PLoS Pathogens最新文献_第2页

Correction: Circular RNA circDtx1 regulates IRF3-mediated antiviral immune responses through suppression of miR-15a-5p-dependent TRIF downregulation in teleost fish.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-07 eCollection Date: 2025-04-01 DOI: 10.1371/journal.ppat.1013058

引用次数: 0

Correction: Long noncoding RNA MARL regulates antiviral responses through suppression miR-122-dependent MAVS downregulation in lower vertebrates.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-07 eCollection Date: 2025-04-01 DOI: 10.1371/journal.ppat.1013059

引用次数: 0

Intact HIV DNA decays in children with and without complete viral load suppression.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-04 DOI: 10.1371/journal.ppat.1013003

Daniel B Reeves, Morgan Litchford, Carolyn S Fish, Anna Farrell-Sherman, Makayla Poindexter, Nashwa Ahmed, Noah A J Cassidy, Jillian Neary, Dalton Wamalwa, Agnes Langat, Daisy Chebet, Hellen Moraa, Annukka A R Antar, Jennifer Slyker, Sarah Benki-Nugent, Lillian B Cohn, Joshua T Schiffer, Julie Overbaugh, Grace John-Stewart, Dara A Lehman

{"title":"Intact HIV DNA decays in children with and without complete viral load suppression.","authors":"Daniel B Reeves, Morgan Litchford, Carolyn S Fish, Anna Farrell-Sherman, Makayla Poindexter, Nashwa Ahmed, Noah A J Cassidy, Jillian Neary, Dalton Wamalwa, Agnes Langat, Daisy Chebet, Hellen Moraa, Annukka A R Antar, Jennifer Slyker, Sarah Benki-Nugent, Lillian B Cohn, Joshua T Schiffer, Julie Overbaugh, Grace John-Stewart, Dara A Lehman","doi":"10.1371/journal.ppat.1013003","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013003","url":null,"abstract":"To inform cure in children living with HIV (CWH), we elucidated the dynamics and mechanisms underlying HIV persistence during antiretroviral therapy (ART). In 120 Kenyan CWH who initiated ART between 1-12 months of age, 55 had durable viral load suppression, and 65 experienced ART interruptions. We measured plasma HIV RNA levels, CD4+ T cell count, and levels of intact and defective HIV DNA proviruses via the cross-subtype intact proviral DNA assay (CS-IPDA). By modeling data from the durably suppressed subset, we found that during early ART (year 0-1 on ART), plasma RNA levels decayed rapidly and biphasically and intact and defective HIV DNA decayed with mean 3 and 9 month half-lives, respectively. After viral suppression was achieved (years 1-8 on ART), intact HIV DNA decay slowed to a mean 22 month half-life, whilst defective HIV DNA no longer decayed. In five CWH, we found individual CD4+ TCRβ clones wax and wane, but average kinetics resembled those of defective DNA and CD4 count, suggesting that differential decay of intact HIV DNA arises from selective pressures overlaying normal CD4+ T cell kinetics. Finally, by modeling HIV RNA and DNA in CWH with treatment interruptions, we linked temporary viremia to transient rises in HIV DNA, but long-term intact reservoirs were not strongly influenced, suggesting brief treatment interruptions may not significantly increase HIV reservoirs in children.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013003"},"PeriodicalIF":5.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-04 DOI: 10.1371/journal.ppat.1013033

Shraddha Gandhi, Sindhoora Puravankara, Anish Kumar Mondal, Aakanksha Chauhan, Shashi Prakash Yadav, Kausik Chattopadhyay, Arunika Mukhopadhaya

{"title":"Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly.","authors":"Shraddha Gandhi, Sindhoora Puravankara, Anish Kumar Mondal, Aakanksha Chauhan, Shashi Prakash Yadav, Kausik Chattopadhyay, Arunika Mukhopadhaya","doi":"10.1371/journal.ppat.1013033","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013033","url":null,"abstract":"Vibrio cholerae cytolysin (VCC) is a potent exotoxin secreted by Vibrio cholerae, the etiological agent of the severe diarrheal disease cholera. VCC is a membrane-damaging pore-forming toxin by nature, and is well known for its ability to cause host cell death. Using wild type V. cholerae and VCC-deleted mutant variant of the bacteria, we show that VCC plays an important role in the inflammatory responses during infection in mice. This observation supports that VCC can function as a pathogen-associated molecular pattern (PAMP). Toll-like receptors (TLRs) are the key initiators of inflammation. Upon ligand recognition, TLR1 and TLR6 generally form heterodimers with TLR2 for triggering pro-inflammatory signals. In the present study, we show that VCC engages novel TLR1/4 heterodimer assembly, and elicits pro-inflammatory responses in both dendritic cells (DCs) and macrophages. Along with TLR1/4, VCC-induced pro-inflammatory response in macrophages also involves TLR2. It has been shown earlier that VCC is implicated in the V. cholerae-mediated killing of the immune cells following biofilm formation. Here we show that TLRs play an important role in VCC-mediated killing of DCs and macrophages following V. cholerae infection. Interestingly, we find that TLR1/4 signalling is specifically crucial for the VCC-induced inflammatory and death responses in DCs, as well as in mice. Additionally, we observe that similar to DCs and macrophages, TLR1/4-MyD88 play an important role in VCC-mediated inflammatory responses in another crucial immune cell type, neutrophils. Taken together, our study shows novel TLR heterodimer formation, differential recognition of the same ligand by different TLR combination in cell type-dependent manner, and their implications in the context of V. cholerae and VCC-induced immune cell death and mortality.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013033"},"PeriodicalIF":5.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The evolution of antibiotic resistance in Europe, 1998-2019.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.1371/journal.ppat.1012945

Martin Emons, François Blanquart, Sonja Lehtinen

{"title":"The evolution of antibiotic resistance in Europe, 1998-2019.","authors":"Martin Emons, François Blanquart, Sonja Lehtinen","doi":"10.1371/journal.ppat.1012945","DOIUrl":"10.1371/journal.ppat.1012945","url":null,"abstract":"The evolutionary dynamics of antibiotic resistance are not well understood, particularly the long-term trajectories of resistance frequencies and their dependence on antibiotic consumption. Here, we systematically analyse resistance trajectories for 887 bug-drug-country combinations in Europe across 1998-2019, for eight bacterial species with a considerable resistance-associated public health burden. Our analyses support a model in which, after an initial increase, resistance frequencies reach a stable intermediate equilibrium. The plurality (37%) of analysed trajectories were best described as 'stable' (neither increasing nor decreasing). 21% of trajectories were best described as 'stabilising' - i.e. showing a transition from increasing frequency to a stable plateau; 21% as decreasing and 20% as increasing. The antibiotic consumption in a country predicts both the equilibrium frequency of the corresponding resistance and the speed at which this equilibrium is reached. Moreover, we find weak evidence that temporal fluctuations in resistance frequency are driven by temporal fluctuations in hospital antibiotic consumption. A large fraction of the variability in the speed of increase and the equilibrium level of resistance remains unexplained by antibiotic use, suggesting other factors may also drive resistance dynamics. Overall, our results indicate that ever increasing antibiotic resistance frequencies are not inevitable.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1012945"},"PeriodicalIF":5.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ExoS effector in Pseudomonas aeruginosa Hyperactive Type III secretion system mutant promotes enhanced Plasma Membrane Rupture in Neutrophils. 铜绿假单胞菌超活性 III 型分泌系统突变体中的 ExoS 效应器可促进中性粒细胞浆膜破裂。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-02 DOI: 10.1371/journal.ppat.1013021

Arianna D Reuven, Sarah Katzenell, Bethany W Mwaura, James B Bliska

{"title":"ExoS effector in Pseudomonas aeruginosa Hyperactive Type III secretion system mutant promotes enhanced Plasma Membrane Rupture in Neutrophils.","authors":"Arianna D Reuven, Sarah Katzenell, Bethany W Mwaura, James B Bliska","doi":"10.1371/journal.ppat.1013021","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013021","url":null,"abstract":"Pseudomonas aeruginosa is an opportunistic pathogen responsible for airway infections in immunocompromised individuals, including those with cystic fibrosis (CF). P. aeruginosa has a type III secretion system (T3SS) that translocates effectors into host cells. ExoS is a T3SS effector with ADP ribosyltransferase (ADPRT) activity. ExoS ADPRT activity promotes P. aeruginosa virulence by inhibiting phagocytosis and limiting oxidative burst in neutrophils. The P. aeruginosa T3SS also translocates flagellin, which can activate the NLRC4 inflammasome, resulting in: 1) gasdermin-D pores, release of IL-1β and pyroptosis; and 2) histone 3 citrullination (CitH3), nuclear DNA decondensation and expansion into the neutrophil cytosol with incomplete NET extrusion. However, studies with P. aeruginosa PAO1 indicate that ExoS ADPRT activity inhibits the NLRC4 inflammasome in neutrophils. Here, we identified an ExoS+ CF clinical isolate of P. aeruginosa with a hyperactive T3SS. Variants of the hyperactive T3SS mutant or PAO1 were used to infect neutrophils from C57BL/6 mice that were wildtype or engineered to have a CF genotype or defects in inflammasome assembly. Responses to NLRC4 inflammasome assembly or ExoS ADPRT activity were assayed and found to be similar for C57BL/6 or CF neutrophils. ExoS ADPRT activity in the hyperactive T3SS mutant regulated inflammasome, nuclear DNA decondensation and incomplete NET extrusion responses, like PAO1, but promoted enhanced CitH3 and plasma membrane rupture (PMR). Glycine supplementation inhibited PMR by the hyperactive T3SS mutant, suggesting ninjurin-1 is required for this process. These results identify enhanced neutrophil PMR as a pathogenic activity of ExoS ADPRT in hypervirulent P. aeruginosa.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013021"},"PeriodicalIF":5.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NbPIRIN promotes the protease activity of papain-like cysteine protease NbRD21 to inhibit Chinese wheat mosaic virus infection.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-02 eCollection Date: 2025-04-01 DOI: 10.1371/journal.ppat.1013037

Kaili Zhong, Gecheng Xu, Jingjing Shi, Peng Liu, Aizhu Tu, Mila Wu, Jiaqian Liu, Jianping Chen, Jian Yang

{"title":"NbPIRIN promotes the protease activity of papain-like cysteine protease NbRD21 to inhibit Chinese wheat mosaic virus infection.","authors":"Kaili Zhong, Gecheng Xu, Jingjing Shi, Peng Liu, Aizhu Tu, Mila Wu, Jiaqian Liu, Jianping Chen, Jian Yang","doi":"10.1371/journal.ppat.1013037","DOIUrl":"10.1371/journal.ppat.1013037","url":null,"abstract":"Papain-like cysteine proteases (PLCPs) play critical roles in regulating plant immunity against a range of pathogens and a series of cysteine protease inhibitors have been identified, however, relatively little research has been done on proteins that enhance the protease activity of PLCPs. Here, we identified a protein named NbPIRIN, the silencing of NbPIRIN promotes Chinese wheat mosaic virus (CWMV) infection, whereas the transgenic overexpression of NbPIRIN inhibits CWMV infection in Nicotiana benthamiana. Furthermore, we found that NbPIRIN interacts with papain-like cysteine protease (NbRD21) and increases its protease activity. We demonstrated that the silencing of NbRD21 significantly increased host susceptibility to CWMV infection, whereas the transgenic overexpression of NbRD21 increased host resistance. Interestingly, CWMV CRP was found to interact with both NbPIRIN and NbRD21, thus interfering with the interaction between NbPIRIN and NbRD21 and subsequently inhibiting the protease activity of NbRD21. Since wheat is the natural host of CWMV, we identified TaPIRIN and TaRD21 and found that they had functions similar to those of NbPIRIN and NbRD21 in the CWMV response. These results reveal a previously unreported offensive and defensive strategy between plants and viruses.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013037"},"PeriodicalIF":5.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ATP depletion in anthrax edema toxin pathogenesis.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-01 DOI: 10.1371/journal.ppat.1013017

Jie Liu, Qing Cao, Michael Ewing, Zehua Zuo, Jason R Kennerdell, Toren Finkel, Stephen H Leppla, Shihui Liu

{"title":"ATP depletion in anthrax edema toxin pathogenesis.","authors":"Jie Liu, Qing Cao, Michael Ewing, Zehua Zuo, Jason R Kennerdell, Toren Finkel, Stephen H Leppla, Shihui Liu","doi":"10.1371/journal.ppat.1013017","DOIUrl":"10.1371/journal.ppat.1013017","url":null,"abstract":"Anthrax lethal toxin (LT) and edema toxin (ET) are two of the major virulence factors of Bacillus anthracis, the causative pathogen of anthrax disease. While the roles of LT in anthrax pathogenesis have been extensively studied, the pathogenic mechanism of ET remains poorly understood. ET is a calmodulin-dependent adenylate cyclase that elevates intracellular cAMP by converting ATP to cAMP. Thus, it was postulated that the ET-induced in vivo toxicity is mediated by certain cAMP-dependent events. However, mechanisms linking cAMP elevation and ET-induced damage have not been established. Cholera toxin is another bacterial toxin that increases cAMP. This toxin is known to cause severe intestinal fluid secretion and dehydration by cAMP-mediated activation of protein kinase A (PKA), which in turn activates cystic fibrosis transmembrane conductance regulator (CFTR). The cAMP-activated PKA phosphorylation of CFTR on the surface of intestinal epithelial cells leads to an efflux of chloride ions accompanied by secretion of H2O into the intestinal lumen, causing rapid fluid loss, severe diarrhea and dehydration. Due to similar in vivo effects, it was generally believed that ET and cholera toxin would exhibit a similar pathogenic mechanism. Surprisingly, in this work, we found that cAMP-mediated PKA/CFTR activation is not essential for ET to exert its in vivo toxicity. Instead, our data suggest that ET-induced ATP depletion may play an important role in the toxin's pathogenesis.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013017"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GS143, an inhibitor of E3 ligase β-TrCP, reverses HIV-1 latency without activating T cells via unconventional activation of NFκB.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-01 DOI: 10.1371/journal.ppat.1013018

Srijata Sarkar, Yoshifumi Kobayashi, Timothy Russnak, Jing Shen, Ronald G Nahass, Joseph P Dougherty, Céline Gélinas

{"title":"GS143, an inhibitor of E3 ligase β-TrCP, reverses HIV-1 latency without activating T cells via unconventional activation of NFκB.","authors":"Srijata Sarkar, Yoshifumi Kobayashi, Timothy Russnak, Jing Shen, Ronald G Nahass, Joseph P Dougherty, Céline Gélinas","doi":"10.1371/journal.ppat.1013018","DOIUrl":"https://doi.org/10.1371/journal.ppat.1013018","url":null,"abstract":"HIV-1 persists indefinitely in individuals living with HIV-1 even after effective treatment with antiretroviral therapy (ART). Upon cessation of the therapy, latently infected memory CD4+ T cells allow for a rapid rebound of the virus. The development of latency reversing agents (LRAs) to activate latent virus promoting immune recognition and clearance of the infected cells is pivotal for the elimination of the latent arm of the infection. Success of this strategy requires the development of potent highly specific LRAs with fewer off-target effects. LRA activity displayed by proteasome inhibitors although not highly specific opens the possibility of exploiting the high degree of specificity of the ubiquitin-proteasome system to develop targeted LRAs. Here we demonstrate that a small molecule GS143, which inhibits β-TrCP, the substrate recognition subunit of the SCFβ-TrCP E3 ubiquitin protein ligases, exhibits potent LRA activity both in a primary cell model system of latency and cells from aviremic individuals with HIV-1 treated with ART. Furthermore, GS143 reactivates latent HIV-1 without activating T cells, a desirable attribute for LRAs of clinical use. We showed that GS143 acts in a complementary fashion with at least two other classes of LRAs, thereby representing novel drug combinations for targeting HIV-1 latency. Finally, our results suggest that GS143 triggers a novel signaling pathway to reactivate latent HIV-1 that leads to the unconventional activation of NFκB p65, by initiating the noncanonical signaling via NIK, followed by activation of IKK leading to phosphorylation of p65 on S536 and its nuclear translocation. Moreover, we show that β-catenin inhibitors suppress reactivation HIV-1 by GS143, suggesting that β-catenin supports NF-κB output indirectly. Overall, our results suggest that the β-TrCP E3 ligase inhibitor GS143 represents a new type of LRA.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1013018"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell Transcriptomic Analysis of Kaposi Sarcoma.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2025-04-01 DOI: 10.1371/journal.ppat.1012233

Daniel A Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner

{"title":"Single-Cell Transcriptomic Analysis of Kaposi Sarcoma.","authors":"Daniel A Rauch, Paula Valiño Ramos, Mariam Khanfar, John Harding, Ancy Joseph, Anam Fahad, Paul Simonson, Isabel Risch, Obi Griffith, Malachi Griffith, Lee Ratner","doi":"10.1371/journal.ppat.1012233","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012233","url":null,"abstract":"Kaposi Sarcoma (KS) is a complex tumor caused by KS-associated herpesvirus 8 (KSHV). Histological analysis reveals a mixture of \"spindle cells\", vascular-like spaces, extravasated erythrocytes, and immune cells. In order to elucidate the infected and uninfected cell types in KS tumors, we examined twenty-five skin and blood samples from sixteen subjects by single cell RNA sequence analyses. Two populations of KSHV-infected cells were identified, one of which represented a CD34-negative proliferative fraction of endothelial cells, and the second representing CD34-positive cells expressing endothelial genes found in a variety of cell types including high endothelial venules, fenestrated capillaries, and endothelial tip cells. Although both infected clusters contained cells expressing lytic and latent KSHV genes, the CD34+ cells expressed more K5 and less K12. Novel cellular biomarkers were identified in the KSHV infected cells, including the sodium channel SCN9A. The number of KSHV positive cells was found to be less than 10% of total tumor cells in all samples and correlated inversely with tumor-infiltrating immune cells. T-cell receptor clones were expanded in KS tumors and blood, although in differing magnitudes. Changes in cellular composition in KS tumors after treatment with antiretroviral therapy alone, or immunotherapy were noted. These studies demonstrate the feasibility of single cell analyses to identify prognostic and predictive biomarkers.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 4","pages":"e1012233"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0