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The burgeoning crisis of antibiotic resistance has directed attention to bacteriophages as natural antibacterial agents capable of circumventing bacterial defenses. Central to this are the bacterial defense mechanisms, such as the BREX system, which utilizes the methyltransferase BrxX to protect against phage infection. This study presents the first in vitro characterization of BrxX from Escherichia coli, revealing its substrate-specific recognition and catalytic activity. We demonstrate that BrxX exhibits nonspecific DNA binding but selectively methylates adenine within specific motifs. Kinetic analysis indicates a potential regulation of BrxX by the concentration of its co-substrate, S-adenosylmethionine, and suggests a role for other BREX components in modulating BrxX activity. Furthermore, we elucidate the molecular mechanism by which the T7 phage protein Ocr (Overcoming classical restriction) inhibits BrxX. Despite low sequence homology between BrxX from different bacterial species, Ocr effectively suppresses BrxX's enzymatic activity through high-affinity binding. Cryo-electron microscopy and biophysical analyses reveal that Ocr, a DNA mimic, forms a stable complex with BrxX, highlighting a conserved interaction interface across diverse BrxX variants. Our findings provide insights into the strategic counteraction by phages against bacterial defense systems and offer a foundational understanding of the complex interplay between phages and their bacterial hosts, with implications for the development of phage therapy to combat antibiotic resistance.
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Proteínas de Escherichia coli , Escherichia coli , Proteínas Virales , Escherichia coli/virología , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas Virales/metabolismo , S-Adenosilmetionina/metabolismo , Unión Proteica , Bacteriófago T7/genética , Metiltransferasas/metabolismo , CinéticaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.
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Carcinoma Hepatocelular , Detección Precoz del Cáncer , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Cooperación del Paciente/estadística & datos numéricos , Tamizaje Masivo/métodos , Factores de RiesgoRESUMEN
Synaptic behavior simulation in transistors based on MoS2 has been reported. MoS2 was utilized as the active layer to prepare ambipolar thin-film transistors. The excitatory postsynaptic current phenomenon was simulated, observing a gradual voltage decay following the removal of applied pulses, ultimately resulting in a response current slightly higher than the initial current. Subsequently, ±5 V voltages were separately applied for ten consecutive pulse voltage tests, revealing short-term potentiation and short-term depression behaviors. After 92 consecutive positive pulses, the device current transitioned from an initial value of 0.14 to 28.3 mA. Similarly, following 88 consecutive negative pulses, the device current changed, indicating long-term potentiation and long-term depression behaviors. We also employed a pair of continuous triangular wave pulses to evaluate paired-pulse facilitation behavior, observing that the response current of the second stimulus pulse was â¼1.2× greater than that of the first stimulus pulse. The advantages and prospects of using MoS2 as a material for thin-film transistors were thoroughly displayed.
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Pseudomonas aeruginosa biofilm formation has been considered to be an important determinant of its pathogenicity in most infections. The antibiofilm activity of trans-cinnamaldehyde (TC) against P. aeruginosa was investigated in this study. Results demonstrated that the minimum inhibitory concentration (MIC) of TC against P. aeruginosa was 0.8 mg/mL, and subinhibitory concentrations (SICs) was 0.2 mg/mL and below. Crystal violet staining showed that TC at 0.05-0.2 mg/mL reduced biofilm biomass in 48 h in a concentration-dependent mode. The formation area of TC-treated biofilms was significantly declined (p < 0.01) on the glass slides observed by light microscopy. Field-emission scanning electron microscopy further demonstrated that TC destroyed the biofilm morphology and structure. Confocal laser scanning microscopic observed the dispersion of biofilms and the reduction of exopolysaccharides after TC treatment stained with concanavalin A (Con-A)-fluorescein isothiocyanate conjugate and Hoechst 33258. Meanwhile, TC caused a significant decrease (p < 0.01) in the component of polysaccharides, proteins, and DNA in extracellular polymeric substance. The swimming and swarming motility and quorum sensing of P. aeruginosa was also found to be significantly inhibited (p < 0.01) by TC at SICs. Furthermore, SICs of TC repressed the several genes transcription associated with biofilm formation as determined by real-time quantitative polymerase chain reaction. Overall, our findings suggest that TC could be applied as natural and safe antibiofilm agent to inhibit the biofilm formation of P. aeruginosa.
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Antibacterianos , Pseudomonas aeruginosa , Antibacterianos/farmacología , Matriz Extracelular de Sustancias Poliméricas , Biopelículas , Percepción de Quorum/genéticaRESUMEN
Yersinia enterocolitica (Y. enterocolitica) is a gastrointestinal pathogen that is distributed worldwide, involved in systemic, extraintestinal and invasive infections in immunocompromised patients. Establishment of antibiotic resistance in the pathogen has produced a need for new antibacterial agents. The purpose of this study was to elucidate antibacterial mechanism of protocatechualdehyde (PCA) extracted from the roots of Salvia miltiorrhiza towards Y. enterocolitica, and to investigate effects of PCA on key virulence factors associated with human infection. Present results indicated that PCA exerted its antibacterial activity against Y. enterocolitica mainly by the rapid rise of intracellular reactive oxygen species, leading to change in permeability and integrity of cell membrane, and ultimately decline of membrane potential and intracellular ATP. Furthermore, scanning electron microscopic analysis revealed that Y. enterocolitica presented gradually shrinkage in length and partial wrinkles upon PCA treatment. PCA also effectively decreased motility, biofilm formation, quorum sensing in a dose-dependent manner without affecting bacterial growth. Further, at SICs, PCA substantially suppressed the adhesion and invasion of Y. enterocolitica to HT-29 cells and the downregulation of essential virulence factor-encoding genes unveiled impaired virulence. Overall, the findings revealed the potential of PCA as an alternative antibacterial agent to combat Y. enterocolitica contamination and infections.
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Yersiniosis , Yersinia enterocolitica , Humanos , Yersinia enterocolitica/genética , Yersiniosis/microbiología , Factores de Virulencia/genética , Antibacterianos/farmacologíaRESUMEN
Background: Colorectal, and gastric cancers have the second, and fourth mortality rates worldwide, respectively. Endoscopic screening is a crucial diagnostic tool for colorectal, and gastric cancers. Effective interventions can improve adherence to endoscopic screening in high-risk populations, which is important for cancer prevention and mortality reduction. This study aimed to identify interventions that could improve adherence to endoscopic screening for cancer in high-risk populations. Methods: Combination keywords including colorectal cancer, gastric cancer, screening adherence, and interventions were used to search for articles in PubMed, Web of Science, Cochrane Library, and MEDLINE Complete. The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR). Results: A total of 12 articles were included in this review: 9 randomized controlled trials(RCT) and 3 quasi-experimental studies(QEDs). Among the extracted studies, 11 were about colorectal cancer, and 1 was about gastric cancer. Most studies used lecture-based or Information Technology-based health education interventions. Narrative interventions have proven to be novel and effective approaches for promoting adherence to endoscopic screening. Health education interventions included cancer epidemiology, cancer risk factors, warning symptoms, and screening methods. Conclusion: All interventions involved were effective in increasing individual knowledge of cancer-related endoscopic screening, willingness to undergo screening, and screening behaviors. These findings provide a reference for designing endoscopy-related cancer screening interventions.
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In this study, Listeria monocytogenes from minced pork was evaluated for changes in resistance to thermal treatment and gastric fluid following environmental stresses during food processing. Bacteria were exposed to cold stress, followed by successive exposures to different stressors (lactic acid (LA), NaCl, or Nisin), followed by thermal treatments, and finally, their gastrointestinal tolerance was determined. Adaptation to NaCl stress reduced the tolerance of L. monocytogenes to subsequent LA and Nisin stress. Adaptation to LA stress increased bacterial survival in NaCl and Nisin-stressed environments. Bacteria adapted to Nisin stress showed no change in tolerance to subsequent stress conditions. In addition, treatment with NaCl and LA enhanced the thermal tolerance of L. monocytogenes, but treatment with Nisin decreased the thermal tolerance of the bacteria. Almost all of the sequential stresses reduced the effect of a single stress on bacterial thermal tolerance. The addition of LA and Nisin as a second step of stress reduced the tolerance of L. monocytogenes to gastric fluid, whereas the addition of NaCl enhanced its tolerance. The results of this study are expected to inform processing conditions and sequences for meat preservation and processing and reduce uncertainty in risk assessment of foodborne pathogens due to stress adaptation.