ACS Bio & Med Chem Au最新文献

{"title":"Leveraging the Gut Microbiota for Mechanistically Informed Therapeutics against Body-First Parkinson’s Disease","authors":"Julia M. Balsamo,&nbsp;Elizabeth N. Bess","doi":"10.1021/acsbiomedchemau.6c00110","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00110","url":null,"abstract":"<p>Althoughsome symptoms of Parkinson’s disease can be pharmacologicallyalleviated, stopping disease progression is not currently possible.Motor impairment in Parkinson’s disease is associated withaccumulation of aggregates of the protein α-synuclein (α-syn)in dopaminergic neurons in the brain. In some Parkinson’s diseasecases, these pathogenic aggregates accumulate in the intestinal liningyears before motor symptoms manifest. This long prodromal period providesa window of opportunity to detect Parkinson’s disease and haltits progression. Specifically, elucidating the factors involved indisease onset in the gut would enable prevention of α-syn aggregationbefore it spreads to the brain. In this perspective, we highlightdiscoveries of gut bacteria that induce aggregation of intestinalα-syn as well as efforts to decipher the molecular-level mechanismsby which this process occurs. We also showcase the rationale and potentialbreadth of applications focused on manipulating the gut microbiome,including biotics, fecal microbiome transplants, and microbial editing.By understanding molecular mechanisms of intestinal α-syn aggregation,the microbiome may be harnessed to control the factors responsiblefor their pathogenic formation and spread. Such insights will ultimatelyenable the development of more effective therapeutics for preventionand treatment of Parkinson’s disease.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"508–521"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational Tuning of Intracellular Release Kinetics in PROTAC–Peptide Conjugates via Positional Modulation of Functional Peptide Domains","authors":"Maho Miyamoto,&nbsp;Atsuki Hirama,&nbsp;Kosuke Saito,&nbsp;Naoki Shida,&nbsp;Mahito Atobe,&nbsp;Hidetomo Yokoo,&nbsp;Yosuke Demizu","doi":"10.1021/acsbiomedchemau.6c00158","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00158","url":null,"abstract":"<p>Proteolysis-targetingchimeras (PROTACs) can induce degradationof otherwise challenging proteins, but their large size and unfavorablephysicochemical properties often limit cellular delivery. We designedPROTAC–peptide conjugates containing a nona-arginine cell-penetratingpeptide (<strong>R9</strong>), a redox-sensitive disulfide linker, andan aromatic-rich peptide sequence previously described as an endosomalescape domain (EED). The EED sequence was positioned at either theN- or C-terminus to examine how peptide-domain arrangement affectsintracellular fluorescence, payload release, and BRD4 degradation.At 10 and 100 nM, the C-terminal variant <strong>MZ1-R9-EED</strong> produceda greater reduction in BRD4 abundance at 24 h than <strong>MZ1-R9</strong> and <strong>MZ1-EED-R9</strong>, although the two-concentration comparisondid not permit determination of DC₅₀, <em>D</em>_max, or hook effects. FAM-based flow cytometry yieldedpH-sensitive cell-associated fluorescence signals that could not beinterpreted as an absolute measure of total cellular uptake. Qualitativeconfocal microscopy showed punctate fluorescence with apparent LysoTrackeroverlap but did not provide quantitative evidence of endosomal escape.Under a defined cell-free reducing condition, <strong>MZ1-R9-EED</strong> underwent faster apparent disulfide cleavage, with a half-life of0.21 h versus 0.36–0.47 h for the other conjugates, and yieldedhigher apparent intracellular free <strong>MZ1</strong> levels under identicalanalytical conditions. Square-wave voltammetry revealed no substantialdifferences in reduction potential, whereas molecular dynamics simulationssuggested a possible contribution of local steric accessibility. Thesefindings associate peptide-domain positioning with cleavage kinetics,free-payload levels, and BRD4 reduction, identifying domain arrangementas a design variable for disulfide-linked PROTAC–peptide conjugateswithout establishing cleavage as the rate-limiting or causal mechanism.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"744–751"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Structural and Dynamic Perspective on Xenobiotic Metabolism by Cytochrome P450","authors":"Vaibhav Bhatt,&nbsp;Kshatresh Dutta Dubey","doi":"10.1021/acsbiomedchemau.6c00119","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00119","url":null,"abstract":"<p>Xenobiotic detoxificationis the biotransformation of exogenouscompounds entering the human body through enzymatic catalysis in orderto assist their eventual elimination. In the past, static active-sitemodels that mainly focus on substrate binding and oxidation chemistryhave been employed to understand the xenobiotic functionality of CYP450s.However, modern computational approaches in the field of enzymologyhave changed this perspective, which show that the P450 machineryutilizes significant structural flexibility and electrostatic controlto achieve its function. This review aims to unify these developmentsinto an integrated mechanistic framework that encompasses substrateorientation, conformational gating, catalytic-site organization, transientwater-channel assembly, and modulation of the electronic-structurelandscape via classical electrostatic and steric confinement. Specialfocus has been given on how flexible loops/helices, gating residues,transient access channels, along with second-shell residues, dictatexenobiotic accommodation, regio-, stereo-, and chemoselectivity acrossvarious members of the CYP450 superfamily.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"544–559"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When, Where, and How Much: Toward Smarter Design and Delivery of CAR T-Cell Therapy","authors":"Eshwar Sathiyamoorthy,&nbsp;Nikhita H. Poole,&nbsp;Heather H. Gustafson","doi":"10.1021/acsbiomedchemau.6c00127","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00127","url":null,"abstract":"<p>Chimeric antigen receptor (CAR) T-cell therapies havefundamentallyreshaped clinical oncology by achieving durable remissions in refractoryhematologic malignancies. However, their broader translation remainsbottlenecked by severe, treatment-associated hyperinflammatory toxicities,including cytokine release syndrome (CRS), immune effector cell–associatedneurotoxicity syndrome (ICANS), and immune effector cell-associatedhemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Currentmanagement strategies are reactive and rely on systemic immunosuppressants,such as corticosteroids and the anti-IL-6 receptor antibody tocilizumab.While these interventions blunt acute inflammation, they can exertsystemic effects that have the possibility to impair CAR-T cell persistence,prolong cytopenias, and compromise long-term antitumor efficacy. Inthis review, we challenge the conventional paradigm that treats toxicityas a uniform, unavoidable consequence of systemic immune activation.Instead, we present emerging evidence demonstrating that CAR-T-associatedtoxicities possess discrete spatial, temporal, and kinetic organizationacross distinct tissue compartments and biological phases. We proposea cohesive engineering framework that leverages advanced drug deliverytechnologies to convert toxicity management from a reactive clinicalhurdle into a systems-level design problem. By organizing future therapeuticstrategies around three core pillars: temporal control (gating interventionsto specific phases of immune escalation), dosing and kinetic control(flattening proliferation slopes via fractionated delivery, dynamicfeedback loops, and mathematical modeling), and spatial control (anatomicaltargeting of inflamed vasculature, lymphoid organs, and the centralnervous system), it may be possible to selectively decouple localizedtoxic inflammatory cascades from therapeutic CAR-T cell expansion.Ultimately, integrating these spatiotemporal and kinetic parametersprovides a blueprint for engineering the next generation of safer,scalable, and highly efficacious cellular immunotherapies.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"579–593"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Assembly of a Fully Functionalized-Fragment Library for Photoaffinity Labeling Applications via Mild A3-Coupling in Water","authors":"Thomas Bauhoff,&nbsp;Andrea Federici,&nbsp;Andreas Gollner,&nbsp;Peter Gärtner,&nbsp;Nicolas Kratena","doi":"10.1021/acsbiomedchemau.6c00160","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00160","url":null,"abstract":"<p>In classical photoaffinity labeling (PAL) probes, diazirineandalkyne handles are attached via a flexible spacer, which inherentlymodulates biological activity. We herein report a diazirine-tolerantA³-coupling (aldehyde–amine–alkyne) catalyzedby AuCl₃ in water at room temperature, enabling directassembly of fully functionalized fragments (FFFs) with rigidly positionedcross-linking and retrieval tags. This mild protocol accommodatesdiverse aldehydes endowed with benzenes or aliphatic systems, andso far underdeveloped heteroaromatic moieties such as pyridines, quinolines,and indoles, thus delivering FFFs exhibiting more complex structuralscaffolds, which are of interest in medicinal chemistry. Postfunctionalizationvia a mild Suzuki coupling demonstrates how chemical diversity canbe further expanded. A library of over 60 compounds were accessed,establishing the methodology’s broad scope. Furthermore, biologicaltesting tentatively showed that these new probes exhibit reactivitywith the proteome, enabling labeling in human cells.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"752–760"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Thioether Crosslinks Installed by a SPASM-Containing Radical SAM Enzyme from Methanogenic Archaea","authors":"Emily M. Dieter,&nbsp;Austin M. Woodard,&nbsp;Jared C. Green,&nbsp;Jin Xiong,&nbsp;Yisong Guo,&nbsp;William E. Broderick,&nbsp;Douglas A. Mitchell,&nbsp;Joan B. Broderick","doi":"10.1021/acsbiomedchemau.6c00133","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00133","url":null,"abstract":"<p>Cysteine is a vitalamino acid with wide biological utility,servingfunctions in catalysis, ligand binding, and maintenance of proteinstructures. In a subset of natural products, termed ribosomally synthesizedand post-translationally modified peptides (RiPPs), multiple subclassesare defined by the enzymatic modification of cysteine residues toform thioether bridges. However, RiPPs are short peptides and experimentalvalidation of enzymatically installed thioether crosslinks on largeprotein substrates is limited. We hypothesized that cysteine-richproteins whose genes are adjacent to those for enzymes predicted tocatalyze RiPP-like modifications might be substrates for such modifications.Thus, we set out to investigate cysteine-rich prokaryotic proteomesfor such examples. A bioinformatic analysis identified methanogenicarchaea as suitable candidates for further investigation due to thehigh overall proteome cysteine content, and through targeted proteomescanning, we identified a suitable biosynthetic gene cluster (BGC;Crp) from <em>Methanococcus voltae</em> to characterize.Purification and reconstitution of an annotated radical <em>S</em>-adenosyl-<span>l</span>-methionine (RS) enzyme, CrpC, confirmed thatthe protein binds three [4Fe-4S] clusters, two of which are in a SPASMdomain. Enzyme assays determined that CrpC is active after reconstitutionand modifies a cysteine-rich protein substrate in the same BGC, CrpA.Mass spectrometry and chemical derivatization of modified CrpA indicatesthat CrpC installs ranthionine crosslinks onto CrpA. This researchprovides a new path for the discovery of intriguing BGCs and post-translationalmodifications and provides a foundation for the complete structuralelucidation and assessment of the native biological function of thesemodified cysteine-rich proteins.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"694–707"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Peptides Beyond the Petri Dish: Translational Barriers to Therapeutic Development","authors":"Marc Torrent","doi":"10.1021/acsbiomedchemau.6c00126","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00126","url":null,"abstract":"<p>Antimicrobial peptides (AMPs) are promising antibioticswith rapidbactericidal mechanisms, broad-spectrum activity, and efficacy againstdrug-resistant pathogens. Yet, despite decades of research and developmentof many active AMPs, translation to the clinic remains limited. AlthoughAMPs kill bacteria efficiently under optimized conditions, the sameproperties that enable membrane disruption - cationic charge, amphipathicity,and hydrophobicity - also cause their sequestration, degradation,and inactivation in biological fluids and tissues. This review examineshow the major administration routes shape AMP pharmacokinetics andidentifies the barriers that must be overcome for effective clinicaltranslation. Each route imposes different limitations: oral deliveryis limited by proteolytic degradation, bile sequestration, and poorabsorption; intravenous administration by plasma protein binding,proteolysis, restricted tissue penetration, and nephrotoxicity; inhaleddelivery by sequestration and inactivation in mucus and pulmonarysurfactant; and topical delivery by impaired diffusion, sequestration,and proteolysis within wound and biofilm matrices. These limitationsshould be addressed from the outset of AMP design, with clear strategieson how to control serum binding, protect against protease digestion,and optimize charge and hydrophobic moment, to off–target interactionsand toxicity. A pharmacologically informed approach that incorporatesthese barriers as design constraints is essential to transform AMPsinto clinically effective drugs.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"594–614"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemically Induced Proximity in Biological Modulation","authors":"Xiaokang Jin,&nbsp;Chen Zhou,&nbsp;Xiaoyu Zhang","doi":"10.1021/acsbiomedchemau.6c00121","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00121","url":null,"abstract":"<p>Proximity is a fundamental prerequisite for a diverserange ofbiological processes. Chemically induced proximity strategies exploitthis principle to achieve the controllable modulation of targets ofinterest through programmable biomolecular interactions. By rewiringbiological interactions, induced-proximity technologies can regulateprotein stability, activity, localization, transcription, and signaling.Recent advances have greatly expanded the repertoire of recruitableeffector proteins, enabling the manipulation of challenging targetspreviously considered intractable. In this review, we summarize theconceptual evolution and mechanistic diversity of induced-proximitytechnologies, highlighting platforms for targeted protein degradation,stabilization, post-translational modification editing, protein relocalization,and transcriptional control.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"560–578"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human DOPA Decarboxylase in Monoamine Metabolism, Pharmacology, and Synucleinopathies","authors":"Davide Chiasserini,&nbsp;Giovanni Bellomo,&nbsp;Pier Luigi Orvietani,&nbsp;Mirco Dindo","doi":"10.1021/acsbiomedchemau.6c00141","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00141","url":null,"abstract":"<p>Human DOPA decarboxylase is the pyridoxal 5′-phosphate-dependentenzyme that produces dopamine and serotonin. For most of its historyit has been treated as a constitutive downstream step rather thana point of regulation, and it has received correspondingly littlemechanistic attention. The human enzyme is broadly expressed acrosscentral monoaminergic neurons and peripheral neuroendocrine tissues,where it operates in different chemical environments and under differentpharmacological constraints. Structurally, it interconverts betweenan open, cofactor-free apo-form and a closed, catalytically competentholo-form, with conformational dynamics that extend well beyond theactive site. Its activity is further tuned by cofactor availability,by phosphorylation, and by protein partners, of which the most notableis α-synuclein Its effect on the enzyme is documented in cellularsystems but still unresolved at the molecular level. Pharmacologically,carbidopa is its principal peripheral inhibitor, but its mechanismremains incompletely characterized, and chronic therapy raises ratherthan lowers circulating AADC levels. In parallel, AADC measured incerebrospinal fluid has emerged as one of the most discriminatingfluid biomarkers for Parkinson’s disease and dementia withLewy bodies, with changes detectable years before motor onset. Thesedifferent layers, structural, regulatory, pharmacological, and diagnostic,converge on a single enzyme whose biology has long been treated assettled, and which is now being reevaluated as a fundamental nodein the molecular landscape of synucleinopathies.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"615–625"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino Acids in the RSSY Motif of Lipoyl Synthase Control Substrate Binding and Reactivity","authors":"Vivian Robert Jeyachandran,&nbsp;Nicholas D. Lanz,&nbsp;Maria-Eirini Pandelia,&nbsp;Justin M. Rectenwald,&nbsp;Jay V. Pendyala,&nbsp;Ravi K. Maurya,&nbsp;Amie K. Boal,&nbsp;Carsten Krebs,&nbsp;Squire J. Booker","doi":"10.1021/acsbiomedchemau.6c00105","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.6c00105","url":null,"abstract":"<p>The last step in the biosynthesis of the lipoyl cofactor(LipCo)is the addition of two sulfur atoms at C6 and C8 of an <em>n</em>-octanoyl chain attached by an amide linkage to a target lysyl residueof a lipoyl carrier protein. This reaction is catalyzed by lipoylsynthase, a member of the radical <em>S</em>-adenosylmethionine(SAM) superfamily. Lipoyl synthase requires two [4Fe-4S] clusters.One cluster is used to cleave SAM reductively to generate two 5′-deoxyadenosyl5′-radicals (5′-dA•), which abstract the C6 andC8 hydrogen atoms (H•) of the substrate in two sequential steps.The second cluster, termed the auxiliary cluster, is consumed duringturnover to provide the attached sulfur atoms. The auxiliary clusteris ligated by three cysteines in a CX₄CX₅C motifand one serine residue (Ser308 in <em>Escherichia coli</em>) in a highly conserved R³⁰⁶SS³⁰⁸Y motif inthe C-terminal region of the protein. Here, we show that Arg306 andSer308 are absolutely required for LipCo formation. Substitution ofArg306 with Lys results in an essentially inactive protein due topoor substrate binding and positioning in the active site. Multiplesubstitutions of Ser308 were engineered. Most notably, the S308C andS308A variants greatly diminished LipCo formation. However, the S308Cvariant resulted in greater production of the 6-mercaptooctanoyl intermediateand the formation of a desaturated product, identified as a 6-octenoylgroup. Furthermore, the 3Fe cluster formed during degradation of theauxiliary cluster in the course of C6 sulfur substitution in the wild-typereaction is not observed with the S308C variant. Instead, the auxiliarycluster remains tetranuclear and forms a monothiolated cross-linkedspecies with a high-spin, <em>S</em> = 7/2 configuration thatdecays to the 6-octenoyl-containing product. Other amino acids inthe RSSY motif were not essential for catalysis.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"6 5","pages":"676–693"},"PeriodicalIF":3.5,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}