Christina Barth , Hendrik Spreen , Dennis Mulac , Lucas Keuter , Matthias Behrens , Hans-Ulrich Humpf , Klaus Langer
{"title":"Spacer length and serum protein adsorption affect active targeting of trastuzumab-modified nanoparticles","authors":"Christina Barth , Hendrik Spreen , Dennis Mulac , Lucas Keuter , Matthias Behrens , Hans-Ulrich Humpf , Klaus Langer","doi":"10.1016/j.bbiosy.2021.100032","DOIUrl":"10.1016/j.bbiosy.2021.100032","url":null,"abstract":"<div><p>Receptor-mediated active targeting of nanocarriers is a widely investigated approach to specifically address cancerous cells and tissues in the human body. The idea is to use these formulations as drug carriers with enhanced specificity and therefore reduced systemic side effects. Until today a big obstacle to reach this goal remains the adsorption of serum proteins to the nanocarrier's surface after contact with biological fluids. In this context different nanoparticle characteristics could be beneficial for effective active targeting after formation of a protein corona which need to be identified. In this study trastuzumab was used as an active targeting ligand which was covalently attached to human serum albumin nanoparticles. For coupling reaction different molecular weight spacers were used and resulting physicochemical nanoparticle characteristics were evaluated. The <em>in vitro</em> cell association of the different nanoparticle formulations was tested in cell culture experiments with or without fetal bovine serum. For specific receptor-mediated cell interaction SK-BR-3 breast cancer cells with human epidermal growth factor receptor 2 (HER2) overexpression were used. MCF-7 breast cancer cells with normal HER2 expression served as control. Furthermore, serum protein adsorption on respective nanoparticles was characterized. The qualitative and quantitative composition of the protein corona was analyzed by SDS-PAGE and LC-MS/MS and the influence of protein adsorption on active targeting capability was determined.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"5 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/4c/main.PMC9934468.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daomei Chen , Liang Jiang , Tao Lei , Guo Xiao , Yuanfeng Wang , Xiaoqiong Zuo , Bin Li , Lingli Li , Jiaqiang Wang
{"title":"Magnetic CuFe2O4 with intrinsic protease-like activity inhibited cancer cell proliferation and migration through mediating intracellular proteins","authors":"Daomei Chen , Liang Jiang , Tao Lei , Guo Xiao , Yuanfeng Wang , Xiaoqiong Zuo , Bin Li , Lingli Li , Jiaqiang Wang","doi":"10.1016/j.bbiosy.2021.100038","DOIUrl":"10.1016/j.bbiosy.2021.100038","url":null,"abstract":"<div><p>Protease has been widely used in biological and industrial fields. Developing efficient artificial enzyme mimics remains a major technical challenge due to the high stability of peptide bonds. Nanoenzymes with high stability, high activity and low cost, provided new opportunities to break through natural enzyme inherent limitations. However, compared with many nanomaterials with inherent peroxidase activity, the intrinsic mimic proteases properties of magnetic nanomaterials were seldom explored, let alone the interaction between magnetic nanomaterials and cellular proteins. Herein, we reported for the first time that magnetic CuFe<sub>2</sub>O<sub>4</sub> possesses inherent protease activity to hydrolyze bovine serum albumin (BSA) and casein under physiological conditions, and the CuFe<sub>2</sub>O<sub>4</sub> is more resistant to high temperature than the natural trypsin. It also exhibited significantly higher catalytic efficiency than other copper nanomaterials and can be recycled for many times. Protease participated in pathophysiological processes and all stages of tumor progression. Interesting, CuFe<sub>2</sub>O<sub>4</sub> exhibited anti-proliferative effect on A549, SKOV3, HT-29, BABL-3T3 and HUVEC cells, as well as it was particularly sensitive against SKOV3 cells. CuFe<sub>2</sub>O<sub>4</sub> was about 30 times more effective than conventional chemotherapy drugs oxaliplatin and artesunate against SKOV3 cells. In addition, CuFe<sub>2</sub>O<sub>4</sub> also mediated the expression of intracellular proteins, such as MMP-2, MMP-9, F-actin, and NF-<em>k</em>B, which may be associated with global protein hydrolysis by CuFe<sub>2</sub>O<sub>4</sub>, leading to inhibition of cell migration. The merits of the high magnetic properties, good protease-mimic and antitumor activities make CuFe<sub>2</sub>O<sub>4</sub> nanoparticles very prospective candidates for many applications such as proteomics and biotechnology.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"5 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/a9/main.PMC9934488.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A review of strategies for development of tissue engineered meniscal implants","authors":"George J. Klarmann , Joel Gaston , Vincent B. Ho","doi":"10.1016/j.bbiosy.2021.100026","DOIUrl":"10.1016/j.bbiosy.2021.100026","url":null,"abstract":"<div><p>The meniscus is a key stabilizing tissue of the knee that facilitates proper tracking and movement of the knee joint and absorbs stresses related to physical activity. This review article describes the biology, structure, and functions of the human knee meniscus, common tears and repair approaches, and current research and development approaches using modern methods to fabricate a scaffold or tissue engineered meniscal replacement. Meniscal tears are quite common, often resulting from sports or physical training, though injury can result without specific contact during normal physical activity such as bending or squatting. Meniscal injuries often require surgical intervention to repair, restore basic functionality and relieve pain, and severe damage may warrant reconstruction using allograft transplants or commercial implant devices. Ongoing research is attempting to develop alternative scaffold and tissue engineered devices using modern fabrication techniques including three-dimensional (3D) printing which can fabricate a patient-specific meniscus replacement. An ideal meniscal substitute should have mechanical properties that are close to that of natural human meniscus, and also be easily adapted for surgical procedures and fixation. A better understanding of the organization and structure of the meniscus as well as its potential points of failure will lead to improved design approaches to generate a suitable and functional replacement.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100026"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Third body damage and wear in arthroplasty bearing materials: A review of laboratory methods","authors":"Raelene M Cowie, Louise M Jennings","doi":"10.1016/j.bbiosy.2021.100028","DOIUrl":"10.1016/j.bbiosy.2021.100028","url":null,"abstract":"<div><p>Third body wear of arthroplasty bearing materials can occur when hard particles such as bone, bone cement or metal particles become trapped between the articulating surfaces. This can accelerate overall implant wear, potentially leading to early failure. With the development of novel bearing materials and coatings, there is a need to develop and standardise test methods which reflect third body damage seen on retrieved implants. Many different protocols and approaches have been developed to replicate third body wear in the laboratory but there is currently no consensus as to the optimal method for simulating this wear mode, hence the need to better understand existing methods. The aim of this study was to review published methods for experimental simulation of third body wear of arthroplasty bearing materials, to discuss the advantages and limitations of different approaches, the variables to be considered when designing a method and to highlight gaps in the current literature. The methods were divided into those which introduced abrasive particles into the articulating surfaces of the joint and those whereby third body damage is created directly to the articulating surfaces. However, it was found that there are a number of parameters, for example the influence of particle size on wear, which are not yet fully understood. The study concluded that the chosen method or combination of methods used should primarily be informed by the research question to be answered and risk analysis of the device.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Collagen type II: From biosynthesis to advanced biomaterials for cartilage engineering","authors":"Z Wu , SH Korntner , AM Mullen , DI Zeugolis","doi":"10.1016/j.bbiosy.2021.100030","DOIUrl":"10.1016/j.bbiosy.2021.100030","url":null,"abstract":"<div><p>Collagen type II is the major constituent of cartilage tissue. Yet, cartilage engineering approaches are primarily based on collagen type I devices that are associated with suboptimal functional therapeutic outcomes. Herein, we briefly describe cartilage's development and cellular and extracellular composition and organisation. We also provide an overview of collagen type II biosynthesis and purification protocols from tissues of terrestrial and marine species and recombinant systems. We then advocate the use of collagen type II as a building block in cartilage engineering approaches, based on safety, efficiency and efficacy data that have been derived over the years from numerous <em>in vitro</em> and <em>in vivo</em> studies.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advanced non-fluoride approaches to dental enamel remineralization: The next level in enamel repair management","authors":"Bernd Grohe , Silvia Mittler","doi":"10.1016/j.bbiosy.2021.100029","DOIUrl":"10.1016/j.bbiosy.2021.100029","url":null,"abstract":"<div><p>In modern dentistry, a minimally invasive management of early caries lesions or early-stage erosive tooth wear (ETW) with synthetic remineralization systems has become indispensable. In addition to fluoride, which is still the non-plus-ultra in these early caries/ETW treatments, a number of new developments are in the test phase or have already been commercialized. Some of these systems claim that they are comparable or even superior to fluoride in terms of their ability to remineralize enamel. Besides, their use can help avoid some of the risks associated with fluoride and support treatments of patients with a high risk of caries. Two individual non-fluoride systems can be distinguished; intrinsic and extrinsic remineralization approaches. Intrinsic (protein/peptide) systems adsorb to hydroxyapatite crystals/organics located within enamel prisms and accumulate endogenous calcium and phosphate ions from saliva, which ultimately leads to the re-growth of enamel crystals. Extrinsic remineralization systems function on the basis of the external (non-saliva) supply of calcium and phosphate to the crystals to be re-grown. This article, following an introduction into enamel (re)mineralization and fluoride-assisted remineralization, discusses the requirements for non-fluoride remineralization systems, particularly their mechanisms and challenges, and summarizes the findings that underpin the most promising advances in enamel remineralization therapy.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A. Bellio , Cassie Bennett , Alissa Arango , Aisha Khan , Xiumin Xu , Cesar Barrera , Vincent Friedewald , Maria Ines Mitrani
{"title":"Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection","authors":"Michael A. Bellio , Cassie Bennett , Alissa Arango , Aisha Khan , Xiumin Xu , Cesar Barrera , Vincent Friedewald , Maria Ines Mitrani","doi":"10.1016/j.bbiosy.2021.100031","DOIUrl":"10.1016/j.bbiosy.2021.100031","url":null,"abstract":"<div><p>A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (<em>n</em> = 8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF-<span><math><mi>α</mi></math></span>) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/7c/main.PMC8611818.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10741832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olivia R.M. Bagshaw , Fereshteh Moradi , Christopher S. Moffatt , Hillary A. Hettwer , Ping Liang , Jeremy Goldman , Jaroslaw W. Drelich , Jeffrey A. Stuart
{"title":"Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells","authors":"Olivia R.M. Bagshaw , Fereshteh Moradi , Christopher S. Moffatt , Hillary A. Hettwer , Ping Liang , Jeremy Goldman , Jaroslaw W. Drelich , Jeffrey A. Stuart","doi":"10.1016/j.bbiosy.2021.100027","DOIUrl":"10.1016/j.bbiosy.2021.100027","url":null,"abstract":"<div><p>Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc's differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"4 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer","authors":"Tanveer A. Tabish , Michael R. Hamblin","doi":"10.1016/j.bbiosy.2021.100023","DOIUrl":"10.1016/j.bbiosy.2021.100023","url":null,"abstract":"<div><p>The early understanding of mitochondria posited that they were ‘innocent organelles’ solely devoted to energy production and utilisation. Intriguingly, recent findings have outlined in detail the ‘modern-day’ view that mitochondria are an important but underappreciated drug target. Mitochondria have been implicated in the pathophysiology of many human diseases, ranging from neurodegenerative disorders and cardiovascular diseases to infections and cancer. It is now clear that normal mitochondrial function involves the building blocks of a cell to generate lipids, proteins and nucleic acids thereby facilitating cell growth. On the other hand, mitochondrial dysfunction reprograms crucial cellular functions into pathological pathways, and is considered as an integral hallmark of cancer. Therefore, strategies to target mitochondria can provide a wealth of new therapeutic approaches in the fight against cancer, by overcoming a number of problems associated with conventional pharmaceutical drugs, including low solubility, poor bioavailability and non-selective biodistribution. The combination of nanoparticles with ‘classical’ chemotherapeutic drugs to create biocompatible, multifunctional mitochondria-targeted nanoplatforms has been recently studied. This approach is now rapidly expanding for targeted drug delivery systems, and for hybrid nanostructures that can be activated with light (photodynamic and/or photothermal therapy). The selective delivery of nanoparticles to mitochondria is an elegant shortcut to more selective, targeted, and safer cancer treatment. We propose that the use of nanoparticles to target mitochondria be termed “mitoNANO”. The present minireview sheds light on the design and application of mitoNANO as advanced cancer therapeutics, that may overcome drug resistance and show fewer side effects.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100023"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ehsan Akbari , Griffin B. Spychalski , Miles M. Menyhert , Kaushik K. Rangharajan , Joseph W. Tinapple , Shaurya Prakash , Jonathan W. Song
{"title":"Endothelial barrier function is co-regulated at vessel bifurcations by fluid forces and sphingosine-1-phosphate","authors":"Ehsan Akbari , Griffin B. Spychalski , Miles M. Menyhert , Kaushik K. Rangharajan , Joseph W. Tinapple , Shaurya Prakash , Jonathan W. Song","doi":"10.1016/j.bbiosy.2021.100020","DOIUrl":"10.1016/j.bbiosy.2021.100020","url":null,"abstract":"<div><p>Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry generates hemodynamic forces at the bifurcation point distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which is characterized by approximately zero shear stress and 38 dyn•cm<sup>−2</sup> stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of S1P with 3 dyn•cm<sup>−2</sup> laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to bifurcated fluid flow and laminar shear stress is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.</p></div>","PeriodicalId":72379,"journal":{"name":"Biomaterials and biosystems","volume":"3 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbiosy.2021.100020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10758973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}