bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Volume Monitoring: A Clinical Tool to Guide Ultrafiltration in Volume Control and Optimisation of Intradialytic Blood Pressure
Authors: Mahony Stephen , Ward Frank
Published: December 2021

The importance of extracellular volume control and avoidance of volume overload has been well documented in relation to the management of patients with chronic haemodialysis. Chronic volume overload results in poorly controlled hypertension, increased cardiovascular events, and increased all-cause mortality. Traditional methods of dry weight assessment have relied on clinical assessment to guide volume status. The challenge of achieving the balance between dry weights and preventing intradialytic complications is a formidable one. In order to achieve this, reproducible and sensitive methods are desirable to aid objective quantification of volume status. One such method is by the use of blood volume monitoring, which is achieved by real-time calculation of changes in relative blood volume via a cuvette placed in the arterial blood-line, which can be used to guide ultrafiltration targets during the haemodialysis session. This review article examines the use of blood volume monitoring as a tool to guide ultrafiltration during dialysis and to examine the current evidence to supports its use in assessing dry weight and in preventing intradialytic hypotension events.
Relating Field Energy Attenuation in Portland Cement Concrete Pavements to Fracture Mechanics
Authors: Lenngren Carl , Hernandez Maria
Published: December 2021

Asset management of infrastructure is fundamental for maintenance planning and preservation of common property. A robust testing program is needed to assess the present-day status and for proper actions in time to minimize the ongoing depreciation of value. As a matter of fact, Portland Cement Concrete pavements show very little deterioration even after many years in service. Thus, it may be difficult to accurately predict the present asset value, other than using linear relations to the presumed design life. The primary reason for failure is cracking in concrete pavements, so assessing the dissipated energy from the load-deformation relation from a given load could be utilized for the purpose. The dissipated energy, i.e. the work data can be assessed by a falling weight deflectometer test, mimicking the passing of a truck or aircraft wheel load. In the present study, dynamic field data are evaluated, and the input data needed for the fracture mechanics model are used to predict the pavement life regarding cracking. To predict fracture energy and assess rolling resistance as well in concrete pavements, we need to consider the energy balance of the pavement system. To assess dissipated energy, falling weight deflectometer time histories are used to evaluate the pavement contribution to rolling resistance. Such analyses include all layers in the structure including the subgrade, so in the present case a way of sorting the dissipation at various depths is investigated. Field data were collected from a site, at mid-life of the predicted design life. The failure was confirmed several years later, and the remaining life was compared with the assumption that the dissipated energy near the edge was enough to initiate the cracks within the actual time to failure. Conversely, the dissipation at the mid-slab position was below the limit. The data from the field test were also used as an input for a finite element model to see if it was viable to further improve the prediction. The method seems to be promising, but more data are needed as the present set only represents the mid-life status.
AWARENESS OF SOCIAL MEDIA BASIS AS A PROMOTIONAL MEDIUM FOR KULINTANGAN TRADITIONAL MUSIC OF SUNGAI TRIBES AT PAITAN
Authors: Jupin Norezan , Dolhan Nor Atikah , Indang Easther , Lee Abdullah Qistina Donna
Published: December 2021

This article discussed the awareness level of Sungai Tribes on using social media as a promotional medium for Kulintangan traditional music at Paitan. This study used a Quantitative approach through a survey of 377 people who expert in playing Kulintangan traditional music and owned various social media (Facebook, YouTube, Instagram, and WhatsApp). Based on the findings, the level of awareness of the Paitan cult on promoting Kulintangan via social media is moderate with a total average mean of 3.154 with a 1.302 standard deviation. The awareness of Sungai tribes on the usage of social media is more inclined to Whatsapp (ranking number 1 in overall mean and percentages) followed by Facebook, Instagram, and Youtube. Sungai tribes were also found to rarely share the Kulintangan music on social media account. Therefore, the SABAS and Sungai cult should increase the sharing of Kulintangan music via Whatsapp.
Speech Recorder and Translator using Google Cloud Speech-to-Text and Translation
Authors: Wang Hui Hui
Published: December 2021

The most popular video website YouTube has about 2 billion users worldwide who speak and understand different languages. Subtitles are essential for the users to get the message from the video. However, not all video owners provide subtitles for their videos. It causes the potential audiences to have difficulties in understanding the video content. Thus, this study proposed a speech recorder and translator to solve this problem. The general concept of this study was to combine Automatic Speech Recognition (ASR) and translation technologies to recognize the video content and translate it into other languages. This paper compared and discussed three different ASR technologies. They are Google Cloud Speech-to-Text, Limecraft Transcriber, and VoxSigma. Finally, the proposed system used Google Cloud Speech-to-Text because it supports more languages than Limecraft Transcriber and VoxSigma. Besides, it was more flexible to use with Google Cloud Translation. This paper also consisted of a questionnaire about the crucial features of the speech recorder and translator. There was a total of 19 university students participated in the questionnaire. Most of the respondents stated that high translation accuracy is vital for the proposed system. This paper also discussed a related work of speech recorder and translator. It was a study that compared speech recognition between ordinary voice and speech impaired voice. It used a mobile application to record acoustic voice input. Compared to the existing mobile App, this project proposed a web application. It was a different and new study, especially in terms of development and user experience. Finally, this project developed the proposed system successfully. The results showed that Google Cloud Speech-to-Text and Translation were reliable to use in video translation. However, it could not recognize the speech when the background music was too loud. Besides, it had a problem of direct translation, which was challenging. Thus, future research may need a custom trained model. In conclusion, the proposed system in this project was to contribute a new idea of a web application to solve the language barrier on the video watching platform.
Hypothesis of rational expectations in the international economy: developments in different countries
Authors:   SO ", BORZENKO Olena ,   Institute for Economics and Forecasting of the NAS of Ukraine"
Published: December 2021

The article reveals the development of the hypothesis of rational expectations according to the theory of rational expectations (TRO), where economic entities in their forecasts make optimal use of all available information, including the assessment of government policy, to form an opinion on future developments. It turns out that expectations in the economy are very important. Rational expectations are those that can be systematically erroneous. They do not necessarily have to be performed exactly, but this is only because economic processes are subject to random fluctuations that do not depend on the actions of the state, or because the actions of the state in economic policy are unpredictable for economic agents.
Clusterization as a prerequisite for enhancing competitiveness of enterprises in the production sphere of Ukraine in the conditions of global challenges
Authors:   SO ", BOIKO Olena ,   Institute for Economics and Forecasting of the NAS of Ukraine"
Published: December 2021

The article reflects one of the topical issues in modern conditions - the imperatives of global transformations in the development of clustering as a prerequisite for enhancing competitiveness of enterprises in the manufacturing sector. The international experience of peculiarities of clusters’ functioning in the process of globalization and its use in the Ukrainian economy is generalized. The risks of creating and developing clusters have been identified. In order to minimize them, the features of the institutional and legal foundations of the functioning of clusters have been investigated and proposals for further development in Ukraine have been developed.
Tax incentives for R&D in the context of the development of fiscal space
Authors:   SE “Institute for Economics and Forecasting of NAS of Ukraine”, FROLOVA Nataliya
Published: December 2021

The article deals with the main R&D expenditure based tax incentives such as tax credit and enhanced allowances in the context of the development of fiscal space due to their impact on innovative activities of loss-making, small and medium enterprises as well as startups. The author disclosed basic features of R&D expenditure based tax incentives in comparison with tax exemptions and accelerated depreciation. Cross-country comparisons in OECD revealed that it is often a case when SMEs and startups enjoy R&D tax credit and enhanced allowance with higher rates. In addition, they can also claim full reimbursement of unused tax benefits for R&D while large companies can only count on partial or even non-reimbursement of unused tax benefits and limited carry over period. Implied tax subsidy rates on R&D are analyzed through different OECD countries, as well as through enterprises different in size and profitability. In 2019 the largest R&D tax benefits were offered to profitable SMEs in France (ITSR was 43%) and Portugal (ITSR was 39%). The ITSR methodology is used to work out scenarios of introduction of R&D expenditure -based tax incentives in Ukraine. Calculation results are presented. The state of R&D tax incentives in Ukraine in the case of aircraft industry is analyzed. The introduction R&D expenditure -based tax incentives is argued as a replacement of tax exemptions which are currently used as a measure for R&D promotion in the aircraft industry in Ukraine in terms of improvement of R&D tax support efficiency and spur successful development of high value-added industries as an important prerequisite for the development of fiscal space in Ukraine.
Association Between Asthma and Migraine: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Kang Lin-Lin , Chen Pei-En , Tung Tao-Hsin , Chien Ching-Wen
Published: December 2021

Objectives: The purpose of this study was to determine the association between asthma and migraine and assess the risk for migraine in patients with asthma.

Methods: We systematically searched the Cochrane Library, PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Excerpta Medica dataBASE (EMBASE) databases from inception to September 26, 2021, for indexed observational studies that examined either the odds or risk of migraine in subjects with asthma. The qualities of the included studies were evaluated using the Newcastle–Ottawa Scale. A random-effects meta-analysis was performed to calculate the odds ratio for case-control and cross-sectional studies and the risk ratio for cohort studies.

Results: Seven observational studies (four cross-sectional and three cohort studies) with a total of 549,534 study subjects were included in this systematic review and meta-analysis and selected for data extraction. Four articles were considered to be of moderate quality; other studies were considered to be of high quality. Asthma was associated with increased odds (OR, 1.85; 95%CI, 1.39–2.45) and risk of migraine (RR, 1.70; 95%CI, 1.52–1.90).

Conclusions: The available evidence that supports the existence of an association between asthma and migraine is limited. Clinicians should be aware that patients with asthma show both increased prevalence and incidence of migraine. Further studies are warranted to further clarify the relationship between asthma and migraine.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185881, identifier: CRD42020185881.
Recent Trends of Controlling Chaotic Resonance and Future Perspectives
Authors: Nobukawa Sou , Nishimura Haruhiko , Wagatsuma Nobuhiko , Inagaki Keiichiro , Yamanishi Teruya , Takahashi Tetsuya
Published: December 2021

Stochastic resonance is a phenomenon in which the effects of additive noise strengthen the signal response against weak input signals in non-linear systems with a specific barrier or threshold. Recently, several studies on stochastic resonance have been conducted considering various engineering applications. In addition to additive stochastic noise, deterministic chaos causes a phenomenon similar to the stochastic resonance, which is known as chaotic resonance. The signal response of the chaotic resonance is maximized around the attractor-merging bifurcation for the emergence of chaos-chaos intermittency. Previous studies have shown that the sensitivity of chaotic resonance is higher than that of stochastic resonance. However, the engineering applications of chaotic resonance are limited. There are two possible reasons for this. First, the stochastic noise required to induce stochastic resonance can be easily controlled from outside of the stochastic resonance system. Conversely, in chaotic resonance, the attractor-merging bifurcation must be induced via the adjustment of internal system parameters. In many cases, achieving this adjustment from outside the system is difficult, particularly in biological systems. Second, chaotic resonance degrades owing to the influence of noise, which is generally inevitable in real-world systems. Herein, we introduce the findings of previous studies concerning chaotic resonance over the past decade and summarize the recent findings and conceivable approaches for the reduced region of orbit feedback method to address the aforementioned difficulties.
Perspectives on Assembling Coronavirus Spikes on Fiber Optics to Reveal Broadly Recognizing Antibodies and Generate a Universal Coronavirus Detector
Authors: Sypabekova Marzhan , Tosi Daniele , Vangelista Luca
Published: December 2021

In time of COVID-19 biological detection technologies are of crucial relevance. We propose here the use of state of the art optical fiber biosensors to address two aspects of the fight against SARS-CoV-2 and other pandemic human coronaviruses (HCoVs). Fiber optic biosensors functionalized with HCoV spikes could be used to discover broadly neutralizing antibodies (bnAbs) effective against known HCoVs (SARS-CoV, MERS-CoV and SARS-CoV-2) and likely future ones. In turn, identified bnAbs, once immobilized onto fiber optic biosensors, should be capable to detect HCoVs as diagnostic and environmental sensing devices. The therapeutic and preventative value of bnAbs is immense as they can be used for passive immunization and for the educated development of a universal vaccine (active immunization). Hence, HCoV bnAbs represent an extremely important resource for future preparedness against coronavirus-borne pandemics. Furthermore, the assembly of bnAb-based biosensors constitutes an innovative approach to counteract public health threats, as it bears diagnostic competence additional to environmental detection of a range of pandemic strains. This concept can be extended to different pandemic viruses, as well as bio-warfare threats that entail existing, emerging and extinct viruses (e.g., the smallpox-causing Variola virus). We report here the forefront fiber optic biosensor technology that could be implemented to achieve these aims.
Improved Osteogenesis by Mineralization Combined With Double-Crosslinked Hydrogel Coating for Proliferation and Differentiation of Mesenchymal Stem Cells
Authors: Ma Yiqun , You Yuwang , Cao Lu , Liang Bing , Tian Bo , Dong Jian , Lin Hong
Published: December 2021

In consideration of improving the interface problems of poly-L-lactic acid (PLLA) that hindered biomedical use, surface coatings have been explored as an appealing strategy in establishing a multi-functional coating for osteogenesis. Though the layer-by-layer (LBL) coating developed, a few studies have applied double-crosslinked hydrogels in this technique. In this research, we established a bilayer coating with double-crosslinked hydrogels [alginate–gelatin methacrylate (GelMA)] containing bone morphogenic protein (BMP)-2 [alginate-GelMA/hydroxyapatite (HA)/BMP-2], which displayed great biocompatibility and osteogenesis. The characterization of the coating showed improved properties and enhanced wettability of the native PLLA. To evaluate the biosafety and inductive ability of osteogenesis, the behavior (viability, adherence, and proliferation) and morphology of human bone mesenchymal stem cells (hBMSCs) on the bilayer coatings were tested by multiple exams. The satisfactory function of osteogenesis was verified in bilayer coatings. We found the best ratios between GelMA and alginate for biological applications. The Alg70-Gel30 and Alg50-Gel50 groups facilitated the osteogenic transformation of hBMSCs. In brief, alginate-GelMA/HA/BMP-2 could increase the hBMSCs’ early transformation of osteoblast lineage and promote the osteogenesis of bone defect, especially the outer hydrogel layer such as Alg70-Gel30 and Alg50-Gel50.
Biopharmaceutical-Type Chinese Hamster Ovary Cell Cultivation Under Static Magnetic Field Exposure: A Study of Genotoxic Effect
Authors: Rekena Alina , Livkisa Dora , Kamolins Edmunds , Vanags Juris , Loca Dagnija
Published: December 2021

The lack of a sufficient research base is the reason for the ongoing discussion regarding the genotoxic effect of magnetic field (MF) exposure on mammalian cell cultures. Chinese hamster ovary (CHO) suspension-type cells, which are widely used for biopharmaceutical production, are potentially subjected to an increased MF when cultivated in bioreactors equipped with bottom-placed magnetically coupled stirring mechanisms. The main challenge for conducting research in this field remains the availability of a suitable experimental setup that generates an appropriate MF for the raised research question. In the present study, a simple and cost-effective experimental setup was developed that generated a static MF, similar to what has been modeled in large-scale bioreactors and, at the same time, was suitable for experimental cell cultivation in laboratory conditions. The measured maximum magnetic flux density to which the cells were exposed was 0.66 T. To assess the possible genotoxic effect, cells were continuously subcultivated in laboratory petri dishes for a period of 14 days, corresponding to a typical duration of a biopharmaceutical production process in a conventional fed-batch regime. The genotoxic effect was assessed using the cytokinesis-block micronucleus assay with fluorescent staining. Results showed that a 0.66-T static MF exposure had no significant long-term effect on cell viability and chromosomal damage but demonstrated a short-term effect on cell apoptosis. Significant increase in nuclear bud formation was observed. These findings may encourage other researchers in future studies investigating cellular responses to MF exposure and contribute relevant data for comparison.
The Feasibility of Targeted Magnetic Iron Oxide Nanoagent for Noninvasive IgA Nephropathy Diagnosis
Authors: Wu Yaoyao , Huang Qiang , Wang Junli , Dai Yuhua , Xiao Ming , Li Yangyang , Zhang Hongbo , Xiao Wenbo
Published: December 2021

IgA nephropathy is the most common glomerular disease in the world and has become a serious threat to human health. Accurate and non-invasive molecular imaging to detect and recognize the IgA nephropathy is critical for the subsequent timely treatment; otherwise, it may progress to end-stage renal disease and lead to glomerular dysfunction. In this study, we have developed a sensitive, specific, and biocompatible integrin αvβ3-targeted superparamagnetic Fe3O4 nanoparticles (NPs) for the noninvasive magnetic resonance imaging (MRI) of integrin αvβ3, which is overexpressed in glomerular mesangial region of IgA nephropathy. The rat model of IgA nephropathy was successfully established and verified by biochemical tests and histological staining. Meanwhile, the clinical 18F-AlF-NOTA-PRGD2 probe molecule was utilized to visualize and further confirmed the IgA nephropathy in vivo via positron emission computed tomography. Subsequently, the Fe3O4 NPs were conjugated with arginine–glycine–aspartic acid (RGD) molecules (Fe3O4-RGD), and their integrin αvβ3-targeted T2-weighted imaging (T2WI) potential has been carefully evaluated. The Fe3O4-RGD demonstrated great relaxation in vivo. The T2WI signal of renal layers in the targeted group at 3 h after intravenous injection of Fe3O4-RGD was distinctly lower than baseline, indicating MRI signal decreased in the established IgA nephropathy rat model. Moreover, the TEM characterization and Prussian blue staining confirmed that the Fe3O4-RGD was located at the region of glomerulus and tubular interstitium. Moreover, no obvious signal decreased was detected in the untargeted Fe3O4 treated and normal groups. Collectively, our results establish the possibility of Fe3O4-RGD serving as a feasible MRI agent for the noninvasive diagnosis of IgA nephropathy.
Crosstalk Between the Immune System and Plant-Derived Nanovesicles: A Study of Allergen Transporting
Authors: Stanly Christopher , Kim Hyoseon , Antonucci Giuseppe , Fiume Immacolata , Guescini Michele , Kim Kwang Pyo , Ciardiello Maria Antonietta , Giangrieco Ivana , Mari Adriano , Pocsfalvi Gabriella
Published: December 2021

Background: Nanometer-sized membrane-surrounded vesicles from different parts of plants including fruits are gaining increasing attention due to their anti-inflammatory and anticancer effects demonstrated by in vitro and in vivo studies, and as nanovectors for molecular delivery of exogenous substances. These nanomaterials are very complex and contain a diverse arsenal of bioactive molecules, such as nucleic acids, proteins, and lipids. Our knowledge about the transport of allergens in vesicles isolated from plant food is limited today.

Methods: Here, to investigate the allergenicity of strawberry-derived microvesicles (MVs), nanovesicles (NVs), and subpopulations of NV, we have set up a multidisciplinary approach. The strategy combines proteomics-based protein identification, immunological investigations, bioinformatics, and data mining to gain biological insights useful to evaluate the presence of potential allergens and the immunoglobulin E (IgE) inhibitory activity of vesicle preparations.

Results: Immunological test showed that several proteins of strawberry-derived vesicles compete for IgE binding with allergens spotted on the FABER biochip. This includes the known strawberry allergens Fra a 1, Fra a 3, and Fra a 4, and also other IgE-binding proteins not yet described as allergens in this food, such as gibberellin-regulated proteins, 2S albumin, pectate lyase, and trypsin inhibitors. Proteomics identified homologous sequences of the three strawberry allergens and their isoforms in total protein extract (TPE) but only Fra a 1 and Fra a 4 in the vesicle samples. Label-free quantitative proteomic analysis revealed no significant enrichment of these proteins in strawberry vesicles with respect to TPE.

Conclusion: Immunological tests and bioinformatics analysis of proteomics data sets revealed that MVs and NVs isolated from strawberries can carry functional allergens their isoforms as well as proteins potentially allergenic based on their structural features. This should be considered when these new nanomaterials are used for human nutraceutical or biomedical applications.
Characterization and Cytotoxicity of Pseudomonas Mediated Rhamnolipids Against Breast Cancer MDA-MB-231 Cell Line
Authors: Mishra Neelam , Rana Kavita , Seelam Siva Deepthi , Kumar Rakesh , Pandey Vijyendra , Salimath Bharathi P. , Agsar Dayanand
Published: December 2021

A biosurfactant producing bacterium was identified as Pseudomonas aeruginosa DNM50 based on molecular characterization (NCBI accession no. MK351591). Structural characterization using MALDI-TOF revealed the presence of 12 different congeners of rhamnolipid such as Rha-C8-C8:1, Rha-C10-C8:1, Rha-C10-C10, Rha-C10-C12:1, Rha-C16:1, Rha-C16, Rha-C17:1, Rha-Rha-C10:1-C10:1, Rha-Rha-C10-C12, Rha-Rha-C10-C8, Rha-Rha-C10-C8:1, and Rha-Rha-C8-C8. The radical scavenging activity of rhamnolipid (DNM50RL) was determined by 2, 3-diphenyl-1-picrylhydrazyl (DPPH) assay which showed an IC50 value of 101.8 μg/ ml. The cytotoxic activity was investigated against MDA-MB-231 breast cancer cell line by MTT (4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay which showed a very low IC50 of 0.05 μg/ ml at 72 h of treatment. Further, its activity was confirmed by resazurin and trypan blue assay with IC50 values of 0.01 μg/ml and 0.64 μg/ ml at 72 h of treatment, respectively. Thus, the DNM50RL would play a vital role in the treatment of breast cancer targeting inhibition of p38MAPK.
How can UK Housing Projects be Brought in Line With Net-Zero Carbon Emission Targets?
Authors: Jankovic Ljubomir , Bharadwaj Purvesh , Carta Silvio
Published: December 2021

Numerous local authorities are committed to constructing buildings to net-zero carbon emissions performance, and have declared carbon emergency, striving to reach carbon neutrality well before 2050. However, buildings in the UK are currently being designed and constructed to current building regulations which do not require net-zero performance, and these buildings will last well beyond 2050. This paper presents a case study of a housing development in Hertfordshire, UK, where a structured approach for achieving net-zero carbon performance homes was developed. The methodology was based on dynamic simulation modelling to design buildings which achieve net-zero operational emissions, and an industry standard inventory of carbon and energy database was used to evaluate embodied emissions in building materials. The approach comprised of developing dynamic simulation models to investigate the improvement in energy performance of the development through fabric-first approach, focusing on building envelope design prior to introducing renewable energy systems, in order to achieve operational net-zero carbon performance. Carbon emissions (operational and embodied) were investigated to assess the appropriateness of the deployed strategies. Dynamic simulation results combined with embodied emissions analysis illustrated that, by combining embodied and operational emissions, a net-zero carbon performance would be achievable by the 2050 target only if alternative building materials based on photosynthetic bio-composites are used. This analysis also highlighted the limitations of conventional retrofit interventions carried out 10 years after the construction as they resulted in increased embodied carbon emissions, thus lengthening the time period well beyond the 2050 target for achieving net-zero carbon performance. As the use of conventional materials appeared to delay the achievement of net-zero emissions by several decades, the only way to achieve net-zero targets before 2050 is to design new buildings to be carbon negative from the operational point of view and to use photosynthetic materials for their construction.
A Global Sensitivity Analysis Framework for Hybrid Simulation with Stochastic Substructures
Authors: Tsokanas Nikolaos , Zhu Xujia , Abbiati Giuseppe , Marelli Stefano , Sudret Bruno , Stojadinović Božidar
Published: December 2021

Hybrid simulation is an experimental method used to investigate the dynamic response of a reference prototype structure by decomposing it to physically-tested and numerically-simulated substructures. The latter substructures interact with each other in a real-time feedback loop and their coupling forms the hybrid model. In this study, we extend our previous work on metamodel-based sensitivity analysis of deterministic hybrid models to the practically more relevant case of stochastic hybrid models. The aim is to cover a more realistic situation where the physical substructure response is not deterministic, as nominally identical specimens are, in practice, never actually identical. A generalized lambda surrogate model recently developed by some of the authors is proposed to surrogate the hybrid model response, and Sobol’ sensitivity indices are computed for substructure quantity of interest response quantiles. Normally, several repetitions of every single sample of the inputs parameters would be required to replicate the response of a stochastic hybrid model. In this regard, a great advantage of the proposed framework is that the generalized lambda surrogate model does not require repeated evaluations of the same sample. The effectiveness of the proposed hybrid simulation global sensitivity analysis framework is demonstrated using an experiment.
HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1
Authors: Li Jianqin , Xia Yalin , Fan Xiaoru , Wu Xiaofang , Yang Feiyun , Hu Shaoyan , Wang Zhaoyue
Published: December 2021

Background: Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder and the decreased number and immunosuppressive dysfunction of Treg cells are key promoters of ITP. However, their mechanisms in ITP development have not been fully clarified.

Methods: HUWE1 mRNA and protein levels in CD4+ T cells in peripheral blood from ITP patients were assessed by quantitative real-time PCR and Western blot. HUWE1 function in ITP was estimated using flow cytometry, enzyme-linked immunosorbent assay and immunosuppression assay. Besides, the HUWE1 mechanism in reducing the number and function of Treg cells in ITP was investigated by immunoprecipitation, cycloheximide-chase assay, ubiquitin experiment and immunofluorescence assay.

Results: HUWE1 expression was elevated in CD4+ T cells in peripheral blood from ITP patients and HUWE1 mRNA level was negatively correlated with platelet counts and Treg cell percentage. Moreover, the interference with HUWE1 increased the number of Treg cells and enhanced its immunosuppressive function, and the HUWE1 overexpression produced the opposite results. For the exploration of mechanism, HUWE1 interacted with E26 transformation-specific-1 (Ets-1) and this binding was dependent on the negative regulation of the phosphorylation level of Ets-1 (Thr38) and HUWE1 facilitated the ubiquitin degradation of Ets-1 protein to restrain Treg cell differentiation and weaken their immunosuppressive functions. The in vivo assay confirmed that the HUWE1 inhibitor alleviated ITP in mice.

Conclusion: HUWE1 induced the immune imbalance in ITP by decreasing the number and weakening the function of Treg cells through the ubiquitination degradation of Ets-1.
Actin Crosslinking Family Protein 7 Deficiency Does Not Impair Hearing in Young Mice
Authors: Gilbert Benjamin L. , Zhu Shaoyuan , Salameh Ahlam , Sun Shenyu , Alagramam Kumar N. , McDermott Brian M.
Published: December 2021

To enable hearing, the sensory hair cell contains specialized subcellular structures at its apical region, including the actin-rich cuticular plate and circumferential band. ACF7 (actin crosslinking family protein 7), encoded by the geneMacf1(microtubule and actin crosslinking factor 1), is a large cytoskeletal crosslinking protein that interacts with microtubules and filamentous actin to shape cells. ACF7 localizes to the cuticular plate and the circumferential band in the hair cells of vertebrates. The compelling expression pattern of ACF7 in hair cells, combined with conserved roles of this protein in the cytoskeleton of various cell types in invertebrates and vertebrates, led to the hypothesis that ACF7 performs a key function in the subcellular architecture of hair cells. To test the hypothesis, we conditionally targetMacf1in the inner ears of mice. Surprisingly, our data show that in young, but mature, conditional knockout mice cochlear hair cell survival, planar cell polarity, organization of the hair cells within the organ of Corti, and capacity to hear are not significantly impacted. Overall, these results fail to support the hypothesis that ACF7 is an essential hair cell protein in young mice, and the purpose of ACF7 expression in the hair cell remains to be understood.
Anti-Tumor Necrosis Factor Receptor 2 Antibody Combined With Anti-PD-L1 Therapy Exerts Robust Antitumor Effects in Breast Cancer
Authors: Fu Qiang , Shen Qian , Tong Jin , Huang Liu , Cheng Yi , Zhong Wei
Published: December 2021

Breast cancer is a leading type of malignant tumor in women; however, the immunotherapy in breast cancer is still underappreciated. In this study, we demonstrated that tumor necrosis factor receptor 2 (TNFR2) is highly expressed in both breast tumor tissue and tumor-infiltrating immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs). We found that TNFR2 antagonistic antibody reduced Foxp3 expression and the proliferation of Tregs and impaired the inhibitory effect of Tregs on CD4+CD25– effector T (Teff) cells in a dose-dependent manner. The treatment of anti-TNFR2 antibody not only inhibited the proliferation of breast tumor cells in vitro but also suppressed the tumorigenesis of murine mammary carcinoma 4T1 cells in vivo. Mice recovered from tumor growth also developed 4T1-specific immunity. Furthermore, we demonstrated that anti-TNFR2 antibody in combination with anti-PD-L1 exhibited augmented antitumor effects than monotherapy. Anti-TNFR2 treatment also tended to increase the expression of proinflammatory cytokines in tumor tissues. In conclusion, our study suggests that TNFR2 antagonist could potentially offer a clinical benefit as a single agent or in combination with immune checkpoint blockade treatment for breast cancer immunotherapy.
Derivedness Index for Estimating Degree of Phenotypic Evolution of Embryos: A Study of Comparative Transcriptomic Analyses of Chordates and Echinoderms
Authors: Leong Jason Cheok Kuan , Li Yongxin , Uesaka Masahiro , Uchida Yui , Omori Akihito , Hao Meng , Wan Wenting , Dong Yang , Ren Yandong , Zhang Si , Zeng Tao , Wang Fayou , Chen Luonan , Wessel Gary , Livingston Brian T. , Bradham Cynthia , Wang Wen , Irie Naoki
Published: December 2021

Species retaining ancestral features, such as species called living fossils, are often regarded as less derived than their sister groups, but such discussions are usually based on qualitative enumeration of conserved traits. This approach creates a major barrier, especially when quantifying the degree of phenotypic evolution or degree of derivedness, since it focuses only on commonly shared traits, and newly acquired or lost traits are often overlooked. To provide a potential solution to this problem, especially for inter-species comparison of gene expression profiles, we propose a new method named “derivedness index” to quantify the degree of derivedness. In contrast to the conservation-based approach, which deals with expressions of commonly shared genes among species being compared, the derivedness index also considers those that were potentially lost or duplicated during evolution. By applying our method, we found that the gene expression profiles of penta-radial phases in echinoderm tended to be more highly derived than those of the bilateral phase. However, our results suggest that echinoderms may not have experienced much larger modifications to their developmental systems than chordates, at least at the transcriptomic level. In vertebrates, we found that the mid-embryonic and organogenesis stages were generally less derived than the earlier or later stages, indicating that the conserved phylotypic period is also less derived. We also found genes that potentially explain less derivedness, such as Hox genes. Finally, we highlight technical concerns that may influence the measured transcriptomic derivedness, such as read depth and library preparation protocols, for further improvement of our method through future studies. We anticipate that this index will serve as a quantitative guide in the search for constrained developmental phases or processes.
High Expression MicroRNA-206 Inhibits the Growth of Tumor Cells in Human Malignant Fibrous Histiocytoma
Authors: Li Dejian , Zhao Kai , Zhao Ziwen , Jiang Bo , Gong Xianxu , Zhang Yan , Guo Yingqi , Xiao Han , Wang Ye , Liu Hui , Yi Chengqing , Gu Wenguang
Published: December 2021

Background: Malignant fibrous histiocytoma (MFH) is a common type of soft tissue sarcoma and a serious threat to human health. MFH often relapses locally after the curettage is related to the residual cancer stem cells (CSCs). Currently, the dysregulation of microRNA (miRNA) has been found to be closely related to the recurrence of CSCs. However, whether dysregulations of miRNAs exist in MFH, CSCs remained unknown.

Methods: In this study, miRNAs in MFH CSCs and MFH common cells were examined by gene probe. Then, target genes and their functions involved in the signal pathway were predicted by the relevant database. Finally, the miRNAs’ target regulatory network was constructed. Furthermore, the miRNAs and target genes were identified by quantitative polymerase chain reaction, whereas miRNA analogs and antagonists were transfected in tumor cells to investigate cell proliferation ability further.

Results: Results showed that a total of 47 miRNAs were found, including 16 that were upregulated and 31 that were downregulated. The screened differential miRNA showed a different expression in the cell resistant strains compared with the control group. Quantitative polymerase chain reaction analysis confirmed that the relative abundance of seven miRNAs and four target genes varied significantly. The encouraging issue is that we found Hsa-miR-206 significantly inhibited MFH proliferative activity.

Conclusion: Hsa-miR-206 played a key role in regulating MFH CSC properties that might be a representative marker and target for the diagnosis and treatment of MFH in the future.
Therapeutic Effect of Schistosoma japonicum Cystatin on Atherosclerotic Renal Damage
Authors: Yang Huijuan , Li Hongqi , Chen Weidong , Mei Zhijie , Yuan Yuan , Wang Xiaoli , Chu Liang , Xu Yu , Sun Yan , Li Dingru , Gao Hongyu , Zhan Bin , Li Huihui , Yang Xiaodi
Published: December 2021

Atherosclerosis is a chronic inflammation of the arterial vessel wall driven by lipid metabolism disorders. Although helminthic infection and their derivatives have been identified to attenuate the chronic inflammatory diseases, the immunomodulatory effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) on metabolic diseases and atherosclerosis has not been reported. In this study, we investigated the therapeutic efficacy of rSj-Cys on atherosclerotic renal damage and explored the related immunological mechanism. The results demonstrated that treatment with rSj-Cys significantly reduced body weight gain, hyperlipidemia, and atherosclerosis induced by the high-fat diet in apoE–/– mice. The treatment of rSj-Cys also significantly improved kidney functions through promoting macrophage polarization from M1 to M2, therefore inhibiting M1 macrophage–induced inflammation. The possible mechanism underlying the regulatory effect of rSj-Cys on reducing atherosclerosis and atherosclerotic renal damage is that rSj-Cys stimulates regulatory T cell and M2 macrophage polarization that produce regulatory cytokines, such as interleukin 10 and transforming growth factor β. The therapeutic effect of rSj-Cys on atherosclerotic renal damage is possibly through inhibiting the activation of TLR2/Myd88 signaling pathway. The results in this study provide evidence for the first time that Schistosoma-derived cystatin could be developed as a therapeutic agent to treat lipid metabolism disorder and atherosclerosis that threats million lives around the world.
Combined Metallomics/Transcriptomics Profiling Reveals a Major Role for Metals in Wound Repair
Authors: Wilkinson Holly N. , Guinn Barbara-Ann , Hardman Matthew J.
Published: December 2021

Endogenous metals are required for all life, orchestrating the action of diverse cellular processes that are crucial for tissue function. The dynamic wound healing response is underpinned by a plethora of such cellular behaviours, occurring in a time-dependent manner. However, the importance of endogenous metals for cutaneous repair remains largely unexplored. Here we combine ICP-MS with tissue-level RNA-sequencing to reveal profound changes in a number of metals, and corresponding metal-regulated genes, across temporal healing in mice. Wound calcium, magnesium, iron, copper and manganese are elevated at 7 days post-wounding, while magnesium, iron, aluminium, manganese and cobalt increase at 14 days post-wounding. At the level of transcription, wound-induced pathways are independently highly enriched for metal-regulated genes, and vice versa. Moreover, specific metals are linked to distinct wound-induced biological processes and converge on key transcriptional regulators in mice and humans. Finally, we reveal a potential role for one newly identified transcriptional regulator, TNF, in calcium-induced epidermal differentiation. Together, these data highlight potential new and diverse roles for metals in cutaneous wound repair, paving the way for further studies to elucidate the contribution of metals to cellular processes in the repair of skin and other tissues.
Colon Cancer-Related Genes Identification and Function Study Based on Single-Cell Multi-Omics Integration
Authors: Sun Xuepu , Guo Yu , Zhang Yu , Zhao Peng , Wang Zhaoqing , Wei Zheng , Qiao Haiquan
Published: December 2021

Transcriptomes and DNA methylation of colon cancer at the single-cell level are used to identify marker genes and improve diagnoses and therapies. Seven colon cancer subtypes are recognized based on the single-cell RNA sequence, and the differentially expressed genes regulated by dysregulated methylation are identified as marker genes for different types of colon cancer. Compared with normal colon cells, marker genes of different types show very obvious specificity, especially upregulated genes in tumors. Functional enrichment analysis for marker genes indicates a possible relation between colon cancer and nervous system disease, moreover, the weak immune system is verified in colon cancer. The heightened expression of markers and the reduction of methylation in colon cancer promote tumor development in an extensive mechanism so that there is no biological process that can be enriched in different types.
Oncolytic Virotherapy: From Bench to Bedside
Authors: Yang Ludi , Gu Xiang , Yu Jie , Ge Shengfang , Fan Xianqun
Published: December 2021

Oncolytic viruses are naturally occurring or genetically engineered viruses that can replicate preferentially in tumor cells and inhibit tumor growth. These viruses have been considered an effective anticancer strategy in recent years. They mainly function by direct oncolysis, inducing an anticancer immune response and expressing exogenous effector genes. Their multifunctional characteristics indicate good application prospects as cancer therapeutics, especially in combination with other therapies, such as radiotherapy, chemotherapy and immunotherapy. Therefore, it is necessary to comprehensively understand the utility of oncolytic viruses in cancer therapeutics. Here, we review the characteristics, antitumor mechanisms, clinical applications, deficiencies and associated solutions, and future prospects of oncolytic viruses.
Feasibility Study of Vacuum Pressure Swing Adsorption for CO2 Capture From an SMR Hydrogen Plant: Comparison Between Synthesis Gas Capture and Tail Gas Capture
Authors: Chen Yan , Ahn Hyungwoong
Published: December 2021

In this paper, a feasibility study was carried out to evaluate cyclic adsorption processes for capturing CO2 from either shifted synthesis gas or H2 PSA tail gas of an industrial-scale SMR-based hydrogen plant. It is expected that hydrogen is to be widely used in place of natural gas in various industrial sectors where electrification would be rather challenging. A SMR-based hydrogen plant is currently dominant in the market, as it can produce hydrogen at scale in the most economical way. Its CO2 emission must be curtailed significantly by its integration with CCUS. Two Vacuum Pressure Swing Adsorption (VPSA) systems including a rinse step were designed to capture CO2 from an industrial-scale SMR-based hydrogen plant: one for the shifted synthesis gas and the other for the H2 PSA tail gas. Given the shapes of adsorption isotherms, zeolite 13X and activated carbon were selected for tail gas and syngas capture options, respectively. A simple Equilibrium Theory model developed for the limiting case of complete regeneration was taken to analyse the VPSA systems in this feasibility study. The process performances were compared to each other with respect to product recovery, bed productivity and power consumption. It was found that CO2 could be captured more cost-effectively from the syngas than the tail gas, unless the desorption pressure was too low. The energy consumption of the VPSA was comparable to those of the conventional MDEA processes.
Electrochemical Ammonia: Power to Ammonia Ratio and Balance of Plant Requirements for Two Different Electrolysis Approaches
Authors: Allen Jessica , Panquet Sebastien , Bastiani Adrian
Published: December 2021

Electrochemical ammonia generation allows direct, low pressure synthesis of ammonia as an alternative to the established Haber-Bosch process. The increasing need to drive industry with renewable electricity central to decarbonisation and electrochemical ammonia synthesis offers a possible efficient and low emission route for this increasingly important chemical. It also provides a potential route for more distributed and small-scale ammonia synthesis with a reduced production footprint. Electrochemical ammonia synthesis is still early stage but has seen recent acceleration in fundamental understanding. In this work, two different ammonia electrolysis systems are considered. Balance of plant (BOP) requirements are presented and modelled to compare performance and determine trade-offs. The first option (water fed cell) uses direct ammonia synthesis from water and air. The second (hydrogen-fed cell), involves a two-step electrolysis approach firstly producing hydrogen followed by electrochemical ammonia generation. Results indicate that the water fed approach shows the most promise in achieving low energy demand for direct electrochemical ammonia generation. Breaking the reaction into two steps for the hydrogen fed approach introduces a source of inefficiency which is not overcome by reduced BOP energy demands, and will only be an attractive pathway for reactors which promise both high efficiency and increased ammonia formation rate compared to water fed cells. The most optimised scenario investigated here with 90% faradaic efficiency (FE) and 1.5 V cell potential (75% nitrogen utilisation) gives a power to ammonia value of 15 kWh/kg NH3 for a water fed cell. For the best hydrogen fed arrangement, the requirement is 19 kWh/kg NH3. This is achieved with 0.5 V cell potential and 75% utilisation of both hydrogen and nitrogen (90% FE). Modelling demonstrated that balance of plant requirements for electrochemical ammonia are significant. Electrochemical energy inputs dominate energy requirements at low FE, however in cases of high FE the BOP accounts for approximately 50% of the total energy demand, mostly from ammonia separation requirements. In the hydrogen fed cell arrangement, it was also demonstrated that recycle of unconverted hydrogen is essential for efficient operation, even in the case where this increases BOP energy inputs.