BioTech最新文献

{"title":"Industrial Biotechnology Conservation Processes: Similarities with Natural Long-Term Preservation of Biological Organisms.","authors":"Alexis Laurent,&nbsp;Corinne Scaletta,&nbsp;Philippe Abdel-Sayed,&nbsp;Wassim Raffoul,&nbsp;Nathalie Hirt-Burri,&nbsp;Lee Ann Applegate","doi":"10.3390/biotech12010015","DOIUrl":"https://doi.org/10.3390/biotech12010015","url":null,"abstract":"<p><p>Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., -196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g., cryptobiosis) in biological organisms. Specifically, examples of survival to extreme physical parameters by small multi-cellular animals (e.g., tardigrades) are discussed, opening further considerations about the possibility to reversibly slow or temporarily arrest the metabolic activity rates of defined complex organisms in controlled conditions. Key examples of biological organism adaptation capabilities to extreme environmental parameters finally enabled a discussion about the emergence of early primordial biological lifeforms, from natural biotechnology and evolutionary points of view. Overall, the provided examples/similarities confirm the interest in further transposing natural processes and phenomena to controlled laboratory settings with the ultimate goal of gaining better control and modulation capacities over the metabolic activities of complex biological organisms.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765421","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":"Cell Immortalization: In Vivo Molecular Bases and In Vitro Techniques for Obtention.","authors":"Javier Curi de Bardet, Celeste Ramírez Cardentey, Belkis López González, Deanira Patrone, Idania Lores Mulet, Dario Siniscalco, María de Los Angeles Robinson-Agramonte","doi":"10.3390/biotech12010014","DOIUrl":"10.3390/biotech12010014","url":null,"abstract":"<p><p>Somatic human cells can divide a finite number of times, a phenomenon known as the Hayflick limit. It is based on the progressive erosion of the telomeric ends each time the cell completes a replicative cycle. Given this problem, researchers need cell lines that do not enter the senescence phase after a certain number of divisions. In this way, more lasting studies can be carried out over time and avoid the tedious work involved in performing cell passes to fresh media. However, some cells have a high replicative potential, such as embryonic stem cells and cancer cells. To accomplish this, these cells express the enzyme telomerase or activate the mechanisms of alternative telomere elongation, which favors the maintenance of the length of their stable telomeres. Researchers have been able to develop cell immortalization technology by studying the cellular and molecular bases of both mechanisms and the genes involved in the control of the cell cycle. Through it, cells with infinite replicative capacity are obtained. To obtain them, viral oncogenes/oncoproteins, myc genes, ectopic expression of telomerase, and the manipulation of genes that regulate the cell cycle, such as p53 and Rb, have been used.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765419","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 Synergistic pH-Responsive Serum Albumin-Based Drug Delivery System Loaded with Doxorubicin and Pentacyclic Triterpene Betulinic Acid for Potential Treatment of NSCLC.","authors":"Zally Torres-Martinez, Daraishka Pérez, Grace Torres, Sthephanie Estrada, Clarissa Correa, Natasha Mederos, Kimberly Velazquez, Betzaida Castillo, Kai Griebenow, Yamixa Delgado","doi":"10.3390/biotech12010013","DOIUrl":"10.3390/biotech12010013","url":null,"abstract":"<p><p>Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene that has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds, doxorubicin (Dox) and the triterpene BeA, using an oil-water-like micro-emulsion method. We used spectrophotometric assays to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy, confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h at pH 6.8, while less drug was released at pH 7.4 in this period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against non-small-cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA-(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed the cellular internalization of the DDS and the accumulation of the Dox in the nucleus. We determined the mechanism of action of the BSA-(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10288077","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":"Varietal Differences in Juice, Pomace and Root Biochemical Characteristics of Four Rhubarb (<i>Rheum rhabarbarum</i> L.) Cultivars.","authors":"Viktor Kharchenko,&nbsp;Nadezhda Golubkina,&nbsp;Alessio Tallarita,&nbsp;Maria Bogachuk,&nbsp;Helene Kekina,&nbsp;Anastasia Moldovan,&nbsp;Vladimir Tereshonok,&nbsp;Marina Antoshkina,&nbsp;Olga Kosheleva,&nbsp;Sergey Nadezhkin,&nbsp;Gianluca Caruso","doi":"10.3390/biotech12010012","DOIUrl":"https://doi.org/10.3390/biotech12010012","url":null,"abstract":"<p><p>The complex evaluation of varietal biochemical differences in rhubarb juice, pomace and roots is highly useful to develop an efficient processing technology. Research was carried out to compare four rhubarb cultivars (Malakhit, Krupnochereshkovy, Upryamets and Zaryanka) in terms of the quality and antioxidant parameters of juice, pomace and roots. The laboratory analyses showed a high juice yield (75-82%) with a relatively high content of ascorbic acid (125-164 mg L^-1) and other organic acids (16-21 g L^-1). Citric, oxalic and succinic acids accounted for 98% of the total acids amount. The juice of the cultivar Upryamets demonstrated high levels of the natural preservatives sorbic (36.2 mg L^-1) and benzoic acids (11.7 mg L^-1), which are highly valuable in juice production. The juice pomace proved to be an excellent source of pectin and dietary fiber, whose concentrations reached 21-24% and 59-64%, respectively. The total antioxidant activity decreased according to the following sequence: root pulp (161-232 mg GAE g^-1 d.w.) > root peel (115-170 mg GAE g^-1 d.w.) > juice pomace (28.3-34.4 mg GAE g^-1 d.w.) > juice (4.4-7.6 mg GAE g^-1 f.w.), suggesting that root pulp is a highly valuable antioxidant source. The results of this research highlight the interesting prospects of the complex rhubarb plant processing for the production of juice, containing a wide spectrum of organic acids and natural stabilizers (sorbic and benzoic acids), dietary fiber and pectin (juice pomace) and natural antioxidants (roots).</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765418","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":"Acknowledgment to the Reviewers of <i>BioTech</i> in 2022.","authors":"BioTech Editorial Office","doi":"10.3390/biotech12010011","DOIUrl":"https://doi.org/10.3390/biotech12010011","url":null,"abstract":"<p><p>High-quality academic publishing is built on rigorous peer review [...].</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764931","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":"Recent Developments on the Performance of Algal Bioreactors for CO₂ Removal: Focusing on the Light Intensity and Photoperiods.","authors":"Zarook Shareefdeen,&nbsp;Ali Elkamel,&nbsp;Zaeem Bin Babar","doi":"10.3390/biotech12010010","DOIUrl":"https://doi.org/10.3390/biotech12010010","url":null,"abstract":"<p><p>This work presents recent developments of algal bioreactors used for CO₂ removal and the factors affecting the reactor performance. The main focus of the study is on light intensity and photoperiods. The role of algae in CO₂ removal, types of algal species used in bioreactors and conventional types of bioreactors including tubular bioreactor, vertical airlift reactor, bubble column reactor, flat panel or plate reactor, stirred tank reactor and specific type bioreactors such as hollow fibre membrane and disk photobioreactors etc. are discussed in details with respect to utilization of light. The effects of light intensity, light incident, photoinhibition, light provision arrangements and photoperiod on the performance of algal bioreactors for CO₂ removal are also discussed. Efficient operation of algal photobioreactors cannot be achieved without the improvement in the utilization of incident light intensity and photoperiods. The readers may find this article has a much broader significance as algae is not only limited to removal or sequestration of CO₂ but also it is used in a number of commercial applications including in energy (biofuel), nutritional and food sectors.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603643","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":"High-Level Production of Soluble Cross-Reacting Material 197 in <i>Escherichia coli</i> Cytoplasm Due to Fine Tuning of the Target Gene's mRNA Structure.","authors":"Yulia Alexandrovna Khodak,&nbsp;Alexandra Yurievna Ryazanova,&nbsp;Ivan Ivanovich Vorobiev,&nbsp;Alexander Leonidovich Kovalchuk,&nbsp;Nikolay Nikolaevich Ovechko,&nbsp;Petr Gennadievich Aparin","doi":"10.3390/biotech12010009","DOIUrl":"https://doi.org/10.3390/biotech12010009","url":null,"abstract":"<p><p>Cross-reacting material 197 (CRM197) is a non-toxic mutant of the diphtheria toxin and is widely used as a carrier protein in conjugate vaccines. This protein was first obtained from the supernatant of the mutant <i>Corynebacterium diphtheriae</i> strain. This pathogenic bacteria strain is characterized by a slow growth rate and a relatively low target protein yield, resulting in high production costs for CRM197. Many attempts have been made to establish high-yield protocols for the heterologous expression of recombinant CRM197 in different host organisms. In the present work, a novel CRM197-producing <i>Escherichia coli</i> strain was constructed. The target protein was expressed in the cytoplasm of SHuffle T7 <i>E. coli</i> cells without any additional tags and with a single potential mutation-an additional Met [-1]. The fine tuning of the mRNA structure (the disruption of the single hairpin in the start codon area) was sufficient to increase the CRM197 expression level several times, resulting in 150-270 mg/L (1.1-2.0 mg/g wet biomass) yields of pure CRM197 protein. Besides the high yield, the advantages of the obtained expression system include the absence of the necessity of CRM197 refolding or tag removal. Thus, an extensive analysis of the mRNA structure and the removal of the unwanted hairpins in the 5' area may significantly improve the target protein expression rate.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603642","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":"Formulation of a Simulated Wastewater Influent Composition for Use in the Research of Technologies for Managing Wastewaters Generated during Manned Long-Term Space Exploration and Other Similar Situations-Literature-Based Composition Development.","authors":"Bimi Shrestha,&nbsp;Rafael Hernandez,&nbsp;Dhan Lord B Fortela,&nbsp;Wayne Sharp,&nbsp;Andrei Chistoserdov,&nbsp;Daniel Gang,&nbsp;Emmanuel Revellame,&nbsp;William E Holmes,&nbsp;Mark E Zappi","doi":"10.3390/biotech12010008","DOIUrl":"https://doi.org/10.3390/biotech12010008","url":null,"abstract":"<p><p>The prospect of humans inhabiting planetary bodies is gaining interest among research and development communities, with the moon being considered as a transitory base camp and Mars the next planet humans will inhabit. NASA's Mission to Mars program is set to have humans inhabiting Mars within on-planet space camps by the Year 2030, which has tremendously increased research and development for space exploration-including research oriented toward human life support in long-term planetary lodging camps. The sustenance of human life on Mars will not be trivial due to the unavailability of an appropriate atmosphere and usable water. This situation requires a self-sustaining human life support system that can provide the basic needs such are breathable air, potable water, food, and energy. The feasibility of sending a payload with resources adequate to support long-term human inhabitation is not reasonable, which means every resource within a Mars space camp is valuable, including human-produced wastes. A biorefinery system that treats wastewater and can also produce valuable products such as oxygen, food, and energy offers a form of circular utilization of valuable resources. To conduct research for such systems requires a wastewater influent that is representative of the wastewater to be generated by the space crew within this isolated, confined environment, which is different from what is generated on Earth due to limited variability in diet, human activity, and lifestyle in this confined area. Collection of actual wastewater influent from an isolated environment supporting humans is challenging. Additionally, to ensure a safe working environment in the laboratory and avoid the imposed threat of handling actual human feces, the proposed synthetic, non-human feces containing wastewater influent formulation offers an easy-to-produce and safer-to-handle option. This paper reviews several synthetic wastewater compositions that have been formulated for space exploration purposes. None of the formulations were found to be realistic nor adequate for a space-camp-type scenario. Thus, the formulation of a synthetic wastewater for simulating a wastewater influent from a human space-based camp is proposed in this paper. In addition, the physical, chemical, and biodegradation characteristics of the final formulation designed are presented to illustrate the value of the proposed influent formulation.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603639","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":"An Optimized CoBRA Method for the Microfluidic Electrophoresis Detection of Breast Cancer Associated <i>RASSF1</i> Methylation.","authors":"Claire Aibel,&nbsp;Adriana Coll De Peña,&nbsp;Anubhav Tripathi","doi":"10.3390/biotech12010007","DOIUrl":"https://doi.org/10.3390/biotech12010007","url":null,"abstract":"<p><p>Although breast cancer screening assays exist, many are inaccessible and have high turnaround times, leaving a significant need for better alternatives. Hypermethylation of tumor suppressor genes is a common epigenetic marker of breast cancer. Methylation tends to occur most frequently in the promoter and first exon regions of genes. Preliminary screening tests are crucial for informing patients whether they should pursue more involved testing. We selected <i>RASSF1</i>, previously demonstrated to be aberrantly methylated in liquid biopsies from breast cancer patients, as our gene of interest. Using CoBRA as our method for methylation quantification, we designed unique primer sets that amplify a portion of the CpG island spanning the 5' end of the <i>RASSF1</i> first exon. We integrated the CoBRA approach with a microfluidics-based electrophoresis quantification system (LabChip) and optimized the assay such that insightful results could be obtained without post-PCR purification or concentration, two steps traditionally included in CoBRA assays. Circumventing these steps resulted in a decreased turnaround time and mitigated the laboratory machinery and reagent requirements. Our streamlined technique has an estimated limit of detection of 9.1 ng/μL of input DNA and was able to quantify methylation with an average error of 4.3%.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549897","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":"Novel CaLB-like Lipase Found Using ProspectBIO, a Software for Genome-Based Bioprospection.","authors":"Gabriela C Brêda,&nbsp;Priscila E Faria,&nbsp;Yuri S Rodrigues,&nbsp;Priscila B Pinheiro,&nbsp;Maria Clara R Nucci,&nbsp;Pau Ferrer,&nbsp;Denise M G Freire,&nbsp;Rodrigo V Almeida,&nbsp;Rafael D Mesquita","doi":"10.3390/biotech12010006","DOIUrl":"https://doi.org/10.3390/biotech12010006","url":null,"abstract":"<p><p>Enzymes have been highly demanded in diverse applications such as in the food, pharmaceutical, and industrial fuel sectors. Thus, in silico bioprospecting emerges as an efficient strategy for discovering new enzyme candidates. A new program called ProspectBIO was developed for this purpose as it can find non-annotated sequences by searching for homologs of a model enzyme directly in genomes. Here we describe the ProspectBIO software methodology and the experimental validation by prospecting for novel lipases by sequence homology to <i>Candida antarctica</i> lipase B (CaLB) and conserved motifs. As expected, we observed that the new bioprospecting software could find more sequences (1672) than a conventional similarity-based search in a protein database (733). Additionally, the absence of patent protection was introduced as a criterion resulting in the final selection of a putative lipase-encoding gene from <i>Ustilago hordei</i> (UhL). Expression of UhL in <i>Pichia pastoris</i> resulted in the production of an enzyme with activity towards a tributyrin substrate. The recombinant enzyme activity levels were 4-fold improved when lowering the temperature and increasing methanol concentrations during the induction phase in shake-flask cultures. Protein sequence alignment and structural modeling showed that the recombinant enzyme has high similarity and capability of adjustment to the structure of CaLB. However, amino acid substitutions identified in the active pocket entrance may be responsible for the differences in the substrate specificities of the two enzymes. Thus, the ProspectBIO software allowed the finding of a new promising lipase for biotechnological application without the need for laborious and expensive conventional bioprospecting experimental steps.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549892","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}