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1.
J Cell Biol ; 221(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34813648

RESUMO

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

2.
J Mol Histol ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727293

RESUMO

Glaucoma filtration surgery (GFS) is a classic operation for the treatment of glaucoma, which is the second leading cause of blindness, and scar formation caused by excessive human Tenon's capsule fibroblasts (HTFs) activation is responsible for surgery failure. However, the mechanism underlying excessive HTFs activation is largely unknown. Studies have revealed that N6-methyladenosine (m6A), which is one of the most common posttranscriptional modifications, plays an important role in multiple types of cellular processes. First, we isolated and identified primary HTFs and found that transforming growth factor-ß1 (TGF-ß1) enhanced cell viability and promoted cell proliferation and extracellular matrix (ECM) deposition in HTFs. We subsequently found that TGF-ß1 elevated the quantity of m6A and promoted the expression of m6A "writers", in the process from DNA to RNA, adenylate was methylated at the sixth N position by methylases methyltransferase-like 3 (METTL3). Furthermore, we demonstrated that METTL3 repression inhibited the promotion of cell viability, proliferation and ECM deposition in HTFs treated with TGF-ß1. We then illustrated that increased METTL3 played a role by promoting Smad3 in TGF-ß1-induced HTFs. We subsequently demonstrated that the METTL3/Smad3 regulatory axis was aberrantly expressed in the rabbit model of GFS. Thus, our study reveals that METTL3 indeed plays a role in modulating Smad3 in TGF-ß1-induced HTFs and further provides novel theoretical strategies based on METTL3 for the inhibition of scar formation after GFS.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34731424

RESUMO

The current discourse addresses fiscal issues, financial decentralization, and environmental quality and significantly affects economic development and sustainability. This investigation aims to address the research gap in fiscal decentralization and haze pollution for innovation and sustainable growth. This study uses the annual data of 270 Chinese cities from 2007 to 2016 for comprehensive analysis and employs spatial regression methods. The key findings imply that haze pollution in neighbouring cities causes further ecological issues. While the environmental regulations of China tend to have negative impacts on pollution, fiscal decentralization was found to be a key contributor to environmental pollution in Chinese cities. Overall, the study supports the validity of the pollution refuge hypothesis in China. Lastly, the conclusions allow us to conclude that China might need micro-level reforms regarding fiscal decentralization, environmental tax laws, and encouragement of cleaner production technologies.

6.
TechTrends ; : 1-12, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34806091

RESUMO

Research on how university faculty design courses has been limited and marked by modest detail on faculty design processes. Addressing this gap, seven faculty members supported by an educational developer at a teaching-intensive university used collaborative autoethnography (CAE) to explain how university faculty engage in reflective, iterative approaches to learning design. Collaborative analysis and interpretation of systematically collected data drawn from individual experiences in learning design reveal how faculty use reflection as a tool in learning design to recognize problems, devise solutions and constructively process emotions. Through reflection, faculty identify design solutions that are responsive to circumstances during course delivery, capture reasoning that informs design solutions for future course iterations and accurately gauge the appropriate timing of design changes based on factors such as scale and feasibility. This article offers detailed ethnographic evidence and new findings that enrich our understanding of claims made in previous interview-based studies of faculty design.

7.
Sensors (Basel) ; 21(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34770448

RESUMO

Sustained attention is essential for older adults to maintain an active lifestyle, and the deficiency of this function is often associated with health-related risks such as falling and frailty. The present study examined whether the well-established age-effect on reducing mind-wandering, the drift to internal thoughts that are seen to be detrimental to attentional control, could be replicated by using a robotic experimenter for older adults who are not as familiar with online technologies. A total of 28 younger and 22 older adults performed a Sustained Attention to Response Task (SART) by answering thought probes regarding their attention states and providing confidence ratings for their own task performances. The indices from the modified SART suggested a well-documented conservative response strategy endorsed by older adults, which were represented by slower responses and increased omission errors. Moreover, the slower responses and increased omissions were found to be associated with less self-reported mind-wandering, thus showing consistency with their higher subjective ratings of attentional control. Overall, this study demonstrates the potential of constructing age-related cognitive profiles with attention evaluation instruction based on a social companion robot for older adults at home.


Assuntos
Robótica , Idoso , Humanos , Memória de Curto Prazo , Autorrelato , Interação Social , Análise e Desempenho de Tarefas
8.
Medicine (Baltimore) ; 100(46): e27772, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797304

RESUMO

ABSTRACT: To evaluate the self-rate health (SRH) status and explore influence factors of middle-aged and elderly in China.China Health and Retirement Longitudinal Survey was conducted in 2011, 2013, 2015 and 2018. Data of the China Health and Retirement Longitudinal Survey in 2018 was used in our study and a total of 17898 participants were included. SRH status was graded as "very good, good, average, bad, very bad." Participants who answered "very good" and "good" were regarded as self-rated good health and who answered "average," "bad" and "very bad" were regarded as self-rated poor health. Odds ratio and 95% confidence interval of Logistics regression were calculated to evaluate the correlation between SRH and chronic diseases, demographic characteristics and lifestyle of middle-aged and elderly participants.A total of 4476 (25.01%) participants reported they had good health, and 13422 (74.99%) reported they had poor health. 9975 participants self-rated they had no chronic disease (55.73%), and 7923 (44.27%) participants self-rated they suffered from one and above chronic diseases. The prevalence of chronic diseases showed significant odds ratio and trend with SRH poor rate of participants. The more kinds of chronic diseases they suffered from, the poorer SRH was reported in middle-aged and elderly participants. Except for the chronic diseases, participants with higher age, living in rural, with high Center for Epidemiological Survey-Depression Scale score of depression and fewer time of physical activities also correlated with higher SRH (poor) rate.The SRH (good) rate was very low in middle-aged and elderly, participants who accompanied with more kinds of chronic diseases, fewer physical activities, higher age and living in the rural had a worse health status. A more comprehensive and integrated health framework should be strengthened to improve the health of middle-aged and elderly in China.

9.
World J Gastroenterol ; 27(40): 6888-6907, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34790013

RESUMO

BACKGROUND: Fuzi (Radix aconiti lateralis)-Gancao (Radix glycyrrhizae) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure. AIM: To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile. METHODS: The pharmacodynamic effect of F-G on CCl4 induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver. RESULTS: Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group. CONCLUSION: F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.


Assuntos
Ácidos e Sais Biliares , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , Diterpenos , Medicamentos de Ervas Chinesas , Fígado , Metabolômica , Ratos
10.
J Bone Miner Res ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783092

RESUMO

Amputation of the mouse digit tip results in blastema-mediated regeneration. In this model, new bone regenerates de novo to lengthen the amputated stump bone resulting in a functional replacement of the terminal phalangeal element along with associated non-skeletal tissues. Physiological examples of bone repair, such as distraction osteogenesis and fracture repair, are well known to require mechanical loading. However, the role of mechanical loading during mammalian digit tip regeneration is unknown. In this study, we demonstrate that reducing mechanical loading inhibits blastema formation by attenuating bone resorption and wound closure, resulting in the complete inhibition of digit regeneration. Mechanical unloading effects on wound healing and regeneration are completely reversible when mechanical loading is restored. Mechanical unloading after blastema formation results in a reduced rate of de novo bone formation demonstrating mechanical load-dependence of the bone regenerative response. Moreover, enhancing the wound healing response of mechanically unloaded digits with the cyanoacrylate tissue adhesive DermabondTM improves wound closure and partially rescues digit tip regeneration. Taken together, these results demonstrate that mammalian digit tip regeneration is mechanical load-dependent. Given that human fingertip regeneration shares many characteristics with the mouse digit tip, these results identify mechanical load as a previously unappreciated requirement for de novo bone regeneration in humans.

11.
Cancers (Basel) ; 13(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771466

RESUMO

Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94-0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25-0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15-3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04-2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20-2.45, p = 0.003).

12.
Cell Death Dis ; 12(12): 1090, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789744

RESUMO

Certain immune cells and inflammatory cytokines are essential components in the tumor microenvironment to promote breast cancer progression. To identify key immune players in the tumor microenvironment, we applied highly invasive MDA-MB-231 breast cancer cell lines to co-culture with human monocyte THP-1 cells and identified CXCL7 by cytokine array as one of the increasingly secreted cytokines by THP-1 cells. Further investigations indicated that upon co-culturing, breast cancer cells secreted CSF1 to induce expression and release of CXCL7 from monocytes, which in turn acted on cancer cells to promote FAK activation, MMP13 expression, migration, and invasion. In a xenograft mouse model, administration of CXCL7 antibodies significantly reduced abundance of M2 macrophages in tumor microenvironment, as well as decreased tumor growth and distant metastasis. Clinical investigation further suggested that high CXCL7 expression is correlated with breast cancer progression and poor overall survival of patients. Overall, our study unveils an important immune cytokine, CXCL7, which is secreted by tumor infiltrating monocytes, to stimulate cancer cell migration, invasion, and metastasis, contributing to the promotion of breast cancer progression.

13.
Bioengineered ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781817

RESUMO

Osteosarcoma is one of the common primary malignant tumors of bone in adolescents. Human umbilical vein endothelial cells (HUVECs) derived exosomes are associated with osteosarcoma cell stemness. Little is known about the function of HUVECs-exosomes in osteosarcoma cell stemness. This work aimed to investigate the mechanism of action of HUVECs-exosomes in regulating stem cell-like phenotype of osteosarcoma cells. HUVECs were treated with GW4869 (exosome inhibitor). Human osteosarcoma cells (U2OS and 143B) were treated with HUVECs supernatant, HUVECs-exosomes with or without RO4929097 (γ secretase inhibitor, used to block Notch signaling pathway). We found that HUVECs supernatant and HUVECs-exosomes enhanced the proportions of STRO-1+CD117+ cells and the expression of stem cell-related proteins Oct4 and Sox2. Both HUVECs supernatant and HUVECs-exosomes promoted the sarcosphere formation efficiency of U2OS and 143B cells. These stem-like phenotypes of U2OS and 143B cells conferred by HUVECs-exosomes were repressed by GW4869. Moreover, HUVECs-exosomes promoted the expression of Notch1, Hes1 and Hey1 in the U2OS and 143B cells. RO4929097 treatment reversed the impact of HUVECs-exosomes on Notch1, Hes1 and Hey1 expression by inhibiting Notch1 signaling pathway. In conclusion, this work demonstrated that HUVECs-exosomes promoted cell stemness in osteosarcoma through activating Notch signaling pathway. Thus, our data reveals the mechanism of HUVECs-exosomes in regulating cell stemness of osteosarcoma, and provides a theoretical basis for osteosarcoma treatment by exosomes.

14.
J Clin Lab Anal ; : e23773, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767671

RESUMO

BACKGROUND: miR-145 is closely related to vascular smooth muscle cells (VSMC) phenotype transformation; however, the regulatory mechanisms through which miR-145 regulates the VSMC phenotype transformation under mechanical stretching are unclear. In this study, we evaluated the roles of miR-145 in VSMCs subjected to mechanical stretching in aortic dissection (AD). METHODS: The expression of miR-145 in the aortic vessel wall of model animals and patients with AD was analyzed by quantitative polymerase chain reaction. miR-145-related protein-protein interaction networks and Wikipathways were used to analyze VSMC phenotypic transformation pathways regulated by miR-145. We used gain- and loss-of-function studies to evaluate the effects of miR-145 on VSMC differentiation under mechanical stretch induction and assessed whether Krüppel-like factor 4 (KLF4) was regulated by miR-145 in the aorta under mechanical stretch conditions. RESULTS: miR-145 was abundantly expressed in the walls of the normal human aorta, but was significantly downregulated in animal models and the walls of patients with dissection. We found that contractile phenotype-related proteins were downregulated in VSMCs subjected to mechanical stretching, whereas the expression of secreted phenotype-related proteins increased. miR-145 overexpression also downregulated contractile phenotype-related proteins in VSMCs and suppressed upregulation of phenotype-related proteins. Finally, under mechanical stretching, KLF4 expression was significantly increased in VSMCs, and overexpression of miR-145 blocked this effect. CONCLUSION: Our results confirmed that mechanical stretch-induced phenotypic transformation of VSMCs to promote AD via upregulation of KLF4; this mechanism was regulated by miR-145, which directly modulated KLF4 expression and VSMC differentiation.

15.
Int J Syst Evol Microbiol ; 71(11)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34731078

RESUMO

A growing interest in fungi that occur within symptom-less plants and lichens (endophytes) has uncovered previously uncharacterized species in diverse biomes worldwide. In many temperate and boreal forests, endophytic Coniochaeta (Sacc.) Cooke (Coniochaetaceae, Coniochaetales, Sordariomycetes, Ascomycota) are commonly isolated on standard media, but rarely are characterized. We examined 26 isolates of Coniochaeta housed at the Gilbertson Mycological Herbarium. The isolates were collected from healthy photosynthetic tissues of conifers, angiosperms, mosses and lichens in Canada, Sweden and the United States. Their barcode sequences (nuclear ribosomal internal transcribed spacer and 5.8S; ITS rDNA) were ≤97% similar to any documented species available through GenBank. Phylogenetic analyses based on two loci (ITS rDNA and translation elongation factor 1-alpha) indicated that two isolates represented Coniochaeta cymbiformispora, broadening the ecological niche and geographic range of a species known previously from burned soil in Japan. The remaining 24 endophytes represented three previously undescribed species that we characterize here: Coniochaeta elegans sp. nov., Coniochaeta montana sp. nov. and Coniochaeta nivea sp. nov. Each has a wide host range, including lichens, bryophytes and vascular plants. C. elegans sp. nov. and C. nivea sp. nov. have wide geographic ranges. C. montana sp. nov. occurs in the Madrean biome of Arizona (USA), where it is sympatric with the other species described here. All three species display protease, chitinase and cellulase activity in vitro. Overall, this study provides insight into the ecological and evolutionary diversity of Coniochaeta and suggests that these strains may be amenable for studies of traits relevant to a horizontally transmitted, symbiotic lifestyle.


Assuntos
Ascomicetos , Endófitos , Animais , Ascomicetos/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Caenorhabditis elegans , DNA Bacteriano/genética , Endófitos/genética , Ácidos Graxos/química , Montana , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Estados Unidos
16.
Front Pharmacol ; 12: 757194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744733

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common primary cancers, and its pathogenesis is complicated and difficult to screen. Currently, there is no effective treatment. In traditional Chinese medicine, a large proportion of patients with HCC have been diagnosed with spleen deficiency (SD) syndrome and treated with tonifying traditional Chinese medicine, which has significant clinical efficacy. However, the role and molecular mechanism of SD in HCC remain unclear. In this study, 40 mice were randomly divided into four groups: control, SD, HCC, and SD-HCC groups. The liver cancer model of SD was established by reserpine induction and orthotopic transplantation. The effects of SD on the proliferation, apoptosis, invasion, and metastasis of HCC cells were studied by cell proliferation, cell apoptosis, cell scratch, and transwell assay. We found that compared with the HCC group, the protein expressions of cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), phosphatase and tensin homolog (PTEN), and AKT (also known as protein kinase B or PKB) in the exosomes of the SD-HCC group were upregulated. In addition, the metastases and self-renewal of exosomes in the SD-HCC group were more aggressive than those in the HCC group, which could be partially reversed with the addition of CTLA-4 inhibitors. Further studies showed that in the internal environment of SD, CTLA-4 promoted tumor invasion and metastasis by regulating the PTEN/CD44 pathway. In conclusion, our findings suggest that during SD in the internal environment, exosome CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.

17.
Skeletal Radiol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757481

RESUMO

OBJECTIVE: To evaluate the utility of multidetector computed tomography MDCT quantitative measurements in identifying sarcopenia. MATERIALS AND METHODS: The clinical data and MDCT images of 64 patients of sarcopenia and 184 non-sarcopenic participants between October 2020 and January 2021were retrospectively analyzed. Propensity score matching was used to match the sarcopenic patients with the non-sarcopenic participants. Two radiologists independently measured the cross-sectional area (CSA) of skeletal muscle and intramuscular fat tissue and CT density of skeletal muscle at the middle L3 vertebral level on CT images of all participants. Intra-observer agreement was evaluated via intraclass correlation coefficients (ICC). A receiver operating characteristic (ROC) curve was built for each variable. Correlations between CT parameters and clinical data were assessed via Pearson or Spearman correlation coefficient. RESULTS: A total of 74 participants (mean age 72 ± 4 years, range 66-85 years; 38 men and 36 women) were included, comprising 37 sarcopenic patients and 37 non-sarcopenic participants. There were no significant intergroup differences regarding age, sex ratio, and body mass index (BMI) (P < 0.05). The CSA and density of skeletal muscle measured by two radiologists were reliable (ICC ≥ 0.75, P < 0.001). Compared with the sarcopenic group, the non-sarcopenic group had a significantly greater CSA and CT density of the total skeletal muscle (TSM) and paraspinal skeletal muscle (PSM) and skeletal muscle index at L3 level (L3 SMI) (P < 0.05). The fat infiltration ratio (FIR) of TSM, PSM, and psoas muscle was significantly higher in the sarcopenic group than that in non-sarcopenic participants (P < 0.05). ROC curve analysis showed the PSM FIR + PSM CT density (PSM D) had the best predictive value for sarcopenia (AUC = 0.836). The PSM FIR and age were moderately positively correlated (r = 0.410, P < 0.001). CONCLUSION: Fat infiltration of skeletal muscle had better predictive value than L3 SMI in the diagnosis of sarcopenic. The PSM FIR + PSMD had the best predictive value for sarcopenia, which was moderately positively correlated with age.

18.
Front Chem ; 9: 718856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604169

RESUMO

The chloride ion is an essential ion in organisms, which plays an important role in maintaining normal cell functions. It is involved in many cell activities, such as cell proliferation, cell excitability regulation, immune response, and volume regulation. Accurate detection of the chloride ion can balance its concentration in vivo, which is of great significance. In this study, we developed a green fluorescent carbon quantum dot to detect chloride concentration through the "off-on" mechanism. First, the fluorescence of carbon dots is quenched by the complex of sulfhydryl and silver ions on the surface of carbon dots. Then, the addition of chloride ions pulls away the silver ions and restores the fluorescence. The fluorescence recovery is linearly related to the concentration of chloride ions, and the limit of detection is 2.817 µM, which is much lower than those of other reported chloride probes. Besides, cell and zebrafish experiments confirmed the biosafety and biocompatibility of the carbon dots, which provided a possibility for further applications in bioimaging in vivo.

19.
Chembiochem ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606179

RESUMO

The imaging of peptidoglycan (PGN) dynamics in living bacteria facilitates the understanding of PGN biosynthesis and wall-targeting antibiotics. The main tools for imaging bacterial PGN are fluorescent probes, such as the well-known PGN metabolic labeling probes. However, fluorescent small-molecule probes for labeling key PGN-synthesizing enzymes, especially for transglycosylases (TGases), remain to be explored. In this work, the first imaging probe for labeling TGase in bacterial cell wall studies is reported. We synthesized various fluorescent MoeA-based molecules by derivatizing the natural antibiotic moenomycin A (MoeA), and used them to label TGases in living bacteria, monitor bacterial growth and division cycles by time-lapse imaging, and study cell wall growth in the mecA-carrying methicillin-resistant Staphylococcus aureus (MRSA) strains when the ß-lactam-based probes were unsuitable.

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