bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardioluminescence in Transgenic Zebrafish Larvae: A Calcium Imaging Tool to Study Drug Effects and Pathological Modeling
Authors: Vicente Manuel , Salgado-Almario Jussep , Collins Michelle M. , Martínez-Sielva Antonio , Minoshima Masafumi , Kikuchi Kazuya , Domingo Beatriz , Llopis Juan
Published: September 2021

Zebrafish embryos and larvae have emerged as an excellent model in cardiovascular research and are amenable to live imaging with genetically encoded biosensors to study cardiac cell behaviours, including calcium dynamics. To monitor calcium ion levels in three to five days post-fertilization larvae, we have used bioluminescence. We generated a transgenic line expressing GFP-aequorin in the heart, Tg(myl7:GA), and optimized a reconstitution protocol to boost aequorin luminescence. The analogue diacetylh-coelenterazine enhanced light output and signal-to-noise ratio. With this cardioluminescence model, we imaged the time-averaged calcium levels and beat-to-beat calcium oscillations continuously for hours. As a proof-of-concept of the transgenic line, changes in ventricular calcium levels were observed by Bay K8644, an L-type calcium channel activator and with the blocker nifedipine. The β-adrenergic blocker propranolol decreased calcium levels, heart rate, stroke volume, and cardiac output, suggesting that larvae have a basal adrenergic tone. Zebrafish larvae treated with terfenadine for 24 h have been proposed as a model of heart failure. Tg(myl7:GA) larvae treated with terfenadine showed bradycardia, 2:1 atrioventricular block, decreased time-averaged ventricular calcium levels but increased calcium transient amplitude, and reduced cardiac output. As alterations of calcium signalling are involved in the pathogenesis of heart failure and arrhythmia, the GFP-aequorin transgenic line provides a powerful platform for understanding calcium dynamics.
Magnolol Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells through JNK1/2 and p38 Pathways
Authors: Chen Yi-Tzu , Lin Chiao-Wen , Su Chun-Wen , Yang Wei-En , Chuang Chun-Yi , Su Shih-Chi , Hsieh Ming-Ju , Yang Shun-Fa
Published: September 2021

Magnolol is a natural compound extracted from Chinese herbal medicine and can induce apoptosis in numerous types of cancer cells. However, the molecular mechanisms of magnolol in oral cancer are still unclear. In this study, we investigated the anti-cancer effects and underlying mechanisms of magnolol in human oral cancer cell lines. Our results exhibited that magnolol inhibited the cell proliferation via inducing the sub-G1 phase and cell apoptosis of HSC-3 and SCC-9 cells. The human apoptosis array and Western blot assay showed that magnolol increased the expression of cleaved caspase-3 proteins and heme oxygenase-1 (HO-1). Moreover, we proved that magnolol induces apoptosis in oral cancer cell lines via the c-Jun N-terminal kinase (JNK)1/2 and p38 pathways. Overall, the current study supports the role for magnolol as a therapeutic approach for oral cancer through JNK1/2- and p38-mediated caspase activation.
The Combined Beneficial Effects of Postbiotic Butyrate on Active Vitamin D3-Orchestrated Innate Immunity to Salmonella Colitis
Authors: Huang Fu-Chen , Huang Shun-Chen
Published: September 2021

Salmonella spp. Remains a major public health problem globally. Biomedicine is the cornerstone of modern health care and could be a solution for antibiotic-resistant Salmonellosis. Although postbiotics seem to be an effective treatment in various clinical conditions, their clinical effects on Salmonella colitis have not been reported. Our previous report revealed that active vitamin D attenuates the severity of Salmonella colitis and invasiveness by reducing inflammation and enhancing the production of antimicrobial peptides. Therefore, we investigated the synergistic effects of butyrate, the most studied postbiotic, and active vitamin D on the severity of Salmonella colitis, invasiveness of Salmonella, and host immune responses, as well as its novel mechanisms, using in vitro and in vivo studies. We demonstrated that a combination of butyrate and active vitamin D (1 alpha, 25-dihydroxyvitamin D3) synergically reduced the severity of Salmonella colitis in C57BL/6 mice and reduced cecal inflammatory mIL-6, mIL-8, mTNF-α, and mIL-1β mRNA expression, but enhanced the antimicrobial peptide mhBD-3 mRNA, compared to a single treatment. Additionally, upregulated vitamin D receptor (VDR) plays a critical role in the synergistic effects. This suggests combined benefits of butyrate and active vitamin D on Salmonella colitis through VDR-mediated antibacterial and anti-inflammatory responses. The combined use of both supplements could be a potential biomedicine for infectious and autoimmune colitis.
Myostatin and Follistatin—New Kids on the Block in the Diagnosis of Sarcopenia in IBD and Possible Therapeutic Implications
Authors: Skrzypczak Dorota , Skrzypczak-Zielińska Marzena , Ratajczak Alicja Ewa , Szymczak-Tomczak Aleksandra , Eder Piotr , Słomski Ryszard , Dobrowolska Agnieszka , Krela-Kaźmierczak Iwona
Published: September 2021

Sarcopenia, which is a decrease in muscle strength and quality of muscle tissue, is a common disorder among patients suffering from inflammatory bowel disease. This particular group of patients often presents with malnutrition and shows low physical activity, which increases the risk of sarcopenia. Another important factor in the development of sarcopenia is an imbalanced ratio of myostatin and follistatin, which may stem from inflammation as well as genetic factors. Currently, research in this area continues, and is aimed at identifying an effective medication for the treatment of this condition. Additionally, we still have no sarcopenia markers that can be used for diagnosis. In this paper, we address the role of myostatin and follistatin as potential markers in the diagnosis of sarcopenia in patients with Crohn’s disease and ulcerative colitis, particularly in view of the genetic and biological aspects. We also present data on new perspectives in the pharmacotherapy of sarcopenia (i.e., myostatin inhibitors and gene therapy). Nevertheless, knowledge is still scarce about the roles of follistatin and myostatin in sarcopenia development among patients suffering from inflammatory bowel disease, which warrants further study.
Emerging SARS-CoV-2 Variants of Concern (VOCs): An Impending Global Crisis
Authors: Thye Angel Yun-Kuan , Law Jodi Woan-Fei , Pusparajah Priyia , Letchumanan Vengadesh , Chan Kok-Gan , Lee Learn-Han
Published: September 2021

The worldwide battle against the SARS-CoV-2 virus rages on, with millions infected and many innocent lives lost. The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a beta coronavirus that belongs to the Coronaviridae family. Many clinically significant variants have emerged, as the virus’s genome is prone to various mutations, leading to antigenic drift and resulting in evasion of host immune recognition. The current variants of concern (VOCs) include B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617/B.1.617.2 (Delta), and P.1 (Gamma). The emerging variants contain various important mutations on the spike protein, leading to deleterious consequences, such as immune invasion and vaccine escape. These adverse effects result in increased transmissibility, morbidity, and mortality and the evasion of detection by existing or currently available diagnostic tests, potentially delaying diagnosis and treatment. This review discusses the key mutations present in the VOC strains and provides insights into how these mutations allow for greater transmissibility and immune evasion than the progenitor strain. Continuous monitoring and surveillance of VOC strains play a vital role in preventing and controlling the virus’s spread.
A Review of THz Technologies for Rapid Sensing and Detection of Viruses including SARS-CoV-2
Authors: Akter Naznin , Hasan Muhammad , Pala Nezih
Published: September 2021

Virus epidemics such as Ebola virus, Zika virus, MERS-coronavirus, and others have wreaked havoc on humanity in the last decade. In addition, a coronavirus (SARS-CoV-2) pandemic and its continuously evolving mutants have become so deadly that they have forced the entire technical advancement of healthcare into peril. Traditional ways of detecting these viruses have been successful to some extent, but they are costly, time-consuming, and require specialized human resources. Terahertz-based biosensors have the potential to lead the way for low-cost, non-invasive, and rapid virus detection. This review explores the latest progresses in terahertz technology-based biosensors for the virus, viral particle, and antigen detection, as well as upcoming research directions in the field.
Rolling Circle Amplification as an Efficient Analytical Tool for Rapid Detection of Contaminants in Aqueous Environments
Authors: Zhang Kuankuan , Zhang Hua , Cao Haorui , Jiang Yu , Mao Kang , Yang Zhugen
Published: September 2021

Environmental contaminants are a global concern, and an effective strategy for remediation is to develop a rapid, on-site, and affordable monitoring method. However, this remains challenging, especially with regard to the detection of various contaminants in complex water environments. The application of molecular methods has recently attracted increasing attention; for example, rolling circle amplification (RCA) is an isothermal enzymatic process in which a short nucleic acid primer is amplified to form a long single-stranded nucleic acid using a circular template and special nucleic acid polymerases. Furthermore, this approach can be further engineered into a device for point-of-need monitoring of environmental pollutants. In this paper, we describe the fundamental principles of RCA and the advantages and disadvantages of RCA assays. Then, we discuss the recently developed RCA-based tools for environmental analysis to determine various targets, including heavy metals, organic small molecules, nucleic acids, peptides, proteins, and even microorganisms in aqueous environments. Finally, we summarize the challenges and outline strategies for the advancement of this technique for application in contaminant monitoring.
Effects of Individual Discount Rate and Uncertainty Perception on Compliance with Containment Measures during the COVID-19 Pandemic
Authors: Calluso Cinzia , Grande Eleonora , Erario Alessia , Tosoni Annalisa , Committeri Giorgia
Published: September 2021

Anti-contagion measures restricting individual freedom, such as social distancing and wearing a mask, are crucial to contain the COVID-19 pandemic. Decision-making patterns and attitudes about uncertainty can highly influence the adherence to these restrictive measures. Here we investigated the relationship between risky behavior and individual preferences for immediate vs. delayed reward, as indexed by temporal discounting (TD), as well as the association between these measures and confidence in the future, perceived risk and confidence in the containment measures. These measures were collected through an online survey administered on 353 participants at the end of the more restrictive phase of the first Italian lockdown. The results showed an unexpected inverse relationship between the individual pattern of choice preferences and risky behavior, with an overall greater adherence to containment measures in more discounter participants. These findings were interpreted in terms of a reframing process in which behaviors aimed at protecting oneself from contagion turn into immediate gains rather than losses. Interestingly, an excessive confidence in a better future was correlated with a higher tendency to assume risky behavior, thereby highlighting the downside of an overly and blindly optimistic view.
Exterior Wood-Frame Walls—Wind–Vapour Barrier Ratio in Denmark
Authors: Morelli Martin , Rasmussen Torben Valdbjørn , Therkelsen Marcus
Published: September 2021

Wood-frame walls in cold climates are traditional constructed with a vapour barrier that also constitutes the air-tightness layer. Polyethylene foil as a vapour barrier is likely used; however, other building materials can be used to obtain correspondingly sufficient properties. 1D hygrothermal simulations were conducted for a wood-frame structure to investigate the wind–vapour barrier ratio, and if the vapour barrier of polyethylene foil could be omitted and replaced by other materials. The results were postprocessed using the VTT mould model. The results showed how wood-frame walls can be designed with respect to internal humidity class and diffusion resistance divided into three categories: no risk for mould growth, needs further investigation, and is not performing well as the risk for mould growth is present. For internal humidity classes 1–3, the ratio between wind and vapour barrier must be about 1:5, and 1:10 for classes 4 and 5 to be on the safe side. Simulations were performed for the climate of Lund, Sweden, which were used to simulate climate in Denmark too. Nevertheless, the results are related to climate data and, thus, the location.
Artificial Intelligence in Thyroid Field—A Comprehensive Review
Authors: Bini Fabiano , Pica Andrada , Azzimonti Laura , Giusti Alessandro , Ruinelli Lorenzo , Marinozzi Franco , Trimboli Pierpaolo
Published: September 2021

Artificial intelligence (AI) uses mathematical algorithms to perform tasks that require human cognitive abilities. AI-based methodologies, e.g., machine learning and deep learning, as well as the recently developed research field of radiomics have noticeable potential to transform medical diagnostics. AI-based techniques applied to medical imaging allow to detect biological abnormalities, to diagnostic neoplasms or to predict the response to treatment. Nonetheless, the diagnostic accuracy of these methods is still a matter of debate. In this article, we first illustrate the key concepts and workflow characteristics of machine learning, deep learning and radiomics. We outline considerations regarding data input requirements, differences among these methodologies and their limitations. Subsequently, a concise overview is presented regarding the application of AI methods to the evaluation of thyroid images. We developed a critical discussion concerning limits and open challenges that should be addressed before the translation of AI techniques to the broad clinical use. Clarification of the pitfalls of AI-based techniques results crucial in order to ensure the optimal application for each patient.
Current Applications and Future Development of Magnetic Resonance Fingerprinting in Diagnosis, Characterization, and Response Monitoring in Cancer
Authors: Ding Hao , Velasco Carlos , Ye Huihui , Lindner Thomas , Grech-Sollars Matthew , O’Callaghan James , Hiley Crispin , Chouhan Manil , Niendorf Thoralf , Koh Dow-Mu , Prieto Claudia , Adeleke Sola
Published: September 2021

Magnetic resonance imaging (MRI) has enabled non-invasive cancer diagnosis, monitoring, and management in common clinical settings. However, inadequate quantitative analyses in MRI continue to limit its full potential and these often have an impact on clinicians’ judgments. Magnetic resonance fingerprinting (MRF) has recently been introduced to acquire multiple quantitative parameters simultaneously in a reasonable timeframe. Initial retrospective studies have demonstrated the feasibility of using MRF for various cancer characterizations. Further trials with larger cohorts are still needed to explore the repeatability and reproducibility of the data acquired by MRF. At the moment, technical difficulties such as undesirable processing time or lack of motion robustness are limiting further implementations of MRF in clinical oncology. This review summarises the latest findings and technology developments for the use of MRF in cancer management and suggests possible future implications of MRF in characterizing tumour heterogeneity and response assessment.
Comparative Analysis of Vascular Mimicry in Head and Neck Squamous Cell Carcinoma: In Vitro and In Vivo Approaches
Authors: Hujanen Roosa , Almahmoudi Rabeia , Salo Tuula , Salem Abdelhakim
Published: September 2021

Tissue vasculature provides the main conduit for metastasis in solid tumours including head and neck squamous cell carcinoma (HNSCC). Vascular mimicry (VM) is an endothelial cell (EC)-independent neovascularization pattern, whereby tumour cells generate a perfusable vessel-like meshwork. Yet, despite its promising clinical utility, there are limited approaches to better identify VM in HNSCC and what factors may influence such a phenomenon in vitro. Therefore, we employed different staining procedures to assess their utility in identifying VM in tumour sections, wherein mosaic vessels may also be adopted to further assess the VM-competent cell phenotype. Using 13 primary and metastatic HNSCC cell lines in addition to murine- and human-derived matrices, we elucidated the impact of the extracellular matrix, tumour cell type, and density on the formation and morphology of cell-derived tubulogenesis in HNSCC. We then delineated the optimal cell numbers needed to obtain a VM meshwork in vitro, which revealed cell-specific variations and yet consistent expression of the EC marker CD31. Finally, we proposed the zebrafish larvae as a simple and cost-effective model to evaluate VM development in vivo. Taken together, our findings offer a valuable resource for designing future studies that may facilitate the therapeutic exploitation of VM in HNSCC and other tumours.
Epstein–Barr Virus in Inborn Immunodeficiency—More Than Infection
Authors: Lino Ciro Novaes Rosa , Ghosh Sujal
Published: September 2021

Epstein–Barr Virus (EBV) is a ubiquitous virus affecting more than 90% of the world’s population. Upon infection, it establishes latency in B cells. It is a rather benign virus for immune-competent individuals, in whom infections usually go unnoticed. Nevertheless, EBV has been extensively associated with tumorigenesis. Patients suffering from certain inborn errors of immunity are at high risk of developing malignancies, while infection in the majority of immune-competent individuals does not seem to lead to immune dysregulation. Herein, we discuss how inborn mutations in TNFRSF9, CD27, CD70, CORO1A, CTPS1, ITK, MAGT1, RASGRP1, STK4, CARMIL2, SH2D1A, and XIAP affect the development, differentiation, and function of key factors involved in the immunity against EBV, leading to increased susceptibility to lymphoproliferative disease and lymphoma.
Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer
Authors: Kim Ryungsa , Kin Takanori
Published: September 2021

How primary breast cancer can be cured after (neo)adjuvant therapy remains unclear at the molecular level. Immune activation by anticancer agents may contribute to residual tumor cell eradication with postsurgical (neo)adjuvant chemotherapy. Chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation with memory effector T cells, leading to a primary breast cancer cure. Anthracycline and taxane treatments cause ICD and immunogenic modulations, resulting in the activation of antitumor immunity through damage-associated molecular patterns (DAMPs), such as adenosine triphosphate, calreticulin, high mobility group box 1, heat shock proteins 70/90, and annexin A1. This response may eradicate residual tumor cells after surgical treatment. Although DAMP release is also implicated in tumor progression, metastasis, and drug resistance, thereby representing a double-edged sword, robust immune activation by anticancer agents and the subsequent acquisition of long-term antitumor immune memory can be essential components of the primary breast cancer cure. This review discusses the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted anti-DAMP therapy. Our aim was to improve the understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines.
Overcoming Immune Resistance in Prostate Cancer: Challenges and Advances
Authors: Movassaghi Miyad , Chung Rainjade , Anderson Christopher B. , Stein Mark , Saenger Yvonne , Faiena Izak
Published: September 2021

The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer. The lethality of metastatic castrate-resistant prostate cancer is driven by the lack of therapeutic regimens capable of generating durable responses. Multiple strategies are currently being tested to overcome immune resistance including combining various classes of treatment modalities. Several completed and ongoing trials have shown that combining vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody–drug conjugates, chimeric antigen receptor T cell therapy, or chemotherapy may enhance immune responses and induce long-lasting clinical responses without significant toxicity. Here, we review the current state of immunotherapy for prostate cancer, as well as tumor-specific mechanisms underlying therapeutic resistance, with a comprehensive look at the current preclinical and clinical immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and impaired cellular immunity that have largely limited the utility of immunotherapy in advanced prostate cancer.
Fe-TiO2/AC and Co-TiO2/AC Composites: Novel Photocatalysts Prepared from Waste Streams for the Efficient Removal and Photocatalytic Degradation of Cibacron Yellow F-4G Dye
Authors: Machado Garcia Roberto , Carleer Robert , Arada Pérez Maria , Puente Torres Jeamichel , Gu Ying , Samyn Pieter , Yperman Jan
Published: September 2021

Fe-TiO2/AC and Co-TiO2/AC composites were prepared from activated carbon (AC) derived from residues of peanut hulls and TiO2 photocatalyst, electrochemically prepared from titanium scrap, and doped with Fe and Co, respectively. The adsorption capacity and photocatalytic activity of the Fe-TiO2/AC and Co-TiO2/AC composites were studied for removing and degrading Cibacron Yellow F-4G (CYF-4G) from wastewater. Doped ACs were characterized by thermogravimetry (TGA), scanning electron microscopy (SEM), X-ray diffraction (XRD), a new X-ray absorption technique (XRA), and elemental analysis (EA). Interesting relationships were found between SEM, XRA, and TGA data and the doped amount of catalyst on ACs. Optimal dye adsorption was found at a pH of 2.0. The CYF-4G adsorption kinetics are followed according to the pseudo-second order model. The experimental data revealed that the Langmuir model fits better than the Freundlich and Temkin models. A decrease in adsorption capacity was observed when the catalyst dope percentage increased. A removal and degradation efficiency of the dye close to 100% was achieved around 120 min. A synergistic adsorption and photocatalytic degradation effect of the Fe-TiO2/AC and Co-TiO2/AC composites could be observed when adsorption experiments were conducted under simulated visible radiation.
Expression of CD38 in Mast Cells: Cytological and Histotopographic Features
Authors: Atiakshin Dmitri , Samoilova Vera , Buchwalow Igor , Tiemann Markus
Published: September 2021

The biological significance of the CD38 molecule goes beyond metabolic, enzymatic, and proliferative functions. CD38 possesses the functions of an exoenzyme and receptor, and is actively involved in the mechanisms of adhesion, migration, intercellular signaling, formation of immune synapses, and modulation of the activity of a wide range of immune and non-immune cells. The aim of this study was the immunohistochemical assessment of the cytological and histotopographic characteristics of CD38 expression in mast cells. CD38 expression was found in a minority of the mast cell population. It is characterized by wide variability from low to high levels. The intensity of CD38 expression in mast cells has organ-specific features and depends on the development of pathological processes in a specific tissue microenvironment. The mechanisms of intercellular interaction between mast cells and CD38+ cells foster new understanding of the protumorigenic or antitumor potential of tryptase.
Central Nervous System Tissue Regeneration after Intracerebral Hemorrhage: The Next Frontier
Authors: Zhang Ruiyi , Xue Mengzhou , Yong Voon Wee
Published: September 2021

Despite marked advances in surgical techniques and understanding of secondary brain injury mechanisms, the prognosis of intracerebral hemorrhage (ICH) remains devastating. Harnessing and promoting the regenerative potential of the central nervous system may improve the outcomes of patients with hemorrhagic stroke, but approaches are still in their infancy. In this review, we discuss the regenerative phenomena occurring in animal models and human ICH, provide results related to cellular and molecular mechanisms of the repair process including by microglia, and review potential methods to promote tissue regeneration in ICH. We aim to stimulate research involving tissue restoration after ICH.
Irradiation Suppresses IFNγ-Mediated PD-L1 and MCL1 Expression in EGFR-Positive Lung Cancer to Augment CD8+ T Cells Cytotoxicity
Authors: Wang Chun-I. , Chang Yi-Fang , Sie Zong-Lin , Ho Ai-Sheng , Chang Jung-Shan , Peng Cheng-Liang , Cheng Chun-Chia
Published: September 2021

Tumor cells express immune checkpoints to exhaust CD8+ T cells. Irradiation damages tumor cells and augments tumor immunotherapy in clinical applications. However, the radiotherapy-mediated molecular mechanism affecting CD8+ T cell activity remains elusive. We aimed to uncover the mechanism of radiotherapy augmenting cytotoxic CD8+ T cells in non-small-cell lung cancer (NSCLC). EGFR-positive NSCLC cell lines were co-cultured with CD8+ T cells from healthy volunteers. Tumor cell viability and apoptosis were consequently measured. IFNγ was identified secreted by CD8+ T cells and PBMCs. Therefore, RNAseq was used to screen the IFNγ-mediated gene expression in A549 cells. The irradiation effect to IFNγ-mediated gene expression was investigated using qPCR and western blots. We found that the co-culture of tumor cells stimulated the increase of granzyme B and IFNγ in CD8+ T, but A549 exhibited resistance against CD8+ T cytotoxicity compared to HCC827. Irradiation inhibited A549 proliferation and enhanced apoptosis, augmenting PBMCs-mediated cytotoxicity against A549. We found that IFNγ simultaneously increased phosphorylation on STAT1 and STAT3 in EGFR-positive lung cancer, resulting in overexpression of PD-L1 (p < 0.05). In RNAseq analysis, MCL1 was identified and increased by the IFNγ-STAT3 axis (p < 0.05). We demonstrated that irradiation specifically inhibited phosphorylation on STAT1 and STAT3 in IFNγ-treated A549, resulting in reductions of PD-L1 and MCL1 (both p < 0.05). Moreover, knockdowns of STAT3 and MCL1 increased the PBMCs-mediated anti-A549 effect. This study demonstrated that A549 expressed MCL1 to resist CD8+ T cell-mediated tumor apoptosis. In addition, we found that irradiation suppressed IFNγ-mediated STAT3 phosphorylation and PD-L1 and MCL1 expression, revealing a potential mechanism of radiotherapy augmenting immune surveillance.
Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression
Authors: Ghallab Ahmed , Myllys Maiju , Friebel Adrian , Duda Julia , Edlund Karolina , Halilbasic Emina , Vucur Mihael , Hobloss Zaynab , Brackhagen Lisa , Begher-Tibbe Brigitte , Hassan Reham , Burke Michael , Genc Erhan , Frohwein Lynn Johann , Hofmann Ute , Holland Christian H. , González Daniela , Keller Magdalena , Seddek Abdel-latif , Abbas Tahany , Mohammed Elsayed S. I. , Teufel Andreas , Itzel Timo , Metzler Sarah , Marchan Rosemarie , Cadenas Cristina , Watzl Carsten , Nitsche Michael A. , Kappenberg Franziska , Luedde Tom , Longerich Thomas , Rahnenführer Jörg , Hoehme Stefan , Trauner Michael , Hengstler Jan G.
Published: September 2021

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of ‘rest-and-jump genes’ that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30–48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.
The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise
Authors: Espinos Estelle , Lai Raymond , Giuriato Sylvie
Published: September 2021

Autophagy has been described as harboring a dual role in cancer development and therapy. Depending on the context, it can exert either pro-survival or pro-death functions. Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL. We first present our main findings on the role and regulation of autophagy in these cells. Then, we provide literature-driven hypotheses that could explain mechanistically the pro-survival properties of autophagy in crizotinib-treated bulk and stem-like ALK+ ALCL cells. Finally, we discuss how the potentiation of autophagy, which occurs with combined therapies (ALK and BCL2 or ALK and RAF1 co-inhibition), could convert it from a survival mechanism to a pro-death process.
MagnetoPlasmonic Waves/HOMO-LUMO Free π-Electron Transitions Coupling in Organic Macrocycles and Their Effect in Sensing Applications
Authors: Manera Maria Grazia , Giancane Gabriele , Bettini Simona , Valli Ludovico , Borovkov Victor , Colombelli Adriano , Lospinoso Daniela , Rella Roberto
Published: September 2021

Optical and magneto-optical surface plasmon resonance (MOSPR) characterization and preliminary sensing test onto single- and multi-layers of two organic macrocycles have been performed; TbPc2(OC11H21)8 phthalocyanine and CoCoPo2 porphyrin were deposited by the Langmuir-Schäfer (LS) technique onto proper Au/Co/Au magneto-optical transducers. Investigations of the MOSPR properties in Kretschmann configuration by angular modulation, gives us an indication about the potential discrimination of two organic macrocycles with absorption electronic transition in and out of the propagating plasmon energy spectral range. An improved molecular vapors sensitivity increase by the MOSPR sensing probe can be demonstrated depending on the overlap between the plasmonic probe energy and the absorption electronic transitions of the macrocycles under investigation. If the interaction between the plasmon energy and molecular HOMO-LUMO transition is preserved, a variation in the complex refractive index takes place. Under this condition, the magneto-plasmonic effect reported as 1/|MOSPR| signal allows us to increase the detection of molecules deposited onto the plasmonic transducer and their gas sensing capacity. The detection mechanism appears strongly enhanced if the Plasmon Wave/HOMO-LUMO transitions energy are in resonance. Under coupling conditions, a different volatile organic compounds (VOC) sensing capability has been demonstrated using n-butylamine as the trial molecule.
Learning Disabilities in Reading and Writing and Type of Delivery in Twin Births
Authors: González-Valenzuela María-José , López-Montiel Dolores , Cazorla-Granados Olga , González-Mesa Ernesto-Santiago
Published: September 2021

The aim of this study was to analyse the relationship between the type of delivery (vaginal or caesarean), as a risk factor, and the likelihood of having learning disabilities in reading (reading accuracy) and writing (phonetic and visual orthography), controlling for the interaction and/or confounding effect of gestational, obstetric, and neonatal variables (maternal age at delivery, gestational age, foetal presentation, Apgar 1, and newborn weight) among six-year-old children born in twin births. In this retrospective cohort study, the exposed and non-exposed cohorts consisted of children born by caesarean section and vaginal delivery, respectively. A total of 124 children born in twin births were evaluated in year one of primary education. Intelligence was measured using the K-BIT test; reading and writing variables were evaluated using the Evalúa-1 battery of tests, and clinical records were used to measure gestational, obstetric, and neonatal variables. Binary logistic regressions applied to each dependent variable indicated that caesarean delivery is a possible independent risk factor for difficulties in reading accuracy and phonetic and visual orthography. Future research using larger samples of younger children is required to analyse the relationship between obstetric and neonatal variables and the different basic indicators of reading and writing.
Durable and Superhydrophobic Aluminium Alloy with Microscale Hierarchical Structures and Anti-Drag Function Inspired by Diving Bell Spider
Authors: Chen You , Quan Zijing , Sun Yuhan , Chi Deqiang , Liu Delei , Zhou Liang , Zhang Junqiu , Mu Zhengzhi , Wang Ze , Li Bo , Niu Shichao , Han Zhiwu , Ren Luquan
Published: September 2021

Coating materials with special surface wettability are widely applied in marine paint systems used in the naval industry to reduce the corrosion and viscous drag of seawater. However, traditional coatings are inefficient and limited, either by poor durability or insufficient anti-drag capacity. Here, inspired by the diving bell spider, a bionic superhydrophobic coating with multiscale hierarchical architecture was successfully prepared on the surface of aluminium alloy. It possesses excellent mechanical abrasion durability, chemical durability, and low adhesion. Remarkably, the water contact angles could remain over 150.9° after more than 15 abrasion cycles or strong acid/alkali conditions. In addition, the impacting water droplet lifted off the surface of bionic superhydrophobic aluminium alloy (BSAA) within 13 ms, illustrating an excellent low adhesion property. In fact, when the BSAA is immersed in water, it could absorb bubbles and form a gas membrane. The existence of the gas membrane could prevent water and anaerobic organisms from contacting and even corroding the BSAA. Meanwhile, the gas membrane acts as a lubricant and significantly deceases friction at the solid–liquid interface, reducing the drag for BSAA. The BSAA proposed in this work has broad application prospects, such as medical devices, microfluidic chips, gas separation and collection in water.
Preparation of High-Efficiency Flame-Retardant and Superhydrophobic Cotton Fabric by a Multi-Step Dipping
Authors: Huang Jingda , Li Mengmeng , Ren Changying , Huang Wentao , Wu Qiang , Li Qian , Zhang Wenbiao , Wang Siqun
Published: September 2021

Cotton fabric, as an important material, is suffering from some defects such as flammability, easy pollution and so on; therefore, it is important to make a flame-retardant and superhydrophobic modification on cotton fabric. In this study, we demonstrated a preparation of high-efficiency flame-retardant and superhydrophobic cotton fabric with double coated construction by a simple multi-step dipping. First, the fabric was immersed in branched poly(ethylenimine) (BPEI) and ammonium polyphosphate (APP) water dispersions successively, and then immersed in polydimethylsiloxane (PDMS)/cellulose nanocrystals (CNC)-SiO2 toluene dispersion to form a BPEI/APP/PDMS/CNC-SiO2 (BAPC) composite coating on the surface of the cotton fabric. Here, the hydrophobic modified CNC-SiO2 rods were used to construct the superhydrophobic layer and the BPEI/APP mixture was used as the flame-retardant layer, as well as SiO2 particles which could further improve the flame-retardant effect. PDMS was mainly used as an adhesive between the BPEI/APP layer and the CNC-SiO2 layer. The resulting cotton fabric shows outstanding flame-retardant properties, in that the value of oxygen index meter (LOI) reaches 69.8, as well as excellent superhydrophobicity, in that the water contact angle (WCA) is up to 156.6°. Meanwhile, there is a good abrasion resistance, the superhydrophobicity is not lost until the 16th abrasion cycles and the flame retardant retains well, even after 100 abrasion cycles in an automatic vertical flammability cabinet under a pressure of 8.8 kPa.
Experimental and Simulation Analysis of the Evolution of Residual Stress Due to Expansion via CMAS Infiltration in Thermal Barrier Coatings
Authors: Tseng Shaochen , Chao Chingkong , Li Dongxu , Fan Xueling
Published: September 2021

The failure behavior of thermal barrier coatings (TBCs) involves multilayered systems infiltrated with calcium–magnesium–alumino-silicates (CMAS). The metastable tetragonal phase is mainly composed of 7YSZ (7 mol.% Y2O3-stabilized ZrO2), and it destabilizes into the Y-lean tetragonal phase, which may be induced by CMAS infiltration, and transforms into a monoclinic phase during cooling. The phase transformation leads to volume expansion around the CMAS-rich layer. Furthermore, it is shown that the spalling of the coating system emerges when the surface of the coating system is subjected to significant residual stress. In this study, a double-cantilever beam model is established to describe the macroscopic phenomenon of thermal buckling induced via CMAS. The result of the buckle height is used to demonstrate the consistency of the experiment and finite element simulation. The experimental parameters are imported into a multilayer cantilever beam model to analyze the interfacial stresses due to CMAS infiltration. The finite element results indicate that the phase transformation leads to damage in the coating system wherein the interfacial stresses due to phase transformation are 27% higher than those in the model without phase transformation.
Characterization of Pure Rutile Titania Nanoparticle Prepared by Feasible Method for Coatings and Visible Light-Driven Dye Removal Application
Authors: Rajabathar Jothi Ramalingam , Al-Lohedan Hamad A. , Arokiyaraj Selvaraj , Issa Zuheir A. , Dash Chandra Sekhar , Murugesan Sundararajan , Khadheer Pasha Shaik K. , Al-dhayan Dhaifallah M. , Appaturi Jimmy Nelson
Published: September 2021

The pure phase of rutile titanium dioxide or titania (R-TiO2) was prepared by means of a strong acidic sol–gel process followed by treatment using a hydrothermal method. The as-prepared titania nanoparticles existed purely in the rutile phase instead of the mixed anatase phase of the respective titania (R-TiO2). The optimized reaction condition and precursor usage were the critical parameters for the formation of the particle size and uniform crystallinity of the rutile phase of TiO2 nanoparticle fabrication. XRD (X-ray diffraction), and Raman spectroscopic techniques were utilized to confirm the formation of the pure rutile phase of titania. SEM (scanning electron microscope) and TEM (Transmission electron microscope) images showed the cauliflower-like morphology of the as-prepared R-TiO2; reduced particle sizes of below 5 nm were observed and confirmed through high resolution images. The catalytic activity of the as-prepared R-TiO2 was tested under visible light irradiation for methylene blue dye degradation reactions. Dye degradation occurred very effectively, even at higher concentrations of methylene blue (MB), at reduced time intervals from 5 to 3 h of reaction time. The as-prepared rutile phase of pure titania nanoparticles was applied in a catalysis application for the purpose of inducing various types of organic dye degradation or catalytic transformation in the presence of visible light.
Ferroelectric Properties and Spectroscopic Characterization of Pb(Mg1/3Nb2/3)O3-32PbTiO3:Er3+/Sc3+ Crystal
Authors: Zhang Jin , Xi Zengzhe , Wang Xinzhe , Feng Hao , Long Wei , He Aiguo
Published: September 2021

An Er3+/Sc3+ co-doped 0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3 ferroelectric single crystal was grown by high-temperature flux method. The remnant polarization Pr is 27.97 µC/cm2 and the coercive field Ec is 8.26 kV/cm for [100] oriented crystal. Green (524 and 551 nm) and red (654 nm) emission bands are generated at the 980 nm excitation, which corresponds to the 2H11/2→ 4I15/2, 4S3/2→ 4I15/2 and 4F9/2→ 4I15/2 transitions of Er3+, respectively. Judd–Ofelt theory has been applied to predict the spectroscopic characteristics of the as-grown crystals. The obtained J–O intensity parameters Ωt (t = 2, 4 and 6) are Ω2 = 0.76 × 10−20 cm2, Ω4 = 1.0 × 10−20 cm2, Ω6 = 0.55 × 10−20 cm2. Spectroscopic characteristics, including optical transition probabilities, branching ratio, and radiative lifetime of Er3+ in the crystal, are determined. The calculated radiative lifetimes of 4I13/2 and 4I11/2 energy levels are 2.82 ms and 2.61 ms, respectively. These investigations provide possibilities for the crystal Pb(Mg1/3Nb2/3)O3-0.32PbTiO3:Er3+/Sc3+ to be a new type of multifunctional crystal integrating electricity-luminescence.
An Image-Based Workflow for Objective Vessel Wall Enhancement Quantification in Intracranial Aneurysms
Authors: Veeturi Sricharan S. , Pinter Nandor K. , Monteiro Andre , Baig Ammad A. , Rai Hamid H. , Waqas Muhammad , Siddiqui Adnan H. , Rajabzadeh-Oghaz Hamidreza , Tutino Vincent M.
Published: September 2021

Background: VWE in contrast-enhanced magnetic resonance imaging (MRI) is a potential biomarker for the evaluation of IA. The common practice to identify IAs with VWE is mainly based on a visual inspection of MR images, which is subject to errors and inconsistencies. Here, we develop and validate a tool for the visualization, quantification and objective identification of regions with VWE. Methods: N = 41 3D T1-MRI and 3D TOF-MRA IA images from 38 patients were obtained and co-registered. A contrast-enhanced MRI was normalized by the enhancement intensity of the pituitary stalk and signal intensities were mapped onto the surface of IA models generated from segmented MRA. N = 30 IAs were used to identify the optimal signal intensity value to distinguish the enhancing and non-enhancing regions (marked by an experienced neuroradiologist). The remaining IAs (n = 11) were used to validate the threshold. We tested if the enhancement area ratio (EAR—ratio of the enhancing area to the IA surface-area) could identify high risk aneurysms as identified by the ISUIA clinical score. Results: A normalized intensity of 0.276 was the optimal threshold to delineate enhancing regions, with a validation accuracy of 81.7%. In comparing the overlap between the identified enhancement regions against those marked by the neuroradiologist, our method had a dice coefficient of 71.1%. An EAR of 23% was able to discriminate high-risk cases with an AUC of 0.7. Conclusions: We developed and validated a pipeline for the visualization and objective identification of VWE regions that could potentially help evaluation of IAs become more reliable and consistent.
The Promising Role of a Superb Microvascular Imaging Technique in the Evaluation of Raynaud’s Syndrome in Systemic Sclerosis: Theory and Practical Challenges
Authors: Jasionyte Gabija , Seskute Goda , Rugiene Rita , Butrimiene Irena
Published: September 2021

In recent years, a novel Doppler ultrasonography (US) modality—superb microvascular imaging (SMI)—has been presented as a reliable method to evaluate small vessel blood flow with minimised motion artefacts. In this review, we present the challenges of incorporating SMI in daily practice with detailed and comparable US images of a fingertip. The main focus of this paper is the discussion of all tested US techniques, artefacts, and practical challenges for evaluating Raynaud’s syndrome in systemic sclerosis. Despite a few reports on SMI use in assessing nailfold capillaries, there is still a need for more evidence of its value and possibilities for its standardisation.
New Adapted In Vitro Technology to Evaluate Biofilm Formation and Antibiotic Activity Using Live Imaging under Flow Conditions
Authors: Pouget Cassandra , Dunyach-Remy Catherine , Pantel Alix , Schuldiner Sophie , Sotto Albert , Lavigne Jean-Philippe
Published: September 2021

The polymicrobial nature of biofilms and bacterial interactions inside chronic wounds are keys for the understanding of bacterial cooperation. The aim of this present study was to develop a technique to study and visualize biofilm in live imaging under flow conditions (Bioflux™ 200, Fluxion Biosciences). The BiofluxTM system was adapted using an in vitro chronic wound-like medium (CWM) that mimics the environment encountered in ulcers. Two reference strains of Staphylococcus aureus (Newman) and Pseudomonas aeruginosa (PAO1) were injected in the BiofluxTM during 24 h to 72 h in mono and coculture (ratio 1:1, bacteria added simultaneously) in the CWM vs. a control medium (BHI). The quantification of biofilm formation at each time was evaluated by inverted microscopy. After 72 h, different antibiotics (ceftazidime, imipenem, linezolid, oxacillin and vancomycin) at 1x MIC, 10x MIC and 100x MIC were administrated to the system after an automatic increase of the flow that mimicked a debridement of the wound surface. Biofilm studies highlighted that the two species, alone or associated, constituted a faster and thicker biofilm in the CWM compared to the BHI medium. The effect of antibiotics on mature or “debrided” biofilm indicated that some of the most clinically used antibiotic such as vancomycin or imipenem were not able to disrupt and reduce the biofilm biomass. The use of a life cell imaging with an in vitro CWM represents a promising tool to study bacterial biofilm and investigate microbial cooperation in a chronic wound context.