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BACKGROUND: In the realm of endometrial cancer (EC) therapeutics and prognostic assessments, lymph nodes' status is paramount. The sentinel lymph node (SLN) detection, recognized for its reliability, has been progressively adopted as a standard procedure, posing a compelling alternative to conventional systematic lymphadenectomy. However, there remains a lack of agreement on the most effective choice of tracers for this procedure. OBJECTIVE: This investigation was dedicated to a comparative analysis of various tracers to identify the most effective combination that achieves the highest detection rate. This endeavor sought to enhance the efficacy of SLN biopsy in the surgical management of EC. METHODS: A systematic review was conducted across multiple databases, including the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, and clinicaltrials.gov, to analyze studies employing different tracers for SLN biopsy during surgery in EC. Using Bayesian network meta-analysis, we compared the total and bilateral detection rates of various tracers. RESULTS: After screening 1431 articles, 11 studies including 2699 participants were selected in this network meta-analysis. The combination of radioactive isotopes and indocyanine green (ICG) emerged as the most efficacious method in total and bilateral detection rates, with the Surface Under the Cumulative Ranking Curve (SUCRA) scores of 80.00% and 86.36%, respectively. Additionally, carbon nanoparticles (CNPs) demonstrated superior performance in the detection of para-aortic lymph nodes with an SUCRA score of 97.77%. CONCLUSION: Network meta-analysis shows that the application of radioactive isotopes and ICG is the optimal tracer combination for SLN biopsy during surgery in EC.
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Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.
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Infecções por Astroviridae , Aves , Fezes , Variação Genética , Genoma Viral , Filogenia , Animais , Hong Kong , Aves/virologia , Fezes/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Animais Selvagens/virologia , Doenças das Aves/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Avastrovirus/genética , Avastrovirus/classificação , Avastrovirus/isolamento & purificação , RNA Viral/genética , Fases de Leitura Aberta , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/classificaçãoRESUMO
Background: The primary objective of this paper was to assess and analyze the top 100 most cited articles currently cited in studies of fertility-sparing treatments for cervical cancer. Methods: Searching the Web of Science Core Collection database for the top 100 most cited articles on fertility-sparing treatments for cervical cancer, different aspects of the articles were analyzed, including countries, journals, institutions, authors, keywords and topics. Results: The search was conducted up to August 2023, and the number of citations for the top 100 articles ranged from 19 to 212. These articles originated from 28 different countries, with Professor Plante, M. from Canada and Professor Sonoda, Y. from the USA having the highest number of articles, both with 10. Professor Plante, M. was the first author of 9 articles and corresponding author of 9 articles. The Memorial Sloan Kettering Cancer Center in the USA published the most articles (21) and received a total of 258 citations. Gynecologic Oncology published 37 of the top 100 articles, with 524 citations and an average of 14.16 citations per article. Conclusions: The study concludes that the USA has made the most significant contributions to this field based on the number of articles, authors, and institutions. Additionally, keyword clustering and burst analysis revealed the research hotspots and future trends in this area.
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With the increasing occurrence of global warming, drought is becoming a major constraint for plant growth and crop yield. Plant cell walls experience continuous changes during the growth, development, and in responding to stressful conditions. The plant WRKYs play pivotal roles in regulating the secondary cell wall (SCW) biosynthesis and helping plant defend against abiotic stresses. qRT-PCR evidence showed that OsWRKY12 was affected by drought and ABA treatments. Over-expression of OsWRKY12 decreased the drought tolerance of the rice transgenics at the germination stage and the seedling stage. The transcription levels of drought-stress-associated genes as well as those genes participating in the ABA biosynthesis and signaling were significantly different compared to the wild type (WT). Our results also showed that less lignin and cellulose were deposited in the OsWRKY12-overexpressors, and heterogenous expression of OsWRKY12 in atwrky12 could lower the increased lignin and cellulose contents, as well as the improved PEG-stress tolerance, to a similar level as the WT. qRT-PCR results indicated that the transcription levels of all the genes related to lignin and cellulose biosynthesis were significantly decreased in the rice transgenics than the WT. Further evidence from yeast one-hybrid assay and the dual-luciferase reporter system suggested that OsWRKY12 could bind to promoters of OsABI5 (the critical component of the ABA signaling pathway) and OsSWN3/OsSWN7 (the key positive regulators in the rice SCW thickening), and hence repressing their expression. In conclusion, OsWRKY12 mediates the crosstalk between SCW biosynthesis and plant stress tolerance by binding to the promoters of different downstream genes.
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Parede Celular , Secas , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Oryza/genética , Oryza/metabolismo , Parede Celular/metabolismo , Parede Celular/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Lignina/biossíntese , Lignina/metabolismo , Plantas Geneticamente Modificadas , Celulose/biossíntese , Celulose/metabolismo , Ácido Abscísico/metabolismoRESUMO
Clinical experiences of herbal medicine (HM) have been used to treat a variety of human intractable diseases. As the treatment of diseases using HM is characterized by multi-components and multi-targets, it is difficult to determine the bio-active components, explore the molecular targets and reveal the mechanisms of action. Metabolomics is frequently used to characterize the effect of external disturbances on organisms because of its unique advantages on detecting changes in endogenous small-molecule metabolites. Its systematicity and integrity are consistent with the effective characteristics of HM. After HM intervention, metabolomics can accurately capture and describe the behavior of endogenous metabolites under the disturbance of functional compounds, which will be used to decode the bioactive ingredients of HM and expound the molecular targets. Metabolomics can provide an approach for explaining HM, addressing unclear clinical efficacy and undefined mechanisms of action. In this review, the metabolomics strategy and its applications in HM are systematically introduced, which offers valuable insights for metabolomics methods to characterizing the pharmacological effects and molecular targets of HM.
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Medicamentos de Ervas Chinesas , Plantas Medicinais , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica/métodosRESUMO
BACKGROUND: Plasma circular (circ)RNAs detected by droplet digital polymerase chain reaction (ddPCR) may be ideal markers for liquid biopsy. However, ddPCR detection of circRNAs in plasma for diagnosis of lung adenocarcinoma has been rarely reported. METHODS: An RNA sequencing analysis was performed in plasma from patients with early lung adenocarcinoma and healthy individuals. Droplet digital PCR was used to verify the differentially expressed genes. RESULTS: The copy numbers of circle RNALZIC (circLZIC)and circle RNACEP350 (circCEP350) in the plasma of lung adenocarcinoma patients were significantly higher than in plasma of healthy people, and the copy numbers in postoperative plasma of the same patients were significantly lower than those in preoperative plasma. CircLZIC and circCEP350 alone and in combination had diagnostic value in lung adenocarcinoma and early lung adenocarcinoma. CircLZIC and circCEP350 had more binding sites with multiple microRNAs. Their target genes were enriched in several signaling pathways. CONCLUSION: The copy numbers of circLZIC and circCEP350 were higher in plasma of lung adenocarcinoma patients than in plasma of healthy controls, significantly correlated with tumor size and TNM stage, and closely related to the occurrence and development of tumors. These circRNAs may serve as molecular markers for the diagnosis of lung adenocarcinoma.
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Infections caused by Candida albicans (C. albicans) and increasing resistance to commonly used drugs lead to a variety of mucosal diseases and systemic infectious diseases. We previously confirmed that the essential oil of Clausena lansium (Lour.) Skeels seeds (CSEO) had antifungal activity against C. albicans, but the detailed mechanism between the chemical components and antifungal activity is unclear. In this study, a quantitative analysis of five volatile components of CSEO, including sabinene, α-phellandrene, ß-phellandrene, 4-terpineol, and ß-caryophyllene, was carried out using the gas chromatography-mass spectrometry (GC-MS) method. Both the broth dilution and kinetic growth methods proved that the antifungal activity of CSEO against fluconazole-resistant C. albicans was better than that of its main components (sabinene and 4-terpineol). To further investigate the inhibitory mechanism, the transcriptional responses of C. albicans to CSEO, sabinene, and 4-terpineol treatment were determined based on RNA-seq. The Venn diagram and clustering analysis pattern of differential expression genes showed the mechanism of CSEO and 4-terpineol's anti-C. albicans activity might be similar from the perspective of the genes. Functional enrichment analysis suggested that CSEO regulated adherence-, hyphae-, and biofilm-formation-related genes, which may be CSEO's active mechanism of inhibiting the growth of fluconazole-resistant C. albicans. Overall, we preliminarily revealed the molecular mechanism between the chemical components and the antifungal activity of CSEO against C. albicans. This study provides new insights to overcome the azole resistance of C. albicans and promote the development and application of C. lansium (Lour.) Skeels seeds.
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Clausena , Óleos Voláteis , Candida albicans/genética , Óleos Voláteis/química , Antifúngicos/química , Clausena/química , Cromatografia Gasosa-Espectrometria de Massas , Fluconazol , RNA-Seq , Sementes/química , Perfilação da Expressão Gênica , Testes de Sensibilidade MicrobianaRESUMO
Metabolic abnormalities are a hallmark of cancer cells and are essential to tumor progression. Oncometabolites have pleiotropic effects on cancer biology and affect a plethora of processes, from oncogenesis and metabolism to therapeutic resistance. Targeting oncometabolites, therefore, could offer promising therapeutic avenues against tumor growth and resistance to treatments. Recent advances in characterizing the metabolic profiles of cancer cells are shedding light on the underlying mechanisms and associated metabolic networks. This review summarizes the diverse detection methods, molecular mechanisms, and therapeutic targets of oncometabolites, which may lead to targeting oncometabolism for cancer therapy.
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Neoplasias , Humanos , Neoplasias/metabolismo , Carcinogênese , Transformação Celular Neoplásica/metabolismo , Redes e Vias Metabólicas , MetabolomaRESUMO
Chemodynamic immunotherapy that utilizes catalysts to produce reactive oxygen species (ROS) for killing tumor cells and arousing antitumor immunity has received considerable attention. However, it is still restricted by low ROS production efficiency and insufficient immune activation, due to intricate redox homeostasis in the tumor microenvironment (TME). Herein, a metalloprotein-like hybrid nanozyme (FeS@GOx) is designed by in situ growth of nanozyme (ferrous sulfide, FeS) in a natural enzyme (glucose oxidase, GOx) to amplify ROS cascade for boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows the conversion of endogenous glucose to gluconic acid and hydrogen peroxide, which provides favorable increasing hydrogen peroxide for subsequent Fenton reaction of FeS nanozymes, thus reinforcing ROS production. Notably, hydrogen sulfide (H2 S) release is activated by the gluconic acid generation-related pH decrease, which can suppress the activity of endogenous thioredoxin reductase and catalase to further inhibit ROS elimination. Thus, FeS@GOx can sustainably amplify ROS accumulation and perturb intracellular redox homeostasis to improve chemodynamic therapy and trigger robust immunogenic cell death for effective immunotherapy combined with immune checkpoint blockade. This work proposes a feasible H2 S amplified ROS cascade strategy employing a bioinspired hybrid nanozyme, providing a novel pathway to multi-enzyme-mediated TME modulation for precise and efficient chemodynamic immunotherapy.
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Peróxido de Hidrogênio , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio , Imunoterapia , Microambiente TumoralRESUMO
Two new aphidicolane diterpenoids, termed Scopadulinol A (1) and B (2), were obtained from whole plants of Scoparia dulcis. Their structures were elucidated by applying various spectroscopic techniques, including 1D- and 2D-NMR and HR-ESI-MS. The absolute configurations of 1 and 2 were determined by applying the calculated electronic circular dichroism (ECD). In addition, both compounds were tested for their effects on glucose consumption in HL-7702 cells and on palmitic acid (PA) induced viability in MIN6 cells at different concentrations. The results showed that they significantly promoted glucose consumption and attenuated the PA-induced decrease of cell viability. Additionally, 2 was tested to determine whether it could activate AMP-activated protein kinase (AMPK), but it showed no such effect at the tested dosage. These results indicated that the new compounds might promote glucose consumption through other pathways but not by activating AMPK. Collectively, we highlighted the isolation of two new aphidicolane diterpenoids from S. dulcis and found that they could promote glucose consumption and attenuate PA-induced decrease of cell viability.
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Diterpenos , Scoparia , Glucose , Scoparia/química , Sobrevivência Celular , Proteínas Quinases Ativadas por AMP , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/químicaRESUMO
Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes.
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Klebsiella pneumoniae (KP) is one of the microorganisms that can acquire carbapenem-resistance (CR), and few antimicrobial therapy options exist for infections caused by Carbapenem-Resistant KP (CRKP). In recent years, with the increase of carbapenem resistance rates, treating CRKP has become a serious public health threat in clinical practice. We have collected 2,035 clinical KP isolates from a tertiary hospital in China. Whole genome sequencing data coupled with their binary antimicrobial susceptibility testing data were obtained to conduct the genome-wide association study using a bayesian-based method, including single nucleotide polymorphisms (SNPs) and genes. We identified 28 and 37 potential maker genes associated with imipenem and meropenem resistance, respectively. Among which 19 of them were selected in both drugs by genome-wide association study (GWAS), 11 genes among them were simultaneously validated in independent datasets. These genes were likely related to biofilm formation, efflux pump, and DNA repairing. Moreover, we identified 13 significant CR related SNPs in imipenem or meropenem, with one SNP located in the non-coding region and validated in the independent datasets. Our study indicates complex mechanisms of carbapenems resistance and further investigation of CRKP-related factors are warranted to better understand their contributions to carbapenems resistance. These identified biomarkers may provide targets for future drug interventions or treatments.
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Background: Acetaminophen-related hepatic injury (ARHI) is a kind of acute hepatic injury caused by overdosing acetaminophen, which is mainly related to toxic metabolite production, oxidative stress, and mitochondrial dysfunction. The extract of Paederia scandens (Lour.) Merr. (PSM) has the abilities of anti-inflammatory, antivirus, and antioxidation. Research studies showed that PSM could improve acute or chronic hepatic injury, while the mechanism of which is still indistinct. Methods: Here, the authors applied the approach based on serum metabonomics combined with network pharmacology to study the protection of PSM on ARHI rats. Results: 10 serum potential biomarkers were found to be closely related to ARHI by metabonomics, while 3 compounds (L-ascorbyl 2,6-dipalmitate, squalene, and tributyl O-acetylcitrate) and 3 targets (NOS2, MAOB, and PDE3A) were found that might be the potential active components and active site of PSM on treating ARHI by network pharmacology analysis. Furthermore, molecular biology strategy was performed to validate whether iNOS/NF-κB signaling pathway is the potential mechanism of PSM treating ARHI. Conclusions: This study indicated that PSM could ameliorate ARHI by iNOS/NF-κB signaling pathway. During ARHI treatment by PSM, L-ascorbyl 2, 6-dipalmitate, squalene, and tributyl O-acetylcitrate might be the potential active components, while the possible active site might be NOS2, MAOB, and PDE3A.
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OBJECTIVES: Current research shows that the resistance of Escherichia coli (E. coli) is mainly related to integron gene cassettes. To assess the resistance of E. coli of goose origin and the carriage of its integron genes in four farms in Heilongjiang Province, antibiotic resistance phenotypes and the presence of various types of integrons were investigated. METHODS: In this study, test strains were sampled and isolated from the farms, and 109 test strains were tested for drug sensitivity of 15 different antimicrobial drugs by the Kb disc diffusion method. Polymerase chain reaction was used to detect E. coli in three types of integrase genes (intI1, intI2, and intI3) and for sequencing analysis of the class I integron gene cassette. RESULTS: Susceptibility test results show that more than 70% of tested strains exhibit resistant phenotypes to ampicillin, amoxicillin, imipenem, tetracycline, and doxycycline. The detection rate of class I integrons was 68.91%, while class II integrons and class III integrons were not detected. The detection rate of class I integrin gene cassette was 7.42%. Sequence analysis showed that strains carried different integron gene cassettes: dfrA17-aadA5, dfrA1-aadA1, dfrA27-arr-3, and aminoglycoside 3''-nucleotidyltransferase. CONCLUSIONS: Results suggest that the detection rate of class I integrons is highly correlated with their drug resistance. Class I integrons provide a valuable guide to studying the spread and the expression of resistance genes and thus finding effective measures to prevent bacterial resistance.
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Escherichia coli , Integrons , Animais , Integrons/genética , Gansos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genéticaRESUMO
Zoonotic and pandemic influenza continue to pose threats to global public health. Pandemics arise when novel influenza A viruses, derived in whole or in part from animal or avian influenza viruses, adapt to transmit efficiently in a human population that has little population immunity to contain its onward transmission. Viruses of previous pandemic concern, such as influenza A(H7N9), arose from influenza A(H9N2) viruses established in domestic poultry acquiring a hemagglutinin and neuraminidase from influenza A viruses of aquatic waterfowl. We report a novel influenza A(H3N8) virus in chicken that has emerged in a similar manner and that has been recently reported to cause zoonotic disease. Although they are H3 subtype, these avian viruses are antigenically distant from contemporary human influenza A(H3N2) viruses, and there is little cross-reactive immunity in the human population. It is essential to heighten surveillance for these avian A(H3N8) viruses in poultry and in humans.
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Vírus da Influenza A Subtipo H3N8 , Subtipo H7N9 do Vírus da Influenza A , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Animais , Galinhas , China/epidemiologia , Hemaglutininas , Hong Kong/epidemiologia , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Vírus da Influenza A Subtipo H9N2/genética , Influenza Humana/epidemiologia , Neuraminidase/genética , Filogenia , Aves DomésticasRESUMO
Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells. Tool compounds ICeD-1 and ICeD-2 ("inducer of cell death-1 and 2"), optimized for potency and selectivity from screening hits, were used to deconvolute the mechanism of action using a combination of chemoproteomic, biochemical, pharmacological, and genetic approaches. We determined that these compounds function by modulating dipeptidyl peptidase 9 (DPP9) and activating the caspase recruitment domain family member 8 (CARD8) inflammasome. Efficacy of ICeD-1 and ICeD-2 was dependent on HIV-1 protease activity and synergistic with efavirenz, which promotes premature activation of HIV-1 protease at high concentrations in infected cells. This in vitro synergy lowers the efficacious cell kill concentration of efavirenz to a clinically relevant dose at concentrations of ICeD-1 or ICeD-2 that do not result in complete DPP9 inhibition. These results suggest engagement of the pyroptotic pathway as a potential approach to eliminate HIV-1 infected cells.
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Infecções por HIV , HIV-1 , Alcinos , Benzoxazinas , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Ciclopropanos , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Humanos , Inflamassomos/metabolismo , Leucócitos Mononucleares , Proteínas de Neoplasias/metabolismoRESUMO
Several zoonotic influenza A viruses detected in humans contain genes derived from avian H9N2 subtypes. We uncovered a Eurasian avian-like H1N1 swine influenza virus with polymerase basic 1 and matrix gene segments derived from the H9N2 subtype, suggesting that H9N2 viruses are infecting pigs and reassorting with swine influenza viruses in China.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H9N2 , Influenza Humana , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Aves , China/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H9N2/genética , Influenza Humana/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Filogenia , Vírus Reordenados/genética , Suínos , Doenças dos Suínos/epidemiologiaRESUMO
Global dissemination of K. pneumoniae clones poses health hazards to the public. Genomic epidemiology studies with comprehensive data set further revealed clone divergence, showing a high complexity in evolution. Moreover, clones carrying both acquired virulent and antimicrobial-resistant genes emerged and might replace the carbapenem-resistant clones. Co-occurrence of virulence and resistance is emerging. An unbiased collection of 3,061 clinical K. pneumoniae isolates (January 5, 2013 to July 24, 2018) underwent whole-genome sequencing. Pairwise core-genome single-nucleotide polymorphism (cgSNP) distances identified clone divergence and transmission events. A sum of 2,193 nonduplicated genomes clustered into four phenotypically indistinguishable species complexes. 93% (n = 2,035) were KpI with its largest clonal group (CG) being CG11 (n = 406). Three hundred ninety-three were ST11 and three hundred seventy-four carried blaKPC-2. Noticeably, CG11 is divided into two main subclones based on the capsule synthesis K loci (KL). CG11-KL64 showed a clear hypervirulent plus antimicrobial-resistant (hv+AMR) characteristic. Besides, the phylogenetic structure revealed the clone divergence of CG25, and this is the first report with sufficient CG25 genomes to identify the divergence. The outcomes of the hv+AMR CG25 cluster 1 affected patients were poorer (P < 0.05). Moreover, two episodes of strain transmissions were associated with CG25 cluster 1. Other transmissions were associated with ST20 and ST307. Genomic epidemiology identified clone divergence of CG11 and CG25. The hv+AMR subclones pose greater threats on a global scale. Nosocomial transmissions of the high-risk clones raised our concerns about the evolution and transmission of emerging clones among newborns and critically ill patients. IMPORTANCE The convergence of AMR and acquired virulence posing higher risks to the public is a focusing point. With sufficient genomes and genotypes, we successfully identify the convergence in two subclones, the previously reported CG11-KL64, and the newly reported CG25 cluster 1. The novel finding of the CG25 divergence was not only revealed by the phylogenetic tree but also confirmed by the clinical outcome data and the accessory genome patterns. Moreover, the transmission subclones circulated in two clinically important wards highlights the deficiency of infection control program using conventional methods. Without the assistance of whole-genome sequencing, the transmissions of high-risk clones could not be identified.
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Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Células Clonais , Farmacorresistência Bacteriana Múltipla/genética , Genômica , Humanos , Recém-Nascido , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Filogenia , beta-Lactamases/genéticaRESUMO
Phototheranostic offers a regional-focused tumor treatment upon photoirradiation. However, it is difficult to completely eradicate solid tumors using a conventional phototheranostic owing to the residual tumor cells outside the laser irradiation range. Herein, we fabricated a metallopolysaccharide-based smart nanotheranostic (Fe-dHA) via a nanoassembly-driven method, in which Fe3+ ions were coordinated to dopamine-modified biopolysaccharide hyaluronic acid (dHA). Taking advantage of the structural backbone and intrinsic dual-information-related functions of HA as well as the bi-functional Fe(III)-coordination centers, Fe-dHA can efficiently target tumor cells for phototheranostic. Additionally, it can be activated by endogenous overexpressed hyaluronidase to achieve sequential ferroptosis in tumor cells. The precise imaging and effective tumor inhibition using this metallopolysaccharide-based nanotheranostic were significantly demonstrated in vivo and in vitro. Thus, this rationally designed Fe-dHA provided a simple metallopolysaccharide strategy to develop an "all-in-one" smart nanotheranostic to synergize different therapeutic modalities for improving cancer therapy.