搜索结果：Computational and structural biotechnology journal

Lipases have received great attention as industrial biocatalysts in areas like oils and fats processing, detergents, baking, cheese making, surface cleaning, or fine chemistry [1Schmidt RD Verger R Lipases: Interfacial enzymes with attractive applications.Angew Chem Int Edit. 1998; 37: 1608-1633Crossref PubMed Google Scholar, 2Villeneuve P Muderhwa JM Graille J Haas MJ Customizing lipases for biocatalysis: a survey of chemical, physical and molecular biological approaches.Journal of Molecular Catalysis B-Enzymatic. 2000; 9: 113-148Crossref Scopus (459) Google Scholar]. They can catalyse reactions of insoluble substrates at the lipid-water interface, preserving their catalytic activity in organic solvents [3Patel MT Nagarajan R Kilara A Lipase-catalyzed biochemical reactions in novel media: A review.Chemical Engineering Communications. 1996; 152–53: 365-404Crossref Scopus (27) Google Scholar]. This makes of lipases powerful tools for catalysing not only hydrolysis, but also various reverse reactions such as esterification, transesterification, aminolysis, or thiotransesterifications in anhydrous organic solvents [4Patel RN Biocatalytic synthesis of intermediates for the synthesis of chiral drug substances.Curr Opin Biotechnol. 2001; 12: 587-604Crossref PubMed Scopus (133) Google Scholar, 5Gupta R Gupta N Rathi P Bacterial lipases: an overview of production, purification and biochemical properties.Applied Microbiology and Biotechnology. 2004; 64: 763-781Crossref PubMed Scopus (876) Google Scholar]. Moreover, lipases catalyse reactions with high specificity, regio and enantioselectivity, becoming the most used enzymes in synthetic organic chemistry [6Reetz MT Directed evolution as a means to create enantioselective enzymes.Abstracts of Papers American Chemical Society. 2002; 224: 302Google Scholar]. Therefore, they display important advantages over classical catalysts, as they can catalyse reactions with reduced side products, lowered waste treatment costs, and under mild temperature and pressure conditions [7Cambon E Bourlieu C Salum TFC Piombo G Dubreucq E et al.Ability of Vasconcellea heilbornii lipase to catalyse the synthesis of alkyl esters from vegetable oils.Process Biochemistry. 2009; 44: 1265-1269Crossref Scopus (14) Google Scholar]. Accordingly, the use of lipases holds a great promise for green and economical process chemistry [8Antranikian G Bornscheuer UT Liese A Highlights in Biocatalysis.ChemCatChem. 2010; 2: 879-880Crossref Scopus (10) Google Scholar, 9Bornscheuer UT Bessler C Srinivas R Krishna SH Optimizing lipases and related enzymes for efficient application.Trends in Biotechnology. 2002; 20: 433-437Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar]. However, performance of a lipase is not always sufficient for an industrial application [9Bornscheuer UT Bessler C Srinivas R Krishna SH Optimizing lipases and related enzymes for efficient application.Trends in Biotechnology. 2002; 20: 433-437Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar] and most enzymes have sub-optimal properties for processing conditions [10Bommarius A Bommarius-Riebel B Fundamentals of Biocatalysis. Weinheim-Wiley-VCH, 2005Google Scholar]. In fact, there are still disproportionally few examples of commercial scale applications of such biocatalysts in the manufacture of fine chemicals. In order to improve enzyme-mediated process efficiency, two different pathways can be followed: i) fitting the process to the available biocatalyst by medium engineering or modification of the manufacturing system to suit the sensitivities of the biocatalyst [11Luetz S Giver L Lalonde J Engineered enzymes for chemical production.Biotechnol Bioeng. 2008; 101: 647-653Crossref PubMed Scopus (146) Google Scholar], or ii) obtaining better biocatalysts through different strategies that can be run in parallel [9Bornscheuer UT Bessler C Srinivas R Krishna SH Optimizing lipases and related enzymes for efficient application.Trends in Biotechnology. 2002; 20: 433-437Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar]. These strategies (Figure 1) include the exploration of biodiversity to expand the sources and number of new biocatalysts, immobilization of existing enzymes, reaction conditions modification [12Du C Zhao B Li C Wang P Wang Z et al.Improvement of the enantioselectivity and activity of lipase from Pseudomonas sp. via adsorption on a hydrophobic support: kinetic resolution of 2-octanol.Biocatalysis and Biotransformation. 2009; 27: 340-347Crossref Scopus (15) Google Scholar, 13Tian R Yang CH Wei XF Xun EN Wang R et al.Optimization of APE1547-catalyzed Enantioselective Transesterification of (R/S)-2-methyl-1-butanol in an Ionic Liquid.Biotechnology and Bioprocess Engineering. 2011; 16: 337-342Crossref Scopus (17) Google Scholar], or the proper modification of these biocatalysts to get the most suitable variant for a defined industrial process [9Bornscheuer UT Bessler C Srinivas R Krishna SH Optimizing lipases and related enzymes for efficient application.Trends in Biotechnology. 2002; 20: 433-437Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar]. In this case the use of rational protein design to improve enzymes for which the 3D structure has been elucidated or homology-modelled [14Henke E Pleiss J Bornscheuer UT Activity of Lipases and esterases towards tertiary alcohols: Insights into structure-function relationships.Angewandte Chemie-International Edition. 2002; 41: 3211Crossref PubMed Scopus (142) Google Scholar], or the use of directed evolution can provide optimal biocatalysts [15Arnold G Methods in Molecular Biology. Methods in Molecular Biology. Humana Press Inc, 2003Google Scholar]. Rational protein design requires both, the availability of the structure of the enzyme and knowledge about the relationship between sequence, structure and mechanism-function. If the structural data of the enzyme are not available, the structure of a homologous enzyme can be used as a model [16Kazlauskas RJ Molecular modeling and biocatalysis: explanations, predictions, limitations, and opportunities.Curr Opin Chem Biol. 2000; 4: 81-88Crossref PubMed Scopus (97) Google Scholar, 17Bornscheuer UT Pohl M Improved biocatalysts by directed evolution and rational protein design.Current Opinion in Chemical Biology. 2001; 5: 137-143Crossref PubMed Scopus (364) Google Scholar]. All this information can be used to identify specific residues that can be mutated in order to improve a specific property, such as substrate specificity or thermal robustness. The selected residues are then targeted for site-directed mutagenesis, and the variant expressed, purified and analyzed for the desired property [17Bornscheuer UT Pohl M Improved biocatalysts by directed evolution and rational protein design.Current Opinion in Chemical Biology. 2001; 5: 137-143Crossref PubMed Scopus (364) Google Scholar, 18Johannes TW Zhao HM Directed evolution of enzymes and biosynthetic pathways.Current Opinion in Microbiology. 2006; 9: 261-267Crossref PubMed Scopus (168) Google Scholar]. In contrast to rational protein design, directed evolution does not rely on a detailed understanding of the relationship between enzyme structure and function. It relies on the darwinian principles of mutation and selection [18Johannes TW Zhao HM Directed evolution of enzymes and biosynthetic pathways.Current Opinion in Microbiology. 2006; 9: 261-267Crossref PubMed Scopus (168) Google Scholar]. In general terms, directed evolution consists on repeated cycles of random mutagenesis (and/or gene recombination) of a target gene, coupled with selection or high-throughput screening for isolation of the functionally improved variants. In this case, enough diversity can be created in the starting gene so that an improvement in the desired property will be represented in a library of variants. Subsequently, screening or selection methods are used to identify these variants, and then they are used as a template for the next generation of mutagenesis and selection [15Arnold G Methods in Molecular Biology. Methods in Molecular Biology. Humana Press Inc, 2003Google Scholar, 19Williams GJ Nelson AS Berry A Directed evolution of enzymes for biocatalysis and the life sciences.Cellular and Molecular Life Sciences. 2004; 61: 3034-3046Crossref PubMed Scopus (60) Google Scholar]. More recent developments have focused on making smaller libraries by using a combination of rational protein design and directed evolution procedures [20Bornscheuer UT Huisman GW Kazlauskas RJ Lutz S Moore JC et the of PubMed Scopus Google Scholar]. These methods use information on enzyme and target specific residues or on the protein in evolution (Figure on this mutagenesis has been used in recent enzyme improvement This to the of at a defined or to the of two or in an enzyme evolution of specificity by mutagenesis of an 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, MT mutagenesis for directed evolution of 2: PubMed Scopus Google Scholar]. In this case the is smaller and to this as a new and efficient for directed evolution of enzymes MT mutagenesis for directed evolution of 2: PubMed Scopus Google Scholar, MT of A of for Chem Int Edit. 2011; PubMed Scopus Google Scholar]. on a of the protein with cycles of mutagenesis at of an this the molecular biological and the screening MT J A et the substrate of by 2006; 12: PubMed Scopus Google Scholar]. rational protein design and directed evolution can be repeated or the biocatalyst with the desired property is Therefore, these protein engineering strategies have as efficient tools to improve properties of enzymes MT mutagenesis for directed evolution of 2: PubMed Scopus Google Scholar, MT J A et the substrate of by 2006; 12: PubMed Scopus Google Scholar, M M et evolution of an from Pseudomonas a with enantioselectivity and activity for the kinetic resolution of a chiral 2006; PubMed Scopus Google Scholar]. More of such procedures have been by that provide high screening methods for G B et of a enantioselective through gene mutagenesis of the American Chemical Society. PubMed Scopus Google Scholar] or for of the properties of different through Directed evolution of specificity by gene 2010; PubMed Scopus Google Scholar]. Moreover, in recent protein design is and attention as a novel to the of on protein or of libraries of enzyme by means of in Engineering for on Biotechnology. PubMed Scopus Google Scholar]. The for the for modification on the of the catalytic property to be improved MT J A et the substrate of by 2006; 12: PubMed Scopus Google Scholar, MT J A mutagenesis on the of B as a for protein Chemie-International Edition. 2006; PubMed Scopus Google Scholar]. the so of biocatalysts a of and can be [20Bornscheuer UT Huisman GW Kazlauskas RJ Lutz S Moore JC et the of PubMed Scopus Google Scholar], as focused libraries the of screening and can that the application conditions [11Luetz S Giver L Lalonde J Engineered enzymes for chemical production.Biotechnol Bioeng. 2008; 101: 647-653Crossref PubMed Scopus (146) Google Scholar, S methods for directed evolution of not Opin Biotechnol. 2004; PubMed Scopus Google Scholar]. In this for chemical manufacturing the target for directed evolution are substrate specificity, and can be improved in a to the process [11Luetz S Giver L Lalonde J Engineered enzymes for chemical production.Biotechnol Bioeng. 2008; 101: 647-653Crossref PubMed Scopus (146) Google Scholar, J MT in to Improved to from PubMed Scopus Google Scholar]. a library to or MT the of an by Directed and 2011; 12: PubMed Scopus Google Scholar] be used as in the of the from the J MT in to Improved to from PubMed Scopus Google Scholar]. a in protein a better understanding of protein structure protein properties and a of the protein engineering is Kazlauskas RJ of protein engineering in protein E Scholar, RJ Bornscheuer UT better protein engineering Chemical Biology. 2009; 5: PubMed Scopus Google Scholar]. this a of tools have been for of the relationship between sequence, structure and of lipases and related the Engineering M Pleiss J The Engineering a and for protein PubMed Scopus Google Scholar], the M M Pleiss J a data system for protein 2006; PubMed Scopus Google Scholar] or the R S R et as a for 2010; PubMed Scopus Google Scholar]. These sequence, structure and information available in like J et 2002; PubMed Scopus Google Scholar], HM et 2002; PubMed Scopus Google Scholar] and tools to identify functionally residues from the and for the design of with improved properties M Pleiss J The Engineering a and for protein PubMed Scopus Google Scholar]. these the of lipases for chemical manufacturing can be in the is a for commercial enzymes, for industrial as thermal is a of enzyme R RN M et al.Improvement of via of from of Molecular Sciences. 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If in the is an for enantioselectivity modification of the the can also to enzyme and a variant of with enantioselectivity in the kinetic resolution of and by mutagenesis to the residues a at the of the of such residues by not only in a variant with enantioselectivity but also with A A J Bornscheuer UT by Engineering in an from Pseudomonas 2009; PubMed Scopus Google Scholar]. knowledge of target enzymes has of strategies in of the a variant of with high enantioselectivity in the kinetic resolution of esters by a mutagenesis the substrate into model structure of residues the substrate A mutagenesis on these obtaining a which that the substrate an activity and enantioselectivity J of the lipase A substrate for enantioselectivity using an of the of of the of PubMed Scopus Google Scholar]. A by and et of lipase of Biology. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar], a the of by from and obtaining enantioselectivity in the kinetic resolution of Moreover, the enantioselectivity of the most variant by directed evolution et of lipase of Biology. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar]. the new not enantioselectivity, the novel on the evolution of lipases for for enzyme improvement are coupled with structure-function knowledge (Figure new rational for enantioselectivity can This the case for esterases at the kinetic resolution of tertiary that only esterases a can tertiary esters and the of the can enantioselectivity [14Henke E Pleiss J Bornscheuer UT Activity of Lipases and esterases towards tertiary alcohols: Insights into structure-function relationships.Angewandte Chemie-International Edition. 2002; 41: 3211Crossref PubMed Scopus (142) Google Scholar, M Pleiss J The Engineering a and for protein PubMed Scopus Google Scholar, J M M C RD engineering and of Molecular Catalysis B-Enzymatic. 2000; Scopus Google Scholar, E Bornscheuer UT RD Pleiss J A Molecular of of by J of Chem 4: Scopus Google Scholar]. to the structure-function data existing on this to from an enzyme towards tertiary into a biocatalyst with enantioselectivity, the for structural data A M R P et of for of 2010; 2: Scopus Google Scholar]. A protein the of by a with enantioselectivity M J R S et the enantioselectivity of for of Molecular Catalysis B 2009; Scopus (15) Google Scholar, B R L Bornscheuer UT enantioselective kinetic resolution of two tertiary using of an from Engineering 20: PubMed Scopus Google Scholar, R S Bornscheuer UT enantioselective synthesis of tertiary using of an from Scopus Google Scholar], an variant with enantioselectivity A M R P et of for of 2010; 2: Scopus Google Scholar]. for enantioselectivity lipase substrate specificity can be with few in the protein sequence, a of such the with the J N M et of a into a lipase by a random Chemie-International Edition. 44: PubMed Scopus Google Scholar]. random mutagenesis only the into a on a the that the mutated a with that a of the enzyme the catalytic to substrates J N M et of a into a lipase by a random Chemie-International Edition. 44: PubMed Scopus Google Scholar]. of protein has information for substrate specificity modification in order to lipases to industrial process on two residues in the substrate and for mutagenesis to the of these on substrate of the a specificity from to that such has a on substrate of the side of to in the substrate on and of and in of and of and 2010; PubMed Scopus Google Scholar]. 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A by and of to a lipase B variant esters with and in library of and in by the with and activity and by directed the only activity the but not This the of in to variants, the high screening Pleiss J Engineering of lipase B for of of Biotechnology. 2010; PubMed Scopus Google Scholar]. the of a number of enzyme improvement have to the lipase variant with the desired the case for a enzyme for which obtaining an in the of provide an and for of such enzyme B P of the lipase and of Pseudomonas to a lipase in Microbiology and Biotechnology. 2010; PubMed Scopus Google Scholar]. that a in Pseudomonas sp. the lipase to the of of MJ et and from Pseudomonas at of lipase in the of the of 2001; PubMed Scopus Google Scholar], to this in to the desired of by random mutagenesis to and the for activity in the of variant C of Pseudomonas sp. and lipases of Scholar], a for a in protein a better understanding of protein structure protein properties and a of the protein engineering be RJ Bornscheuer UT better protein engineering Chemical Biology. 2009; 5: PubMed Scopus Google Scholar]. there is a in protein engineering to design libraries a high of enzyme with in the properties of [11Luetz S Giver L Lalonde J Engineered enzymes for chemical production.Biotechnol Bioeng. 2008; 101: 647-653Crossref PubMed Scopus (146) Google Scholar]. 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For some time now, healthcare has been shifting from treating diseases in hospitals to managing health with the involvement of patients and healthy citizens, while at the same time emphasizing the need for improved quality of care and value creation [1Wolfe A Institute of Medicine Report: Crossing the Quality Chasm: A New Health Care System for the 21st Century, Policy, Politics, & Nursing Practice, 2(3), 233–235, 2001.Google Scholar, 2Evans J.M. Baker G.R. Berta W. Barnsley J. The evolution of integrated health care strategies.Adv Health Care Manag. 2013; 15: 125-161https://doi.org/10.1108/s1474-8231(2013)0000015011Crossref PubMed Google Scholar]. To much extent this transition is enabled but mature technology with successful implementations in the real-world setting. For example, a recent publication reviewed data from more than 2000 studies evaluating telemedicine implementations in the 53 countries of the WHO European region [[3]Saigí-Rubió F. Borges do Nascimento I.J. Robles N. Ivanovska K. Katz C. Azzopardi-Muscat N. Novillo Ortiz D. The current status of telemedicine technology use across the world health organization european region: an overview of systematic reviews.J Med Internet Res. 2022; 24e40877https://doi.org/10.2196/40877Crossref Scopus (14) Google Scholar]. Pooled results show a clear benefit of telemedicine interventions to reduce time to respond, and to reduce unnecessary visits to the hospitals and unnecessary referrals to specialists. Streamlining patient empowerment, using technology amongst else, is also driving the healthcare evolution, thus leading to increasingly more informed patients and individuals who are actively engaged with their health and wellbeing [[4]Dukhanin V. Topazian R. DeCamp M. Metrics and evaluation tools for patient engagement in healthcare organization- and system-level decision-making: a systematic review.Int J Health Policy Manag. 2018; 7: 889-903https://doi.org/10.15171/ijhpm.2018.43Crossref PubMed Scopus (50) Google Scholar]. Another key facilitator is the wide adoption of technology for personal and continuous monitoring of numerous health and disease related parameters, in the hospital, on the go and at the point of care [[5]Nardini C. Osmani V. Cormio P.G. Frosini A. Turrini M. Lionis C. Neumuth T. Ballensiefen W. Borgonovi E. D’Errico G. The evolution of personalized healthcare and the pivotal role of European regions in its implementation.Pers Med. 2021; 18: 283-294https://doi.org/10.2217/pme-2020-0115Crossref PubMed Scopus (28) Google Scholar]. This wealth of health data, collected for the first time in significantly large amounts, can in turn enable meaningful analytics to support personalized risk prediction, timely and correct differential diagnosis, precision therapy, and prognosis and delivery of the right preventive intervention at the opportune moment for each individual. Health care evolution is further driven by the realization of a global underinvestment in health personnel. The ensuing crucial shortage of healthcare workforce which is recorded worldwide overstresses healthcare systems, rendering access to expert personnel and treatment a challenge [[6]Boniol M. Kunjumen T. Nair T.S. Siyam A. Campbell J. Diallo K. The global health workforce stock and distribution in 2020 and 2030: a threat to equity and ‘universal’ health coverage? BMJ.Glob Health. 2022; 7 (0.1136/bmjgh-2022-009316)e009316PubMed Google Scholar]. Given the potential of current technology and the pressing healthcare problems, WHO has identified the integration of new technologies in healthcare as one of the most pressing challenges of the 21st century [[7]Ghebreyesus T.A., WHO urgent health challenges for the next decade, 13 Jan 2020, Retrieved on 25/11/2023 from https://www.who.int/news-room/photo-story/photo-story-detail/urgent-health-challenges-for-the-next-decade.Google Scholar]. Although it may be difficult to predict what future healthcare may look like, there is little doubt that the concept of today’s hospital will be revolutionized by current developments in information technology, entering the era of the smart hospital. Although the term appears in scientific literature around the late 80’s [[8]Quaranta-Finsiel A.A. "Smart hospitals" in the environment and in the territory.J Clin Comput. 1988; 17: 23-27PubMed Google Scholar], the concept of a smart hospital emerges systematically only during the last 20 years [[9]Kwon H. An S. Lee H.Y. Cha W.C. Kim S. Cho M. Kong H.J. Review of smart hospital services in real healthcare environments.Health Inf Res. 2022; 28: 3-15https://doi.org/10.4258/hir.2022.28.1.3Crossref PubMed Scopus (31) Google Scholar]. Spawned by administrative needs and assets management, a smart hospital was initially regarded as an organization with the mindset and procedures in place to reduce costs and accidents related to healthcare service provision, mainly via better assets management. At this early stage, research focused on the smart building aspects of the hospital, including distributed sensors and networks to enable automation of processes, be it professional workflows or patient position monitoring and transferring inside the establishment. With the wide deployment of wearable sensors to monitor health parameters and the respective advancement of network infrastructures and networked ehealth services, the smart hospital could tear down its walls and advance to a concept much wider than the smart building, bringing ‘smartness’ to the core of health service delivery itself. Automation is still distinctive of a smart hospital, only nowadays, automation extends to multiple levels. Traditionally, a smart hospital supports automation in administrative workflows to boost productivity, reduce errors, and tackle the shortage of workforce. However, with the current advancement in artificial intelligence and robotics, automation is now emerging also in core medical tasks, such as diagnostic imaging, patient monitoring, fine surgical procedures and patient nursing, prevention and rehabilitation. Achieving this complex automation requires breakthroughs in engineering and artificial intelligence, data and knowledge management and analytics. Moreover, the contemporary smart hospital goes far beyond smart building functions, adding also smart medical products and procedures, including 3D printed tools and implants, new and bio-printed biomaterials, smart micro and nano-devices and personalized drugs and therapies. Today, a smart hospital is primarily a hospital without borders. A core set of complex and critical interventions are reserved for in-hospital service delivery. However, an increasing volume of services are offered via functionally connected remote units providing healthcare services, including other hospitals, clinics, primary health care, ambulatory care settings and social care. Furthermore, the smart hospital extends to any place of interest outside the health system, encompassing any place where the patient or the healthy individual resides, such as home and workplace, recreational areas, any point of care. Such connected, distributed settings place major requirements on data security and privacy, quality of service, interoperability of data and services and network and communication infrastructures. The contemporary smart hospital ultimately aims to enhance patient experience, alleviate workload from the workforce and reduce costs and accidents. Evidence from evaluations of related technology shows clear benefit of technological interventions for valid, reliable and accurate healthcare services, including screening, diagnosis, treatment, follow-up and rehabilitation. Full and successful deployment towards the smart hospital of the future requires continuous advancement of current technology. Furthermore, successful implementations require rigorous assessment and updates on the clinical protocols to meaningfully incorporate new technologies. This in turn would help to carefully assess cost-effectiveness and social dimensions of technology use, provide feedback to update regulatory, legal and insurance frameworks, and point to the appropriate design and deployment of training and change management for clinicians and patients alike. Although there is a vast body of literature and respective scientific journals that address individual aspects of research that contribute towards the smart hospital, a dedicated scientific forum to holistically report research pertaining to the smart hospital is currently missing. The Smart Hospital Section of the Computational and Structural Biotechnology Journal aims to cover this niche. Specific areas of interest include all aspects of novel technology and related research contributing to the making of the smart hospital. These cover advancements in traditional areas such as network infrastructure, connected devices, hospital information systems and automation of related value chains; but also emerging enabling technologies, including but not limited to personalized, continuous, real-time monitoring at the point of care, big data analytics, extended reality, robotics and artificial intelligence as applied to create the continuum of health care. The Smart Hospital Section also highlights research on privacy and security frameworks required to achieve meaningful real-world implementations, and insights on advancing regulatory frameworks, ethics and policies that will safeguard the smooth transition to the hospital of the future. The emergent smart hospital of the future has the potential to revolutionize healthcare delivery, focusing on enhancing the patient experience while offloading considerable amount of routine work to smart components operating mostly independently inside or outside the healthcare establishment. The Smart Hospital Section of the Computational and Structural Biotechnology Journal aims to provide a forum for scientific discussion and to document the research advancements towards this disruptive transition.

BACKGROUND: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. METHODS: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. FINDINGS: Global DALYs increased from 2·63 billion (95% UI 2·44-2·85) in 2010 to 2·88 billion (2·64-3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7-17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8-6·3) in 2020 and 7·2% (4·7-10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0-234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7-198·3]), neonatal disorders (186·3 million [162·3-214·9]), and stroke (160·4 million [148·0-171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3-51·7) and for diarrhoeal diseases decreased by 47·0% (39·9-52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54-1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5-9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0-19·8]), depressive disorders (16·4% [11·9-21·3]), and diabetes (14·0% [10·0-17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7-27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6-63·6) in 2010 to 62·2 years (59·4-64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6-2·9) between 2019 and 2021. INTERPRETATION: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. FUNDING: Bill & Melinda Gates Foundation.

We are thrilled to announce the establishment of the new speciality section on Quantum Biology and Biophotonics within the Computational and Structural Biotechnology Journal (CSBJ). This speciality section advocates for a transdisciplinary approach that integrates diverse perspectives to unravel the intricate mechanisms underpinning the interplay between quantum phenomena and biological systems. Furthermore, this section focuses on tremendous innovations in optics and photonic tools, methods, and technologies to address questions in quantum biology and its potential impact on biotechnology, biomedicine, and healthcare. Quantum Biology has emerged as a vibrant interdisciplinary research field, propelled by recent advancements in physics, biology, and chemistry. It posits that quantum mechanics play a pivotal role in diverse biological processes, including animal navigation, olfactory sensing, vision, cellular metabolic regulation, cell physiology, photosynthesis, quantum tunnelling in enzymes and DNA mutation, electron-spin dependent chemical reactions in biology, bioelectronics, ion channel functions in neurobiology, and more. This is an exciting and emerging scientific exploration, paving the way for innovative discoveries and developments that will revolutionize healthcare. Integrating observations of quantum biology phenomena across various length and time scales remains a significant challenge. Additionally, language and methodology barriers hinder community building efforts. The success of quantum biology endeavours hinges on interdisciplinarity, multi-scale approaches, and close collaboration between theory and experiment, attainable only within a robust research collaboration network. On the other hand, quantum technology has ushered in an unprecedented era of sensitivity and capability in physical measurements, harnessing the principles of quantum mechanics to transcend the limitations insurmountable by classical physics. Despite these remarkable achievements, translating these quantum technology breakthroughs into practical applications in biosciences and medicine remains a formidable challenging. This new specialized section on quantum biology and biophotonics will serve as a dedicated platform for disseminating and discussing cutting-edge research in the field of quantum biology and biophotonics, fostering communication links among the currently siloed scientists worldwide. We invite you to join these endeavours and establish this prominent and high-visibility open-access forum dedicated to quantum biology and biophotonics.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

The evolution of the SARS-CoV-2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor-binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS-CoV-2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y), and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.

via interactions with other molecules. Identifying the residues participating in these interactions not only provides biological insights for protein function studies but also has great significance for drug discoveries. Therefore, predicting protein-ligand binding sites has long been under intense research in the fields of bioinformatics and computer aided drug discovery. In this review, we first introduce the research background of predicting protein-ligand binding sites and then classify the methods into four categories, namely, 3D structure-based, template similarity-based, traditional machine learning-based and deep learning-based methods. We describe representative algorithms in each category and elaborate on machine learning and deep learning-based prediction methods in more detail. Finally, we discuss the trends and challenges of the current research such as molecular dynamics simulation based cryptic binding sites prediction, and highlight prospective directions for the near future.

The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (PubMed Central (PMC), Bookshelf and PubReader), health (ClinVar, dbGaP, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen), genomes (BioProject, Assembly, Genome, BioSample, dbSNP, dbVar, Epigenomics, the Map Viewer, Nucleotide, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser and the Trace Archive), genes (Gene, Gene Expression Omnibus (GEO), HomoloGene, PopSet and UniGene), proteins (Protein, the Conserved Domain Database (CDD), COBALT, Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB) and Protein Clusters) and chemicals (Biosystems and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for most of these databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Crustaceans form the second largest subphylum on Earth, which includes Litopeneaus vannamei (Pacific whiteleg shrimp), one of the most cultured shrimp worldwide. Despite efforts to study the shrimp microbiota, little is known about it from shrimp obtained from the open sea and the role that aquaculture plays in microbiota remodeling. Here, the microbiota from the hepatopancreas and intestine of wild type (wt) and aquacultured whiteleg shrimp and pond sediment from hatcheries were characterized using sequencing of seven hypervariable regions of the 16S rRNA gene. Cultured shrimp with AHPND/EMS disease symptoms were also included. We found that (i) microbiota and their predicted metagenomic functions were different between wt and cultured shrimp; (ii) independent of the shrimp source, the microbiota of the hepatopancreas and intestine was different; (iii) the microbial diversity between the sediment and intestines of cultured shrimp was similar; and (iv) associated to an early development of AHPND/EMS disease, we found changes in the microbiome and the appearance of disease-specific bacteria. Notably, under cultured conditions, we identified bacterial taxa enriched in healthy shrimp, such as Faecalibacterium prausnitzii and Pantoea agglomerans, and communities enriched in diseased shrimp, such as Aeromonas taiwanensis, Simiduia agarivorans and Photobacterium angustum.

UNLABELLED: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server. AVAILABILITY: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org.

This paper describes the database on U.S. patents that we have developed over the past decade, with the goal of making it widely accessible for research. We present main trends in U. S. patenting over the last 30 years, including a variety of original measures constructed with citation data, such as backward and forward citation lags, indices of "originality" and "generality", self-citations, etc. Many of these measures exhibit interesting differences across the six main technological categories that we have developed (comprising Computers and Communications, Drugs and Medical, Electrical and Electronics, Chemical, Mechanical and Others), differences that call for further research. To stimulate such research, the entire database-about 3 million patents and 16 million citations-is now available on the NBER website. We discuss key issues that arise in the use of patent citations data, and suggest ways of addressing them. In particular, significant changes over time in the rate of patenting and in the number of citations made, as well as the inevitable truncation of the data, make it very hard to use the raw number of citations received by different patents directly in a meaningful way. To remedy this problem we suggest two alternative approaches: the fixed-effects approach involves scaling citations by the average citation count for a group of patents to which the patent of interest belongs; the quasi-structural approach attempts to distinguish the multiple effects on citation rates via econometric estimation.

An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.

MDAnalysis (http://mdanalysis.org) is a library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories and individual protein structures. MD simulations of biological molecules have become an important tool to elucidate the relationship between molecular structure and physiological function. Simulations are performed with highly optimized software packages on HPC resources but most codes generate output trajectories in their own formats so that the development of new trajectory analysis algorithms is confined to specific user communities and widespread adoption and further development is delayed. MDAnalysis addresses this problem by abstracting access to the raw simulation data and presenting a uniform object-oriented Python interface to the user. It thus enables users to rapidly write code that is portable and immediately usable in virtually all biomolecular simulation communities. The user interface and modular design work equally well in complex scripted work flows, as foundations for other packages, and for interactive and rapid prototyping work in IPython / Jupyter notebooks, especially together with molecular visualization provided by nglview and time series analysis with pandas. MDAnalysis is written in Python and Cython and uses NumPy arrays for easy interoperability with the wider scientific Python ecosystem. It is widely used and forms the foundation for more specialized biomolecular simulation tools.

UCSF ChimeraX is the next-generation interactive visualization program from the Resource for Biocomputing, Visualization, and Informatics (RBVI), following UCSF Chimera. ChimeraX brings (a) significant performance and graphics enhancements; (b) new implementations of Chimera's most highly used tools, many with further improvements; (c) several entirely new analysis features; (d) support for new areas such as virtual reality, light-sheet microscopy, and medical imaging data; (e) major ease-of-use advances, including toolbars with icons to perform actions with a single click, basic "undo" capabilities, and more logical and consistent commands; and (f) an app store for researchers to contribute new tools. ChimeraX includes full user documentation and is free for noncommercial use, with downloads available for Windows, Linux, and macOS from https://www.rbvi.ucsf.edu/chimerax.

Stroke, the third leading cause of death and disability worldwide, is undergoing a change in perspective with the emergence of new ideas on neurodegeneration. The concept that stroke is a disorder solely of blood vessels has been expanded to include the effects of a detrimental interaction between glia, neurons, vascular cells, and matrix components, which is collectively referred to as the neurovascular unit. Following the acute stroke, the majority of which are ischemic, there is secondary neuroinflammation that both promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery. The proinflammatory signals from immune mediators rapidly activate resident cells and influence infiltration of a wide range of inflammatory cells (neutrophils, monocytes/macrophages, different subtypes of T cells, and other inflammatory cells) into the ischemic region exacerbating brain damage. In this review, we discuss how neuroinflammation has both beneficial as well as detrimental roles and recent therapeutic strategies to combat pathological responses. Here, we also focus on time-dependent entry of immune cells to the ischemic area and the impact of other pathological mediators, including oxidative stress, excitotoxicity, matrix metalloproteinases (MMPs), high-mobility group box 1 (HMGB1), arachidonic acid metabolites, mitogen-activated protein kinase (MAPK), and post-translational modifications that could potentially perpetuate ischemic brain damage after the acute injury. Understanding the time-dependent role of inflammatory factors could help in developing new diagnostic, prognostic, and therapeutic neuroprotective strategies for post-stroke inflammation.

High-throughput drug screening has facilitated the discovery of drug combinations in cancer. Many existing studies adopted a full matrix design, aiming for the characterization of drug pair effects for cancer cells. However, the full matrix design may be suboptimal as it requires a drug pair to be combined at multiple concentrations in a full factorial manner. Furthermore, many of the computational tools assess only the synergy but not the sensitivity of drug combinations, which might lead to false positive discoveries. We proposed a novel cross design to enable a more cost-effective and simultaneous testing of drug combination sensitivity and synergy. We developed a drug combination sensitivity score (CSS) to determine the sensitivity of a drug pair, and showed that the CSS is highly reproducible between the replicates and thus supported its usage as a robust metric. We further showed that CSS can be predicted using machine learning approaches which determined the top pharmaco-features to cluster cancer cell lines based on their drug combination sensitivity profiles. To assess the degree of drug interactions using the cross design, we developed an S synergy score based on the difference between the drug combination and the single drug dose-response curves. We showed that the S score is able to detect true synergistic and antagonistic drug combinations at an accuracy level comparable to that using the full matrix design. Taken together, we showed that the cross design coupled with the CSS sensitivity and S synergy scoring methods may provide a robust and accurate characterization of both drug combination sensitivity and synergy levels, with minimal experimental materials required. Our experimental-computational approach could be utilized as an efficient pipeline for improving the discovery rate in high-throughput drug combination screening, particularly for primary patient samples which are difficult to obtain.

Breast cancer is a global cause for concern owing to its high incidence around the world. The alarming increase in breast cancer cases emphasizes the management of disease at multiple levels. The management should start from the beginning that includes stringent cancer screening or cancer registry to effective diagnostic and treatment strategies. Breast cancer is highly heterogeneous at morphology as well as molecular levels and needs different therapeutic regimens based on the molecular subtype. Breast cancer patients with respective subtype have different clinical outcome prognoses. Breast cancer heterogeneity emphasizes the advanced molecular testing that will help on-time diagnosis and improved survival. Emerging fields such as liquid biopsy and artificial intelligence would help to under the complexity of breast cancer disease and decide the therapeutic regimen that helps in breast cancer management. In this review, we have discussed various risk factors and advanced technology available for breast cancer diagnosis to combat the worst breast cancer status and areas that need to be focused for the better management of breast cancer.