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1.
Computer Systems Science and Engineering ; 44(3):2501-2519, 2023.
Article in English | Scopus | ID: covidwho-2026579

ABSTRACT

New information and communication technologies (ICT) are being applied in various industries to upgrade the value of the major service items. Moreover, data collection, storage, processing, and security applications have led to the creation of an interrelated ICT environment in which one industry can directly influence the other. This is called the "internet of blended environments" (IoBE), as it is an interrelated data environment based on internet-ofthings collection activities. In this environment, security incidents may increase as size and interconnectivity of attackable operations grow. Consequently, preemptive responses to combined security threats are needed to securely utilize IoBE across industries. For example, the medical industry has more stringent information protection measures than other industries. Consequently, it has become a major target of attackers, as more clinician-patient interactions occur over the internet owing to COVID-19. Therefore, this study aims to acquire security for IoBE while focusing on the medical industry. Among the various types of medical ICT services, this study analyzes data flow and potential security threats from the e-prescription lifecycle perspective, which is highly utilized, strongly data-centric, and has numerous security issues. Based on our analysis, we propose a secure authentication and data-sharing scheme. © 2023 CRL Publishing. All rights reserved.

2.
Sustainability ; 14(17):11081, 2022.
Article in English | ProQuest Central | ID: covidwho-2024219

ABSTRACT

The aging population and the increasing number of sub-healthy people in all age groups in China have brought huge opportunities for related industries. From the perspective of marketing and consumer psychology, there is a great demand for health care properties, especially those that provide long-term medical care. Against this situation, almost all the leading real estate companies have entered this field and tried to occupy more market shares through different products and brand marketing sustainably. In this context, it is urgent to explore a comprehensive community model combining medical and nursing care that covers all stages of life, so as to promote the health of diverse populations. In China, existing research on the growth of medical care communities for sustainable needs started relatively late, and insufficient attention has been paid to the supply–demand linkage among psychological demand, health behavior, spatial bearing, and service supply. Taking Wuzhishan city for example, we deduce the Medical-Care Maslow’s Hierarchy of Needs System according to classical theories. Based on motivation theory and marketing strategy, a theoretical model of Health demand-behavior-facilities and Spatial Interaction (HBSI) mediated by healthy behavior is constructed. Then, expert group decision making processes and the Fuzzy Delphi Method (DFM) were used to screen 67 spatial impact factors of 14 categories in five dimensions, including life safety, physical health, mental health, social adaptation and resilience recovery, which fit users’ multi-dimensional health needs. Finally, to provide a spatial strategy reference for the construction of sustainable and adaptive medical caring communities, spatial planning strategies and guidelines are offered based on correlation analysis, so as to fit the changeable market pattern, meet the psychological expectations and life-cycle caring needs of consumers.

3.
Sustainability ; 14(17):10658, 2022.
Article in English | ProQuest Central | ID: covidwho-2024190

ABSTRACT

Decarbonization of the aviation sector is crucial to reaching the global climate targets. We quantified the environmental impacts of Power-to-Liquid kerosene produced via Fischer-Tropsch Synthesis from electricity and carbon dioxide from air as one broadly discussed alternative liquid jet fuel. We applied a life-cycle assessment considering a well-to-wake boundary for five impact categories including climate change and two inventory indicators. Three different electricity production mixes and four different kerosene production pathways in Germany were analyzed, including two Direct Air Capture technologies, and compared to fossil jet fuel. The environmental impacts of Power-to-Liquid kerosene varied significantly across the production pathways. E.g., when electricity from wind power was used, the reduction in CO2-eq. compared to fossil jet fuel varied between 27.6–46.2% (with non-CO2 effects) and between 52.6–88.9% (without non-CO2 effects). The reduction potential regarding CO2-eq. of the layout using low-temperature electrolysis and high-temperature Direct Air Capture was lower compared to the high-temperature electrolysis and low-temperature Direct Air Capture. Overall, the layout causing the lowest environmental impacts uses high-temperature electrolysis, low-temperature Direct Air Capture and electricity from wind power. This paper showed that PtL-kerosene produced with renewable energy could play an important role in decarbonizing the aviation sector.

4.
Sustainability ; 14(17):10478, 2022.
Article in English | ProQuest Central | ID: covidwho-2024172

ABSTRACT

A considerable amount of construction and demolition wood waste (CDWW) is generated, mostly landfilled, contributing to severe environmental effects. The management of CDWW is a significant challenge as it is a hazardous contaminated waste. In this context, the circular economy (CE) concept is a solution as it comprises waste minimisation and efficient recovery of resources. Although much research is found in the literature on CDWW end-of-life management, research on CE implementation considering every life cycle stage is still scarce. In this review, we endeavour to integrate CE in CDWW to identify the waste management strategies involved in the life cycle phases. The databases were searched from 2009 to 2020 and were analysed using CiteSpace version 5.7.R1 software. Forty-nine articles were identified, and the six life cycle stages were explored. The analysis shows that CE for wood waste is essential and has greater growth potential. While the LCA studies are limited to environmental viewpoints, combining economic and social perspectives is necessary for sustainable development. Overall, based on the research findings, a theoretical framework was proposed. This study, as a consequence, promotes the application of recycled wood into multiple valuable products and thus encourages waste management to boost CE and sustainability.

5.
Sustainability ; 14(16):10314, 2022.
Article in English | ProQuest Central | ID: covidwho-2024154

ABSTRACT

Sustainable building practices are a response to environmental issues. Businesses and industries are assessing how their activities affect the environment. The architecture, engineering and construction (AEC) industries have significant impacts on the environment and economy, while the industry is considered one of the largest contributors to greenhouse gas (GHG) emissions and has, therefore, been highlighted by researchers as a key area of intervention with a great potential to reduce environmental impacts. This paper critically reviews and evaluates the current state of sustainable building certification systems with the purpose of having a good understanding of the status quo and possibilities for future directions in Saudi Arabia. It reviews the academic literature on Saudi Arabia’s green/sustainable building codes, standards, certification systems, methods and tools. It starts by addressing sustainability in the broadest sense. Then, it investigates sustainability strategies and evaluates the building certification systems in Saudi Arabia, followed by an introduction to the new practice of sustainable healthcare building assessment. Life cycle assessment (LCA) and building information modelling (BIM) techniques have also been investigated. The paper introduces the updated Saudi Building Code (SBC) with further evaluation of the Saudi Green Building Code (SBC 1001-CR). Finally, the paper clearly highlights the key role of sustainable building practices and the need to develop a certification system that considers the new trends and the local context.

6.
10th International Conference on Sustainable Tourism, ST 2022 ; 256(2022):109-120, 2022.
Article in English | Scopus | ID: covidwho-2022486

ABSTRACT

Department of Business and Administration, University of Cantabria, Spain Sustainable tourism should be promoted as a new system for the sustainable management of resources from a socioeconomic and environmental point of view. For this purpose, it is necessary to develop a tool capable of assessing the impacts associated with each of the stages of the sector and to identify which actions are currently being addressed in the tourism sector in order to achieve the desired sustainability in the sector. This timely study aims to describe the current framework of life cycle assessment (LCA) and its application to the tourism sector. To address these questions, the geographical distribution, the temporal evolution of the publications, as well as the most relevant characteristics of the tourism industry articles were evaluated such as the functional unit and system boundaries considered. The study identifies key recommendations on the progression of LCA for this increasingly important sustaining tourism sector. As important results, it stands out that 94% of articles focused on LCA methodology were from the last decade and almost 26% of the articles reviewed cover sustainable tourism term, considering environmental, social and economic aspects. Specifically, LCA is a highly effective tool capable of assessing direct and indirect carbon emissions at all stages of the activity as well as the socioeconomic and environmental impacts generated in the tourism sector. This review showed that the most common environmental indicator in the LCA methodology is the carbon footprint. COVID-19 pandemic is also an object of discussion in the framework of the sustainable tourism together with advocating support for the eco-labelling and digitalisation of the tourism experiences as valuable tools to minimize environmental negativities, to promote mechanisms to access green markets and to frame successful synergies. © 2022 WIT Press.

7.
Journal of Safety Science and Resilience ; 3(4):321-329, 2022.
Article in English | Scopus | ID: covidwho-2015727

ABSTRACT

Herein, a matching method for varied epidemic phase characteristics and appropriate strategies is presented, aiming at the complexities of the novel coronavirus disease 2019 pandemic and the hysteresis of strategies. The classical diffusion dynamic models of the epidemic spread are compared. Furthermore, the Bass diffusion model is selected to study more characteristics of an epidemic, such as the diversities in regional internal and external infection rates. Thereafter, the classical division method vis-à-vis a pandemic life cycle is improved. A specific approach is proposed to portray more detailed characteristics of the pandemic by dividing it into more phases. Next, a four-level epidemic prevention and control measure system is concretized. The applicable phases and strategic effectiveness of each measure are integrated into the different phases of the pandemic life cycle. Finally, the matching method is applied to analyze two cases of the spread of the outbreak in cities and significant events. The findings provide a certain reference for the effectiveness of the matching method in the post-peak epidemic period. © 2022

8.
Journal of Commercial Biotechnology ; 27(1):181-189, 2022.
Article in English | EMBASE | ID: covidwho-2010466

ABSTRACT

In order to solve the problem of high energy consumption caused by unable to extract color space parameters in multimedia resource compression and transmission algorithm, the application of virtual reality technology in multimedia resource compression and transmission algorithm is studied. The pixels are classified according to labeled and unlabeled, the multimedia resource allocation strategy is established, the resource target area is extracted by virtual reality technology, and the over segmentation is controlled to a small extent, so as to control the quality of resources. In order to reduce the number of data transmission and reception in the process of data aggregation in the network, a transmission signal reconstruction model is constructed, and the data is compressed and encoded. A compression transmission algorithm is designed, which uses compressed sensing and network coding to reduce the amount of data transmission. The experimental results demonstrate that the energy consumption of the compression transmission algorithm proposed in this work increases the single hop distance with the slowest rate and is also the least energy-intensive. Taking the bit rate of 0.25bpp as an example, the maximum energy consumption of the algorithm is 3.89J, which is 4.97J and 2.45J less than the direct transmission algorithm and the centralized compression transmission algorithm, respectively. Therefore, the algorithm can reduce energy consumption and prolong the life cycle of transmission network.

9.
Annals of the Rheumatic Diseases ; 81:590, 2022.
Article in English | EMBASE | ID: covidwho-2008867

ABSTRACT

Background: SB5, an adalimumab (ADL) biosimilar, was developed in a low-concentration (40 mg/0.8 mL, SB5-LC) aligned with the reference ADL product. Pharmacokinetics (PK) equivalence of SB5 and reference ADL was demonstrated in a Phase I study conducted in healthy subjects1. Equivalent efficacy and comparable safety between 40 mg/0.8 mL SB5 and 40 mg/0.8 mL reference ADL were demonstrated in a Phase III study conducted in patients with rheumatoid arthritis2. High-concentration, low-volume, citrate-free SB5 (40 mg/0.4 mL, SB5-HC) has been developed as a part of life cycle management in line with the reference ADL formulation. Objectives: To compare the PK, safety, and tolerability of the newly developed SB5-HC (40 mg/0.4 mL) to prior SB5-LC (40 mg/0.8 mL) in healthy male subjects. Methods: This study was a randomised, single-blind, two-arm, parallel group, single-dose study in healthy male subjects. Subjects were randomised in a ratio of 1:1 to receive a single dose of either SB5-HC or SB5-LC by subcutaneous injection on Day 1 and then observed for 57 days during which the PK, safety, and immunogenicity were evaluated. The serum concentration of ADL was measured using an enzyme-linked immunosorbent assay. The primary PK parameters were area under the concentration-time curve from time zero to infnity (AUCinf) and maximum serum concentration (Cmax). Equivalence for the primary PK parameters was to be concluded if the 90% confdence intervals (CIs) for the ratio of geometric least squares means (LSMeans) of the treatment groups compared were completely contained within the pre-defned equivalence margin of 0.80 to 1.25 using an analysis of variance. Results: Of 188 randomised subjects, 187 subjects were analysed as PK Analysis Set (PKS) (n=93 in SB5-HC and n=94 in SB5-LC). One subject was excluded from the PKS in SB5-HC group (major protocol deviation for not being withdrawn in the event of confrmed COVID-19). The geometric LSMeans ratios for the comparison of SB5-HC and SB5-LC for AUCinf and Cmax were 0.920 and 0.984, respectively, and the corresponding 90% CIs were within the pre-defned equivalence margin of 0.80 to 1.25 (Table 1), indicating the two treatment groups are bioequivalent. There were no deaths, serious adverse events or discontinuation of the study due to treatment-emergent adverse events (TEAEs) during the study. The proportions of subjects who experienced TEAEs were comparable between the two treatment groups (44.7% in SB5-HC vs 51.1% in SB5-LC). The most frequent TEAEs were headache (10.6% in SB5-HC vs 12.8% in SB5-LC). Conclusion: This study demonstrated PK equivalence between SB5-HC and SB5-LC in healthy subjects. Both SB5-HC and SB5-LC were generally well tolerated with similar safety profiles.

10.
Zeitschrift fur Rheumatologie ; 2022.
Article in German | EMBASE | ID: covidwho-2007138

ABSTRACT

The introduction of the term reactive arthritis (ReA) for the joint inflammation observed after infection with Yersinia enterocolitica, in which “a causative pathogen cannot be isolated from the synovial fluid”, and the association with the HLA-B27 were the historical milestones for a new classification and assignment to the spondylarthritides (SpA). The division into postinfectious and reactive arthritis proposed in 1976 was put into perspective in the 1990s because of investigations with the newly available molecular biological method of the polymerase chain reaction. Microbial products could be identified from joint samples of patients with ReA. Therefore, it was proposed to abandon the distinction between the two groups of diseases and to prefer the term ReA for both. This created a terminological and nosological issue. On the one hand, there are generally accepted classification and diagnostic criteria for the classical HLA-B27-associated ReA that are assigned to SpA. On the other hand, an increasing number of bacterial pathogens, viruses, amoebas, helminths as well as antiviral and antibacterial vaccinations are described as triggers of arthritis, which have been published under the term ReA. Since the beginning of the SARS-CoV‑2 pandemic, cases of acute post-COVID-19 arthritis have been described, which were also classified as ReA because of comparable clinical features.

11.
Sustain Prod Consum ; 33: 271-282, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2000712

ABSTRACT

During the COVID-19 pandemic, different strategies emerged to combat shortages of certified face masks used in the healthcare sector. These strategies included increasing production from the original manufacturing sites, commissioning new production facilities locally, exploring and allowing the reuse of single-use face masks via various decontamination methods, and developing reusable mask alternatives that meet the health and safety requirements set out in European Standards. In this article, we quantify and evaluate the life-cycle environmental impacts of selected mask options available for use by healthcare workers in the UK, with the objective of supporting decision- and policy-making. We investigate alternatives to traditional single-use face masks like surgical masks and respirators (or FFP3 masks), including cloth masks decontaminated in washing machines; FFP3 masks decontaminated via vapour hydrogen peroxide, and rigid half masks cleaned with antibacterial wipes. Our analysis demonstrates that: (1) the reuse options analysed are environmentally preferential to the traditional "use then dispose" of masks; (2) the environmental benefits increase with the number of reuses; and (3) the manufacturing location and the material composition of the masks have great influence over the life-cycle environmental impacts of each mask use option, in particular for single-use options.

12.
IOP Conference Series : Earth and Environmental Science ; 718, 2021.
Article in English | CAB Abstracts | ID: covidwho-1998231

ABSTRACT

This proceedings contains 96 papers on ocean biodiversity;breeding, reproduction, feeding and diseases of aquacultured fish and shellfish;water quality;fishery management, seafood preservation and quality;aquaculture and fishery economics and the impact of COVID-19 on aquaculture and fishery production.

13.
Sustainability ; 14(15):8984, 2022.
Article in English | ProQuest Central | ID: covidwho-1994146

ABSTRACT

The main topics of this Special Issue include the following: (i) building management, (ii) building costs, (iii) mass appraisal methods, (iv) econometric models, (v) real estate risk management, (vi) economic valuation of real estate investment projects, (vii) real estate market, (viii) social housing, (ix) urban economics, (x) land, (xi) transport economics, (xii) real estate economics and finance, (xiii) sustainable building transformations and economic effects on environment, (xiv) green buildings, (xv) resilient cities, (xvi) COVID-19 pandemic and (xvii) Environmental, Social and Governance (ESG). [...]the universities or research institutes affiliations to which the Authors belong are distributed throughout the world: in the Europe the authors come from Spain, France, Portugal, Netherland, Germany, Belgium, United Kingdom, Poland, and Hungary;in Asia from China, Korea, Russia, Malaysia, and United Arab Emirates;in South America from Colombia and Chile;in Africa from Ghana;and in Oceania from Australia. In particular, in the study the central role played by public-private partnership (PPP) to combine the competencies of the public sector and both the financial and managerial commitment of the private entities in the process of delivering infrastructure, to fulfilling social and economic needs, to rise the quality of life, and to support sustainable development, is recognized and, then, a conceptual model for the identification and classification of stakeholders in this projects typology, is developed and tested [5]. By selecting a single-story 3D-printed house in the United Arab Emirates, the authors implement the life cycle assessment (LCA) framework to quantify the environmental loads of raw materials extraction and manufacturing, as well as energy consumption during construction and operation phases;the authors also identify the economics of the selected structural systems through life cycle costing analysis (LCCA).

14.
Applied Sciences ; 12(15):7534, 2022.
Article in English | ProQuest Central | ID: covidwho-1993921

ABSTRACT

In order to cope with the changing era of the innovative management paradigm of the manufacturing industry, it is necessary to advance the construction of smart factories in the domestic manufacturing industry, and in particular, the 3D design and manufacturing content sector is highly growthable. In particular, the core technologies that enable digital transformation VR (Virtual Reality)/AR (Augmented Reality) technologies have developed rapidly in recent years, but have not yet achieved any particular results in industrial engineering. In the manufacturing industry, digital threads and collaboration systems are needed to reduce design costs that change over and over again due to the inability to respond to various problems and demands that should be considered when designing products. To this end, we propose a VR/AR collaboration model that increases efficiency of manufacturing environments such as inspection and maintenance as well as design simultaneously with participants through 3D rendering virtualization of facilities or robot 3D designs in VR/AR. We implemented converting programs and middleware CPS (Cyber Physical System) servers that convert to BOM (Bill of Material)-based 3D graphics models and CPS models to test the accuracy of data and optimization of 3D modeling and study their performance through robotic arms in real factories.

15.
International Journal of Production Research ; 2022.
Article in English | Scopus | ID: covidwho-1984636

ABSTRACT

Food supply chains hold significant embodied carbon emissions that need to be mitigated and neutralized. This study aimed to explore the historical Greenhouse Gas (GHG) emissions associated with household food consumption at a local scale i.e. across the eight English regions and the four nations that comprise the United Kingdom (UK). UK EatWell guidelines were used to explore the potential change in emissions and food costs in a scenario of transitions to healthier diets across the study areas. These emissions were calculated based on food consumption data before the advent of the Covid-pandemic i.e. between the years 2001 and 2018. Spatial data analysis was used to explore if the study areas had any significant correlations with respect to the emissions during the study period. The results displayed a potential reduction in GHG emissions for all study areas in the explored scenario. Further impacts include a reduction in household food costs across a majority of the areas during the study period. However, a consistent trend of significant correlations among the study areas was absent. This study concludes that local or regional policymaking should take precedence over national regulations to achieve healthier diets that are both carbon-neutral and affordable for the households. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

16.
Energy Science & Engineering ; 10(8):2930-2939, 2022.
Article in English | ProQuest Central | ID: covidwho-1981667

ABSTRACT

Trombe walls figure among many passive devices used in the Mediterranean climate to minimize heating demands in residential buildings. The thickness of this massive wall is a critical parameter that influences the effectiveness of the system. Insufficient wall thickness conducts to an important interior temperature fluctuation, and huge wall thickness will increase costs and thermal resistance. In this paper, the optimum thickness of four different construction materials (concrete, stone, adobe, and brick), which can be used in the Trombe wall, was determined using an energetic and economic analysis. The energetic results with TRNSYS software show that the best materials, which can contribute to a reduction by 50% in heating loads of a single room, are stone and concrete. For the economic analysis, the life cycle cost and the payback period were calculated for each construction material. The results show that the optimum thickness for stone and concrete are, respectively, 34 and 32 cm with a payback period of 2.85 and 2.65 years.

17.
Pharmaceutical and Biomedical Research ; 8(2):101-112, 2022.
Article in English | EMBASE | ID: covidwho-1980474

ABSTRACT

Background: The outbreak of severe acute respiratory syndrome coronavirus-2, also called ‘coronavirus disease 2019’ (COVID-19), first appeared in December 2019 in Wuhan, China. COVID-19 is caused by an enveloped single-stranded RNA virus, which has affected more than 14 million people around the world and caused a high rate of mortality. It is notable that discovering new drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is time-consuming. Therefore, reviewing drugs, which have been previously designed for other purposes can be helpful and effective. Objectives: Studying the effects of previously approved drugs is important;thus, in this article, we reviewed studies on proposed drugs against COVID-19. Methods: The articles and information were collected from Google Scholar, ScienceDirect, and Scopus databases. We did our research based on keywords, like “therapeutics”, “pharmacology”, “Coronavirus”, “COVID-19”, “SARS”, and “MERS-CoV”. We also applied some filters, such as title/, and ignored factors that could lead to bias and selective selection. Results: There is currently no cure for coronavirus, and most treatments have been effective to relieve symptoms. The treatment methods and drugs addressed in this article are chosen either from previous drugs against MERS and SARS, drugs that disrupt the life cycle of the coronavirus, or drugs that have been reviewed in retrospective studies and clinical trials. Conclusion: Prevention and treatment of COVID-19 remain a challenge, in particular for coronavirus and the treatments based on boosting the immune system and preventing virus replication. Epidemiological studies have shown that COVID-19 and SARS-COV transmission are relatively similar. This can help to select the appropriate drug. Thus, anti-inflammatory and antiviral drugs, such as remdesivir are used. Antimalarial drugs, such as hydroxychloroquine (HCQ) and chloroquine (CQ) along with estrogen receptor inhibitors, such as toremifene citrate, which has shown effective results against SARS and MERS, can influence the treatment process. However, more clinical trials are needed to determine the efficacy and side effects of drugs

18.
Sustainable Cities and Society ; 85:15, 2022.
Article in English | Web of Science | ID: covidwho-1977817

ABSTRACT

Shared micromobillity has been extensively developed globally in the past few decades, but its impact on the environment remains unclear. This study quantitatively estimates the effects of global shared micromobillity programs on greenhouse gas (GHG) emissions using a life cycle assessment (LCA) perspective. Specifically, it takes major countries and cities around the world as examples to empirically analyze the impact of station-based bike-sharing (SBBS), free-floating bike-sharing (FFBS), free-floating e-bike sharing (FFEBS), and free-floating escooter sharing (FFESS) programs on the GHG emissions of urban transportation. The results show that, with the exception of SBBS, the other shared micromobillity programs have not achieved desirable GHG emissions reduction benefits. Contrarily to subjective expectations, although the rapid progress of technology in recent years has promoted the vigorous development of shared micromobility, it has brought negative impacts on the GHG emissions rather than the positive benefits claimed by related promoters and operators. The overcommercialization and low utilization rate makes shared micromobility more likely to be an environmentallyunfriendly mode of transportation. In addition, the regional differences in mode choice, operational efficiency, fleet scale, and market potential of shared micromobility and the corresponding impacts on GHG emissions vary greatly. Therefore, authorities should formulate appropriate shared micromobility plans based on the current conditions and goals of the region. This empirical study helps to better understand the environmental impact of the global shared micromobility program and offers valuable references for improving urban sustainability.

19.
Resour Conserv Recycl ; 186: 106509, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1976392

ABSTRACT

The COVID-19 pandemic has changed people's habits, causing them to use large amounts of disposable items and exacerbating the already existing issue of pollution. One way to reduce the environmental impact of this shift in daily habits is to recycle these items, e.g. surgical masks that are the most common personal protective equipment against the virus, to produce panels for building applications. In this work, both the thermal and acoustical performance of such panels are evaluated using a small and a large scale investigation under real-world conditions. Small scale thermal tests are performed by means of the Hot Disk instrument while the acoustic investigations are performed by means of the impedance tube. Large scale tests are carried out in a reverberation chamber assessing both the heat flow passing through the wall and the acoustic absorption coefficient of the panels. Finally, the environmental impact of the innovative recycled panel is also investigated in a life cycle perspective. Overall, the material behavior scored well on these tests, suggesting that the proposed approach may be a good recycling method.

20.
FEBS Open Bio ; 12:287, 2022.
Article in English | EMBASE | ID: covidwho-1976659

ABSTRACT

The global pandemic prompted by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has already caused more than 6 million deaths worldwide, calling for urgent effective therapeutic measures. A deep understanding of the mechanisms involved in viral replication is required. Among the nonstructural proteins (nsps) encoded by SARS-CoV-2 genome, there is the nsp14 ribonuclease, the main object of study in this work. Ribonucleases are key factors in the control of all biological processes, ensuring maturation, degradation, and quality control of all types of RNAs. Nsp14 is a bifunctional protein, holding a 3'- 5' exoribonucleolytic activity (ExoN) in the N-terminal domain, stimulated through the interaction with nsp10, and a C-terminal N7-methyltransferase activity (MTase). Both are critical for the coronavirus life cycle. In this work, we provide a complete biochemical characterization of SARS-CoV-2 nsp14-nsp10, addressing several aspects of the complex for the first time. Moreover, using a homology model, we have identified residues involved in the nsp14-nsp10 interaction that were extensively studied. We have confirmed the SARS-CoV-2 nsp14 dual function and we have shown that both ExoN and MTase activities are functionally independent. We demonstrate that the nsp14 MTase activity is independent of nsp10, contrarily to nsp14 ExoN that is upregulated in the presence of the cofactor. Additionally, our results show that the ExoN motif I has a prominent role on the ribonucleolytic activity of SARS-CoV-2 nsp14, contrasting to what was previously observed in other coronaviruses, which can be related to the pathogenesis of SARS-CoV-2. The knowledge provided in this work can serve as a basis to design effective drugs that target the pinpointed residues in order to disturb the complex assembly and affect the viral replication, ultimately, treating COVID-19 and other CoV infections.

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