RESUMEN

Using halloysite clay and vitamin B1 hydrochloride, a novel acidic halloysite-dendrimer catalytic composite has been developed for conversion of fructose to 5-hydroxymthylfurfural. To grow the dendritic moiety on halloysite, it was first functionalized and then reacted with melamine, epichlorohydrin and vitamin B1 hydrochloride respectively. Then, the resulting composite was treated with ZnCl2 to furnish Lewis acid sites. Use of vitamin B1 as the cationic moiety of ionic liquid obviated use of toxic chemicals and resulted in more environmentally friendly composite. Similarly, dendritic moiety of generation 2 was also grafted on halloysite and the activity of both catalysts for conversion of fructose to 5-hydroxymthylfurfural was investigated to disclose the role of dendrimer generation. For the best catalytic composite, the reaction variables were optimized via RSM and it was revealed that use of 0.035 g catalyst per 0.1 g fructose at 95 °C furnished HMF in 96% yield in 105 min. Turnover numbers (TONs) and frequencies (TOFs) were estimated to be 10,130 and 5788 h-1, respectively. Kinetic studies also underlined that Ea was 22.85 kJ/mol. The thermodynamic parameters of Δ H ≠ , Δ S ≠ and Δ G ≠ , were calculated to be 23 kJ/mol, - 129.2 J/mol and 72.14 kJ/mol, respectively. Notably, the catalyst exhibited good recyclability and hot filtration approved heterogeneous nature of catalysis.

Asunto(s)

Arcilla , Dendrímeros , Furaldehído , Tiamina , Catálisis , Arcilla/química , Furaldehído/análogos & derivados , Furaldehído/química , Dendrímeros/química , Dendrímeros/síntesis química , Tiamina/química , Tiamina/análogos & derivados , Fructosa/química , Cinética , Silicatos de Aluminio/química , Triazinas/química , Cloruros/química , Compuestos de Zinc/química

RESUMEN

Expanding target pesticide species and intelligent pesticide recognition were formidable challenges for existing cholinesterase inhibition methods. To improve this status, multi-active Mel-Cu nanozyme with mimetic Cu-N sites was prepared for the first time. It exhibited excellent laccase-like and peroxidase-like activities, and can respond to some pesticides beyond the detected range of enzyme inhibition methods, such as glyphosate, carbendazim, fumonisulfuron, etc., through coordination and hydrogen bonding. Inspired by the signal complementarity of Mel-Cu and cholinesterase, an integrated sensor array based on the Mel-Cu laccase-like activity, Mel-Cu peroxidase-like activity, acetylcholinesterase, and butyrylcholinesterase was creatively constructed. And it could successfully discriminate 12 pesticides at 0.5-50 µg/mL, which was significantly superior to traditional enzyme inhibition methods. Moreover, on the basis of above array, a unified stepwise prediction model was built using classification and regression algorithms in machine learning, which enabled concentration-independent qualitative identification as well as precise quantitative determination of multiple pesticide targets, simultaneously. The sensing accuracy was verified by blind sample analysis, in which the species was correctly identified and the concentration was predicted within 10% error, suggesting great intelligent recognition ability. Further, the proposed method also demonstrated significant immunity to interference and practical application feasibility, providing powerful means for pesticide residue analysis.

Asunto(s)

Acetilcolinesterasa , Técnicas Biosensibles , Butirilcolinesterasa , Cobre , Aprendizaje Automático , Plaguicidas , Triazinas , Triazinas/química , Triazinas/análisis , Plaguicidas/análisis , Técnicas Biosensibles/métodos , Cobre/química , Acetilcolinesterasa/química , Butirilcolinesterasa/química , Butirilcolinesterasa/análisis , Inhibidores de la Colinesterasa/análisis , Inhibidores de la Colinesterasa/química , Límite de Detección

RESUMEN

PURPOSE: Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6-7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. METHODS: Eligible mother-child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6-7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. RESULTS: Of 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). CONCLUSIONS: Consistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

Asunto(s)

Anticonvulsivantes , Carbamazepina , Epilepsia , Lamotrigina , Levetiracetam , Efectos Tardíos de la Exposición Prenatal , Ácido Valproico , Humanos , Femenino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Anticonvulsivantes/efectos adversos , Niño , Embarazo , Masculino , Levetiracetam/efectos adversos , Ácido Valproico/efectos adversos , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Carbamazepina/efectos adversos , Epilepsia/tratamiento farmacológico , Pruebas Neuropsicológicas , Triazinas/efectos adversos , Estudios de Cohortes , Piracetam/análogos & derivados , Piracetam/efectos adversos , Adulto , Cognición/efectos de los fármacos , Estudios Prospectivos , Inteligencia/efectos de los fármacos

RESUMEN

Monkeypox (MPXV) is one of the infectious viruses which caused morbidity and mortality problems in these years. Despite its danger to public health, there is no approved drug to stand and handle MPXV. On the other hand, drug repurposing is a promising screening method for the low-cost introduction of approved drugs for emerging diseases and viruses which utilizes computational methods. Therefore, drug repurposing is a promising approach to suggesting approved drugs for the MPXV. This paper proposes a computational framework for MPXV antiviral prediction. To do this, we have generated a new virus-antiviral dataset. Moreover, we applied several machine learning and one deep learning method for virus-antiviral prediction. The suggested drugs by the learning methods have been investigated using docking studies. The target protein structure is modeled using homology modeling and, then, refined and validated. To the best of our knowledge, this work is the first work to study deep learning methods for the prediction of MPXV antivirals. The screening results confirm that Tilorone, Valacyclovir, Ribavirin, Favipiravir, and Baloxavir marboxil are effective drugs for MPXV treatment.

Asunto(s)

Antivirales , Aprendizaje Profundo , Reposicionamiento de Medicamentos , Monkeypox virus , Antivirales/farmacología , Monkeypox virus/efectos de los fármacos , Reposicionamiento de Medicamentos/métodos , Pirazinas/farmacología , Simulación del Acoplamiento Molecular , Dibenzotiepinas , Amidas/farmacología , Ribavirina/farmacología , Triazinas/farmacología , Mpox/tratamiento farmacológico , Mpox/virología , Humanos , Aprendizaje Automático , Morfolinas , Piridonas

RESUMEN

The high speed enrichment of benzoylurea insecticides (BUs) in complex matrices is an essential and challenging step. The present study focuses on the synthesis of a hierarchical pore nitrogen-doped carbon material for magnetic solid phase extraction (MSPE) of BUs. This material was prepared through the carbonization of a composite material ZIF-67@MCA which assembly with hydrogen-bonded organic frameworks (melamine-cyanurate, MCA) and zeolitic imidazolate framework (ZIF-67) at room temperature. The optimal adsorption effect is achieved when the mass ratio of ZIF-67 to MCA is 1/3, and the carbonization was performed at 600 °C, the such obtained carbon material was denoted as 1/3ZIF-67@MCA-DCs-600. The material was characterized with various physical methods including X-ray diffractometry (XRD), Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET), vibrating sample magnetometer (VSM), water contact angle measurement, Raman spectrometry. 1/3ZIF-67@MCA-DCs-600 exhibits a macro-mesoporous 3D structure with a high degree of nitrogen doping and relatively large specific surface area, making it suitable for magnetic solid phase extraction (MSPE). The adsorption of BUs with concentration of 100 ng mL-1 can reach equilibrium within 5 s. The interaction between BUs and the adsorbent, facilitated by π-π stacking, hydrophobic interactions, hydrogen bonding forces, as well as the material's porosity, enables efficient extraction recoveries ranging from 45 % to 92 %. The enrichment of BUs was achieved through the establishment of an MSPE method under optimized conditions, which was further coupled with high performance liquid chromatography (HPLC) for the determination of the four BUs. The linear range spans from 5 ng ml-1 to 1000 ng ml-1 with the correlation coefficient (R2) of ≥ 0.99, Meanwhile, the detection limit for these four BUs falls within the range of 0.01 to 0.10 ng ml-1. The material exhibits good reusability and can be reused for at least 5 cycles. Inter day and intra-day precision ranges from 2.1-7.9 % and 1.0-5.4 %, respectively. The method demonstrates a high level of reliability in practical applications for the determination of BUs.

Asunto(s)

Carbono , Enlace de Hidrógeno , Insecticidas , Nitrógeno , Extracción en Fase Sólida , Insecticidas/análisis , Insecticidas/química , Insecticidas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Adsorción , Carbono/química , Nitrógeno/química , Estructuras Metalorgánicas/química , Porosidad , Triazinas/química , Triazinas/aislamiento & purificación , Límite de Detección , Urea/química , Zeolitas/química

RESUMEN

The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase in obesity, and is striking ever younger patients. Only a minority of patients with T2D attain glycemic targets, indicating a clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow the progressive loss of ß-cells. Two entirely novel classes of antidiabetic agents-glucokinase activators and imeglimin-have recently been approved and will be the subject of this review.Allosteric activators of glucokinase, an enzyme stimulating insulin secretion in ß-cells and suppressing hepatic glucose production, are oral low-molecular-weight drugs. One of these, dorzagliatin, is approved in China for use in adult patients with T2D, either as monotherapy or as an add-on to metformin. It remains to be seen whether the drug will produce sustained antidiabetic effects over many years and whether the side effects that led to the discontinuation of early drug candidates will limit the usefulness of dorzagliatin.Imeglimin-which shares structural similarities with metformin-targets mitochondrial dysfunction and was approved in Japan against T2D. In preclinical studies, the drug has also shown promising ß-cell protective and preservative effects that may translate into disease-modifying effects.Hopefully, these two newcomers will contribute to filling the great medical need for new treatment modalities, preferably with disease-modifying potential. It remains to be seen where they will fit in contemporary treatment algorithms, which combinations of drugs are effective and which should be avoided. Time will tell to what extent these new antidiabetic agents will add value to the current treatment options against T2D in terms of sustained antidiabetic effect, acceptable safety, utility in combination therapy, and impact on hard end-points such as cardiovascular disease.

Asunto(s)

Diabetes Mellitus Tipo 2 , Glucoquinasa , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Glucoquinasa/metabolismo , Activadores de Enzimas/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Animales , Triazinas

RESUMEN

Silver nanoparticles were successfully incorporated into a melamine-based polymer, resulting in the synthesis of (Ag NPs@Bipy-PAN) through a reverse double solvent approach. The synthesised Ag NPs@Bipy-PAN polymer underwent extensive characterisation through Powder X-ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy and Energy Dispersive X-ray (EDX) and Thermal Gravimetric Analysis. PXRD analysis confirmed the successful encapsulation of Ag nanoparticles and provided insights into the amorphous nature of the polymer following encapsulation. SEM and EDX analyses further corroborated the presence and distribution of Ag nanoparticles on the polymer surface. The biological efficacy of the Ag NPs@Bipy-PAN polymer was evaluated through antibacterial, anti-breast cancer, and biocompatibility assays. The results demonstrated notable antibacterial and anticancer activities, with significant efficacy against bacterial strains and breast cancer cells. Biocompatibility assessments indicated acceptable compatibility, particularly at a concentration of 2.5 mg/mL, compared to untreated control cells. These findings suggest that Ag NPs@Bipy-PAN has considerable potential as a candidate for cancer-targeted and antimicrobial drug delivery systems. The incorporation of silver nanoparticles into the melamine-based polymer enhances the safety profile of these systems in in vivo conditions, making them a viable option for advanced therapeutic applications.

Asunto(s)

Antibacterianos , Antineoplásicos , Nanopartículas del Metal , Plata , Triazinas , Plata/química , Plata/farmacología , Triazinas/química , Triazinas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas del Metal/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Pruebas de Sensibilidad Microbiana , Células MCF-7 , Femenino , Polímeros/química , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Difracción de Rayos X

RESUMEN

Melamine is a recognized food contaminant that can arise incidentally or intentionally in specific categories of food. This study aimed to validate the melamine detection and quantification in infant formula and milk powders and also analyzed 40 samples consist of infant formula and milk powders from commercially available food products, from different geographic regions of Iran. The approximate content of melamine in samples was measured by High-performance liquid chromatography-ultra violet (HPLC-UV) system. A calibration curve (R2 = 0.9925) was established for detection of melamine in the range of 0.1-1.2 µg mL-1. Limit of quantification and limit of detection were 1 µg mL-1 and 3 µg mL-1, respectively. The presence of melamine in infant formula and milk powdered was investigated and it was observed that the amount of melamine in samples of infant formulas and milk powders was 0.001-0.095 mg kg-1 and 0.001-0.004 mg kg-1, respectively. These values were found to be within the prescribed limits by the European Union and Codex Alimentarius Commission legislation. It is important to note that the consumption of these dairy products, which contain low content of melamine, does not pose any significant threat to consumer health. Furthermore, the results of the risk assessment confirmed this issue.

Asunto(s)

Contaminación de Alimentos , Fórmulas Infantiles , Leche , Triazinas , Triazinas/análisis , Fórmulas Infantiles/química , Fórmulas Infantiles/análisis , Irán , Contaminación de Alimentos/análisis , Humanos , Leche/química , Lactante , Polvos , Cromatografía Líquida de Alta Presión/métodos , Animales

RESUMEN

This retrospective cohort study analyzed data from a Japanese health insurance database to assess the effectiveness of baloxavir (n = 4822) for preventing severe events compared with oseltamivir (n = 10,523) in patients with influenza B. The primary endpoint was hospitalization incidence (Days 2-14). The secondary endpoints included intravenous antibacterial drug use, pneumonia hospitalization, heart failure hospitalization, inhalational oxygen requirement, and use of other anti-influenza drugs. The hospitalization incidence was significantly lower with baloxavir (0.15% vs. 0.37%; risk ratio: 2.48, 95% confidence interval: 1.13-5.43). Pneumonia and additional anti-influenza therapy were also less frequent with baloxavir, thus supporting its use. Trial Registration: UMIN Clinical Trials Registry Study ID: UMIN000051382.

Asunto(s)

Antivirales , Dibenzotiepinas , Virus de la Influenza B , Gripe Humana , Morfolinas , Oseltamivir , Pacientes Ambulatorios , Piridonas , Triazinas , Humanos , Gripe Humana/tratamiento farmacológico , Dibenzotiepinas/uso terapéutico , Oseltamivir/uso terapéutico , Antivirales/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Adulto , Piridonas/uso terapéutico , Morfolinas/uso terapéutico , Triazinas/uso terapéutico , Anciano , Virus de la Influenza B/efectos de los fármacos , Adulto Joven , Adolescente , Hospitalización/estadística & datos numéricos , Niño , Piridinas/uso terapéutico , Japón/epidemiología , Preescolar , Resultado del Tratamiento , Lactante , Anciano de 80 o más Años

RESUMEN

Macroporous three-dimensional (3D) framework structured melamine foam-based Enzyme-Linked Immunosorbent Assay (f-ELISA) biosensors were developed for rapid, reliable, sensitive, and on-site detection of trace amount of biomolecules and chemicals. Various ligands can be chemically immobilized onto the melamine foam, which brings in the possibility of working with antibodies, nanobodies, and peptides, respectively, as affinity probes for f-ELISA biosensors with improved stability. Different chemical reagents can be used to modify the foam materials, resulting in varied reactivities with antibodies, nanobodies, and peptides. As a result, the f-ELISA sensors produced from these modified foams exhibit varying levels of sensitivity and performance. This study demonstrated that the chemical reagents used for immobilizing antibodies, nanobodies, and peptides could affect the sensitivities of the f-ELISA sensors, and their storage stabilities under different temperatures varied depending on the sensing probes used, with f-ELISA sensors employing nanobodies as probes exhibiting the highest stability. This study not only showcases the versatility of the f-ELISA system but also opens new avenues for developing cost-effective, portable, and user-friendly diagnostic tools with optimized sensitivity and stability.

Asunto(s)

Técnicas Biosensibles , Ensayo de Inmunoadsorción Enzimática , Anticuerpos de Dominio Único , Triazinas , Triazinas/análisis , Triazinas/química , Ensayo de Inmunoadsorción Enzimática/métodos , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/química , Técnicas Biosensibles/métodos , Péptidos/química , Anticuerpos/inmunología , Anticuerpos/química , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química , Límite de Detección

RESUMEN

Sunitinib, N-desmethyl imatinib, dasatinib, imatinib, and bosutinib are tyrosine kinase inhibitors (TKIs) that are commonly employed in the treatment of a multitude of cancers. However, the inappropriate concentrations of TKIs can result in ineffective treatment or the emergence of multiple adverse effects. Consequently, the development of a rapid and sensitive analytical method for TKIs is of paramount importance for the safe administration of drugs. In this work, solid-phase microextraction (SPME) probe combined with an electrospray ionization mass spectrometry (ESI-MS) coupling platform was constructed for rapid and sensitive determination of TKIs. The covalent organic frameworks (COFs) coated SPME probe was made of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and 2,5-dibutoxyterephthalaldehyde (DBTA) by in-situ layer-by-layer chemical bonding synthesis strategy. The TAPT-DBTA-SPME probe exhibited several advantageous properties which rendered it suitable for the enrichment of TKIs. Under the optimal conditions, the developed analytical method demonstrated a broad linear range (0.05-500.00 µg/L), a low limit of detection (0.02 µg/L) and a high enrichment factor (51-203) for TKIs. The developed analytical method was successfully applied to a pharmacokinetic study of TKIs in mouse plasma and tissue matrix, demonstrating that the proposed analytical method has promise for clinical applications and metabolic monitoring.

Asunto(s)

Límite de Detección , Inhibidores de Proteínas Quinasas , Microextracción en Fase Sólida , Espectrometría de Masa por Ionización de Electrospray , Microextracción en Fase Sólida/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Animales , Ratones , Inhibidores de Proteínas Quinasas/análisis , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/sangre , Estructuras Metalorgánicas/química , Acero Inoxidable/química , Triazinas/análisis , Triazinas/química , Triazinas/sangre , Reproducibilidad de los Resultados

RESUMEN

PURPOSE: The purpose of this study was to evaluate the effect of UGT1A4 and UGT2B7 polymorphisms on the plasma concentration of lamotrigine in Chinese patients with bipolar disorder. METHODS: A total of 104 patients were included in this study. Steady-state plasma lamotrigine concentrations were determined in each patient after at least 21 days of continuous treatment with a set dose of the drug. Lamotrigine plasma concentrations were ascertained using ultra-performance liquid chromatography. Simultaneously, plasma samples were used for patient genotyping. RESULTS: The age, sex, BMI, daily lamotrigine dose, plasma lamotrigine concentration, and lamotrigine concentration/dose ratio of patients exhibited significant differences, and these were associated with differences in the genotype [ UGT1A4 -142T>G and UGT2B7 -161C>T ( P  < 0.05)]. Patients with the GG and GT genotypes in UGT1A4 -142T>G had significantly higher lamotrigine concentration/dose values (1.6 ±â€…1.1 and 1.7 ±â€…0.5 µg/ml per mg/kg) than those with the TT genotype (1.4 ±â€…1.1 µg/ml per mg/kg). Likewise, patients with the UGT2B7 -161C>T TT genotype had significantly higher lamotrigine concentration/dose values (1.6 ±â€…1.1 µg/ml per mg/kg) than those with the CC genotype (1.3 ±â€…1.3 µg/ml per mg/kg). Multiple linear regression analysis showed that sex, lamotrigine dose, UGT1A4 -142T>G, and UGT2B7 -161C>T were the most important factors influencing lamotrigine pharmacokinetics ( P  < 0.001). CONCLUSION: The study results suggest that the UGT1A4 -142T>G and UGT2B7 -161C>T polymorphisms affect lamotrigine plasma concentrations in patients with bipolar disorder.

Asunto(s)

Trastorno Bipolar , Glucuronosiltransferasa , Lamotrigina , Triazinas , Humanos , Lamotrigina/sangre , Lamotrigina/farmacocinética , Lamotrigina/administración & dosificación , Lamotrigina/uso terapéutico , Glucuronosiltransferasa/genética , Masculino , Femenino , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Trastorno Bipolar/sangre , Adulto , Triazinas/farmacocinética , Triazinas/sangre , Triazinas/administración & dosificación , Triazinas/uso terapéutico , Persona de Mediana Edad , Genotipo , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico/genética

RESUMEN

Irgarol 1051 is an herbicide extensively utilized in antifouling paint due to its ability to inhibit photosynthesis. Irgarol and its photodegradation products are highly persistent in waters and sediments, although they are present in low concentrations. However, our understanding of the harmful effects of Irgarol on non-target organisms remains limited. In this study, we assessed the effects of acute (24 h) and chronic (14 days across three generations) exposure to different concentrations (including the 1/10 NOEC, NOEC, and 1/10 LC50 calculated from the 24-h acute toxicity test) of Irgarol using the water flea Moina macrocopa. Acute exposure to 1/10 LC50 significantly decreased survival, feeding rate, thoracic limb activity, heart rate, and acetylcholinesterase activity. Elevated levels of intracellular reactive oxygen species and malondialdehyde, along with a significant increase in catalase and superoxide dismutase activity, suggested the induction of oxidative stress in response to 1/10 LC50. An initial boost in glutathione level and the enzymatic activities of glutathione peroxidase and glutathione reductase, followed by a plunge, implies some compromise in the antioxidant defense system. Upon chronic exposure to the NOEC value, both generations F1 and F2 displayed a significant decrease in survival rate, body length, number of neonates per brood, and delayed sexual maturation, suggesting maternal transfer of potential damage through generations. Taken together, Irgarol induced acute toxicity through physiological and cholinergic damage, accompanied by the induction of oxidative stress, in the water flea. Even its sub-lethal concentrations can induce detrimental effects across generations when consistently exposed.

Asunto(s)

Biomarcadores , Triazinas , Animales , Biomarcadores/metabolismo , Triazinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Siphonaptera/efectos de los fármacos , Desinfectantes/toxicidad , Pruebas de Toxicidad Aguda , Especies Reactivas de Oxígeno/metabolismo , Acetilcolinesterasa/metabolismo , Antioxidantes/metabolismo , Cladóceros

RESUMEN

Babesia and Plasmodium pathogens, the causative agents of babesiosis and malaria, are vector-borne intraerythrocytic protozoan parasites, posing significant threats to both human and animal health. The widespread resistance exhibited by these pathogens to various classes of antiparasitic drugs underscores the need for the development of novel and more effective therapeutic strategies. Antifolates have long been recognized as attractive antiparasitic drugs as they target the folate pathway, which is essential for the biosynthesis of purines and pyrimidines, and thus is vital for the survival and proliferation of protozoan parasites. More efficacious and safer analogs within this class are needed to overcome challenges due to resistance to commonly used antifolates, such as pyrimethamine, and to address liabilities associated with the dihydrotriazines, WR99210 and JPC-2067. Here, we utilized an in vitro culture condition suitable for the continuous propagation of Babesia duncani, Babesia divergens, Babesia MO1, and Plasmodium falciparum in human erythrocytes to screen a library of 50 dihydrotriazines and 29 biguanides for their efficacy in vitro and compared their potency and therapeutic indices across different species and isolates. We identified nine analogs that inhibit the growth of all species, including the P. falciparum pyrimethamine-resistant strain HB3, with IC50 values below 10 nM, and display excellent in vitro therapeutic indices. These compounds hold substantial promise as lead antifolates for further development as broad-spectrum antiparasitic drugs.

Asunto(s)

Babesia , Eritrocitos , Plasmodium falciparum , Triazinas , Triazinas/farmacología , Humanos , Babesia/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrollo , Eritrocitos/parasitología , Eritrocitos/efectos de los fármacos , Babesiosis/tratamiento farmacológico , Babesiosis/parasitología , Antimaláricos/farmacología , Pruebas de Sensibilidad Parasitaria , Antagonistas del Ácido Fólico/farmacología

RESUMEN

In search of novel therapeutic options to treat influenza virus (IV) infections, we previously identified a series of inhibitors that act by disrupting the interactions between the PA and PB1 subunits of the viral RNA polymerase. These compounds showed broad-spectrum antiviral activity against human influenza A and B viruses and a high barrier to the induction of drug resistance in vitro. In this short communication, we investigated the effects of combinations of the PA-PB1 interaction inhibitor 54 with oseltamivir carboxylate (OSC), zanamivir (ZA), favipiravir (FPV), and baloxavir marboxil (BXM) on the inhibition of influenza A and B virus replication in vitro. We observed a synergistic effect of the 54/OSC and 54/ZA combinations and an antagonistic effect when 54 was combined with either FPV or BXM. Moreover, we demonstrated the efficacy of 54 against highly pathogenic avian influenza viruses (HPAIVs) both in cell culture and in the embryonated chicken eggs model. Finally, we observed that 54 enhances OSC protective effect against HPAIV replication in the embryonated eggs model. Our findings represent an advance in the development of alternative therapeutic strategies against both human and avian IV infections.

Asunto(s)

Antivirales , Sinergismo Farmacológico , Virus de la Influenza A , Oseltamivir , Pirazinas , Proteínas Virales , Replicación Viral , Oseltamivir/farmacología , Oseltamivir/análogos & derivados , Animales , Antivirales/farmacología , Humanos , Replicación Viral/efectos de los fármacos , Pirazinas/farmacología , Virus de la Influenza A/efectos de los fármacos , Embrión de Pollo , Proteínas Virales/metabolismo , Proteínas Virales/antagonistas & inhibidores , Amidas/farmacología , Dibenzotiepinas/farmacología , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/fisiología , Zanamivir/farmacología , Triazinas/farmacología , Piridonas/farmacología , Gripe Aviar/tratamiento farmacológico , Gripe Aviar/virología , Morfolinas/farmacología , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Perros , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , ARN Polimerasa Dependiente del ARN/metabolismo , Línea Celular , Células de Riñón Canino Madin Darby

RESUMEN

The extensively applied triazine herbicides are easily transported by ocean currents over long distances. This study analyzed ten triazine herbicides in the Antarctic marginal seas and the Southern Indian Ocean during the austral summer for the first time, addressing their largely unexplored behavior in remote marine environments. The total triazine herbicides showed great spatial heterogeneity, with a range of 20-790 pg/L and an average of 31 ± 66 pg/L. The waterborne transport of triazine herbicides in the Antarctic was affected by hydrological processes, especially the blocking and accumulation effect of the polar front. Variations in sea ice extent and temperature were also important influencing factors, resulting in elevated triazine herbicides in surface seawater of East Antarctica, but reduced levels in West Antarctica. Furthermore, the source apportionment results indicated that approximately 55 % of the herbicides originated from sugarcane cultivation, 28 % from algaecide use, and 16 % from corn and sorghum farming.

Asunto(s)

Monitoreo del Ambiente , Herbicidas , Triazinas , Contaminantes Químicos del Agua , Herbicidas/análisis , Triazinas/análisis , Contaminantes Químicos del Agua/análisis , Regiones Antárticas , Agua de Mar/química , Océanos y Mares

RESUMEN

The flattened bamboo board (FB) represents a promising innovation in the bamboo industry. To address the challenges of flammability and hygroscopicity, composite coatings consisting of melamine (MEL), phytic acid (PA), cerium ions (Ce3+), and sodium laurate (La) are assembled on the FB surface through an in-situ impregnation strategy. The resulting MEL/PA-Ce3+@La FB exhibits exceptional flame retardancy. It achieves a V-0 rating in the vertical burning test (UL-94) and boasts a high limiting oxygen index (LOI) value of 38.5 %. The coated FB exhibits superhydrophobicity, evidenced by a water contact angle of 156.5°, which can be attributed to the in-situ growth of PA-Ce3+ complexes (for constructing micro/nanoscale coarse structures) and the modification with La (for reducing surface energy).This superhydrophobic surface imparts both self-cleaning and anti-mold properties to the coated FB. Moreover, the coated FB exhibits excellent mechanical stability, withstanding 36 cycles of sandpaper abrasion and tape peeling without losing its hydrophobicity. In summary, this work provides an innovative strategy for the bamboo processing industry to produce flattened bamboo boards with combined flame retardancy, superhydrophobic and anti-mold properties. Such versatility holds significant potential to facilitate the utilization of flattened bamboo boards in the construction and decorative materials industries.

Asunto(s)

Retardadores de Llama , Interacciones Hidrofóbicas e Hidrofílicas , Retardadores de Llama/análisis , Triazinas/química , Propiedades de Superficie , Ácido Fítico/química , Agua/química , Cerio/química , Humectabilidad

RESUMEN

Rapid and precise detection of harmful substances in food products is essential for ensuring public health and safety. This study introduces a novel surface-enhanced Raman spectroscopy (SERS) substrate, composed of a molybdenum disulfide­silver nanocomposite, applied to flexible, water-resistant filter paper for detecting melamine and bisphenol A (BPA) in milk. Optimized molybdenum disulfide (NMS) nanoflowers (NFs) were synthesized through hydrothermal methods and high-temperature annealing, then modified with silver (Ag) nanoparticles to form the NMS-Ag nanocomposite (NMSA6). This substrate greatly enhances the Raman signal, achieving an enhancement factor of approximately 1.49 × 107 and a detection limit as low as 10-11 M for simultaneous multi-component analysis. Finite-difference time-domain (FDTD) simulations confirm the enhancement mechanism. The NMSA6 substrate demonstrates remarkably low detection limits for BPA and melamine, facilitating the analysis of various hazardous substances. These findings highlight the substrate's potential for highly sensitive, label-free detection, presenting a viable tool for food safety monitoring.

Asunto(s)

Compuestos de Bencidrilo , Contaminación de Alimentos , Límite de Detección , Leche , Papel , Fenoles , Plata , Espectrometría Raman , Triazinas , Leche/química , Contaminación de Alimentos/análisis , Plata/química , Animales , Fenoles/análisis , Fenoles/química , Espectrometría Raman/métodos , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/química , Triazinas/análisis , Molibdeno/química , Nanocompuestos/química , Disulfuros/química , Nanopartículas del Metal/química

RESUMEN

eEF2K, an atypical alpha-kinase, is responsible for regulating protein synthesis and energy homeostasis. Aberrant eEF2K function has been linked to various human cancers, including triple-negative breast cancer (TNBC). However, limited cellular activity of current eEF2K modulators impedes their clinical application. Based on the 2-phenyl-1,2,4-triazine-3,5(2H,4H)-dione scaffold of our hits I4 and C1, structure-activity relationship analysis led to the discovery of several more active derivatives (e.g., 19, 34, and 36) in inhibiting the viability of TNBC cell line MDA-MB-231. Moreover, the most potent compound 36 significantly suppresses the viability, proliferation, and migration of both MDA-MB-231 and HCC1806 cell lines. Mechanistically, compound 36 has a high binding affinity for the eEF2K protein and effectively induces its degradation. Additionally, 36 exerts a comparable tumor-suppressive effect to paclitaxel in an MDA-MB-231 cell xenograft mouse model with no obvious toxicity, demonstrating that compound 36 could be developed as a potential novel therapeutic for TNBC treatment.

Asunto(s)

Antineoplásicos , Proliferación Celular , Quinasa del Factor 2 de Elongación , Triazinas , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Relación Estructura-Actividad , Animales , Quinasa del Factor 2 de Elongación/metabolismo , Quinasa del Factor 2 de Elongación/antagonistas & inhibidores , Triazinas/farmacología , Triazinas/química , Triazinas/síntesis química , Triazinas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Femenino , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Movimiento Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos

RESUMEN

Biocatalytic membranes have great potential in various industrial sectors, with the immobilization of enzymes being a crucial stage. Immobilizing enzymes through covalent bonds is a complex and time-consuming process for large-scale applications. Polydopamine (PDA) offers a more sustainable and eco-friendly alternative for enzyme immobilization. Therefore, surface modification with polydopamine as mussel-inspired antifouling coatings has increased resistance to fouling. In this study, α-amylase enzyme was covalently bound to a bioactive PDA-coated polyethersulfone (PES) membrane surface using cyanuric chloride as a linker. The optimal activity of α-amylase enzyme immobilized on PES/PDA membrane was obtained at temperature and pH of 55°C and 6.5, respectively. The immobilized enzyme can be reused up to five reaction cycles with 55 % retention of initial activity. Besides, it maintained 60 % of its activity after being stored for five weeks at 4°C. Additionally, the immobilized enzyme demonstrated increased Michaelis constant and maximum velocity values during starch hydrolysis. The results of the biofouling experiment of various membranes in a dead-end cell demonstrated that the PES membrane's water flux increased from 6722.7 Lmh to 7560.2 Lmh after PDA modification. Although α-amylase immobilization reduced the flux to 7458.5 Lmh due to enhanced hydrophilicity, compared to unmodified membrane. The findings of this study demonstrated that the membrane produced through co-deposition exhibited superior hydrophilicity, enhanced coating stability, and strong antifouling properties, positioning it as a promising candidate for industrial applications.

Asunto(s)

Estabilidad de Enzimas , Enzimas Inmovilizadas , Indoles , Membranas Artificiales , Polímeros , Sulfonas , alfa-Amilasas , Indoles/química , Polímeros/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Sulfonas/química , alfa-Amilasas/metabolismo , alfa-Amilasas/química , Concentración de Iones de Hidrógeno , Incrustaciones Biológicas/prevención & control , Temperatura , Hidrólisis , Triazinas