosis remains a leading cause of death worldwide. Direct oral anticoagulants (i.e., factor IIa- and factor Xa-inhibitors) now dominate clinical practice because of their favorable pharmacological profile and ease of use, particularly in venous thromboembolism (VTE) treatment and stroke prevention in atrial fibrillation. However, despite having a better safety profile than vitamin K antagonists, their bleeding risk is not insignificant. This is true for all currently available anticoagulants, and a high bleeding risk is considered a contraindication to anticoagulation. As a result, ongoing research focuses on developing future anticoagulants with an improved safety profile. Several promising approaches to reduce the bleeding risk involve targeting the intrinsic (or contact activation) pathway of coagulation, with the ultimate goal of preventing thrombosis without impairing hemostasis. Based on epidemiological data on hereditary factor deficiencies and preclinical studies factor XI (FXI) emerged as the most promising candidate target. In this review, we highlight unmet clinical needs of anticoagulation therapy, outlay the rationale and evidence for inhibiting FXI, discuss FXI inhibitors in current clinical trials, conduct an exploratory meta-analysis on their efficacy and safety, and provide an outlook on the potential clinical application of these novel anticoagulants.
Hot Spring Gas Geochemical Characteristics and Geological Implications of the Northern Yadong-Gulu Rift in the Tibetan Plateau
Authors: Yu Xiaoli , Wei Zhifu , Wang Gen , Ma Xueyun , Zhang Ting , Yang Hui , Li Liwu , Zhou Shixin , Wang Xianbin
Published: May 2022

To reveal the heat source and its formation mechanism of the northern Yadong-Gulu rift (YGR), we analyzed the helium isotope, carbon isotope (δ13CCO2), and CO2/3He and CH4/3He ratios of hot spring gases for tracing the source of volatiles and discussing their geological significance. The results show the following: helium is mainly derived from the crust, and the radioactive decay of the thicker crust and granites provided more 4He to the low helium isotopes; thermal decomposition of carbonate rocks is the main source of CO2; CH4 may be of organic origin. To sum up, the gas geochemical characteristics of hot springs in the northern YGR indicate that the volatiles are mainly derived from the crust. The crust/mantle heat flow ratios (qc/qm) calculated by helium isotopes cover a range of 0.84–1.48, suggesting that the heat is mainly contributed by the crust. The crustal origin gas and heat flow demonstrates that the heat source beneath the northern YGR is formed by the process of interior crust. Combined with geophysical data, we suggest that the stress heat caused by the collision of the Indo-Eurasian plate and the radiant heating of the crust lead to the heat source (partial melting) and provide heat for thermal activities.
Application of GPR System With Convolutional Neural Network Algorithm Based on Attention Mechanism to Oil Pipeline Leakage Detection
Authors: Li Jiadai , Yang Ding , Guo Cheng , Ji Chenggao , Jin Yangchao , Sun Haijiao , Zhao Qing
Published: May 2022

High-efficiency and high-quality detection of oil pipeline will significantly reduce environmental pollution and economic loss, so an unconventional oil pipeline anomaly detection convolutional neural network (CNN) algorithm based on attention mechanism is proposed in this article. By taking the simulated ground-penetrating radar (GPR) data as prior knowledge, the structure of the convolutional neural network based on the attention mechanism is constructed, and finally, the location and working condition of the underground oil pipeline are recognized in the simulation data and measured data. The simulation results show that after using the new optimized convolutional neural network, the accuracy rates of the leakage discrimination from horizontal data acquired along the oil pipeline and the classification of the target from longitudinal data acquired perpendicular to the oil pipeline are 94.5% and 84.6%, respectively. Compared with the original convolutional neural network without an attention mechanism, the accuracy rates of the leakage discrimination and the classification of the target are improved by 6.2% and 7.8%, respectively. We further train measured data with an optimized convolutional neural network, results show that compared with a conventional network, the new network can increase the corresponding accuracy rates of the leakage discrimination and the targets classification by 5.4% and 6.9%, reaching 92.3% and 84.4%, respectively. According to our study, the ground-penetrating radar oil pipeline recognition algorithm based on an attention mechanism can well accomplish the identification of underground oil pipelines.
Live Online Education Efficiency Mediators From the Actor Network Theory Perspective
Authors: Czahajda Radoslaw , Čairović Neda , Černko Mitja
Published: May 2022

Purpose

The purpose of this research was to explore the conceptual network of live online education efficiency from the Actor Network Theory perspective to reveal different aspects influencing the quality of online training less accounted for in previous research.

Methodology

Actor Network Theory was used to analyse the qualitative feedback from 100 live online education sessions. Responses from 90 educators and 556 participants were coded into enablers and inhibitors of education quality and further clustered into different actors that might mediate learning success.

Findings

The key finding of this research is a visual representation of the complex network of actors potentially affecting live online education quality, revealing the interplay of non-human aspects (e.g., hardware, software, session design, and descriptions), as well as human elements (participants and their expectations, educators and their emotional reactions attributed to different actors of the network, organisers, and external mentors/experts).

Limitations

The piloting qualitative research was conducted within the framework of one educational event, where participants opted in voluntarily to attend and participate in the study. It is a specific educational context different from workplace training and other non-formal education.

Practical Implications

Learning and development practitioners can find 10 recommendations designed to support the instructional design and delivery of their (online) sessions based on the collective experiences of the study participants and authors.

Originality/value

It is the first research in the field of live online education, acknowledging and mapping the role of multiple actors posited to play an influential role in the overall quality. It also calls for a transition from “content-focused and controlling” to “contextually-aware and responsive” educator in future research.
Critical Global Citizenship Education: A Study on Secondary School Students
Authors: González-Valencia Gustavo , Massip Sabater Mariona , Santisteban Fernández Antoni
Published: May 2022

This article describes a study conducted in Catalonia (Spain) that examines the dimensions of global citizenship education (GCE) that emerge when secondary school students analyse images taken from the digital platforms of the mainstream media. We followed a mixed methodology for the research. To analyse the data, we employed content analysis, in the form of descriptive and inferential statistics. The results show that students in the final year of compulsory secondary education (aged 15–16) have great difficulty with analysing the information and images contained in media from a global citizenship perspective. While students tend to adopt a perspective of social responsibility, they do not have the tools necessary for critical interpretation of social facts and problems; they are still less able to formulate arguments or make decisions relating to actions within the parameters of social justice.
Characterization of lncRNA Profiles of Plasma-Derived Exosomes From Type 1 Diabetes Mellitus
Authors: Pang Haipeng , Fan Wenqi , Shi Xiajie , Li Jiaqi , Wang Yimeng , Luo Shuoming , Lin Jian , Huang Gan , Li Xia , Xie Zhiguo , Zhou Zhiguang
Published: May 2022

Backgrounds

Exosomes contain several types of transcripts, including long non-coding RNAs (lncRNAs), and have been shown to exert important effects in human diseases. However, the roles of exosomal lncRNAs in type 1 diabetes mellitus (T1DM) have not been well investigated. In the present study, we characterized the plasma-derived exosomal lncRNAs expression profiles of T1DM and predict their potential function in the pathogenesis of T1DM.

Material and Methods

Exosomal lncRNA expression profiles were detected by Illumina Hiseq platform (T1DM subjects N=10; age-, sex- matched Control subjects N=10). Six exosomal lncRNAs were selected to validate their expression level by using quantitative real-time PCR (qRT-PCR) (T1DM subjects N=30; age-, sex- matched Control subjects N=30). Bioinformatics analysis approaches were carried out to explore the potential biological function of differentially expressed lncRNAs.

Results

A total of 162 differentially expressed exosomal lncRNAs were identified in T1DM patients compared with control subjects, among which 77 up-regulated and 85 down-regulated. The expression level of the selected six lncRNAs didn’t show significant difference in the following qRT-PCR analysis. Gene Ontology analysis enriched terms such as activation of phospholipase D activity, neuronal cell body membrane, and calcium sensitive guanylate cyclase activator activity for cis-acting genes of lncRNAs, and metal ion binding for trans-acting genes. The most enriched Kyoto Encyclopedia of Genes and Genomes pathways for the lncRNAs were associated with oxidative phosphorylation and Parkinson’s disease for cis-acting genes, and pathways in cancer as well as focal adhesion for trans-acting genes.

Conclusions

This study characterized the lncRNA profiles of plasma-derived exosomes from T1DM for the first time and these results highlighted the potential role of exosomal lncRNAs in T1DM pathogenesis. A better understanding of exosomal lncRNA profiling will provide novel insights into its molecular mechanisms.
Vitamin D Deficiency During Development Permanently Alters Liver Cell Composition and Function
Authors: Lundy Kassidy , Greally John F. , Essilfie-Bondzie Grace , Olivier Josephine B. , Doña-Termine Reanna , Greally John M. , Suzuki Masako
Published: May 2022

Vitamin D, a fat-soluble vitamin, plays a critical role in calcium homeostasis, the immune system, and normal development. Many epidemiological cohort studies globally have found high prevalence rates of vitamin D deficiency and insufficiency, recognized as an important health issue that needs to be solved. In particular, reproductive age and pregnant women low in vitamin D status may confer risks of diseases like obesity on their offspring. While observational studies have suggested associations between prenatal vitamin D deficiency and metabolic phenotypes in offspring, not yet determined is whether prenatal vitamin D deficiency permanently alters the development of the liver, a major metabolic organ. We tested the histopathology and the transcriptomic profiles of livers from male C57BL/6J mice exposed to prenatal vitamin D deficiency through a maternal dietary intervention model. We found that prenatal vitamin D deficiency increases the prevalence of histopathological changes in the liver, and alters its gene expression profile. Cell subtype proportion analysis showed that the liver of prenatal vitamin D deficiency alters non-parenchymal cells of the liver, specifically macrophages, a subset of endothelial cells, and dendritic cells. Our results indicate the long-term memory of prenatal vitamin D deficiency exposure in the adult liver, a potential contributor to offspring health risks.
Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms
Authors: Pánico Pablo , Velasco Myrian , Salazar Ana María , Picones Arturo , Ortiz-Huidobro Rosa Isela , Guerrero-Palomo Gabriela , Salgado-Bernabé Manuel Eduardo , Ostrosky-Wegman Patricia , Hiriart Marcia
Published: May 2022

Exposure to arsenic in drinking water is a worldwide health problem. This pollutant is associated with increased risk of developing chronic diseases, including metabolic diseases. Metabolic syndrome (MS) is a complex pathology that results from the interaction between environmental and genetic factors. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, and cancer. The MS includes at least three of the following signs, central obesity, impaired fasting glucose, insulin resistance, dyslipidemias, and hypertension. Here, we summarize the existing evidence of the multiple mechanisms triggered by arsenic to developing the cardinal signs of MS, showing that this pollutant could contribute to the multifactorial origin of this pathology.
Irisin Serum Levels and Skeletal Muscle Assessment in a Cohort of Charcot-Marie-Tooth Patients
Authors: Colaianni Graziana , Oranger Angela , Dicarlo Manuela , Lovero Roberto , Storlino Giuseppina , Pignataro Patrizia , Fontana Antonietta , Di Serio Francesca , Ingravallo Angelica , Caputo Giuseppe , Di Leo Alfredo , Barone Michele , Grano Maria
Published: May 2022

Background

Charcot-Marie-Tooth (CMT) indicates a group of inherited polyneuropathies whose clinical phenotypes primarily include progressive distal weakness and muscle atrophy. Compelling evidence showed that the exercise-mimetic myokine irisin protects against muscle wasting in an autocrine manner, thus possibly preventing the onset of musculoskeletal atrophy. Therefore, we sought to determine if irisin serum levels correlate with biochemical and muscle parameters in a cohort of CMT patients.

Methods

This cohort study included individuals (N=20) diagnosed with CMT disease. Irisin and biochemical markers were quantified in sera. Skeletal muscle mass (SMM) was evaluated by bioelectric impedance analysis, muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio.

Results

CMT patients (m/f, 12/8) had lower irisin levels than age and sex matched healthy subjects (N=20) (6.51 ± 2.26 vs 9.34 ± 3.23 μg/ml; p=0.003). SMM in CMT patients was always lower compared to SMM reference values reported in healthy Caucasian population matched for age and sex. Almost the totality of CMT patients (19/20) showed low muscle quality and therefore patients were evaluated on the basis of muscle strength. Irisin was lower in presence of pathological compared to normal muscle strength (5.56 ± 1.26 vs 7.67 ± 2.72 μg/ml; p=0.03), and directly correlated with the marker of bone formation P1PN (r= 0.669; 95%CI 0.295 to 0.865; p=0.002), but inversely correlated with Vitamin D (r=-0.526; 95%CI -0,791 to -0,095; p=0.017). Surprisingly, in women, irisin levels were higher than in men (7.31 ± 2.53 vs 5.31 ± 1.02 μg/ml, p=0.05), and correlated with both muscle strength (r=0.759; 95%CI 0.329 to 0.929; p=0.004) and muscle quality (r=0.797; 95%CI 0.337 to 0.950; p=0.006).

Conclusion

Our data demonstrate lower irisin levels in CMT patients compared to healthy subjects. Moreover, among patients, we observed, significantly higher irisin levels in women than in men, despite the higher SMM in the latter. Future studies are necessary to establish whether, in this clinical contest, irisin could represent a marker of the loss of muscle mass and strength and/or bone loss.
Case Report: A Chinese Family of Type A Insulin Resistance Syndrome With Diabetes Mellitus, With a Novel Heterozygous Missense Mutation of the Insulin Receptor Gene
Authors: You Wei , Yang Jianming , Wang Lu , Liu Yanqun , Wang Wen , Zhu Li , Wang Wei , Yang Jun , Chen Fangyuan
Published: May 2022

Type A Insulin resistance syndrome (TAIRS) is an autosomal dominant or recessive genetic disorder caused by insulin dysfunction resulting from insulin receptor (INSR) gene mutation. The main features of TAIRS include hyperinsulinemia, abnormal glucose metabolism, and changes in acanthosis nigricans. We identified, in China, a TAIRS family with a novel heterozygous missense gene mutation type. One patient from the Chinese Han family exhibited signs and symptoms of TAIRS and was presented for evaluation. Whole-exome sequencing revealed a heterozygous mutation. Both the patient proband and his father were identified with insulin receptor exon 19c.3472C>T(p.Arg1158Trp), which resulted in a missense mutation that led to replace by a base in the amino acid codon. We found that the patient proband and his father exhibited high insulin and C-peptide release after glucose stimulation by insulin and C-peptide release tests. At the same time, we also ruled out the possibility of islet βcell tumor through relevant examinations. These findings indicate that the INSR gene mutation may cause pancreatic β cell functional impairment and contribute to the development of diabetes.
Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration
Authors: Diao Lei , Turek Paul J. , John Constance M. , Fang Fang , Reijo Pera Renee A.
Published: May 2022

Spermatogonial stem cells (SSCs) are a group of adult stem cells in the testis that serve as the foundation of continuous spermatogenesis and male fertility. SSCs are capable of self-renewal to maintain the stability of the stem cell pool and differentiation to produce mature spermatozoa. Dysfunction of SSCs leads to male infertility. Therefore, dissection of the regulatory network of SSCs is of great significance in understanding the fundamental molecular mechanisms of spermatogonial stem cell function in spermatogenesis and the pathogenesis of male infertility. Furthermore, a better understanding of SSC biology will allow us to culture and differentiate SSCsin vitro, which may provide novel stem cell-based therapy for assisted reproduction. This review summarizes the latest research progress on the regulation of SSCs, and the potential application of SSCs for fertility restoration throughin vivoandin vitrospermatogenesis. We anticipate that the knowledge gained will advance the application of SSCs to improve male fertility. Furthermore,in vitrospermatogenesis from SSCs sets the stage for the production of SSCs from induced pluripotent stem cells (iPSCs) and subsequent spermatogenesis.