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Foodborne illness remains a pressing global issue due to the complexities of modern food supply chains and the vast array of potential contaminants that can arise at every stage of food processing from farm to fork. Traditional food safety control systems are increasingly challenged to identify these intricate hazards. The U.S. Food and Drug Administration's (FDA) New Era of Smarter Food Safety represents a revolutionary shift in food safety methodology by leveraging cutting-edge digital technologies. Digital food safety control systems employ modern solutions to monitor food quality by efficiently detecting in real time a wide range of contaminants across diverse food matrices within a short timeframe. These systems also utilize digital tools for data analysis, providing highly predictive assessments of food safety risks. In addition, digital food safety systems can deliver a secure and reliable food supply chain with comprehensive traceability, safeguarding public health through innovative technological approaches. By utilizing new digital food safety methods, food safety authorities and businesses can establish an efficient regulatory framework that genuinely ensures food safety. These cutting-edge approaches, when applied throughout the food chain, enable the delivery of safe, contaminant-free food products to consumers.
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Contaminação de Alimentos , Inocuidade dos Alimentos , Humanos , Contaminação de Alimentos/prevenção & controle , Doenças Transmitidas por Alimentos/prevenção & controle , Estados Unidos , Tecnologia Digital , United States Food and Drug Administration , Manipulação de Alimentos/métodosRESUMO
This study was designed to assess the possibility of using bacteriophage-encoded endolysins for controlling planktonic and biofilm cells. The endolysins, LysEP114 and LysEP135, were obtained from plasmid vectors containing the endolysin genes derived from Escherichia coli phages. The high identity (>96 %) was observed between LysEP114 and LysEP135. LysEP114 and LysEP135 were characterized by pH, thermal, and lactic acid stability, lytic spectrum, antibacterial activity, and biofilm eradication. The molecular masses of LysEP114 and LysEP135 were 18.2 kDa, identified as muramidases. LysEP114 and LysEP135 showed high lytic activity against the outer membrane-permeabilized E. coli KCCM 40405 at below 37 °C, between pH 5 to 11, and below 70 mM of lactic acid. LysEP114 and LysEP135 showed the broad rang of lytic activity against E. coli KACC 10115, S. Typhimurium KCCM 40253, S. Typhimurium CCARM 8009, tetracycline-resistant S. Typhimurium, polymyxin B-resistant S. Typhimurium, chloramphenicol-resistant S. Typhimurium, K. pneumoniae ATCC 23357, K. pneumoniae CCARM 10237, and Shigella boydii KACC 10792. LysEP114 and LysEP135 effectively reduced the numbers of planktonic E. coli KCCM by 1.7 and 2.1 log, respectively, when treated with 50 mM lactic acid. The numbers of biofilm cells were reduced from 7.3 to 4.1 log CFU/ml and 2.2 log CFU/ml, respectively, when treated with LysEP114- and LysEP135 in the presence of 50 mM lactic acid. The results suggest that the endolysins in combination with lactic acid could be potential alternative therapeutic agents for controlling planktonic and biofilm cells.
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Antibacterianos , Biofilmes , Endopeptidases , Escherichia coli , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Endopeptidases/farmacologia , Endopeptidases/genética , Endopeptidases/metabolismo , Antibacterianos/farmacologia , Concentração de Íons de Hidrogênio , Plâncton/efeitos dos fármacos , Plâncton/virologia , Colífagos/genética , Colífagos/fisiologia , Ácido Láctico/farmacologia , Bacteriófagos/genética , Temperatura , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Proteínas Virais/genética , Proteínas Virais/farmacologia , Proteínas Virais/metabolismoRESUMO
OBJECTIVE: Non-invasive biomarkers have recently shown promise for seizure forecasting in people with epilepsy. In this work, we developed a seizure-day forecasting algorithm based on nocturnal sleep features acquired using a smart shirt. METHODS: Seventy-eight individuals with epilepsy admitted to the Centre hospitalier de l'Université de Montréal epilepsy monitoring unit wore the Hexoskin biometric smart shirt during their stay. The shirt continuously measures electrocardiography, respiratory, and accelerometry activity. Ten sleep features, including sleep efficiency, sleep latency, sleep duration, time spent in non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM), wakefulness after sleep onset, average heart and breathing rates, high-frequency heart rate variability, and the number of position changes, were automatically computed using the Hexoskin sleep algorithm. Each night's features were then normalized using a reference night for each patient. A support vector machine classifier was trained for pseudo-prospective seizure-day forecasting, with forecasting horizons of 16- and 24-h to include both diurnal and nocturnal seizures (24-h) or diurnal seizures only (16-h). The algorithm's performance was assessed using a nested leave-one-patient-out cross-validation approach. RESULTS: Improvement over chance (IoC) performances were achieved for 48.7% and 40% of patients with the 16- and 24-h forecasting horizons, respectively. For patients with IoC performances, the proposed algorithm reached mean IoC, sensitivity and time in warning of 34.3%, 86.0%, and 51.7%, respectively for the 16-h horizon, and 34.2%, 64.4% and 30.2%, respectively, for the 24-h horizon. SIGNIFICANCE: Smart shirt-based nocturnal sleep analysis holds promise as a non-invasive approach for seizure-day forecasting in a subset of people with epilepsy. Further investigations, particularly in a residential setting with long-term recordings, could pave the way for the development of innovative and practical seizure forecasting devices. PLAIN LANGUAGE SUMMARY: Seizure forecasting with wearable devices may improve the quality of life of people living with epilepsy who experience unpredictable, recurrent seizures. In this study, we have developed a seizure forecasting algorithm using sleep characteristics obtained from a smart shirt worn at night by a large number of hospitalized patients with epilepsy (78). A daily seizure forecast was generated following each night using machine learning methods. Our results show that around half of people with epilepsy may benefit from such an approach.
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Marek's disease (MD), caused by the Marek's disease virus (MDV), is a common infectious tumor disease in chickens and was the first neoplastic disease preventable by vaccination. However, the vaccine cannot completely prevent virulent MDV infections, allowing both the vaccine and virulent MDV to coexist in the same chicken for extended periods. This study aims to investigate the changes in viral load of the very virulent strain Md5 and the rHVT-IBD vaccine in different chicken tissues using a real-time PCR assay. The results showed that the rHVT-IBD vaccine significantly reduced the viral load of MDV-Md5 in different organs, while the load of rHVT-IBD was significantly increased when co-infected with Md5. Additionally, co-infection with Md5 and rHVT-IBD in chickens not only changed the original viral load of both viruses but also affected the positive rate of Md5 at 14 days post-vaccination. The positive rate decreased from 100% to 14.29% (feather tips), 0% (skin), 33.33% (liver), 16.67% (spleen), 28.57% (thymus), 33.33% (bursa), and 66.67% (PBL), respectively. This study enhances our understanding of the interactions between HVT vector vaccines and very virulent MDV in chickens and provides valuable insights for the future development of MD vaccines.
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Galinhas , Coinfecção , Vacinas contra Doença de Marek , Doença de Marek , Doenças das Aves Domésticas , Carga Viral , Animais , Doença de Marek/virologia , Doença de Marek/prevenção & controle , Doença de Marek/imunologia , Galinhas/virologia , Coinfecção/virologia , Coinfecção/veterinária , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas contra Doença de Marek/imunologia , Vacinas contra Doença de Marek/genética , Virulência , Herpesvirus Meleagrídeo 1/imunologia , Herpesvirus Meleagrídeo 1/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/genética , Herpesvirus Galináceo 2/genética , Herpesvirus Galináceo 2/imunologia , Herpesvirus Galináceo 2/patogenicidade , Vacinação , Vetores Genéticos/genéticaRESUMO
Various pathogens have the ability to grow on food matrices and instruments. This grow may reach to form biofilms. Bacterial biofilms are community of microorganisms embedded in extracellular polymeric substances (EPSs) containing lipids, DNA, proteins, and polysaccharides. These EPSs provide a tolerance and favorable living condition for microorganisms. Biofilm formations could not only contribute a risk for food safety but also have negative impacts on healthcare sector. Once biofilms form, they reveal resistances to traditional detergents and disinfectants, leading to cross-contamination. Inhibition of biofilms formation and abolition of mature biofilms is the main target for controlling of biofilm hazards in the food industry. Some novel eco-friendly technologies such as ultrasound, ultraviolet, cold plasma, magnetic nanoparticles, different chemicals additives as vitamins, D-amino acids, enzymes, antimicrobial peptides, and many other inhibitors provide a significant value on biofilm inhibition. These anti-biofilm agents represent promising tools for food industries and researchers to interfere with different phases of biofilms including adherence, quorum sensing molecules, and cell-to-cell communication. This perspective review highlights the biofilm formation mechanisms, issues associated with biofilms, environmental factors influencing bacterial biofilm development, and recent strategies employed to control biofilm-forming bacteria in the food industry. Further studies are still needed to explore the effects of biofilm regulation in food industries and exploit more regulation strategies for improving the quality and decreasing economic losses.
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Biofilmes , Indústria Alimentícia , Microbiologia de Alimentos , Inocuidade dos Alimentos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Percepção de Quorum/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Antibacterianos/farmacologiaRESUMO
Cyclodextrin metal-organic framework (CD-MOF) is an edible and porous material that can serve as a template for synthesizing small-sized metal nanoparticles. However, its highly hydrophilic nature has limited its wider application. Herein, ultra-small gold nanoparticles (U-AuNPs) were loaded into CD-MOF to produce a composite material Au@CD-MOF. The CD-MOF was utilized as a template to control the size of the AuNPs. The synthesized Au@CD-MOF was easily dispersible in aqueous medium and its released U-AuNPs exhibited effective water dispersion stability within 120 days. Additionally, compared to gold nanoparticles prepared using traditional methods (T-AuNPs), the U-AuNPs exhibited superior antibacterial properties. Furthermore, hydrophilic Au@CD-MOF was incorporated into a hydrophobic polydimethylsiloxane (PDMS) matrix (Au@CD-MOF/PDMS) to achieve a humidity-responsive antibacterial function. The composite membrane exhibited remarkable responsiveness to humidity, showing almost no release of U-AuNPs at 0 % humidity. However, it exhibited approximately 89 % release within 1 h, and complete release of U-AuNPs was observed within 4 h under 100 % humidity. These findings highlight the successful preparation of a humidity-responsive antibacterial composite membrane, which has great potential applications in various scenarios, particularly in the field of antibacterial food packaging.
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Antibacterianos , Ciclodextrinas , Ouro , Umidade , Nanopartículas Metálicas , Estruturas Metalorgânicas , Ouro/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas Metálicas/química , Ciclodextrinas/química , Tamanho da Partícula , Testes de Sensibilidade Microbiana , Interações Hidrofóbicas e Hidrofílicas , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Cultured meat, which involves growing meat in a laboratory rather than breeding animals, offers potential benefits in terms of sustainability, health, and animal welfare compared to conventional meat production. However, the cultured meat production process involves several stages, each with potential hazards requiring careful monitoring and control. Microbial contamination risks exist in the initial cell collection from source animals and the surrounding environment. During cell proliferation, hazards may include chemical residues from media components such as antibiotics and growth factors, as well as microbial issues from improper bioreactor sterilization. In the differentiation stage where cells become muscle tissue, potential hazards include residues from scaffolding materials, microcarriers, and media components. Final maturation and harvesting stages risk environmental contamination from nonsterile conditions, equipment, or worker handling if proper aseptic conditions are not maintained. This review examines the key microbiological and chemical hazards that must be monitored and controlled during the manufacturing process for cultured meats. It describes some conventional and emerging novel techniques that could be applied for the detection of microbial and chemical hazards in cultured meat. The review also outlines the current evolving regulatory landscape around cultured meat and explains how thorough detection and characterization of microbiological and chemical hazards through advanced analytical techniques can provide crucial data to help develop robust, evidence-based food safety regulations specifically tailored for the cultured meat industry. Implementing new digital food safety methods is recommended for further research on the sensitive and effective detection of microbiological and chemical hazards in cultured meat.
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Carne , Animais , Carne/microbiologia , Carne/análise , Contaminação de Alimentos/análise , Microbiologia de Alimentos/métodos , Inocuidade dos Alimentos/métodos , Carne in vitroRESUMO
Resin-based dental composites, commonly used in dentistry, offer several advantages including minimally invasive application, esthetically pleasing appearance, and good physical and mechanical properties. However, these dental composites can be susceptible to microcracks due to various factors in the complex oral environment. These microcracks can potentially lead to clinical restoration failure. Conventional materials and methods are inadequate for detecting and repairing these microcracks in situ. Consequently, incorporating self-healing properties into dental composites has become a necessity. Recent years have witnessed rapid advancements in self-healing polymer materials, drawing inspiration from biological bionics. Microcapsule-based self-healing dental composites (SHDCs) represent some of the most prevalent types of self-healing materials utilized in this domain. In this article, we undertake a comprehensive review of the most recent literature, highlighting key insights and findings related to microcapsule-based SHDCs. Our discussion centers particularly on the preparation techniques, application methods, and the promising future of self-healing microcapsules in the field of dentistry.
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The aim of this study was to evaluate the phenotypic and genotypic responses of Salmonella Typhimurium ATCC 19585 (ST) and Staphylococcus aureus KACC 13236 (SA) preadapted to sublethal concentrations of lactic acid (LA) and sodium chloride (NaCl) for 48 hr at 37°C, followed by re-exposure to lethal concentrations of LA and NaCl for 24 hr at 37°C. ST and SA treated in a sequential and ordered manner with LA and NaCl were assigned as LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl. The treatments, LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl, were evaluated by antimicrobial susceptibility, bacterial fluctuation, relative fitness, zeta potential, and gene expression. The MICt/MICc ratios of LA, NaCl, CIP, GEN, and TET against ST treated with LA-LA were 1.0 to 0.8, 0.8, 0.3, 0.4, and 0.5, respectively. The MICt/MICc ratios of NaCl, CIP, GEN, and TET were between 0.5-0.8 for SA treated with LA-LA. ST treated with LA-LA and SA treated with LA-NaCl exhibited the highest coefficient of variance. The lowest relative fitness was observed at ST treated with LA-LA (0.5). ST and SA treated with LA-LA showed the lowest zeta potential. The transporter-, toxin-antitoxin system-, chaperone protein-, and SOS response-related genes were suppressed at ST and SA treated with LA-LA. The transporter-, toxin-antitoxin system-, and chaperone protein-related genes were overexpressed in SA treated with LA-NaCl, NaCl-LA, and NaCl-NaCl. The results suggest that ST and SA treated with LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl could induce collateral sensitivity and cross-resistance.
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Antibacterianos , Genótipo , Ácido Láctico , Testes de Sensibilidade Microbiana , Fenótipo , Salmonella typhimurium , Cloreto de Sódio , Staphylococcus aureus , Cloreto de Sódio/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Ácido Láctico/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Antibacterianos/farmacologia , Microbiologia de AlimentosRESUMO
This study aims to investigate the response of Salmonella Newport to plasma-activated water (PAW), a novel disinfectant that attracts attention due to its broad-spectrum antimicrobial efficacy and eco-friendliness. In this work, we demonstrated that S. Newport of different sequence types (STs) could be induced into the viable but nonculturable (VBNC) state by PAW treatment. Notably, a remarkable 99.96% of S. Newport ST45 strain entered the VBNC state after a 12-min PAW treatment, which was the fastest observed among the five S. Newport STs (ST31, ST45, ST46, ST166, ST2364). Secretion of outer membrane vesicles was observed in ST45, suggesting a potential strategy against PAW treatment. Genes related to oxidative stress (sodA, katE, trxA), outer membrane proteins (ompA, ompC, ompD, ompF) and virulence (pagC, sipC, sopE2) were upregulated in the PAW-treated S. Newport, especially in ST45. A reduction of 38-65% in intracellular ATP level after PAW treatment was observed, indicating a contributor to the formation of the VBNC state. In addition, a rapid method for detecting the proportion of VBNC cells in food products based on pagC was established. This study contributes to understanding the formation mechanism of the VBNC state in S. Newport under PAW stress and offers insights for controlling microbial risks in the food industry.
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BACKGROUND AND OBJECTIVE: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. METHODS: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis-regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis-related proteins. RESULTS: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. CONCLUSION: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis.
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Capsaicina , Mitocôndrias , Osteogênese , Ligamento Periodontal , Porphyromonas gingivalis , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Células-Tronco , Serina-Treonina Quinases TOR , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Células-Tronco/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Capsaicina/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Perda do Osso Alveolar/prevenção & controle , Periodontite/microbiologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células Cultivadas , Modelos Animais de DoençasRESUMO
Since the discovery of penicillin, ß-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to ß-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing ß-lactamases. Therefore, a combination of ß-lactam antibiotics with ß-lactamase inhibitors has been a promising approach to controlling ß-lactam-resistant bacteria. The discovery of novel ß-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of ß-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of ß-lactamases and the synergistic mechanisms of ß-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in ß-lactamase-producing bacteria and designing effective treatment options in combination with BLIs.
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OBJECTIVE: This study aimed to clarify the difference in Fusobacterium nucleatum (F. nucleatum) induced inflammatory cytokines and nod-like receptor protein 3 (NLRP3) inflammasomes dysregulation among three periodontal cells. METHODS: Oral epithelial cells (HIOECs), THP-1 macrophages, and human gingival fibroblasts (HGFs) were exposed to F. nucleatum with/without adenosine triphosphate (ATP) and nigericin (Nig). Cell morphology was assessed by scanning electron microscopy. qRT-PCR, protein microarrays, and bioinformatic methods were used to evaluate the cytokines and their complex interplay. NLRP3 inflammasomes activation was detected by western blotting and ELISA. RESULTS: F. nucleatum adhered to and invaded cells. In HIOECs, F. nucleatum enhanced interleukin (IL)-1α/1ß/6/10/13, TNF-α, and interferon (IFN)-γ expression. In THP-1 macrophages, F. nucleatum up-regulated IL-1α/1ß/6/10 and TNF-α levels. In HGFs, F. nucleatum increased IL-6 levels. F. nucleatum and ATP synergistically boosted IFN-γ level in THP-1 macrophages and IL-13 level in HGFs. IL-1α/1ß/6, and TNF-α served as epicenters of the inflammatory response. Additionally, F. nucleatum activated NLRP3 inflammasomes in HIOECs, and ATP/Nig boosted the activation. F. nucleatum also triggered NLRP3 inflammasomes in THP-1 macrophages, but in HGFs, only NLRP3 and caspase-1 levels were elevated. CONCLUSION: F. nucleatum infiltrated periodontal supporting cells and dysregulated inflammatory cytokines and NLRP3 inflammasomes.
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Herein, we present a novel Catellani-type reaction that employed aryl-thianthrenium salts as aryl substrates to trigger the subsequent palladium/norbornene cooperatively catalyzed progress. This strategy can achieve site-selective C-H difunctionalization of aryl compounds without directing groups or a known initiating reagent. A series of functionalized syntheses of bioactive molecules further demonstrated the potential of this strategy.
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This study aimed to investigate the clinical significance of RNA editing (RE) and RNA editing derived (RED-) neoantigens in melanoma patients treated with immunotherapy. Vardict and VEP were used to identify the somatic mutations. RE events were identified by Reditools2 and filtered by the custom pipeline. miRTar2GO was implemented to predict the RE whether located in miRNA targets within the 3' UTR region. NetMHCpan and NetCTLpan were used to identify and characterize RED-neoantigens. In total, 7116 RE events were identified, most of which were A-to-I events. Using our custom pipeline, 631 RED-neoantigens were identified that show a significantly greater peptide-MHC affinity, and facilitate epitope processing and presentation than wild-type peptides. The OS of the patients with high RED-neoantigens burden was significantly longer ( P â =â 0.035), and a significantly higher RED-neoantigens burden was observed in responders ( P â =â 0.048). The area under the curve of the RED-neoantigen was 0.831 of OS. Then, we validated the reliability of RED-neoantigens in predicting the prognosis in an independent cohort and found that patients with high RED-neoantigens exhibited a longer OS ( P â =â 0.008). To our knowledge, this is the first study to systematically assess the clinical relevance of RED-neoantigens in melanoma patients treated with immunotherapy.
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Melanoma , Neoplasias , Humanos , Melanoma/genética , Melanoma/terapia , Relevância Clínica , Edição de RNA , Reprodutibilidade dos Testes , Antígenos de Neoplasias , ImunoterapiaRESUMO
Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.
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Doxorrubicina , Polietilenoglicóis , Camundongos , Ratos , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Polietilenoglicóis/farmacologia , Portadores de FármacosRESUMO
For metal halide perovskite solar cells, bidentate passivation (BP) is highly effective, but currently, only passivation sites rather than molecular environments are being considered. Here, the authors report an effective approach for high-performance fully printable mesoscopic perovskite solar cells (FP-PSCs) through the BP strategy using the multidentate molecule 6-chloropurine (6-CP). By utilizing density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) characterizations, the competition mechanism is identified of BP between the chlorine atom and neighboring nitrogen atom of the imidazole and pyrimidine rings. Through BP between the chlorine atom and adjacent nitrogen atom in imidazole, the power conversion efficiency (PCE) of the pristine samples is significantly enhanced from 16.25% to 17.63% with 6-CP. The formation of BP enhances interfacial hole selectivity and charge transfer, and suppresses nonradiative recombination, improving device stability under high humidity conditions. The competition mechanism of BP between two aromatic cycles provides a path for designing molecular passivants and selecting passivation pathways to approach theoretical limits.
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BACKGROUND: Disinfectants are important in the food industry to prevent the transmission of pathogens. Excessive use of disinfectants may increase the probability of bacteria experiencing long-term exposure and consequently resistance and cross-resistance to antibiotics. This study aims to investigate the cross-resistance of multidrug-resistant, drug-resistant, and drug-susceptible isolates of Salmonella enterica serovar Typhimurium (S. Typhimurium) with different sequence types (STs) to a group of antibiotics after exposure to different food-grade disinfectants. METHODS: A panel of 27 S. Typhimurium strains with different antibiograms and STs were exposed to increasing concentrations of five food-grade disinfectants, including hydrogen peroxide (H2O2), benzalkonium chloride (BAC), chlorine dioxide (ClO2), sodium hypochlorite (NaClO), and ethanol. Recovered evolved strains were analyzed using genomic tools and phenotypic tests. Genetic mutations were screened using breseq pipeline and changes in resistance to antibiotics and to the same disinfectant were determined. The relative fitness of evolved strains was also determined. RESULTS: Following exposure to disinfectants, 22 out of 135 evolved strains increased their resistance to antibiotics from a group of 14 clinically important antibiotics. The results also showed that 9 out of 135 evolved strains had decreased resistance to some antibiotics. Genetic mutations were found in evolved strains. A total of 77.78% of ST34, 58.33% of ST19, and 66.67% of the other STs strains exhibited changes in antibiotic resistance. BAC was the disinfectant that induced the highest number of strains to cross-resistance to antibiotics. Besides, H2O2 induced the highest number of strains with decreased resistance to antibiotics. CONCLUSIONS: These findings provide a basis for understanding the effect of disinfectants on the antibiotic resistance of S. Typhimurium. This work highlights the link between long-term exposure to disinfectants and the evolution of resistance to antibiotics and provides evidence to promote the regulated use of disinfectants.
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Antibacterianos , Desinfetantes , Humanos , Antibacterianos/farmacologia , Salmonella typhimurium/genética , Sorogrupo , Desinfetantes/farmacologia , Peróxido de Hidrogênio/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Although food-grade disinfectants are extensively used worldwide, it has been reported that the long-term exposure of bacteria to these compounds may represent a selective force inducing evolution including the emergence of antibiotic resistance. However, the mechanism underlying this correlation has not been elucidated. This study aims to investigate the genomic evolution caused by long-term disinfectant exposure in terms of antibiotic resistance in Salmonella enterica Typhimurium. METHODS: S. Typhimurium isolates were exposed to increasing concentrations of benzalkonium chloride (BAC) and variations of their antibiotic susceptibilities were monitored. Strains that survived BAC exposure were analyzed at whole genome perspective using comparative genomics, and Sanger sequencing-confirmed mutations in ramR gene were identified. Next, the efflux activity in ramR-mutated strains shown as bisbenzimide accumulation and expression of genes involved in AcrAB-TolC efflux pump using quantitative reverse transcriptase PCR were determined. RESULTS: Mutation rates of evolved strains varied from 5.82 × 10-9 to 5.56 × 10-8, with fold increase from 18.55 to 1.20 when compared with strains evolved without BAC. Mutations in ramR gene were found in evolved strains. Upregulated expression and increased activity of AcrAB-TolC was observed in evolved strains, which may contribute to their increased resistance to clinically relevant antibiotics. In addition, several indels and point mutations in ramR were identified, including L158P, A37V, G42E, F45L, and R46H which have not yet been linked to antimicrobial resistance. Resistance and mutations were stable after seven consecutive cultivations without BAC exposure. These results suggest that strains with sequence type (ST) ST34 were the most prone to mutations in ramR among the three STs tested (ST34, ST19, ST36). CONCLUSIONS: This work demonstrated that disinfectants, specifically BAC forces S. Typhimurium to enter a specific evolutionary trajectory towards antibiotic resistance illustrating the side effects of long-term exposure to BAC and probably also to other disinfectants. Most significantly, this study provides new insights in understanding the emergence of antibiotic resistance in modern society.
Assuntos
Desinfetantes , Salmonella enterica , Humanos , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Compostos de Benzalcônio/farmacologia , Compostos de Benzalcônio/metabolismo , Sorogrupo , Farmacorresistência Bacteriana Múltipla/genética , Desinfetantes/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy. METHODS: From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement. RESULTS: All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05). CONCLUSION: Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.