Antimicrobial Agents and Chemotherapy最新文献

{"title":"Inhibition of type II NADH dehydrogenase in <i>Mycobacterium tuberculosis</i> reveals collateral vulnerability in the electron transport chain.","authors":"Vien Q T Ho, Vincent Fontaine, Ernesto Anoz-Carbonell, Kamel Djaout, Clement Vigier, Leo Faion, Samsher Singh, Sushovan Dam, Jonathan Chatagnon, Stéphanie Slupek, Rudy Antoine, Aurélie Chauffour, Alexandra Aubry, Benoit Deprez, Kevin Pethe, Nicolas Veziris, Nicolas Willand, Robert Jansen, Baptiste Villemagne, Ruben C Hartkoorn","doi":"10.1128/aac.00756-26","DOIUrl":"https://doi.org/10.1128/aac.00756-26","url":null,"abstract":"<p><p>To sustain the anti-tuberculosis drug development pipeline, novel antibiotics must be developed both as standalone agents and as components of future combination regimens. To this end, tricyclic-spirolactams (TriSLa)-based inhibitors of mycobacterial type II NADH dehydrogenase (Ndh-2) represent a promising novel class of antibiotics, though activity is carbon source dependent. Initial studies established an enhanced understanding of the impact of TriSLa on mycobacteria using metabolomics and transcriptomics. Then, CRISPRi chemical-genetics and extensive <i>in vitro</i> TriSLa-combination studies showed that Ndh-2 inhibition resulted in rendering other components of the electron transport chain vulnerable, even in conditions when TriSLa was inactive alone. Finally, identified <i>in vitro</i> synergistic TriSLa-antibiotic combinations were validated to also give modestly improved <i>in vivo</i> efficacy. Together, this work expands our understanding of how Ndh-2 inhibition impacts bacterial physiology and reveals how it sensitizes the bacterium to electron transport chain inhibitors, providing a foundation for future TriSLa-based combination regimens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0075626"},"PeriodicalIF":4.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Sudarsono et al., \"A novel hollow-fiber infection model (HFIM) for antiviral PK/PD studies of CMV infection\".","authors":"Lalitya M Sudarsono, Suzanne A M Wenker, Xuanlin Liu, Jorn Brink, Dirk-Jan van den Berg, J G C van Hasselt, Anne-Grete Märtson","doi":"10.1128/aac.01045-26","DOIUrl":"https://doi.org/10.1128/aac.01045-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0104526"},"PeriodicalIF":4.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Chou et al., \"Novel Cytomegalovirus UL54 DNA Polymerase Gene Mutations Selected <i>In Vitro</i> That Confer Brincidofovir Resistance\".","authors":"Sunwen Chou, Ronald J Ercolani, E Randall Lanier","doi":"10.1128/aac.01024-26","DOIUrl":"10.1128/aac.01024-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0102426"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sorafenib enforces HIV-1 latency by selectively inhibiting PKC-driven STAT1/3 serine 727 phosphorylation.","authors":"Peipei Wang, Zhuoyue Meng, Jiasheng Zhou, Huixin Wu, Wei Wang, Zhiliang Gao, Ying Zhang, Jinfeng Cai","doi":"10.1128/aac.00540-26","DOIUrl":"10.1128/aac.00540-26","url":null,"abstract":"<p><p>Eliminating the latent HIV-1 reservoir remains a major barrier to achieving a functional cure. The \"block-and-lock\" strategy aims to enforce durable transcriptional silencing of proviruses, thereby preventing viral rebound upon interruption of antiretroviral therapy. However, the molecular mechanisms governing stable latency remain incompletely understood. Here, we identify protein kinase C (PKC)-dependent phosphorylation of STAT1 and STAT3 at serine 727 as a previously unrecognized regulatory checkpoint controlling HIV-1 transcriptional reactivation. Pharmacological inhibition of this axis using sorafenib, a clinically approved multi-kinase inhibitor, robustly suppresses HIV-1 reactivation across multiple latency models and promotes the establishment of latency in primary CD4⁺ T cells. Mechanistically, sorafenib attenuates phorbol 12-myristate 13-acetate (PMA)-induced activation of the JAK-STAT and PI3K-Akt signaling pathways, and selectively blocks PKC-mediated phosphorylation of STAT1/3 at serine 727 without affecting canonical tyrosine phosphorylation (Y701/Y705). This selective inhibition disrupts transcriptional activation at the HIV-1 long terminal repeat (<i>LTR</i>), thereby preventing viral reactivation. Importantly, sorafenib does not induce detectable cytotoxicity or alter activation and exhaustion markers in primary CD4⁺ T cells, supporting a favorable safety profile <i>in vitro</i>. Collectively, our findings define a critical role for STAT1/3 Ser727 in the regulation of HIV-1 latency and establish sorafenib as a promising latency-promoting agent for future applications in the development of a functional cure for HIV-1.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0054026"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NT-A9, a new triazole, exhibits potent antifungal activity against <i>Candida</i> and <i>Cryptococcus</i> species through potent ergosterol biosynthesis inhibition.","authors":"Shuo Zhu, Tingjunhong Ni, Lu Gao, Wanqian Li, Dazhi Zhang, Wenjuan Wu, Yuanying Jiang, Hui Lu","doi":"10.1128/aac.00768-26","DOIUrl":"10.1128/aac.00768-26","url":null,"abstract":"<p><p>Invasive fungal infections (IFIs) remain a major global health threat due to limited therapeutic options and rising azole resistance. NT-a9 is a novel triazole antifungal with potent activity against <i>Candida</i> and <i>Cryptococcus</i> species via strong inhibition of ergosterol biosynthesis. <i>In vitro</i>, NT-a9 exhibited potent and sustained antifungal activity against clinical isolates, with superior potency compared to fluconazole (FLC). It also displayed a prolonged post-antifungal effect (PAFE) against most <i>Candida</i> species, a property rarely seen in conventional azoles. Resistance profiling demonstrated that NT-a9 possesses a high genetic barrier, fully suppressing resistant mutant emergence in <i>Cryptococcus</i> species and maintaining stable susceptibility in <i>Candida albicans</i> during 28 days of continuous exposure. NT-a9 retained potent activity against FLC-resistant <i>Cryptococcus neoformans</i> and multidrug-resistant <i>Candida auris</i>, with minimal influence from drug efflux mechanisms. In murine invasive candidiasis, a single low dose of NT-a9 achieved 100% survival and markedly reduced renal fungal burden, significantly outperforming FLC. NT-a9 also substantially improved survival in mice infected with FLC-resistant <i>C. auris</i>. Mechanistically, NT-a9 binds Erg11 with much higher affinity than FLC by forming key hydrogen bonds with Gly307 and His377, leading to irreversible ergosterol depletion, toxic sterol accumulation, and severe fungal membrane damage. Transcriptomic analysis further confirmed that NT-a9 extensively disrupts sterol biosynthesis and triggers compensatory gene expression that reinforces its antifungal action. As a novel triazole integrating long-lasting efficacy, a high resistance barrier, and potent activity against pan-azole-resistant pathogens, NT-a9 represents a promising clinical candidate for treating IFIs.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0076826"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of <i>mutH</i>^V76G in carbapenem-resistant <i>Klebsiella pneumoniae</i> disrupts DNA mismatch repair and results in a hypermutator phenotype.","authors":"Shaoji Cheng, Cornelius J Clancy, Giuseppe Fleres, Hassan Badrane, Matthew J Culyba, Anthony Newbrough, Liang Chen, M Hong Nguyen","doi":"10.1128/aac.00189-26","DOIUrl":"10.1128/aac.00189-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Hypermutation-driven evolution is a major contributor to antibiotic resistance in some bacterial pathogens, but its role in &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; remains poorly defined. We analyzed 11 KPC-producing ST258 &lt;i&gt;K. pneumoniae&lt;/i&gt; isolates collected serially over ~4 years from a host with persistent colonization and recurrent infections. After &gt;3 years, isolates acquired ceftazidime-avibactam (CZA) resistance with restored carbapenem susceptibility, coinciding with emergence of a V76G substitution in MutH, a conserved endonuclease in the DNA mismatch repair pathway. Isolates carrying &lt;i&gt;mutH&lt;sup&gt;V76G&lt;/sup&gt;&lt;/i&gt; demonstrated sharp increases in within-host genetic diversification (69-179 versus 2-12 SNPs), and accumulated mutations across multiple resistance-associated loci, including &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;KPC-3&lt;/sub&gt;, &lt;i&gt;ompK36&lt;/i&gt;, &lt;i&gt;cirA&lt;/i&gt;, and &lt;i&gt;envZ&lt;/i&gt;. Both clinical &lt;i&gt;mutH&lt;sup&gt;V76G&lt;/sup&gt;&lt;/i&gt; isolates and CRISPR-Cas9-engineered mutants (&lt;i&gt;mutH&lt;/i&gt;&lt;sup&gt;V76G&lt;/sup&gt; and &lt;i&gt;mutH&lt;/i&gt; null mutant) exhibited hypermutator phenotypes and showed accelerated acquisition of resistance or reduced susceptibility to CZA, meropenem-vaborbactam (MVB), and cefiderocol. Using matched isogenic engineered strains, we confirmed that &lt;i&gt;mutH&lt;sup&gt;V76G&lt;/sup&gt;&lt;/i&gt; heightens the pace of resistance evolution &lt;i&gt;in vitro&lt;/i&gt;, enhances plasmid uptake and transfer, and increases bacterial fitness during mouse infections. Resistance pathways that emerged &lt;i&gt;in vivo&lt;/i&gt; paralleled those observed clinically, including &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;KPC-3&lt;/sub&gt; variants under CZA pressure and &lt;i&gt;ompK36&lt;/i&gt; mutations under MVB exposure. The similarity of &lt;i&gt;mutH&lt;sup&gt;V76G&lt;/sup&gt;&lt;/i&gt; and &lt;i&gt;mutH&lt;/i&gt;-null phenotypes indicates that the V76G substitution largely abolishes MutH function. These findings identify MutH-mediated hypermutation as an adaptive strategy in &lt;i&gt;K. pneumoniae&lt;/i&gt; that accelerates resistance to multiple last-line antibiotics and promotes horizontal gene transfer without apparent fitness cost.IMPORTANCEAntibiotic-resistant &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; is a major global health threat, and resistance to new \"last-line\" antibiotics is rising. In this study, we examined a rare collection of carbapenem-resistant &lt;i&gt;K. pneumoniae&lt;/i&gt; isolates obtained over 4 years from a single host, giving us an opportunity to observe how the bacterium evolved over time. During this period, the bacteria acquired a single nucleotide change in a DNA damage repair gene &lt;i&gt;mutH&lt;/i&gt;, which caused them to accumulate mutations far more rapidly than with wild-type &lt;i&gt;mutH&lt;/i&gt;. Through extensive genomic and experimental work, we found that this single change produced a hypermutator strain capable of quickly developing resistance to several key antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam, and also reduced susceptibility to cefiderocol. Using laboratory-engineered strains, animal infection models, and detailed genetic analyses, we confirmed that the &lt;i&gt;mutH&lt;/i&gt; mutation accelerates","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0018926"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive immunity shapes baseline physiology of <i>M. tuberculosis</i> in high-dose versus low-dose infection BALB/c mouse drug treatment models.","authors":"Jo Hendrix, Reem Al Mubarak, Karen Rossmassler, Holly Nielsen, Elizabeth Wynn, Camile Moore, Isabelle L Jones, Martin I Voskuil, Brendan K Podell, Gregory T Robertson, Chuangqi Wang, Nicholas D Walter","doi":"10.1128/aac.00421-26","DOIUrl":"10.1128/aac.00421-26","url":null,"abstract":"<p><p>Preclinical tuberculosis (TB) drug evaluation relies heavily on mouse infection models. Drug efficacy varies depending on inoculum and the timing of treatment initiation. These differences reflect, in part, physiological adaptations of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) to host immune pressure. We used novel molecular markers of pathogen health (RS ratio and SEARCH-TB) to contrast <i>Mtb</i> phenotypes in the BALB/c high dose aerosol (HDA) subacute TB and low dose aerosol (LDA) chronic TB infection models, focusing on the onset of adaptive immunity. We found that the onset of adaptive immunity coincided with a rapid reprogramming of <i>Mtb</i> physiology, characterized by suppressed respiration, metabolism, and biosynthesis, together with induction of stress and nutrient acquisition pathways. Changes in key <i>Mtb</i> processes were concordant with changes in host expression of canonical features of adaptive immunity. Our results also explain key model-specific differences in drug efficacy: when used for drug evaluation, the HDA model begins treatment during the innate immune phase when <i>Mtb</i> are metabolically active, whereas the LDA model initiates therapy after host adaptive immunity has already activated and the bacterial population is immune-constrained. The HDA model is shown to be a mixed model, spanning immune phases with initial treatment acting on replicating bacteria and later treatment acting on immune-constrained populations. Together, the two models offer complementary perspectives on therapeutic activity across the spectrum of bacterial states and provide a framework for designing regimens that are effective against both active and immune-constrained <i>Mtb</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0042126"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Bajpai et al., \"Selective digestive decontamination and antimicrobial resistance: defining thresholds before global implementation\".","authors":"Wanda Cornistein, Maria Inés Staneloni","doi":"10.1128/aac.00712-26","DOIUrl":"10.1128/aac.00712-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0071226"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a liver-on-chip model to evaluate the effects of vancomycin and daptomycin on host immunometabolism and clearance of intracellular reservoirs of <i>Staphylococcus aureus</i> during bacteremia.","authors":"Brent Beadell, Sujung Yi, Makayla Roberts, Kyu Shik Mun, Annie Wong-Beringer","doi":"10.1128/aac.00254-26","DOIUrl":"10.1128/aac.00254-26","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> bacteremia (SAB) causes significant morbidity and mortality, despite treatment with guideline-recommended antibiotics. A critical contributor to SAB treatment failure is the intracellular persistence of SA within liver sinusoidal macrophages (Kupffer cells [KCs]). Antibiotics have been shown to modulate immune cell function, which is governed by cellular metabolism; yet, the effect of antibiotics on host immunometabolic response relative to bacterial clearance is understudied. We developed a liver-on-chip (LoC) model of SAB to recapitulate the liver sinusoid during systemic infection using exclusively liver-derived cells and the GFP USA300 LAC SA strain and compared the effects of vancomycin and daptomycin on host immunometabolism by fluorescence lifetime imaging microscopy and related to intracellular antimicrobial efficacy. Utilizing both murine and human-based LoC infection models, we found that DAP was superior to VAN treatment in clearing intracellular SA from the liver microenvironment, which corresponded to differential host immunometabolic responses. DAP showed low NAD(P)H fluorescence lifetime and low mitochondrial ROS, suggestive of a redox-buffered state that balanced pathogen containment with hepatic metabolic homeostasis, while VAN treatment biased towards greater utilization of OXPHOS. Our findings using a novel <i>in vitro</i> microphysiological system mimicking the liver tissue microenvironment offer insights into antibiotic-mediated bacterial clearance that accounts for host immunometabolism beyond direct antimicrobial activity.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0025426"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imipenem and relebactam pharmacokinetics in peritoneal fluid: microdialysis reveals infection-independent penetration.","authors":"Huan Tong, Zekun Cao, Jiakai Li, Haoming Yang, Yong Qiao, Siwei Guo, Changhui Deng, Xin Li","doi":"10.1128/aac.01838-25","DOIUrl":"10.1128/aac.01838-25","url":null,"abstract":"<p><p>Imipenem/relebactam is a promising therapy for complicated intra-abdominal infections caused by carbapenem-resistant <i>Enterobacterales</i> species. However, data on tissue-site pharmacokinetics are limited. We evaluated the peritoneal penetration of imipenem and relebactam in healthy and infected rats by using microdialysis. The animals received a single intravenous infusion of imipenem (45 mg/kg) and relebactam (22.5 mg/kg), and unbound concentrations were dynamically monitored in the plasma and peritoneal fluid. Imipenem exposure in the peritoneal fluid was consistently lower than that in the plasma, with peritoneal fluid-to-plasma AUC ratios of 0.29 in the control group and 0.27 in the infection group. In contrast, relebactam demonstrated nearly equivalent concentrations in both compartments, with ratios of 0.81 and 0.86, respectively. Both agents reached peak levels at 30 min, and the semi-logarithmic curves showed rapid equilibrium without delay. The partition coefficients estimated by two-compartment modeling for imipenem (0.333-0.342) and relebactam (0.679-0.816) were consistent with non-compartmental results. Infection increased the distribution volume and clearance of relebactam but did not significantly alter peritoneal permeability for either drug. These findings provide the first description of the penetration of relebactam into peritoneal fluid. Subsequent pharmacodynamic target attainment (PTA) analysis showed that under the latest EUCAST PK/PD criteria, PTA values dropped markedly to an MIC of 1 mg/L, indicating a substantially reduced probability of achieving adequate peritoneal exposure. These results highlight the need for dosing strategies to ensure sufficient peritoneal drug concentration to maintain antimicrobial efficacy.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0183825"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}