Swati Tyagi, Srabani Kar, Amit Srivastava, Pratyoosh Shukla
{"title":"Protein Engineering in Cyanobacterial Biotechnology: Tools and Recent Updates.","authors":"Swati Tyagi, Srabani Kar, Amit Srivastava, Pratyoosh Shukla","doi":"10.2174/1389203724666230822100104","DOIUrl":"10.2174/1389203724666230822100104","url":null,"abstract":"<p><p>Cyanobacteria have emerged as a microbial cell factory to produce a variety of bioproducts, including peptides and proteins. Cyanobacteria stand out among other organisms due to their photoautotrophic metabolism and ability to produce a wide range of metabolites. As photoautotrophic hosts can produce industrial compounds and proteins by using minimal resources such as sunlight, atmospheric carbon dioxide, and fewer nutrients, cyanobacteria are cost-effective industrial hosts. Therefore, the use of protein engineering tools for rational protein design, and the desired modification of enzyme activity has become a desirable undertaking in cyanobacterial biology. Protein engineering can improve their biological functions as well as the stability of their intracellular proteins. This review aims to highlight the success of protein engineering in the direction of cyanobacterial biotechnology and outlines the emerging technologies, current challenges, and prospects of protein engineering in cyanobacterial biotechnology.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zohreh Salimi, Mehdi Rostami, Yaser Eshaghi Milasi, Alireza Mafi, Ramin Raoufinia, Amirhossein Kiani, Fariba Sakhaei, Behrooz Ghezelbash, Alexandra E Butler, Maryam Mohammad-Sadeghipour, Amirhossein Sahebkar
{"title":"Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis.","authors":"Zohreh Salimi, Mehdi Rostami, Yaser Eshaghi Milasi, Alireza Mafi, Ramin Raoufinia, Amirhossein Kiani, Fariba Sakhaei, Behrooz Ghezelbash, Alexandra E Butler, Maryam Mohammad-Sadeghipour, Amirhossein Sahebkar","doi":"10.2174/1389203724666230822085951","DOIUrl":"10.2174/1389203724666230822085951","url":null,"abstract":"<p><p>Frequent exposure to various external and internal adverse forces (stresses) disrupts cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Update on Dipeptidyl Peptidase-IV Inhibiting Peptides.","authors":"Sachithanantham Annapoorani Sivaraman, Varatharajan Sabareesh","doi":"10.2174/0113892037287976231212104607","DOIUrl":"10.2174/0113892037287976231212104607","url":null,"abstract":"<p><p>Diabetes is a chronic metabolic disorder. According to the International Diabetes Federation, about 537 million people are living with diabetes. The two types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), among which the population affected by T2DM is relatively higher. A major reason for T2DM is that insulin stimulation is hampered due to the inactivation of incretin hormones. Dipeptidyl peptidase-IV (DPP-IV) is a serine protease that is directly involved in the inactivation of incretin hormones, e.g., glucagon-like peptide-1 (GLP-1). Therefore, the inhibition of DPP-IV can be a promising method for managing T2DM, in addition to other enzyme inhibition strategies, such as inhibition of α-amylase and α -glucosidase. Currently, about 12 different gliptin drugs are available in the market that inhibit DPP-IV in a dose-dependent manner. Instead of gliptins, 'peptides' can also be employed as an alternative and promising way to inhibit DPP-IV. Peptide inhibitors of DPP-IV have been identified from various plants and animals. Chemically synthesized peptides have also been experimented for inhibiting DPP-IV. Most peptides have been analysed by biochemical assays, whereas some <i>in vitro</i> assays have also been reported. Molecular docking analysis has been applied to comprehend the mechanism of inhibition. In this review, certain aspects of natural as well as synthetic peptides are described that have been proven to inhibit DPP-IV.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bile Acids as Signaling Molecules: Role of Ursodeoxycholic Acid in Cholestatic Liver Disease.","authors":"Eduardo Cifuentes-Silva, Claudio Cabello-Verrugio","doi":"10.2174/1389203724666230818092800","DOIUrl":"10.2174/1389203724666230818092800","url":null,"abstract":"<p><p>Ursodeoxycholic acid (UDCA) is a natural substance physiologically produced in the liver. Initially used to dissolve gallstones, it is now successfully used in treating primary biliary cirrhosis and as adjuvant therapy for various hepatobiliary cholestatic diseases. However, the mechanisms underlying its beneficial effects still need to be clarified. Evidence suggests three mechanisms of action for UDCA that could benefit humans with cholestatic liver disease (CLD): protection of cholangiocytes against hydrophobic bile acid (BA) cytotoxicity, stimulation of hepatobiliary excretion, and protection of hepatocytes against BA-induced apoptosis. These mechanisms may act individually or together to potentiate them. At the molecular level, it has been observed that UDCA can generate modifications in the transcription and translation of proteins essential in the transport of BA, correcting the deficit in BA secretion in CLD, in addition to activating signaling pathways to translocate these transporters to the sites where they should fulfill their function. Inhibition of BA-induced hepatocyte apoptosis may play a role in CLD, characterized by BA retention in the hepatocyte. Thus, different mechanisms of action contribute to the improvement after UDCA administration in CLD. On the other hand, the effects of UDCA on tissues that possess receptors that may interact with BAs in pathological contexts, such as skeletal muscle, are still unclear. This work aims to describe the main molecular mechanisms by which UDCA acts in the human body, emphasizing the interaction in tissues other than the liver.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi
{"title":"Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.","authors":"Majed M Masadeh, Haneen Alshogran, Mohammad Alsaggar, Salsabeel H Sabi, Enaam M Al Momany, Majd M Masadeh, Nasr Alrabadi, Karem H Alzoubi","doi":"10.2174/0113892037291252240528110516","DOIUrl":"10.2174/0113892037291252240528110516","url":null,"abstract":"<p><strong>Background: </strong>Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity.</p><p><strong>Methods: </strong>The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity (Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity) was tested on two control (<i>Staphylococcus aureus</i> ATCC 29213, <i>Escherichia coli</i> ATCC 25922) and two resistant (Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC<sub>50</sub> value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood.</p><p><strong>Results: </strong>The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 μM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC<sub>50</sub> value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains.</p><p><strong>Conclusion: </strong>The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.","authors":"Ujwal N Katolkar, Sanjay J Surana","doi":"10.2174/0113892037307940240606075208","DOIUrl":"10.2174/0113892037307940240606075208","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments.</p><p><strong>Aim: </strong>The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations.</p><p><strong>Materials and methods: </strong>The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals.</p><p><strong>Results: </strong>Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities.</p><p><strong>Conclusion: </strong>The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira
{"title":"A Review of the Leishmanicidal Properties of Lectins.","authors":"Yasmim A Grangeiro, Ana L E Santos, Flávia E V Barbosa, Renato R Roma, Racquel O S Souza, Cláudio G L Silva, Claudener S Teixeira","doi":"10.2174/0113892037275751231221053730","DOIUrl":"10.2174/0113892037275751231221053730","url":null,"abstract":"<p><p>Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus <i>Leishmania. In vitro</i> and <i>in vivo</i> tests with promastigotes and amastigotes of <i>Leishmania</i> demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu
{"title":"Combating Aminoglycoside Resistance: From Structural and Functional Characterisation to Therapeutic Challenges with RKAAT.","authors":"Sarah Oluwatobi Otun, Richard Graca, Ikechukwu Achilonu","doi":"10.2174/0113892037278814231226104509","DOIUrl":"10.2174/0113892037278814231226104509","url":null,"abstract":"<p><p>A comprehensive knowledge of aminoglycoside-modifying enzymes (AMEs) and their role in bacterial resistance mechanisms is urgently required due to the rising incidence of antibiotic resistance, particularly in <i>Klebsiella pneumoniae</i> infections. This study explores the essential features of AMEs, including their structural and functional properties, the processes by which they contribute to antibiotic resistance, and the therapeutic importance of aminoglycosides. The study primarily examines the Recombinant <i>Klebsiella pneumoniae</i> Aminoglycoside Adenylyl Transferase (RKAAT), particularly emphasizing its biophysical characteristics and the sorts of resistance it imparts. Furthermore, this study examines the challenges presented by RKAAT-mediated resistance, an evaluation of treatment methods and constraints, and options for controlling infection. The analysis provides a prospective outlook on strategies to address and reduce antibiotic resistance. This extensive investigation seeks to provide vital insights into the continuing fight against bacterial resistance, directing future research efforts and medicinal approaches.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular Players at the Sorting Stations of Malaria Parasite <i>'Plasmodium falciparum'</i>.","authors":"Jasweer Kaur, Prakash Chandra Mishra, Rachna Hora","doi":"10.2174/0113892037282522240130090156","DOIUrl":"10.2174/0113892037282522240130090156","url":null,"abstract":"<p><p>The apicomplexan pathogenic parasite <i>'Plasmodium falciparum</i>' (Pf) is responsible for most of the malaria related mortality. It resides in and refurbishes the infected red blood cells (iRBCs) for its own survival and to suffice its metabolic needs. Remodeling of host erythrocytes involves alteration of physical and biochemical properties of the membrane and genesis of new parasite induced structures within the iRBCs. The generated structures include knobs and solute ion channels on the erythrocyte surface and specialized organelles i.e. Maurer's clefts (MCs) in the iRBC cytosol. The above processes are mediated by exporting a large repertoire of proteins to the host cell, most of which are transported <i>via</i> MCs, the sorting stations in parasitized erythrocytes. Information about MC biogenesis and the molecules involved in maintaining MC architecture remains incompletely elucidated. Here, we have compiled a list of experimentally known MC resident proteins, several of which have roles in maintaining its architecture and function. Our short review covers available data on the domain organization, orthologues, topology and specific roles of these proteins. We highlight the current knowledge gaps in our understanding of MCs as crucial organelles involved in parasite biology and disease pathogenesis.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spectroscopic Analysis of the Effect of Ibuprofen Degradation Products on the Interaction between Ibuprofen and Human Serum Albumin.","authors":"Anna Ploch-Jankowska","doi":"10.2174/0113892037284277240126094716","DOIUrl":"10.2174/0113892037284277240126094716","url":null,"abstract":"<p><strong>Background: </strong>Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most commonly used groups of medicinal compounds in the world. The wide access to NSAIDs and the various ways of storing them due to their easy accessibility often entail the problem with the stability and durability resulting from the exposure of drugs to external factors. The aim of the research was to evaluate <i>in vitro</i> the mechanism of competition between ibuprofen (IBU) and its degradation products, i.e., 4'-isobutylacetophenone (IBAP) and (2RS)-2-(4- formylphenyl)propionic acid (FPPA) during transport in a complex with fatted (HSA) and defatted (dHSA) human serum albumin.</p><p><strong>Methods: </strong>The research was carried out using spectroscopic techniques, such as spectrophotometry, infrared spectroscopy and nuclear magnetic resonance spectroscopy.</p><p><strong>Results: </strong>The comprehensive application of spectroscopic techniques allowed, among others, for the determination of the binding constant, the number of classes of binding sites and the cooperativeness constant of the analyzed systems IBU-(d)HSA, IBU-(d)HSA-FPPA, IBU-(d)HSA-IBAP; the determination of the effect of ibuprofen and its degradation products on the secondary structure of albumin; identification and assessment of interactions between ligand and albumin; assessment of the impact of the presence of fatty acids in the structure of albumin and the measurement temperature on the binding of IBU, IBAP and FPPA to (d)HSA.</p><p><strong>Conclusion: </strong>The conducted research allowed us to conclude that the presence of ibuprofen degradation products and the increase in their concentration significantly affect the formation of the IBU-albumin complex and thus, the value of the association constant of the drug, changing the concentration of its free fraction in the blood plasma. It was also found that the presence of an ibuprofen degradation product in a complex with albumin affects its secondary structure.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}