Biophysical chemistry最新文献

{"title":"Simulating the anti-aggregative effect of fasudil in early dimerisation process of α-synuclein","authors":"Sneha Menon,&nbsp;Jagannath Mondal","doi":"10.1016/j.bpc.2024.107319","DOIUrl":"10.1016/j.bpc.2024.107319","url":null,"abstract":"<div><p>The aggregation of the protein α-synuclein into amyloid deposits is associated with multiple neurological disorders, including Parkinson's disease. Soluble amyloid oligomers are reported to exhibit higher toxicity than insoluble amyloid fibrils, with dimers being the smallest toxic oligomer. Small molecule drugs, such as fasudil, have shown potential in targeting α-synuclein aggregation and reducing its toxicity. In this study, we use atomistic molecular dynamics simulations to demonstrate how fasudil affects the earliest stage of aggregation, namely dimerization. Our results show that the presence of fasudil reduces the propensity for intermolecular contact formation between protein chains. Consistent with previous reports, our analysis confirms that fasudil predominantly interacts with the negatively charged C-terminal region of α-synuclein. However, we also observe transient interactions with residues in the charged N-terminal and hydrophobic NAC regions. Our simulations indicate that while fasudil prominently interacts with the C-terminal region, it is the transient interactions with residues in the N-terminal and NAC regions that effectively block the formation of intermolecular contacts between protein chains and prevent early dimerization of this disordered protein.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107319"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary structure propensities of the Ebola delta peptide E40 in solution and model membrane environments","authors":"Jiayu Li ,&nbsp;David A. Eagles ,&nbsp;Isaac J. Tucker ,&nbsp;Anneka C. Pereira Schmidt ,&nbsp;Evelyne Deplazes","doi":"10.1016/j.bpc.2024.107318","DOIUrl":"10.1016/j.bpc.2024.107318","url":null,"abstract":"<div><p>The Ebola delta peptide is an amphipathic, 40-residue peptide encoded by the Ebola virus, referred to as E40. The membrane-permeabilising activity of the E40 delta peptide has been demonstrated in cells and lipid vesicles suggesting the E40 delta peptide likely acts as a viroporin. The lytic activity of the peptide increases in the presence of anionic lipids and a disulphide bond in the C-terminal part of the peptide. Previous in silico work predicts the peptide to show a partially helical structure, but there is no experimental information on the structure of E40. Here, we use circular dichroism spectroscopy to report the secondary structure propensities of the reduced and oxidised forms of the E40 peptide in water, detergent micelles, and lipid vesicles composed of neutral and anionic lipids (POPC and POPG, respectively). Results indicate that the peptide is predominately a random coil in solution, and the disulphide bond has a small but measurable effect on peptide conformation. Secondary structure analysis shows large uncertainties and dependence on the reference data set and, in our system, cannot be used to accurately determine the secondary structure motifs of the peptide in membrane environments. Nevertheless, the spectra can be used to assess the relative changes in secondary structure propensities of the peptide depending on the solvent environment and disulphide bond. In POPC-POPG vesicles, the peptide transitions from a random coil towards a more structured conformation, which is even more pronounced in negatively charged SDS micelles. In vesicles, the effect depends on the peptide-lipid ratio, likely resulting from vesicle surface saturation. Further experiments with zwitterionic POPC vesicles and DPC micelles show that both curvature and negatively charged lipids can induce a change in conformation, with the two effects being cumulative. Electrostatic screening from Na⁺ ions reduced this effect. The oxidised form of the peptide shows a slightly lower propensity for secondary structure and retains a more random coil conformation even in the presence of PG-PC vesicles.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107318"},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of sodium dodecyl sulfate, Sarkosyl and sodium lauroyl glutamate on the structure of proteins monitored by agarose native gel electrophoresis and circular dichroism","authors":"Teruo Akuta ,&nbsp;Tomoto Ura ,&nbsp;Takeshi Oikawa ,&nbsp;Yui Tomioka ,&nbsp;Akiko Eguchi ,&nbsp;Tsutomu Arakawa","doi":"10.1016/j.bpc.2024.107316","DOIUrl":"10.1016/j.bpc.2024.107316","url":null,"abstract":"<div><p>We have studied binding properties of three detergents, i.e., sodium dodecyl sulfate (SDS), Sarkosyl and sodium lauroyl glutamate (SLG), to model proteins based on their effects on electrophoretic mobilities of the proteins using agarose native gel electrophoresis and circular dichroism (CD). This simple technology can evaluate the dissociative properties of bound detergents from the proteins and their effects on protein structure. SDS influenced the electrophoretic mobilities of all model proteins more strongly than the other two detergents, implying a stronger inclination for protein binding and subsequent alterations in protein structure or reductions in activity, which are supported by CD analysis. On the contrary, Sarkosyl and SLG showed weaker binding and interfered less with the structure and biological activities, indicating that these detergents may be useful for protein purification and analysis. It appeared that SLG was weaker in protein binding than Sarkosyl, although the effects of these two detergents appeared to depend on the proteins.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107316"},"PeriodicalIF":3.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis of aptamer-RNA conjugate interactions with human transferrin receptor","authors":"Daniel Vasconcelos ,&nbsp;André Pina ,&nbsp;Nagy Habib ,&nbsp;Sérgio Sousa","doi":"10.1016/j.bpc.2024.107308","DOIUrl":"10.1016/j.bpc.2024.107308","url":null,"abstract":"<div><p>The human transmembrane protein Transferrin Receptor-1 is regarded as a promising target for the systemic delivery of therapeutic agents, particularly of nucleic acid therapeutics, such as short double stranded RNAs. This ubiquitous receptor is involved in cellular iron uptake, keeping intracellular homeostasis. It is overexpressed in multiple cancer cell types and is internalized via clathrin-mediated endocytosis. In previous studies, a human transferrin receptor-1 RNA aptamer, identified as TR14 ST1–3, was shown to be capable of effectively internalizing into cells in culture and to deliver small, double stranded RNAs in vitro and in vivo, via systemic administration.</p><p>To understand, at the molecular level, the aptamer binding to the receptor and the impact of conjugation with the therapeutic RNA, a multi-level in silico protocol was employed, including protein-aptamer docking, molecular dynamics simulations and free energy calculations. The competition for the binding pocket, between the aptamer and the natural ligand human Transferrin, was also evaluated.</p><p>The results show that the aptamer binds to the same region as Transferrin, with residues from the helical domain showing a critical role. Moreover, the conjugation to the therapeutic RNA, was shown not to affect aptamer binding. Overall, this study provides an atomic-level understanding of aptamer association to human Transferrin Receptor-1 and of its conjugation with a short model-therapeutic RNA, providing also important clues for futures studies aiming to deliver other oligonucleotide-based therapeutics via Transferrin Receptor.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107308"},"PeriodicalIF":3.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introns with branchpoint-distant 3′ splice sites: Splicing mechanism and regulatory roles","authors":"Anupa T Anil ,&nbsp;Rakesh Pandian ,&nbsp;Shravan Kumar Mishra","doi":"10.1016/j.bpc.2024.107307","DOIUrl":"10.1016/j.bpc.2024.107307","url":null,"abstract":"<div><p>The two transesterification reactions of pre-mRNA splicing require highly complex yet well-controlled rearrangements of small nuclear RNAs and proteins (snRNP) in the spliceosome. The efficiency and accuracy of these reactions are critical for gene expression, as almost all human genes pass through pre-mRNA splicing. Key parameters that determine the splicing outcome are the length of the intron, the strengths of its splicing signals and gaps between them, and the presence of splicing controlling elements. In particular, the gap between the branchpoint (BP) and the 3′ splice site (ss) of introns is a major determinant of the splicing efficiency. This distance falls within a small range across the introns of an organism. The constraints exist possibly because BP and 3'ss are recognized by BP-binding proteins, U2 snRNP and U2 accessory factors (U2AF) in a coordinated manner. Furthermore, varying distances between the two signals may also affect the second transesterification reaction since the intervening RNA needs to be accurately positioned within the complex RNP machinery. Splicing such pre-mRNAs requires cis-acting elements in the RNA and many trans-acting splicing regulators. Regulated pre-mRNA splicing with BP-distant 3'ss adds another layer of control to gene expression and promotes alternative splicing.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107307"},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhamnolipids and fengycins interact differently with biomimetic lipid membrane models of Botrytis cinerea and Sclerotinia sclerotiorum: Lipidomics profiles and biophysical studies","authors":"Camille Botcazon ,&nbsp;Francisco Ramos-Martín ,&nbsp;Nely Rodríguez-Moraga ,&nbsp;Thomas Bergia ,&nbsp;Sébastien Acket ,&nbsp;Catherine Sarazin ,&nbsp;Sonia Rippa","doi":"10.1016/j.bpc.2024.107305","DOIUrl":"10.1016/j.bpc.2024.107305","url":null,"abstract":"<div><p>Rhamnolipids (RLs) and Fengycins (FGs) are biosurfactants with very promising antifungal properties proposed to reduce the use of synthetic pesticides in crops. They are amphiphilic molecules, both known to target the plasma membrane. They act differently on <em>Botrytis cinerea</em> and <em>Sclerotinia sclerotiorum</em>, two close Sclerotiniaceae phytopathogenic fungi. RLs are more efficient at permeabilizing <em>S. sclerotiorum,</em> and FGs are more efficient at permeabilizing <em>B. cinerea</em> mycelial cells. To study the link between the lipid membrane composition and the activity of RLs and FGs, we analyzed the lipid profiles of <em>B. cinerea</em> and <em>S. sclerotiorum</em>. We determined that unsaturated or saturated C18 and saturated C16 fatty acids are predominant in both fungi. We also showed that phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylcholine (PC) are the main phospholipids (in this order) in both fungi, with more PA and less PC in <em>S. sclerotiorum</em>. The results were used to build biomimetic lipid membrane models of <em>B. cinerea</em> and <em>S. sclerotiorum</em> for all-atom molecular dynamic simulations and solid-state NMR experiments to more deeply study the interactions between RLs or FGs with different compositions of lipid bilayers. Distinctive effects are exerted by both compounds. RLs completely insert in all the studied model membranes with a fluidification effect. FGs tend to form aggregates out of the bilayer and insert individually more easily into the models representative of <em>B. cinerea</em> than those of <em>S. sclerotiorum</em>, with a higher fluidification effect. These results provide new insights into the lipid composition of closely related fungi and its impact on the mode of action of very promising membranotropic antifungal molecules for agricultural applications.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107305"},"PeriodicalIF":3.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing and gauging of D-Penicillamine xenobiotics in hepatic Wilson disease patients","authors":"Ashish Gupta ,&nbsp;Moinak Sen Sarma ,&nbsp;Anuj Kumar ,&nbsp;Khushbhu Meena ,&nbsp;Bikash Baishya ,&nbsp;Amrita Mathias ,&nbsp;Amresh Kumar Mishra ,&nbsp;Neeraj Kumar Rao ,&nbsp;Nitu Singh ,&nbsp;Parul Singh","doi":"10.1016/j.bpc.2024.107306","DOIUrl":"10.1016/j.bpc.2024.107306","url":null,"abstract":"<div><p>D-penicillamine (PA) is the primary chelator of choice to treat Wilson disease (WD). There are limitations in obtaining comprehensive data on PA metabolites in biological specimens by conventional approaches. Hence, the aim of the present was to identify the major hepatic PA metabolites and draw clear conclusions of the drug's xenobiotic in WD. Urine samples were collected from children with hepatic WD (<em>n</em> = 63, aged 14.8 ± 4 years) 5 h after PA administration (16.3 ± 3.8 mg/kg/day) and age-matched healthy volunteers comprised as controls (<em>n</em> = 30). High-resolution 800 MHz nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry was applied to reveal unambiguous appraisals of different excretory by-products of PA metabolism. Four new products comprising penicillamine disulphide (PD), penicillamine cysteine disulphide (PCD), <em>S</em>-methyl penicillamine (SMP), and <em>N</em>-acetyl penicillamine (NAP) of PA xenobiotic metabolites were identified using high-resolution NMR spectroscopy. Quantitative levels of PCD and SMP were approximately three-fold higher than those of PD and NAP, respectively. High-resolution NMR identifies the major PA metabolites with certainty. Reduction, sulfation, and methylation are the predominant pathways of PA metabolism. There is a potential application for assessing therapeutic monitoring of chelation in hepatic WD.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"313 ","pages":"Article 107306"},"PeriodicalIF":3.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NTPs compete in the active site of RNA polymerases I and II","authors":"Kaila B. Fuller ,&nbsp;Ryan M. Requijo ,&nbsp;David A. Schneider ,&nbsp;Aaron L. Lucius","doi":"10.1016/j.bpc.2024.107302","DOIUrl":"10.1016/j.bpc.2024.107302","url":null,"abstract":"<div><p>Eukaryotes express at least three RNA polymerases (Pols) carry out transcription, while bacteria and archaea use only one. Using transient state kinetics, we have extensively examined and compared the kinetics of both single and multi-nucleotide additions catalyzed by the three Pols. In single nucleotide addition experiments we have observed unexpected extension products beyond one incorporation, which can be attributed to misincorporation, the presence of nearly undetectable amounts of contaminating NTPs, or a mixture of the two. Here we report the development and validation of an analysis strategy to account for the presence of unexpected extension products, when they occur. Using this approach, we uncovered evidence showing that non-cognate nucleotide, thermodynamically, competes with cognate nucleotide for the active site within the elongation complex of Pol I, ΔA12 Pol I, and Pol II. This observation is unexpected because base pairing interactions provide favorable energetics for selectivity and competitive binding indicates that the affinities of cognate and non-cognate nucleotides are within an order of magnitude. Thus, we show that application of our approach will allow for the extraction of additional information that reports on the energetics of nucleotide entry and selectivity.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"314 ","pages":"Article 107302"},"PeriodicalIF":3.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring solid-state DNP methods to the study of α-synuclein LLPS","authors":"Ribal Jabbour ,&nbsp;Sreejith Raran-Kurussi ,&nbsp;Vipin Agarwal ,&nbsp;Asif Equbal","doi":"10.1016/j.bpc.2024.107303","DOIUrl":"10.1016/j.bpc.2024.107303","url":null,"abstract":"<div><p>Dynamic Nuclear Polarization (DNP) is a technique that leverages the quantum sensing capability of electron spins to enhance the sensitivity of nuclear magnetic resonance (NMR) signals, especially for insensitive samples. Glassing agents play a crucial role in the DNP process by facilitating the transfer of polarization from the unpaired electron spins to the nuclear spins along with cryoprotection of biomolecules. <span><math><mi>DNP</mi><mspace></mspace><mi>juice</mi></math></span> comprising of glycerol-<span><math><msub><mi>d</mi><mn>8</mn></msub></math></span>/<span><math><msub><mi>D</mi><mn>2</mn></msub><mi>O</mi></math></span>/<span><math><msub><mi>H</mi><mn>2</mn></msub><mi>O</mi></math></span> has been extensively used for this purpose over the past two decades. Polyethylene glycol (PEG), also used as a cryoprotectant, is often used as a crowding agent in experimental setups to mimic cellular conditions, particularly the <span><math><mi>in</mi><mspace></mspace><mi>vitro</mi></math></span> preparation of liquid-liquid phase separated (LLPS) condensates. In this study, we investigate the efficacy of PEG as an alternative to glycerol in the <em>DNP juice</em>, critical for signal enhancement. The modified DNP matrix leads to high DNP enhancement which enables direct study of LLPS condensates by solid-state DNP methods without adding any external constituents. An indirect advantage of employing PEG is that the PEG signals appear at <span><math><mo>∼</mo></math></span>72.5 ppm and are relatively well-separated from the aliphatic region of the protein spectra. Large cross-effect DNP enhancement is attained for <span><math><msup><mrow></mrow><mn>13</mn></msup><mi>C</mi></math></span>-glycine by employing the PEG-water mixture as a glassing agent and ASYMPOL-POK as the state-of-art polarizing agent, without any deuteration. The DNP enhancement and the buildup rates are similar to results obtained with <em>DNP juice</em>, conforming to that PEG serves as a good candidate for both inducing crowding and glassing agent in the study of LLPS.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"313 ","pages":"Article 107303"},"PeriodicalIF":3.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum","authors":"Emadeldin M. Kamel ,&nbsp;Faris F. Aba Alkhayl ,&nbsp;Haifa A. Alqhtani ,&nbsp;May Bin-Jumah ,&nbsp;Hassan A. Rudayni ,&nbsp;Al Mokhtar Lamsabhi","doi":"10.1016/j.bpc.2024.107304","DOIUrl":"10.1016/j.bpc.2024.107304","url":null,"abstract":"<div><p>Unraveling the intricacies of β-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some <em>Hibiscus trionum</em> phytochemicals as β-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC₅₀ values of 3.97 ± 0.35 μM and 10.32 ± 1.85 μM, respectively. Mechanistic analysis of β-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against β-glucuronidase, while mansonone H exhibited noncompetitive inhibition against β-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with β-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with β-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as β-glucuronidase inhibitors.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"313 ","pages":"Article 107304"},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141838385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}