ACS Chemical Neuroscience最新文献

{"title":"Differential Effects of Aβ Peptides on the Plasmin-Dependent Degradation of ApoE3 and ApoE4.","authors":"Merc M Kemeh, Anthony J Furnelli, Noel D Lazo","doi":"10.1021/acschemneuro.5c00065","DOIUrl":"https://doi.org/10.1021/acschemneuro.5c00065","url":null,"abstract":"<p><p>The <i>ApoE4</i> allele of apolipoprotein E (ApoE4) is the strongest hereditary predisposition to Alzheimer's disease, even though ApoE4 only differs from the more common ApoE3 by a single amino acid substitution. Previous studies have shown that ApoE4 is more susceptible to proteolytic degradation than ApoE3. This is an important finding because of ApoE's role in cholesterol homeostasis and lipid transport in the brain. The molecular determinants of the increased susceptibility of ApoE4 to proteolysis are unknown. Here, we apply a combination of spectrometric and spectroscopic methods to show that amyloid-β (Aβ) peptides, including Aβ(1-40) and Aβ(pyroE3-42), differentially modulate the plasmin-dependent degradation of ApoE3 and ApoE4. In particular, our data reveal that while the Aβ peptides do not affect the proteolysis of ApoE3, the peptides enhance the degradation of ApoE4 significantly. Overall, this work motivates therapeutic development that targets the Aβ-induced dysregulation of ApoE4 homeostasis in individuals carrying the <i>ApoE4</i> allele.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of α-Synuclein Fibrillation and Toxicity by 4-Phenylbutyric Acid.","authors":"Kristos Baffour, Neelima Koti, Tony Nyabayo, Sathvika Balerao, Carissa Sutton, David Johnson, Rishi Patel, Santimukul Santra, Tuhina Banerjee","doi":"10.1021/acschemneuro.4c00709","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00709","url":null,"abstract":"<p><p>The protein misfolding and aggregation of α-synuclein (α-Syn) into neurotoxic amyloids underlies the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Emerging evidence suggests that 4-phenylbutyrate (PBA) may play a role as a potential chemical chaperone for targeting α-Syn aggregation, but its molecular mechanism remains largely unknown. Using in vitro assays, we demonstrate that PBA treatment alters the pattern of α-Syn aggregation, as evidenced by reduced formation of oligomeric species and its increased susceptibility to proteolytic cleavage under the influence of PBA. Proteinase K (PK) assays, surface plasmon resonance (SPR), Nile red assays, and cytotoxicity assays indicate that PBA interacts with the extensive hydrophobic contacts of α-Syn oligomers and significantly reduces α-Syn-amyloid-induced toxicity. Furthermore, using thioflavin T-based assays, we elucidated the kinetics of PBA-mediated modulation of α-Syn aggregation, highlighting its role in accelerating the formation of α-Syn amyloid fibrils. Molecular dynamics (MD) simulations suggest PBA's role in the destabilization of the C-terminus in α-Syn oligomers through multiple residue interactions. Collectively, our findings provide compelling evidence for the neuroprotective potential of PBA in targeting protein misfolding and aggregation in PD and suggest an avenue for disease-modifying interventions in neurodegenerative disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procognitive Potential of Neuroprotective Triazine 5-HT₆ Receptor Antagonists Tested on Chronic Activity In Vivo in Rats: Computer-Aided Insight into the Role of Chalcogen-Differences on the Pharmacological Profile.","authors":"Magdalena Jastrzębska-Więsek, Sabrina Garbo, Agnieszka Cios, Natalia Wilczyńska-Zawal, Anna Partyka, Ewelina Honkisz-Orzechowska, Ewa Żesławska, Jarosław Handzlik, Barbara Mordyl, Monika Głuch-Lutwin, Alessia Raucci, Marius Hittinger, Małgorzata Starek, Monika Dąbrowska, Wojciech Nitek, Tadeusz Karcz, Alicja Skórkowska, Joanna Gdula-Argasińska, Kinga Czarnota-Łydka, Patryk Pyka, Ewa Szymańska, Katarzyna Kucwaj-Brysz, Clemens Zwergel, Anna Wesołowska, Cecilia Battistelli, Jadwiga Handzlik","doi":"10.1021/acschemneuro.4c00873","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00873","url":null,"abstract":"<p><p>Among serotonin receptors, the 5-HT₆ subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. This study aimed to extend the body of preclinical research on two naphthyl-derived methylpiperazine-1,3,5-triazine analogues with thioether (<b>WA-22</b>) or Se-ether (<b>PPK-32</b>) linkers, the newly described compounds having high affinity and selectivity for 5-HT₆ receptors and drug-like parameters in vitro. Thus, crystallography-supported deeper insight into their chemical properties, the comparison of their neuroprotective and pharmacokinetic profiles, and especially their impact on memory disturbances after chronic administration to rats were investigated. As a result, the chronic administration of <b>WA-22</b> completely reversed <b>(+)MK-801</b>-induced memory disturbances evaluated in the novel object recognition test (NORT) in rats. The pharmacokinetic and biochemical results support the notion that this 1,3,5-triazine 5-HT₆ receptor ligand could offer a promising therapeutic tool in CNS-related disorders. The selenium compound <b>PPK-32</b>, with a similar range of activity at acute administration, has shown even broader neuroprotective profiles, especially at the genetic level. However, for therapeutic use, its weaker pharmacokinetics (stability), which is a probable limit for action upon chronic administration, would require improvement, e.g., by an appropriate formulation.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the Parkinson's Disease-Related Protein DJ-1 by Endogenous Neurotoxins of the 1,2,3,4-Tetrahydroisoquinoline Family.","authors":"Catherine Laurent, Gabrielle Poncet, Tristan Herskovits, Rodolphe Alves de Sousa, Laurent Le Corre, Mohammed Al-Azzani, Annekatrin Koenig, Serge Birman, Tiago Fleming Outeiro, Daniel Mansuy, Julien Dairou","doi":"10.1021/acschemneuro.4c00559","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00559","url":null,"abstract":"<p><p>The protein DJ-1 appears to play a protective role in the development of Parkinson's disease (PD). Here, we show that endogenous neurotoxins of the 1,2,3,4-tetrahydroisoquinoline family (TIQs), formed upon reaction of various aldehydes such as methylglyoxal (MGO) with the neurotransmitter dopamine, act as irreversible inhibitors of the esterase activity of human DJ-1, with IC50 values between 15 and 57 μM. The presence of a catechol function appears to be essential for these inhibitory effects, which may be at the origin of the oxidation of cysteine 106, a crucial residue in the DJ-1 active site, thereby leading to DJ-1 inhibition. We also show that these endogenous neurotoxins inhibit the protective effects of DJ-1 against glycated guanosine diphosphate (GDP) formation and against alpha-synuclein (aSyn) aggregation induced by MGO. In total, the observed inhibition of DJ-1 by these endogenous neurotoxins may contribute to their damaging effects on the nervous system and, should be taken into account in therapeutic strategies for PD and related disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of SSR504734, a Selective Glycine Transporter Type 1 Inhibitor, on Seizure Thresholds, Neurotransmitter Levels, and Inflammatory Markers in Mice.","authors":"Nikola Gapińska, Piotr Wlaź, Elżbieta Wyska, Artur Świerczek, Krzysztof Kamiński, Marcin Jakubiec, Michał Abram, Katarzyna Ciepiela, Gniewomir Latacz, Tymoteusz Słowik, Dawid Krokowski, Łukasz Jarosz, Artur Ciszewski, Katarzyna Socała","doi":"10.1021/acschemneuro.5c00039","DOIUrl":"https://doi.org/10.1021/acschemneuro.5c00039","url":null,"abstract":"<p><p>Studies have revealed that inhibition of glycine transporter type 1 (GlyT1) may provide a balanced regulation between excitation and inhibition in some brain structures and, thereby, modulate seizure activity. Data on the role of GlyT1 in epilepsy are, however, very limited. Here, we examined the effect of SSR504734, a highly selective and reversible GlyT1 inhibitor, on three acute seizure tests in mice. We also evaluated its impact on neurotransmitter levels in the relevant brain structures following seizures, possible adverse effects, and changes in the levels of inflammatory mediators in the serum and liver. In addition, in vivo pharmacokinetic profile and in vitro ADME-Tox properties of SSR504734 were investigated. The results show that SSR504734 significantly increased the threshold for tonic hindlimb extension in the MEST test after acute and repeated treatment but had no influence on seizure thresholds in the 6 Hz and i.v. PTZ seizure tests. SSR504734 did not affect the levels of glutamate, GABA, glycine, or adenosine in brain structures of mice with MES-induced seizures. However, after acute treatment, the concentration of glutamate and adenosine in the brainstem of control animals (i.e., without seizures) decreased. Moreover, SSR504734 increased the levels of inflammatory markers (TNF-α, Il-1β, IL-6, IL-10, and TLR4) in serum. In vivo pharmacokinetic profiling and in vitro ADME-Tox data confirmed suitable drug-like properties of SSR504734, including its notable penetration into brain tissue. However, possible hepatotoxicity at higher doses should be taken into account. Further studies should be considered to better characterize the SSR504734-mediated effects as well as to validate GlyT1 as a potential new molecular target in epilepsy treatment.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Pain Sensitization Induced by Chronic Sleep Deprivation: The Role of Dopamine D2 Receptors-Dependent Homer1a Protein.","authors":"Chao Fu, Peng Wu, Fancan Wu, Wanyou He, Qichen Luo, Hongbin Liang, Hanbing Wang, Yalan Li","doi":"10.1021/acschemneuro.4c00640","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00640","url":null,"abstract":"<p><p>Numerous studies have demonstrated a positive correlation between sleep disorders and hyperalgesia. These sleep disorders adversely affect the descending pain regulatory system. Researchers have extensively studied the midbrain dopamine system in relation to pain associated with sleep disturbances. Our study shows that chronic sleep deprivation decreases dopamine responses to noxious stimuli within the mouse nucleus accumbens, regulated by dopamine release and intracellular signals. Furthermore, we confirmed that the dopamine D₂ receptors play a critical role in the pain associated with chronic sleep deprivation. Importantly, we revealed that homer1a in D₂ receptor neurons enhances AMPA receptors expression.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Rapid Evaporative Ionization Mass Spectrometry Classification with Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and Liquid Chromatography-Tandem Mass Spectrometry to Unveil Glioblastoma Overall Survival Prediction.","authors":"Tim F E Hendriks, Angeliki Birmpili, Steven de Vleeschouwer, Ron M A Heeren, Eva Cuypers","doi":"10.1021/acschemneuro.4c00463","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00463","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a median survival of 15 months. Despite advancements in conventional treatment approaches such as surgery and chemotherapy, the prognosis remains poor. This study investigates the use of rapid evaporative ionization mass spectrometry (REIMS) for real-time overall survival time classification of GBM samples and uses matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) to compare lipidomic differences within GBM tumors. A total of 45 GBM biopsies were analyzed to develop a survival prediction model for IDH-wild type GBM. REIMS patterns from 28 patients were classified with a 97.7% correct classification rate, identifying key discriminators between short-term (0-12 months) and prolonged (>12 months) survivors. Cross-validation with additional samples showed that the model correctly classified short-term and prolonged survival with 66.7 and 69.4% accuracy, respectively. MALDI-MSI was performed to confirm the discriminators derived from REIMS data. Results indicated 42 and 33 discriminating features for short-term and prolonged survival, respectively. Proteomic profiling was performed by isolating tumor regions via laser-capture microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, 1387 proteins were identified, of which 79 were significantly altered. In conclusion, this study shows that REIMS rapidly predicts glioblastoma survival times based on lipidomic profiles during electrosurgical dissection. MALDI-MSI confirmed that these differences were specific to the tumor region in the glioblastoma sections. LMD-guided LC-MS/MS-based proteomics revealed significantly altered pathways between short-term and prolonged survival. This research, including the comprehensive predictive survival model for GBM, could guide tumor resection surgeries based on accurate real-time tumor tissue identification as well as provide insights into overall survival mechanisms, possibly related to therapy response.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oroxylin A Attenuates Homocysteine-Induced Blood-Brain Barrier (BBB) Dysfunction by Reducing Endothelial Permeability and Activating the CREB/Claudin-5 Signaling Pathway.","authors":"Yilu Bao, Baiyang Sheng, Ping Lv","doi":"10.1021/acschemneuro.4c00749","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00749","url":null,"abstract":"<p><p>Recent reports have indicated that elevated levels of homocysteine (Hcy) are closely linked to blood-brain barrier (BBB) dysfunction in neurological disorders. Oroxylin A (OA) is a key bioactive flavonoid that has been reported to regulate brain functions. However, the role of OA in Hcy-related BBB dysfunction is less reported. In this study, we aimed to elucidate the role and molecular mechanism of OA in Hcy-mediated BBB dysfunction using both <i>in vivo</i> and <i>in vitro</i> investigations. Our findings indicate that the expression of the tight junction (TJ) protein Claudin-5 declined, and the diffusion of sodium fluorescein elevated in brains of Hcy-challenged mice. These effects were notably rescued by administration of OA. In Hcy-challenged bEnd.3 brain microvascular endothelial cells, increased endothelial permeability, reduced trans-endothelial electrical resistance (TEER), and downregulated Claudin-5 were observed. These effects were significantly reversed by 25 and 50 μM OA. Interestingly, OA treatment restored the dephosphorylation of CREB at Ser133 induced by Hcy. However, the addition of the protein kinase A/cAMP-response element binding protein (PKA/CREB) inhibitor H89 counteracted the protective effects of OA on inhibiting endothelial permeability and promoting Claudin-5 expression. Together, we demonstrate that OA protects against Hcy-induced BBB dysfunction by maintaining the integrity of endothelial barriers. This protective effect is achieved through the activation of the CREB/Claudin-5 signaling pathway, highlighting the potential therapeutic value of OA in addressing BBB-related neurological disorders.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of New Pentapeptide Inhibitors Against Amyloid-β Aggregation Using Word2Vec and Molecular Simulation.","authors":"Yin-Lei Han, Huan-Huan Yin, Chen Li, Jiangyue Du, Yi He, Yi-Xin Guan","doi":"10.1021/acschemneuro.4c00661","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00661","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by the aggregation of amyloid-β (Aβ) peptides into toxic oligomers and fibrils. The efficacy of existing peptide inhibitors based on the central hydrophobic core (CHC) sequence of Aβ42 remains limited due to self-aggregation or poor inhibition. This study aimed to identify novel pentapeptide inhibitors with high similarity and low binding energy to the CHC region LVFFA using a new computational screening workflow based on Word2Vec and molecular simulation. The antimicrobial peptides and human brain protein sequences were used for training the Word2Vec model. After tuning the parameters of the Word2Vec model, 1017 pentapeptides with high similarity to LVFFA were identified. Molecular docking was employed to estimate the affinity of the pentapeptides for the target of Aβ14-42 pentamer, and 103 peptides with favorable docking scores were obtained. Finally, five pentapeptides with a low binding energy and high binding stability via molecular dynamics simulation were experimentally validated using thioflavin T assays. Surprisingly, one pentapeptide, i.e., PALIR, exhibited significant inhibition surpassing the positive control LPFFN. This study demonstrates an effective combinatorial strategy to discover new peptide inhibitors. With PALIR representing a promising lead candidate, further optimization of PALIR could aid in the development of improved therapies to prevent amyloid toxicity in AD.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SeroWare: An Open-Source Software Suite for Voltammetry Data Acquisition and Analysis.","authors":"Cameron S Movassaghi, Rahul Iyer, Maya E Curry, Mila E Wesely, Miguel Alcañiz Fillol, Anne M Andrews","doi":"10.1021/acschemneuro.4c00799","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00799","url":null,"abstract":"<p><p>Voltammetry is widely used for fast, data-dense measurements of redox-active analytes in versatile environments, including the brain. Voltammetry requires minimal hardware beyond a potentiostat, a front-end amplifier, and a computer. Nonetheless, researchers must often develop or modify software packages for application-specific uses. Of the voltammetry software available, significant issues exist with source code inaccessible for updating or customization, nonconfigurable data processing procedures, and hardware incompatibilities. These limitations, coupled with the recent proliferation of waveform types and increased demands for high bandwidth data acquisition and efficient data processing, create the need for sophisticated, powerful, and flexible voltammetry software. We report developing \"SeroWare\", an open-source, end-to-end voltammetry acquisition and analysis software package designed to handle a wide variety of use cases encountered by voltammetry users. Although inspired by neurochemical analyses, this software is flexible, customizable, and compatible with open-source toolkits. The modular software architecture enables users to generate, acquire, and analyze voltammetry data of different types, ranging from pulse and sweep waveforms to fast and slow scans via easily accessible and exportable file formats. Template code is provided for communicating with a variety of standard external devices. We report several novel features for waveform applications and data flow. In-depth documentation in a User Guide and video tutorials are provided to enable new research directions, particularly regarding shareability and lowering the barriers to entry for new investigators.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}