RESUMEN
The rise in antimicrobial resistance, the increasing occurrence of bacterial, and fungal infections, and the challenges posed by polymicrobial biofilms necessitate the exploration of innovative therapeutic strategies. Silver-based antimicrobials have garnered attention for their broad-spectrum activity and multimodal mechanisms of action. However, their effectiveness against single-species or polymicrobial biofilms remains limited. In this study, we present the fabrication of polymer-silver bromide nanocomposites using amino acid conjugated polymers (ACPs) through a green and water-based in situ technique. The nanocomposite architecture facilitated prolonged and controlled release of the active components. Remarkably, the nanocomposites exhibited broad-spectrum activity against multidrug-resistant (MDR) human pathogenic bacteria (MIC = 2-16 µg/mL) and fungi (MIC = 1-8 µg/mL), while displaying no detectable toxicity to human erythrocytes (HC50 > 1024 µg/mL). In contrast to existing antimicrobials and silver-based therapies, the nanocomposite effectively eradicated bacterial, fungal, and polymicrobial biofilms, and prevented the development of microbial resistance due to their membrane-active properties. Furthermore, the lead polymer-silver bromide nanocomposite demonstrated a 99% reduction in the drug-resistant Pseudomonas aeruginosa burden in a murine model of burn wound infection, along with excellent in vivo biocompatibility.
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Biopelículas , Quemaduras , Pruebas de Sensibilidad Microbiana , Nanocompuestos , Polímeros , Infección de Heridas , Biopelículas/efectos de los fármacos , Nanocompuestos/química , Animales , Ratones , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Humanos , Quemaduras/tratamiento farmacológico , Polímeros/química , Polímeros/farmacología , Compuestos de Plata/farmacología , Compuestos de Plata/química , Antibacterianos/farmacología , Antibacterianos/química , Aminoácidos/química , Aminoácidos/farmacología , Bromuros/química , Bromuros/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias/efectos de los fármacosRESUMEN
Rapidly and sensitively evaluating the acid value (AV) of edible oils is significant to ensuring food quality and safety. Cesium lead bromide perovskite nanocrystals (CsPbBr3 NCs) are an effective candidate for AV detection; however, their instability restricts wide applications. Herein, CsPbBr3@ZIF-8 was prepared by confining and growing CsPbBr3 NCs in situ into zeolitic imidazolate framework-8 (ZIF-8) to improve the stability, and a fluorescence sensor was established to evaluate the AV of edible oils. The results present that CsPbBr3 NCs (below 5 nm) with excellent optical properties were confined and grown in situ in micropores and mesopores of ZIF-8. Meanwhile, CsPbBr3@ZIF-8 had better long-term storage, ultraviolet-irradiation, and water-exposure stabilities, compared with CsPbBr3 NCs. Given the fact that free fatty acids (the major contributor of AV) decrease the fluorescence of CsPbBr3 NCs, the fluorescence intensities of CsPbBr3@ZIF-8 were negative-linearly related to oil AV (R2 = 0.9902) in 0.04-6.00 mg of KOH/g with a 0.06 mg of KOH/g limit of detection. Besides, the practical AV recovery was 92-101% with an average relative standard deviation of 2%. Furthermore, the detection time was 20 min. The response mechanism revealed that free fatty acids could remove surface ligands and increase surface defects to prompt the aggregation of CsPbBr3 NCs and the formation of lattice fringe dislocations, inducing a decrease in the fluorescence. Thus, a stable, sensitive, reliable sensor was established to evaluate the AV of edible oils.
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Titanio , Zeolitas , Zeolitas/química , Titanio/química , Nanopartículas/química , Cesio/química , Plomo/análisis , Plomo/química , Aceites de Plantas/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia , Óxidos/química , Bromuros/química , Compuestos de Calcio/química , Estructuras Metalorgánicas/química , ImidazolesRESUMEN
Oligosaccharides have myriad functions throughout biological processes1,2. Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site, stereo- and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose5-8, adding considerable synthetic work. Here we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.
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Glicósidos , Oligosacáridos , Ácidos Borónicos/química , Bromuros/química , Catálisis , Glicósidos/química , Glicósidos/síntesis química , Glicosilación , Enlace de Hidrógeno , Oligosacáridos/química , Oligosacáridos/síntesis química , Sulfonas/químicaRESUMEN
We report a general and functional-group-tolerant method for the Cu-catalyzed amination of base-sensitive aryl bromides including substrates possessing acidic functional groups and small five-membered heteroarenes. The results presented herein substantially expand the scope of Cu-catalyzed C-N coupling reactions. The combination of L8, an anionic N1,N2-diarylbenzene-1,2-diamine ligand, along with the mild base NaOTMS leads to the formation of a stable yet reactive catalyst that resists deactivation from coordination to heterocycles or charged intermediates. This system enables the use of low catalyst and ligand loadings. Exploiting the differences in nucleophile deprotonation in C-O and C-N coupling reactions catalyzed by Cu·L8 we developed a method to chemoselectively N- and O-arylate a variety of amino alcohol substrates. Employing NaOt-Bu as the base resulted exclusively in C-O coupling when the amino alcohols featured primary alcohols and more hindered amines or aniline groups. Utilizing NaOTMS enabled the ability to override the steric-based selectivity of these reactions completely and exclusively promoted C-N coupling regardless of the structure of the amino alcohol. The ability to invert the observed chemoselectivity is distinct from previously described methods that require protecting group manipulations or rely entirely on steric effects to control reactivity. These results substantially improve the scope of Cu-catalyzed C-N coupling reactions using N1,N2-diarylbenzene-1,2-diamine ligands and introduce a new chemoselective method to arylate amino alcohols.
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Amino Alcoholes , Cobre , Cobre/química , Catálisis , Aminación , Amino Alcoholes/química , Estructura Molecular , Bromuros/química , Hidrocarburos Bromados/química , LigandosRESUMEN
An 87-year-old woman was admitted to our hospital with general fatigue, anorexia, nausea, and chest pain, and was diagnosed with Takotsubo cardiomyopathy and a stomal ulcer. Pseudohyperchloremia and a negative anion gap were detected in laboratory tests. She was continuously taking commercially available analgesics, including bromvalerylurea. On the 11th day of hospitalization, her bromide concentration was high (331.2 mg/L). She was readmitted with fatigue and anorexia one and a half years after her last hospitalization. On admission, her serum chloride and bromide levels were also high. Despite being instructed to stop taking analgesics after the first hospitalization, she was unable to stop taking the medication. It took more than two years for her blood bromide concentration to decrease and the withdrawal of the medication to be confirmed. Clinicians should consider bromide intoxication in patients with unclear neuropsychiatric symptoms and high chloride levels.
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Analgésicos , Humanos , Femenino , Anciano de 80 o más Años , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Bromuros/efectos adversos , Bromisovalum/efectos adversos , Enfermedad CrónicaRESUMEN
Recently, the chitosan (CS)-based composites have attracted increasing attention for controlling and preventing the spread of pathogenic microorganisms. Herein, an amphiphilic copolymer containing epoxy and quaternary ammonium groups (PBGDBr) was synthesized via three common acrylate monomers. The epoxy groups of this copolymer were then crosslinked with the amino groups of CS to synthesize a natural/synthetic (PBGDBr-C) composite to increase the water solubility of CS under alkaline conditions and enhance its antibacterial activity based on chemical contact-type modes. Moreover, silver bromide nanoparticles (AgBr NPs)-decorated PBGDBr-C (AgBr@PBGDBr-C) composite was prepared, which aimed to endow the final AgBr@PBGDBr-C composite with a photodynamic antibacterial mode relying on the formation of Ag/AgBr nanostructures catalyzed by visible light on AgBr NPs. The results showed that the final composite possessed satisfactory bactericidal effects at concentrations higher than 64 and 128 µg/mL against Escherichia coli and Staphylococcus aureus, respectively. Additionally, The L929 cells treated with the final composite retained high cell viability (>80 %) at a concentration of 128 µg/mL, indicating its low toxicity to L929 cells. Overall, our synthetic strategy exploits a multi-modal system that enables chemical-photodynamic synergies to treat infections caused by pathogenic bacteria while delaying the development of bacterial resistance.
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Antibacterianos , Bromuros , Quitosano , Escherichia coli , Compuestos de Plata , Staphylococcus aureus , Quitosano/química , Quitosano/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Bromuros/química , Bromuros/farmacología , Compuestos de Plata/química , Compuestos de Plata/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Polímeros/química , Polímeros/farmacología , Ratones , Cationes/química , Nanopartículas/química , Nanopartículas del Metal/química , Animales , Supervivencia Celular/efectos de los fármacos , Línea CelularRESUMEN
Advanced oxidation processes (AOPs) have been developed to decompose toxic pollutants to protect the aquatic environment. AOP has been considered an alternative treatment method for wastewater treatment. Bromine is present in natural waters posing toxic effects on human health and hence, its removal from drinking water sources is necessary. Of the many techniques advanced oxidation is covered in this review. This review systematically examines literature published from 1997 to April 2024, sourced from Scopus, PubMed, Science Direct, and Web of Science databases, focusing on the efficacy of AOPs for pollutant removal from aqueous solutions containing bromide ions to investigate the impact of bromide ions on AOPs. Data and information extracted from each article eligible for inclusion in the review include the type of AOP, type of pollutants, and removal efficiency of AOP under the presence and absence of bromide ion. Of the 1784 documents screened, 90 studies met inclusion criteria, providing insights into various AOPs, including UV/chlorine, UV/PS, UV/H2O2, UV/catalyst, and visible light/catalyst processes. The observed impact of bromide ion presence on the efficacy of AOP processes, alongside the AOP method under scrutiny, is contingent upon various factors such as the nature of the target pollutant, catalyst type, and bromide ion concentration. These considerations are crucial in selecting the best method for removing specific pollutants under defined conditions. Challenges were encountered during result analysis included variations in experimental setups, disparities in pollutant types and concentrations, and inconsistencies in reporting AOP performance metrics. Addressing these parameters in research reports will enhance the coherence and utility of subsequent systematic reviews.
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Bromuros , Oxidación-Reducción , Contaminantes Químicos del Agua , Purificación del Agua , Contaminantes Químicos del Agua/análisis , Bromuros/química , Purificación del Agua/métodos , Aguas Residuales/químicaRESUMEN
Bromide (Br-) was found in the fresh waters at concentrations from 0.1 to 1 mg/L and can be used to activate peroxymonosulfate (PMS) as a widely used chemical oxidation agent. In the present study, the reaction between PMS and Br- ions (PMS/Br- process) for the effective degradation of reactive yellow 145 (RY-145) dye was investigated by changing operational parameters vis solution pH, dosage of Br- ions and PMS, RY-145 concentration, and reaction time. Based on the results, the simultaneous presence of PMS and Br- ions in the solution led to efficient degradation of RY-145 with a synergistic index of 11.89. The degradation efficiency of RY-145 was decreased in severe basic pH and the presence of CO32- ions as a coexisting anion. Likewise, 4 mg/L of humic acid (HA), used as a classic scavenger, led to a 26.53% decrease in the RY-145 degradation efficiency. The free bromine (HOBr/OBr-), superoxide radical (âO2-), and singlet oxygen (1O2) was the dominant oxidation agents in RY-145 degradation, which confirmed the nonradical degradation pathway. In addition, PMS/Br- process showed excellent ability in mineralizing RY-145 in different aqueous solutions (total organic carbon (TOC) decreased 86.39% in deionized water and 78.23% in tap water). Although pollutants such as azo dyes can be effectively removed in the PMS/Br- process, the formation of byproducts should be strategically controlled and special attention should be paid when the PMS-based advance oxidation process is applied to treat Br- containing solutions.
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Compuestos Azo , Bromuros , Peróxidos , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Peróxidos/química , Compuestos Azo/química , Bromuros/química , Oxidación-Reducción , Colorantes/química , Purificación del Agua/métodosRESUMEN
Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.
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Bromuros , Chlorella vulgaris , Chlorella vulgaris/efectos de los fármacos , Bromuros/química , Bromuros/toxicidad , Desinfección , Purificación del Agua , Rayos UltravioletaRESUMEN
The classical Koenigs-Knorr glycosidation of bromides or chlorides promoted with Ag2O or Ag2CO3 works only with reactive substrates (ideally both donor and acceptor). This reaction was found to be practically ineffective with unreactive donors such as per-O-benzoylated mannosyl bromide. Recently, it was discovered that the addition of catalytic (Lewis) acids to a silver salt-promoted reaction has a dramatic effect on the reaction rate and yield. A tentative mechanism for this cooperatively-catalyzed glycosylation reaction has been proposed, and the improved understanding of the reaction led to more efficient protocols and broader applications to a variety of glycosidic linkages. Since Ag2O-mediated activation was introduced by German chemists Koenigs and Knorr, and "cooperatively catalyzed" is Kooperativ Katalysiert in German, we refer to this new reaction as "the 4K reaction."
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Glicósidos , Ácidos de Lewis , Glicosilación , Catálisis , BromurosRESUMEN
Passive thermal management with zero-energy consumption and high compactness has drawn increasing attention. Here, we present a protocol to develop a hygroscopic salt-loaded heat sink with a moisture-permeable membrane encapsulation technique for electronics cooling. We describe steps for preparing lithium bromide solution and heat sink with anti-corrosion graphene coating. We then detail procedures for preparing the hygroscopic salt-loaded membrane-encapsulated heat sinks (HSMHSs). The produced low-cost HSMHS exhibits remarkably high thermal management performance without the risks of leakage and corrosion. For complete details on the use and execution of this protocol, please refer to Sui et al.1.
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Electrónica , Grafito/química , Bromuros/químicaRESUMEN
The coexistence of free chlorine and bromide under sunlight irradiation (sunlight/FC with Br-) is unavoidable in outdoor seawater swimming pools, and the formation of brominated disinfection byproducts could act more harmful than chlorinated disinfection byproducts. In this study, benzotriazole was selected as a model compound to investigate the degradation rate and the subsequent formation of disinfection byproducts via sunlight/FC with Br- process. The rate constants for the degradation of benzotriazole under pseudo first order conditions in sunlight/FC with Br- and sunlight/FC are 2.3 ± 0.07 × 10-1 min-1 and 6.0 ± 0.7 × 10-2 min-1, respectively. The enhanced degradation of benzotriazole can be ascribed to the generation of HOâ¢, bromine species, and reactive halogen species (RHS) during sunlight/FC with Br-. Despite the fact that sunlight/FC with Br- process enhanced benzotriazole degradation, the reaction results in increasing tribromomethane (TBM) formation. A high concentration (37.8 µg/L) of TBM was detected in the sunlight/FC with Br-, which was due to the reaction of RHS. The degradation of benzotriazole was notably influenced by the pH value (pH 4 - 11), the concentration of bromide (0 - 2 mM), and free chlorine (1 - 6 mg/L). Furthermore, the concentration of TBM increased when the free chlorine concentrations increased, implying the formation potential of harmful TBM in chlorinated seawater swimming pools.
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Bromuros , Cloro , Luz Solar , Triazoles , Contaminantes Químicos del Agua , Triazoles/química , Bromuros/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cloro/química , Desinfección , Trihalometanos/química , Agua de Mar/química , Desinfectantes/química , Desinfectantes/análisisRESUMEN
Inorganic halide-based perovskites (e.g., cesium lead bromide) are tremendously useful semiconducting materials due to their unique optoelectronic properties. However, degradation of these perovskites under humid conditions is one of the major drawbacks to prevent their wide applications. Herein, passivated cesium lead bromide nanoparticles are synthesized using p-thiocresol as a passivating ligand, and this stable version of perovskite is later applied successfully as a sensor probe towards cholesterol detection. The designed sensor can detect cholesterol with a lower detection limit of 0.24 ppm and a fast response time of 10 s. The mechanism of quenching PTC@CsPbBr3 upon the gradual addition of cholesterol is discussed. Further, the sensor is successfully applied in the detection of cholesterol in real samples (blood serum). This work presents PTC@CsPbBr3 as a novel sensing platform for detecting cholesterol well in biomedical applications.
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Bromuros , Compuestos de Calcio , Cesio , Colesterol , Plomo , Óxidos , TitanioRESUMEN
BACKGROUND: The prevalence of laryngeal squamous cell carcinoma (LSCC) is increasing, and it poses a significant threat to human health; therefore, identifying specific targets for LSCC remains crucial. METHODS: Bioinformatics analysis was used to compare the different expression genes expressed in LSCC. Immunohistochemical assay and western blotting were used to analysis protein expression. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)((4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide)4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and 5-ethynyl 2'-deoxyuridine (Edu) assay. Flow cytometry was used to measure the cell cycle. Cell migration was measured by wound healing assay and transwell assay. RESULTS: Our analysis revealed 36 upregulated and 65 downregulated differentially expressed genes (DEGs) when comparing LSCC tumors to adjacent tissues, with cornulin (CRNN) identified as a key hub gene connecting these DEGs. We observed a consistent downregulation of CRNN expression in LSCC cell lines and tissues and was associated with poor patient survival and the tumor microenvironment. CRNN overexpression was found to significantly inhibit cell growth, cell cycle progression, migration and invasion, while CRNN knockdown had the opposite effects. Additionally, in vivo experiments demonstrated that CRNN overexpression suppressed tumor growth in nude mice. CONCLUSIONS: CRNN functions as a potential tumor suppressor and regulates important aspects of LSCC, providing valuable insights into the role of CRNN in LSCC pathogenesis and potential for targeted therapeutic interventions.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , MicroARNs , Carcinoma de Células Escamosas de Cabeza y Cuello , Animales , Humanos , Ratones , Bromuros/metabolismo , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Ratones Desnudos , MicroARNs/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Microambiente TumoralRESUMEN
Inorganic cesium lead halide perovskites have evoked wide popularity because of their excellent optoelectronic properties, high photoluminescence (PL) quantum yield (PLQY), and narrowband emission. Here, cesium lead bromide (CsPbBr3 ) quantum dots (QDs) were synthesized via the ligand-assisted re-precipitation method. Post-synthesis treatment of CsPbBr3 QDs using antimony tribromide improved the PL stability and optoelectronic properties of the QDs. In addition, the PLQY of the post-treated sample was enhanced to 91% via post-treatment, and the luminescence observed was maintained for 8 days. The post-synthesis treatment ensured defect passivation and improved the stability of CsPbBr3 perovskite QDs. High-resolution transmission electron microscopy revealed the presence of more ordered, uniform-sized CsPbBr3 QDs after post-synthesis treatment, and the uniformity of the sample improved as the day passed. The formation of a mixed crystal phase was observed from X-ray diffraction in both as-synthesized, as well as post-treated QDs samples with the possibility of a polycrystalline nature in the post-treated CsPbBr3 QDs as per the selected area electron diffraction pattern. The X-ray photoelectron spectroscopy spectra confirmed the presence of antimony and the possibility of defect passivation in the post-treated samples. These QDs can act as potential candidates in various optoelectronic applications such as photodetectors and light-emitting diodes due to their high PLQY and longer lifetime.
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Antimonio , Bromuros , Compuestos de Calcio , Óxidos , Puntos Cuánticos , Titanio , CesioRESUMEN
BACKGROUND: Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi2S3) semiconductor has been severely restricted by its electron-hole pairs (e--h+) separation inefficiency and oxygen (O2) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of Bi2S3 nanoparticles (NPs) in biomedicine. RESULTS: Herein, novel Bi2S3/titanium carbide (Ti3C2) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O2 self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. Bi2S3/Ti3C2 NHs were synthesized via the in situ synthesis method starting from Ti3C2 nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi2S3 NPs, Bi2S3/Ti3C2 NHs significantly extend the absorption to the near-infrared (NIR) region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation, where the hole on the valence band (VB) of Bi2S3 can react with water to supply O2 for the electron on the Ti3C2 NSs to generate ·O2- and ·OH through electron transfer. Furthermore, they also achieve 1O2 generation through energy transfer due to O2 self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi2S3/Ti3C2 NHs, systematic in vitro and in vivo evaluations were conducted, revealing that the synergistic-therapeutic outcome of this nanoplatform enables complete eradication of the U251 tumors without recurrence by NIR laser irradiation, and it can be used for computed tomography (CT) imaging because of the strong X-ray attenuation ability. CONCLUSION: This work expands the phototherapeutic effect of Bi2S3-based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.
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Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Bromuros/uso terapéutico , Terapia Fototérmica , Especies Reactivas de Oxígeno , Titanio/farmacología , Neoplasias/tratamiento farmacológico , Oxígeno , Hipoxia/tratamiento farmacológico , Rayos Infrarrojos , Línea Celular TumoralRESUMEN
The parallel double-stranded DNA (dsDNA) demonstrates potential utility in molecular biology, diagnosis, therapy, and molecular assembly. However, techniques for the characterization of parallel dsDNA are limited. Here, we demonstrate that a series of intensive characteristic Raman bands of three parallel dsDNAs, which are stabilized by reverse Hoogsteen A+·A+ base pairs or hemiprotonated C+·C, G·G minor groove edge, Hoogsteen A·A base pairs, or Hoogsteen T·A, C+·G base pairs, have been observed by surface-enhanced Raman spectroscopy (SERS) when the gold nanoparticles modified by bromine and magnesium ions (Au BMNPs) were used as substrates. The featured bands can not only accurately discriminate parallel dsDNA from antiparallel one but also identify the strand orientation within dsDNA. The proposed approach will have a significant impact on DNA analysis, especially in the detection and differentiation of various DNA conformations.
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Oro , Nanopartículas del Metal , Oro/química , Espectrometría Raman , Bromuros , Nanopartículas del Metal/química , ADN/químicaRESUMEN
OBJECTIVES: During the past few decades, various compounds have been researched for their potential as radioprotectants, and many of them were found to be safe and effective in several preclinical models. However, many of these compounds were found to have serious adverse effects when evaluated in clinical settings, thereby making them unsuitable for human applications. 5-hydroxytryptophan (5-HTP) and S-(2-aminoethyl) isothiouronium bromide hydrobromide (AET) act in a synergistic fashion to promote radioprotection. The present study primarily emphasizes the safety of fixed dose of 5-HTP + AET in the lungs of C57BL/6 mice, a well-known model used in drug safety studies. MATERIALS AND METHODS: Post-administration of the combination of HTP+AET at specific time points, blood and bronchoalveolar lavage fluid (BALF) were collected for the analysis of inflammatory and oxidative stress markers of the lungs. Thereafter, the mice were sacrificed and the lungs were dissected out, weighed, and fixed in formalin for histopathological studies. RESULTS: The inflammatory biomarkers: tumor necrosis factor-alpha and interleukin-10 and oxidative stress biomarkers: 8-isoprostane and 8-hydroxy-2'-deoxyguanosine were found to have normal levels in blood and BALF in both control and treatment groups, which was further supported by normal histological findings. In addition, other endpoints such as food and water intake were found to be within normal limits. CONCLUSION: The present safety study reflects that the combination has no adverse effects on the lungs of the experimental mouse. Further, evaluation in higher mammals including nonhuman primates is essential prior to validation of the safety of the combination in humans.
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Protectores contra Radiación , Humanos , Ratones , Animales , beta-Aminoetil Isotiourea , 5-Hidroxitriptófano , Bromuros/toxicidad , Isotiuronio , Roedores , Ratones Endogámicos C57BL , Pulmón , Biomarcadores , Líquido del Lavado BronquioalveolarRESUMEN
Flavin-dependent halogenases are central enzymes in the production of halogenated secondary metabolites in various organisms and they constitute highly promising biocatalysts for regioselective halogenation. The mechanism of these monooxygenases includes formation of hypohalous acid from a reaction of fully reduced flavin with oxygen and halide. The hypohalous acid then diffuses via a tunnel to the substrate-binding site for halogenation of tryptophan and other substrates. Oxidized flavin needs to be reduced for regeneration of the enzyme, which can be performed in vitro by a photoreduction with blue light. Here, we employed this photoreduction to study characteristic structural changes associated with the transition from oxidized to fully reduced flavin in PyrH from Streptomyces rugosporus as a model for tryptophan-5-halogenases. The effect of the presence of bromide and chloride or the absence of any halides on the UV-vis spectrum of the enzyme demonstrated a halide-dependent structure of the flavin-binding pocket. Light-induced FTIR difference spectroscopy was applied and the signals assigned by selective isotope labeling of the protein moiety. The identified structural changes in α-helix and ß-sheet elements were strongly dependent on the presence of bromide, chloride, the substrate tryptophan, and the product 5-chloro-tryptophan, respectively. We identified a clear allosteric coupling in solution at ambient conditions between cofactor-binding site and substrate-binding site that is active in both directions, despite their separation by a tunnel. We suggest that this coupling constitutes a fine-tuned mechanism for the promotion of the enzymatic reaction of flavin-dependent halogenases in dependence of halide and substrate availability.
Asunto(s)
Proteínas Bacterianas , Flavinas , Oxidorreductasas , Streptomyces , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Flavinas/metabolismo , Flavinas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Streptomyces/enzimología , Oxidación-Reducción , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Halogenación , Bromuros/química , Bromuros/metabolismo , Triptófano/metabolismo , Triptófano/química , Sitios de Unión , Cloruros/metabolismo , Cloruros/químicaRESUMEN
Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-Hâ§â§â§π interactions. The optimal size matching between the carboxylate AP5As and DMBr was â¼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.