bluuebunny/crossref_metadata_2025 huggingface dataset:
A First-Principles Study on Titanium-Decorated Adsorbent for Hydrogen Storage
Authors: Ma Kai , Lv Erfei , Zheng Di , Cui Weichun , Dong Shuai , Yang Weijie , Gao Zhengyang , Zhou Yu
Published: October 2021

Based on density functional theory calculation, we screened suitable Ti-decorated carbon-based hydrogen adsorbent structures. The adsorption characteristics and adsorption mechanism of hydrogen molecules on the adsorbent were also discussed. The results indicated that Ti-decorated double vacancy (2 × 2) graphene cells seem to be an efficient material for hydrogen storage. Ti atoms are stably embedded on the double vacancy sites above and below the graphene plane, with binding energy higher than the cohesive energy of Ti. For both sides of Ti-decorated double vacancy graphene, up to six H2 molecules can be adsorbed around each Ti atom when the adsorption energy per molecule is −0.25 eV/H2, and the gravimetric hydrogen storage capacity is 6.67 wt.%. Partial density of states (PDOS) analysis showed that orbital hybridization occurs between the d orbital of the adsorbed Ti atom and p orbital of C atom in the graphene layer, while the bonding process is not obvious during hydrogen adsorption. We expect that Ti-decorated double vacancy graphene can be considered as a potential hydrogen storage medium under ambient conditions.
Development of Thermochemical Heat Storage Based on CaO/CaCO3 Cycles: A Review
Authors: Yang Ying , Li Yingjie , Yan Xianyao , Zhao Jianli , Zhang Chunxiao
Published: October 2021

Due to the inconsistency and intermittence of solar energy, concentrated solar power (CSP) cannot stably transmit energy to the grid. Heat storage can maximize the availability of CSP plants. Especially, thermochemical heat storage (TCHS) based on CaO/CaCO3 cycles has broad application prospects due to many advantages, such as high heat storage density, high exothermic temperature, low energy loss, low material price, and good coupling with CSP plants. This paper provided a comprehensive outlook on the integrated system of CaO/CaCO3 heat storage, advanced reactor design, heat storage conditions, as well as the performance of CaO-based materials. The challenges and opportunities faced by current research were discussed, and suggestions for future research and development directions of CaO/CaCO3 heat storage were briefly put forward.
Downcycling and Upcycling in Rehabilitation and Adaptive Reuse of Pre-Existing Buildings: Re-Designing Technological Performances in an Environmental Perspective
Authors: Monsù Scolaro Antonello , De Medici Stefania
Published: October 2021

The abandonment of the built heritage, as a result of functional or technological obsolescence or as a consequence of cultural, social, and economic trends, is steadily increasing. This great number of buildings, worldwide spread, offers a huge opportunity to reduce the environmental impacts related to the construction industry. Nonetheless, the recovery and reuse interventions that require the implementation of residual technological performance, to accommodate new uses, are not always environmentally neutral. Therefore, a new design approach needs to be developed so as to improve the buildings’ technological performance and enhance resources and energy already incorporated in buildings. The circular economy principles in the building sector, performance-based building design together with downcycling and upcycling theories are applied to develop a methodology aiming to reduce the environmental impacts within the rehabilitation and refurbishment design process. Starting from the building analysis phase (historical, material, construction) residual performance is evaluated; then the design phase demonstrates that, according to downcycling and upcycling design strategies applied on building components and materials, it is possible improving the building to the required new uses while minimizing transformations and effectively reducing related environmental impacts. The reduction of environmental impacts depends on a careful assessment of the residual technological and structural performance that the building still provides, by involving limited performance implementations to balance rehabilitation needs and environmental protection goals.
Causes of Design Change Depending on Power Project-Types in Ghana
Authors: Afelete Elikplim , Jung Wooyong
Published: October 2021

Design change is a common but significant problem in construction projects. Issues of delay, cost overruns, claims, and disputes in projects occur as a result. However, design change studies in the power-project area are less often discussed. As a result, the primary objective of this study was to identify important cause factors of design changes according to different power-project types in Ghana. Following a thorough assessment of the literature, 36 potential causes were identified, which were narrowed down by expert reviews to 30. In this study, power projects were classified into three categories: power plant, renewable, and distribution and transmission. The results indicate owner-related financial problems as the most important cause of design change for all three project types, followed by the second and third most significant in each of the categories, respectively: errors and omission in design and problems or unforeseen site conditions in power plant projects; deficient quality and quantity of resources and inflation and changes in interest and exchange rates in renewable projects; and problems or unforeseen site conditions and changes of plans in distribution and transmission projects. Based on the findings, power-project stakeholders are able to comprehend the dynamics of design change and develop effective design management strategies to reduce impact.
Development of an Efficient Modelling Approach for Fin-Type Heat-Exchangers in Self-Recuperative Burners
Authors: Dinsing Nicolas , Schmitz Nico , Schubert Christian , Pfeifer Herbert
Published: October 2021

Self-recuperative burners are a common solution for efficient combustion systems in industrial furnaces. Due to the geometric complexity of the recuperators, a detailed CFD simulation is computationally expensive and not feasible for simulation models of burner-integrated systems such as radiant tubes. Especially in the FSI studies of radiant tubes, the temperature of the radiant tube surrounding the burner is decisive for the final results. The exclusion of the recuperator from the simulation models introduces significant uncertainties in the simulations results. The presented paper describes an innovative, efficient approach to model a fin-type recuperator in which the recuperator is geometrically reduced. The resulting acceleration of the numerical simulation makes a fully dynamic modelling of the recuperator in a radiant tube simulation possible. Specifically designed source terms are used to model pressure loss and heat transfer inside the recuperator to match results obtained with a detailed simulation model. The results show deviations in total heat transfer of less than 1.3% with a 98.5% reduction of numerical mesh size. The computational savings enable comprehensive modelling of air preheat for radiant tube simulations and accurately replicate flow and temperature profiles in the recuperator.
Two Statistical Tools for Assessing Functionality and Protein Characteristics of Different Fava Bean (Vicia faba L.) Ingredients
Authors: Sharan Siddharth , Zotzel Jens , Stadtmüller Johannes , Bonerz Daniel , Aschoff Julian , Saint-Eve Anne , Maillard Marie-Noëlle , Olsen Karsten , Rinnan Åsmund , Orlien Vibeke
Published: October 2021

Fava bean (Vicia faba L.) is a promising source of proteins that can be potentially used as nutritional and/or functional agents for industrial food applications. Fava ingredients are industrially produced, modified, and utilized for food applications. Their processing conditions influence physico-chemical protein properties that further impact ingredient functionality. To design a functionally suitable ingredient, an understanding of the interrelationships between different properties is essential. Hence, this work aimed to assess two statistical analytical tools, Pearson’s correlation and Principal Component Analysis (PCA), for investigating the role of the process conditions of fava ingredients on their functional and protein properties. Fava concentrates were processed by pH (2, 4, 6.4 and 11), temperature (55, 75 and 95 ∘C) and treatment duration (30 and 360 min) into different modified ingredients. These were utilized under two application conditions (pH 4 and 7), and their foam and emulsion properties as well as their ingredient characteristics (charge, solubility, and intrinsic fluorescence) were measured. The results show that foam and emulsion properties are not correlated to each other. They are associated with different protein and non-protein attributes as fava concentrate is a multi-component matrix. Importantly, it is found that the results from the two statistical tools are not fully comparable but do complement each other. This highlights that both statistical analytical tools are equally important for a comprehensive understanding of the impact of process conditions on different properties and the interrelationships between them. Therefore, it is recommended to use Pearson’s correlation and principal component analysis in future investigations of new plant-based proteins.
Anti-Inflammation and Protective Effects of Anethum graveolens L. (Dill Seeds) on Esophageal Mucosa Damages in Reflux Esophagitis-Induced Rats
Authors: Nam Hyeon-Hwa , Nan Li , Choo Byung-Kil
Published: October 2021

Anethum graveolens L. (dill seeds) are important medicinal and functional foods in Europe and central and south Asia, often used as a seasoning in daily diets. Anethum graveolens L. seeds (AGS) are used to treat indigestion and have shown physiological activities such as those against hypoglycemia and gastroesophageal disease. This study explored the protective effects of AGS extract on mucosal damages and inflammation in reflux esophagitis rats. AGS inhibited cellular inflammation including NO production and the expression of inflammatory proteins (iNOS and COX2 etc.), cytokines (IL-1β and TNF-α) and nuclear transfer factor related to NF-κB signaling caused by LPS stimulation in vitro. Furthermore, reflux esophagitis-induced rats were used to observe the anti-inflammatory effect of AGS. Tissue staining and inflammation-related protein expression of rats with acute reflux esophagitis indicated that AGS improved this inflammatory response, such as COX-2 and TNF-α in mucosa. In conclusion, AGS have good physiological activity and the possibility of being used as a medicinal food and a functional resource for the prevention and therapy of gastroesophageal diseases.
Increased Provision of Bioavailable Mg through Vegetables Could Significantly Reduce the Growing Health and Economic Burden Caused by Mg Malnutrition
Authors: Liu Dunyi , Lu Ming , Lakshmanan Prakash , Hu Ziyi , Chen Xinping
Published: October 2021

Magnesium (Mg) is an essential mineral nutrient for human health and its deficiency associated with many diseases, including stroke, heart failure, and type 2 diabetes. Vegetables are an important source of dietary Mg for humans. In this study, we quantified vegetable Mg content by a global meat analysis, analyzed human health, and economic impact caused by Mg deficiency. Results revealed that vegetable Mg content showed a large variation with an average value of 19.3 mg 100 g−1 FW. Variation in per capita vegetable-Mg supply in different continents is largely ascribed to continental difference in the amount and the type of vegetables produced. The health and economic loss attributed to Mg deficiency are estimated to be 1.91 million disability-adjusted life years (DALYs) and 15.8 billion dollars (0.14% of GDP), respectively. A scenario analysis indicated that the increasing vegetable production (increased by 8.9% and 20.7% relative to 2017 in 2030 and 2050) and vegetable Mg content (increased by 22% through biofortification) could significantly reduce DALYs (1.24 million years) and economic burden (0.09% of GDP). This study could guide a major re-balance of production practices, species cultivated, and Mg biofortification to provide sufficient vegetable Mg for better human Mg nutrition.
Precision DNA Mixture Interpretation with Single-Cell Profiling
Authors: Ge Jianye , King Jonathan L. , Smuts Amy , Budowle Bruce
Published: October 2021

Wet-lab based studies have exploited emerging single-cell technologies to address the challenges of interpreting forensic mixture evidence. However, little effort has been dedicated to developing a systematic approach to interpreting the single-cell profiles derived from the mixtures. This study is the first attempt to develop a comprehensive interpretation workflow in which single-cell profiles from mixtures are interpreted individually and holistically. In this approach, the genotypes from each cell are assessed, the number of contributors (NOC) of the single-cell profiles is estimated, followed by developing a consensus profile of each contributor, and finally the consensus profile(s) can be used for a DNA database search or comparing with known profiles to determine their potential sources. The potential of this single-cell interpretation workflow was assessed by simulation with various mixture scenarios and empirical allele drop-out and drop-in rates, the accuracies of estimating the NOC, the accuracies of recovering the true alleles by consensus, and the capabilities of deconvolving mixtures with related contributors. The results support that the single-cell based mixture interpretation can provide a precision that cannot beachieved with current standard CE-STR analyses. A new paradigm for mixture interpretation is available to enhance the interpretation of forensic genetic casework.
Analytical and Numerical Investigations Applied to Study the Reflections and Transmissions of a Rectangular Breakwater Placed at the Bottom of a Wave Tank
Authors: Loukili Mohammed , Dutykh Denys , Nadjib Chioukh , Ning Dezhi , Kotrasova Kamila
Published: October 2021

The purpose of the work presented in this paper is to study the reflection and transmission coefficients resulting from the interactions of regular waves with a rectangular breakwater sited at the bottom of a tank. The present investigation is devoted to the analysis of the reflection and transmission coefficients within the framework of linearized potential flow theory using two methods, a numerical method based on the improved version of the meshless singular boundary method, and the analytical approach within the plane wave model. The numerical method is first validated by studying the accuracy of the numerical computations with respect to the number of boundary nodes and the location of the vertical boundaries of the computational domain, for different immersion ratios (h/d) and different relative lengths (w/d) of the obstacle. To assess the limitations of the analytical approach, a comparison analysis is carried out between the analytical and numerical results. To improve the calculations and the effectiveness of the analytical model, slight adjustments are made to the analytical procedure, which is termed here the corrected analytical plane wave model. Finally, the effects of the immersion ratio (h/d) and the relative length (w/d) of the obstacle on the reflection and transmission coefficients are computed using the three methods, and discussed for several wave and structural conditions.
The Experiences of a Complex Arts-Based Intervention for Patients with End-Stage Kidney Disease Whilst Receiving Haemodialysis: A Qualitative Process Evaluation
Authors: Carswell Claire , Reid Joanne , Walsh Ian , McKeaveney Clare , Noble Helen
Published: October 2021

The global prevalence and burden of end-stage kidney disease (ESKD) is increasing, partially as a result of an aging population. Patients with ESKD who receive haemodialysis experience a difficult, protracted treatment regimen that can negatively impact mental health and wellbeing. One way of addressing this issue could be through the provision of arts-based interventions during haemodialysis treatment. A process evaluation was conducted as part of a larger feasibility study, to explore experiences and acceptability of an intra-dialytic (during haemodialysis) arts-based intervention. Thirteen patients and nine healthcare professionals were interviewed. The interviews were transcribed verbatim and thematically analysed. Three themes related to the experience of art on dialysis included: the perception of art participation, as patients described initial anxiety around participating in art, which reduced after they experienced the intervention; the benefits of art participation on both patients and healthcare professionals; the benefits including improved self-esteem, motivation, increased social interaction and an overall improved haemodialysis experience; and the acceptability of the arts-based intervention, as the intervention was highly acceptable, even when delivered by a facilitator who was not a professional artist. This study highlights that arts-based interventions could be used to improve the mental health and wellbeing of patients with ESKD receiving haemodialysis.
Soil Moisture Retrieval Using Polarimetric SAR Data and Experimental Observations in an Arid Environment
Authors: Gharechelou Saeid , Tateishi Ryutaro , Sri Sumantyo Josaphat Tetuko , Johnson Brian Alan
Published: October 2021

Soil moisture is a critical component for Earth science studies, and Synthetic Aperture Radar (SAR) data have high potential for retrieving soil moisture using backscattering models. In this study, polarimetric SAR (PALSAR: Phased Array type L-band Synthetic Aperture Radar) data and polarimetric decompositions including span, entropy/H/alpha, and anisotropy, in combination with surface properties resulting from field and laboratory measurements, are used to categorize the natural surface condition and discriminate the backscatter parameter in the test site for applying the inversion soil moisture retrieval. The work aims to introduce the better of two examined models in the research for soil moisture retrieval over the bare land and sparse vegetation in arid regions. After soil moisture retrieval using the two different models, the results of comparison and validation by field measurement of soil moisture have shown that the Oh model has a more realiable accuracy for soil moisture mapping, although it was very difficult to find the best model due to different characteristics in land cover. It seems the inversion model, with the field observation and polarimetric SAR data, has a good potential for extracting surface natural conditions such as surface roughness and soil moisture; however, over- and under-estimation are observed due to land cover variability. The estimation of accurate roughness and moisture data for each type of land cover can increase the accuracy of the results.
Geo-L: Topological Link Discovery for Geospatial Linked Data Made Easy
Authors: Zinke-Wehlmann Christian , Kirschenbaum Amit
Published: October 2021

Geospatial linked data are an emerging domain, with growing interest in research and the industry. There is an increasing number of publicly available geospatial linked data resources, which can also be interlinked and easily integrated with private and industrial linked data on the web. The present paper introduces Geo-L, a system for the discovery of RDF spatial links based on topological relations. Experiments show that the proposed system improves state-of-the-art spatial linking processes in terms of mapping time and accuracy, as well as concerning resources retrieval efficiency and robustness.
Mechanisms of Long Non-Coding RNAs in Biological Characteristics and Aerobic Glycolysis of Glioma
Authors: Zhao Ningning , Zhang Jiajie , Zhao Qian , Chen Chao , Wang Huijuan
Published: October 2021

Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit a higher rate of glucose uptake, which is accompanied with the metabolic switch from oxidative phosphorylation to aerobic glycolysis. The metabolic reprogramming of cancer cell supports excessive cell proliferation, which are frequently mediated by the activation of oncogenes or the perturbations of tumor suppressor genes. Recently, a growing body of evidence has started to reveal that long noncoding RNAs (lncRNAs) are implicated in a wide spectrum of biological processes in glioma, including malignant phenotypes and aerobic glycolysis. However, the mechanisms of diverse lncRNAs in the initiation and progression of gliomas remain to be fully unveiled. In this review, we summarized the diverse roles of lncRNAs in shaping the biological features and aerobic glycolysis of glioma. The thorough understanding of lncRNAs in glioma biology provides opportunities for developing diagnostic biomarkers and novel therapeutic strategies targeting gliomas.
Rice SUT and SWEET Transporters
Authors: Hu Zhi , Tang Zhenjia , Zhang Yanming , Niu Liping , Yang Fang , Zhang Dechun , Hu Yibing
Published: October 2021

Sugar transporters play important or even indispensable roles in sugar translocation among adjacent cells in the plant. They are mainly composed of sucrose–proton symporter SUT family members and SWEET family members. In rice, 5 and 21 members are identified in these transporter families, and some of their physiological functions have been characterized on the basis of gene knockout or knockdown strategies. Existing evidence shows that most SUT members play indispensable roles, while many SWEET members are seemingly not so critical in plant growth and development regarding whether their mutants display an aberrant phenotype or not. Generally, the expressions of SUT and SWEET genes focus on the leaf, stem, and grain that represent the source, transport, and sink organs where carbohydrate production, allocation, and storage take place. Rice SUT and SWEET also play roles in both biotic and abiotic stress responses in addition to plant growth and development. At present, these sugar transporter gene regulation mechanisms are largely unclear. In this review, we compare the expressional profiles of these sugar transporter genes on the basis of chip data and elaborate their research advances. Some suggestions concerning future investigation are also proposed.
Recruitment of M1 Macrophages May Not Be Critical for Protection against Colitis-Associated Tumorigenesis
Authors: Medina-Andrade Itzel , Olguín Jonadab E. , Guerrero-García Stephanie , Espinosa Jossael A. , Garduño-Javier Elizabeth , Hernández-Gómez Victoria , Vaca-Paniagua Felipe , Rodríguez-Sosa Miriam , Terrazas Luis I.
Published: October 2021

A close connection between inflammation and the risk of developing colon cancer has been suggested in the last few years. It has been estimated that patients diagnosed with some types of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease, have up to a 30% increased risk of developing colon cancer. However, there is also evidence showing that the activation of anti-inflammatory pathways, such as the IL-4 receptor-mediated pathway, may favor the development of colon tumors. Using an experimental model of colitis-associated colon cancer (CAC), we found that the decrease in tumor development in global IL4Rα knockout mice (IL4RαKO) was apparently associated with an inflammatory response mediated by the infiltration of M1 macrophages (F480+TLR2+STAT1+) and iNOS expression in colon tissue. However, when we developed mice with a specific deletion of IL4Rα in macrophages (LysMcreIL4Rα−/lox mice) and subjected them to CAC, it was found that despite presenting a large infiltration of M1 macrophages into the colon, these mice were as susceptible to colon-tumorigenesis as WT mice. These data suggest that in the tumor microenvironment the absence of IL4Rα expression on macrophages, as well as the recruitment of M1 macrophages, may not be directly associated with resistance to developing colon tumors. Therefore, it is possible that IL4Rα expression in other cell types, such as colonic epithelial cells, could have an important role in promoting the development of colitis-associated colon tumorigenesis.
Protein PGLYRP1/Tag7 Peptides Decrease the Proinflammatory Response in Human Blood Cells and Mouse Model of Diffuse Alveolar Damage of Lung through Blockage of the TREM-1 and TNFR1 Receptors
Authors: Sharapova Tatiana N. , Romanova Elena A. , Chernov Aleksandr S. , Minakov Alexey N. , Kazakov Vitaly A. , Kudriaeva Anna A. , Belogurov Alexey A. , Ivanova Olga K. , Gabibov Alexander G. , Telegin Georgii B. , Yashin Denis V. , Sashchenko Lidia P.
Published: October 2021

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.
Advances in Nanoparticle Drug Delivery Systems for Anti-Hepatitis B Virus Therapy: A Narrative Review
Authors: Miao Jing , Gao Peng , Li Qian , He Kaifeng , Zhang Liwen , Wang Junyan , Huang Lingfei
Published: October 2021

Chronic hepatitis B (CHB) is an infectious viral disease that is prevalent worldwide. Traditional nucleoside analogues, as well as the novel drug targets against hepatitis B virus (HBV), are associated with certain critical factors that influence the curative effect, such as biological stability and safety, effective drug delivery, and controlled release. Nanoparticle drug delivery systems have significant advantages and have provided a basis for the development of anti-HBV strategies. In this review, we aim to review the advances in nanoparticle drug delivery systems for anti-hepatitis B virus therapy by summarizing the relevant literature. First, we focus on the characteristics of nanoparticle drug delivery systems for anti-HBV therapy. Second, we discuss the nanoparticle delivery systems for anti-HBV nucleoside drugs, gene-based drugs, and vaccines. Lastly, we provide an overview of the prospects for nanoparticle-based anti-HBV agents.
Controlled Release of Doxorubicin for Targeted Chemo-Photothermal Therapy in Breast Cancer HS578T Cells Using Albumin Modified Hybrid Nanocarriers
Authors: Carrese Barbara , Cavallini Chiara , Sanità Gennaro , Armanetti Paolo , Silvestri Brigida , Calì Gaetano , Pota Giulio , Luciani Giuseppina , Menichetti Luca , Lamberti Annalisa
Published: October 2021

Hybrid nanomaterials have attracted research interest owing to their intriguing properties, which may offer new diagnostic options with triggering features, able to realize a new kind of tunable nanotherapeutics. Hybrid silica/melanin nanoparticles (NPs) containing silver seeds (Me-laSil_Ag-HSA NPs) disclosed relevant photoacoustic contrast for molecular imaging. In this study we explored therapeutic function in the same nanoplatform. For this purpose, MelaSil_Ag-HSA were loaded with doxorubicin (DOX) (MelaSil_Ag-HSA@DOX) and tested to assess the efficiency of drug delivery combined with concurrent photothermal treatment. The excellent photothermal properties allowed enhanced cytotoxic activity at significantly lower doses than neat chemotherapeutic treatment. The results revealed that MelaSil_Ag-HSA@DOX is a promising platform for an integrated photothermal (PT) chemotherapy approach, reducing the efficacy concentration of the DOX and, thus, potentially limiting the several adverse side effects of the drug in in vivo treatments.
Synthesis and Biological Application of Isosteviol-Based 1,3-Aminoalcohols
Authors: Ozsvár Dániel , Nagy Viktória , Zupkó István , Szakonyi Zsolt
Published: October 2021

Starting from isosteviol, a series of diterpenoid 1,3-aminoalcohol derivatives were stereoselectively synthesised. The acid-catalysed hydrolysis and rearrangement of natural stevioside gave isosteviol, which was transformed to the key intermediate methyl ester. In the next step, Mannich condensation of diterpenoid ketone, paraformaldehyde, and secondary amines resulted in the formation of 1,3-aminoketones with different stereoselectivities. During the Mannich condensation with dibenzylamine, an interesting N-benzyl → N-methyl substituent exchange was observed. Reduction of 1,3-aminoketones produced diastereoisomeric 1,3-aminoalcohols. Alternatively, aminoalcohols were obtained via stereoselective hydroxy-formylation, followed by oxime preparation, reduction, and finally, reductive alkylation of the obtained primary aminoalcohols. An alternative 1,3-aminoalcohol library was prepared by reductive amination of the intermediate 3-hydroxyaldehyde obtained from isosteviol in two-step synthesis. Cytotoxic activity of compounds against human tumour cell lines (A2780, SiHa, HeLa, MCF-7 and MDA-MB-231) was investigated. In our preliminary study, the 1,3-aminoalcohol function and N-benzyl substitution seemed to be essential for the reliable antiproliferative activity. To extend their application, a diterpenoid condensed with 2-phenylimino-1,3-thiazine and -1,3-oxazine was also attempted to prepare, but only formation of thioether intermediate was observed.
Mining the Microbiome and Microbiota-Derived Molecules in Inflammatory Bowel Disease
Authors: Bekkers Matthijs , Stojkovic Bojan , Kaiko Gerard E.
Published: October 2021

The intestinal microbiota is a complex community that consists of an ecosystem with a dynamic interplay between bacteria, fungi, archaea, and viruses. Recent advances in model systems have revealed that the gut microbiome is critical for maintaining homeostasis through metabolic digestive function, immune regulation, and intestinal barrier integrity. Taxonomic shifts in the intestinal microbiota are strongly correlated with a multitude of human diseases, including inflammatory bowel disease (IBD). However, many of these studies have been descriptive, and thus the understanding of the cause and effect relationship often remains unclear. Using non-human experimental model systems such as gnotobiotic mice, probiotic mono-colonization, or prebiotic supplementation, researchers have defined numerous species-level functions of the intestinal microbiota that have produced therapeutic candidates for IBD. Despite these advances, the molecular mechanisms responsible for the function of much of the microbiota and the interplay with host cellular processes remain areas of tremendous research potential. In particular, future research will need to unlock the functional molecular units of the microbiota in order to utilize this untapped resource of bioactive molecules for therapy. This review will highlight the advances and remaining challenges of microbiota-based functional studies and therapeutic discovery, specifically in IBD. One of the limiting factors for reviewing this topic is the nascent development of this area with information on some drug candidates still under early commercial development. We will also highlight the current and evolving strategies, including in the biotech industry, used for the discovery of microbiota-derived bioactive molecules in health and disease.
Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?
Authors: Lacroix Vickie , Cassard Alexis , Mas Emmanuel , Barreau Frederick
Published: October 2021

Inflammatory bowel diseases (IBDs), which include Crohn’s disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new ‘omics’ techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by “omics” and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
Functional Depletion of HSP72 by siRNA and Quercetin Enhances Vorinostat-Induced Apoptosis in an HSP72-Overexpressing Cutaneous T-Cell Lymphoma Cell Line, Hut78
Authors: Fujii Kazuyasu , Idogawa Masashi , Suzuki Norihiro , Iwatsuki Keiji , Kanekura Takuro
Published: October 2021

Histone deacetylase inhibitors (HDACis) are one of the therapeutic options for cutaneous T-cell lymphoma (CTCL), but they have limited effects. We previously demonstrated that HSP72 overexpression is associated with chemoresistance to HDACis in lymphoma cells. The purpose of this study was to investigate whether the functional depletion of HSP72 enhances the effect of the HDACi vorinostat. First, we established a stable HSP72-knockdown CTCL cell line and confirmed the influence of HSP72 reduction on the antitumor effects of vorinostat. Next, we studied the effect of quercetin, an inhibitor of HSP72, on the antineoplastic effects of vorinostat. In five CTCL cell lines examined, HSP72 expression was highest in Hut78 cells, and HSP72 knockdown enhanced vorinostat-induced apoptosis in these cells. Low-dose quercetin reduced HSP72 expression, increased HDAC activity, and enhanced vorinostat-induced suppression of Hut78 cell proliferation. A single low dose of quercetin induced G2 arrest and only slightly increased the sub-G1 cell fraction. Quercetin also significantly enhanced vorinostat-induced apoptosis, caspase-3, caspase-8, and caspase-9 activity, and the loss of mitochondrial membrane potential. HSP72 knockdown enhanced vorinostat-induced apoptosis in an HSP72-overexpressing CTCL cell line, and thus, quercetin may be a suitable candidate for combination therapy with vorinostat in clinical settings.
Generation of a Soluble Form of Human Endoglin Fused to Green Fluorescent Protein
Authors: Ruiz-Llorente Lidia , Vega M. Cristina , Fernández Francisco J. , Langa Carmen , Morrell Nicholas W. , Upton Paul D. , Bernabeu Carmelo
Published: October 2021

Endoglin (Eng, CD105) is a type I membrane glycoprotein that functions in endothelial cells as an auxiliary receptor for transforming growth factor β (TGF-β)/bone morphogenetic protein (BMP) family members and as an integrin ligand, modulating the vascular pathophysiology. Besides the membrane-bound endoglin, there is a soluble form of endoglin (sEng) that can be generated by the action of the matrix metalloproteinase (MMP)-14 or -12 on the juxtamembrane region of its ectodomain. High levels of sEng have been reported in patients with preeclampsia, hypercholesterolemia, atherosclerosis and cancer. In addition, sEng is a marker of cardiovascular damage in patients with hypertension and diabetes, plays a pathogenic role in preeclampsia, and inhibits angiogenesis and tumor proliferation, migration, and invasion in cancer. However, the mechanisms of action of sEng have not yet been elucidated, and new tools and experimental approaches are necessary to advance in this field. To this end, we aimed to obtain a fluorescent form of sEng as a new tool for biological imaging. Thus, we cloned the extracellular domain of endoglin in the pEGFP-N1 plasmid to generate a fusion protein with green fluorescent protein (GFP), giving rise to pEGFP-N1/Eng.EC. The recombinant fusion protein was characterized by transient and stable transfections in CHO-K1 cells using fluorescence microscopy, SDS-PAGE, immunodetection, and ELISA techniques. Upon transfection with pEGFP-N1/Eng.EC, fluorescence was readily detected in cells, indicating that the GFP contained in the recombinant protein was properly folded into the cytosol. Furthermore, as evidenced by Western blot analysis, the secreted fusion protein yielded the expected molecular mass and displayed a specific fluorescent signal. The fusion protein was also able to bind to BMP9 and BMP10 in vitro. Therefore, the construct described here could be used as a tool for functional in vitro studies of the extracellular domain of endoglin.
The Pathogenesis, Molecular Mechanisms, and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases
Authors: Ramaswamy Madhu , Tummala Raj , Streicher Katie , Nogueira da Costa Andre , Brohawn Philip Z.
Published: October 2021

Therapeutic success in treating patients with systemic lupus erythematosus (SLE) is limited by the multivariate disease etiology, multi-organ presentation, systemic involvement, and complex immunopathogenesis. Agents targeting B-cell differentiation and survival are not efficacious for all patients, indicating a need to target other inflammatory mediators. One such target is the type I interferon pathway. Type I interferons upregulate interferon gene signatures and mediate critical antiviral responses. Dysregulated type I interferon signaling is detectable in many patients with SLE and other autoimmune diseases, and the extent of this dysregulation is associated with disease severity, making type I interferons therapeutically tangible targets. The recent approval of the type I interferon-blocking antibody, anifrolumab, by the US Food and Drug Administration for the treatment of patients with SLE demonstrates the value of targeting this pathway. Nevertheless, the interferon pathway has pleiotropic biology, with multiple cellular targets and signaling components that are incompletely understood. Deconvoluting the complexity of the type I interferon pathway and its intersection with lupus disease pathology will be valuable for further development of targeted SLE therapeutics. This review summarizes the immune mediators of the interferon pathway, its association with disease pathogenesis, and therapeutic modalities targeting the dysregulated interferon pathway.
Antitumor Activity and Mechanism of Action of Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide
Authors: Couty Mickael , Dusaud Marie , Miro-Padovani Mickael , Zhang Liuhui , Zadigue Patricia , Zargarian Loussiné , Lequin Olivier , de la Taille Alexandre , Delbe Jean , Hamma-Kourbali Yamina , Amiche Mohamed
Published: October 2021

Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapy.
Prion Infectivity and PrPBSE in the Peripheral and Central Nervous System of Cattle 8 Months Post Oral BSE Challenge
Authors: Ackermann Ivett , Ulrich Reiner , Tauscher Kerstin , Fatola Olanrewaju I. , Keller Markus , Shawulu James C. , Arnold Mark , Czub Stefanie , Groschup Martin H. , Balkema-Buschmann Anne
Published: October 2021

After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous system. However, the timeline of this progression has thus far remained widely undetermined. Previous studies were focused on later time points after oral exposure of animals that were already 4 to 6 months old when challenged. In contrast, in this present study, we have orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible BSE infectivity and/or PrPBSE in peripheral nervous tissues during the first eight months post-inoculation (mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse bioassay, while PrPBSE depositions were analyzed by immunohistochemistry (IHC) and by protein misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrPBSE and BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed, and pharmaceutical products produced from young calves.
MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy
Authors: Schrom Silke , Hebesberger Thomas , Wallner Stefanie Angela , Anders Ines , Richtig Erika , Brandl Waltraud , Hirschmugl Birgit , Garofalo Mariangela , Bernecker Claudia , Schlenke Peter , Kashofer Karl , Wadsack Christian , Aigelsreiter Ariane , Heitzer Ellen , Riedl Sabrina , Zweytick Dagmar , Kretschmer Nadine , Richtig Georg , Rinner Beate
Published: October 2021

Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapy-resistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is challenging to treat. The aim of this study was to provide a potential model system for the study of melanoma in pregnancy and to illustrate melanoma heterogeneity. For this purpose, a pigmented and a non-pigmented section of a lymph node metastasis from a pregnant patient were cultured under different conditions and characterized in detail. All four culture conditions exhibited different phenotypic, genotypic as well as tumorigenic properties, and resulted in four newly established melanoma cell lines. To address treatment issues, especially in pregnant patients, the effect of synthetic human lactoferricin-derived peptides was tested successfully. These new BRAF-mutated MUG Mel3 cell lines represent a valuable model in melanoma heterogeneity and melanoma pregnancy research. Furthermore, treatment with anti-tumor peptides offers an alternative to conventionally used therapeutic options—especially during pregnancy.
Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Scutellariae baicalensis radix Extract and Chitosan for Periodontal Diseases Treatment
Authors: Chanaj-Kaczmarek Justyna , Osmałek Tomasz , Szymańska Emilia , Winnicka Katarzyna , Karpiński Tomasz M. , Dyba Magdalena , Bekalarska-Dębek Marta , Cielecka-Piontek Judyta
Published: October 2021

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.
Study on Customized Shuttle Transit Mode Responding to Spatiotemporal Inhomogeneous Demand in Super-Peak
Authors: Zheng Hao , Zhang Xingchen , Chen Junhua
Published: October 2021

Instantaneous mega-traffic flow has long been one of the major challenges in the management of mega-cities. It is difficult for the public transportation system to cope directly with transient mega-capacity flows, and the uneven spatiotemporal distribution of demand is the main cause. To this end, this paper proposed a customized shuttle bus transportation model based on the “boarding-transfer-alighting” framework, with the goal of minimizing operational costs and maximizing service quality to address mega-transit demand with uneven spatiotemporal distribution. The fleet application is constructed by a pickup and delivery problem with time window and transfer (PDPTWT) model, and a heuristic algorithm based on Tabu Search and ALNS is proposed to solve the large-scale computational problem. Numerical tests show that the proposed algorithm has the same accuracy as the commercial solution software, but has a higher speed. When the demand size is 10, the proposed algorithm can save 24,000 times of time. In addition, 6 reality-based cases are presented, and the results demonstrate that the designed option can save 9.93% of fleet cost, reduce 45.27% of vehicle waiting time, and 33.05% of passenger waiting time relative to other existing customized bus modes when encountering instantaneous passenger flows with time and space imbalance.