RESUMEN

Mammalian interleukin-22 (IL-22) attenuates organismal injury by inhibiting reactive oxygen species (ROS) and impeding the NLRP3 inflammasome activation. However, the role of fish IL-22 in this process remains unclear. We characterized MaIL-22, an IL-22 homolog in blunt snout bream (Megalobrama amblycephala). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, Aeromonas hydrophila (A. hydrophila) infection leads to tissue injury in M. amblycephala immune organs and concomitantly altered Mail-22 mRNA expression, suggesting that MaIL-22 was involved in the antimicrobial immune response. To explore MaIL-22's biological functions, we produced recombinant MaIL-22 (rMaIL-22) protein and demonstrated it significantly enhanced the survival of M. amblycephala post-A. hydrophila infection. To unravel its protective mechanisms, we explored the ROS/NLRP3 inflammasome axis and its downstream signaling responses. The results showed that rMaIL-22 treatment significantly elevated antioxidant enzyme (T-SOD, CAT and GSH-PX) activities to inhibit MDA activity and scavenge ROS in visceral tissues. Meanwhile, rMaIL-22 impeded the activation of NLRP3 inflammasome by suppressing NLRP3 protein and mRNA expression. This indicated that rMaIL-22 contributed to inhibit A. hydrophila-induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines (il-1ß, tnf-α and il-6) and proapoptotic genes (caspase-3 and caspase-8) while promoting antiapoptotic genes (bcl-2b and mcl-1a) expression, ultimately mitigating tissue injury in visceral tissues. In conclusion, our research underscores MaIL-22's key role in microbial immune regulation, offering insights for developing IL-22-targeted therapies and breeding programs.

Asunto(s)

Aeromonas hydrophila , Apoptosis , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Inflamasomas , Inflamación , Interleucina-22 , Interleucinas , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno , Animales , Aeromonas hydrophila/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Inflamasomas/inmunología , Apoptosis/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/inmunología , Especies Reactivas de Oxígeno/metabolismo , Interleucinas/metabolismo , Interleucinas/inmunología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Inflamación/inmunología , Proteínas de Peces/metabolismo , Proteínas de Peces/inmunología , Proteínas de Peces/genética , Cyprinidae/inmunología , Cyprinidae/metabolismo , Transducción de Señal

RESUMEN

With the development and application of thermoelectric (TE) devices, it requires not only high-performance of TE materials but also high mechanical properties. Here, we report a medium-temperature liquid material, AgCuTe, with high mechanical properties. The results demonstrate that AgCuTe possesses a multiphase structure characterized by abundant grain boundaries, resulting in reduced lattice thermal conductivity and inherently high mechanical strength. Furthermore, nano-SiC was alloyed into the AgCuTe material to further improve its mechanical and TE properties. Nano-SiC exhibited a button-like distribution within the grain boundaries, introducing a pinning effect that significantly elevated the Vickers hardness of the samples. Additionally, nano-SiC induced strong lattice distortion energy in the vicinity, which promotes Ag/Cu ions to escape from the lattice and enhances the liquid-like behavior of Ag/Cu ions. Finally, these enhancements led to a 21% improvement in the mechanical properties and a 40% improvement in the TE properties for AgCuTe. Notably, AgCuTe achieved its peak TE performance, with a latest peak ZT value of 1.32 at 723 K. This research expands the potential applications of AgCuTe.

RESUMEN

The types and quantities of new psychoactive substances synthesized based on structural modifications have increased rapidly in recent years and pose a great challenge to clinical and forensic laboratories. N-benzyl derivatives of phenethylamines, 25B-NBOH, 25E-NBOH, 25H-NBOH, and 25iP-NBOMe have begun to flow into the black market and have caused several poisoning cases and even fatal cases. The aim of this study was to avoid false negative results by detecting the parent drug and its metabolites to extend the detection window in biological matrices and provide basic data for the simultaneous determination of illegal drugs and metabolites in forensic and emergency cases. To facilitate the comparison of metabolic characteristics, we divided the four compounds into two groups of types, 25X-NBOH and 25X-NBOMe. The in vitro phase I and phase II metabolism of these four compounds was investigated by incubating 10 mg mL-1 pooled human liver microsomes with co-substrates for 180 min at 37 â„ƒ, and then analyzing the reaction mixture using ultrahigh-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. In total, 70 metabolites were obtained for the four compounds. The major biotransformations were O-demethylation, hydroxylation, dehydrogenation, N-dehydroxybenzyl, N-demethoxybenzyl, oxidate transformation to ketone and carboxylate, glucuronidation, and their combination reactions. We recommended the major metabolites with high peak area ratio as biomarkers, B2-1 (56.61%), B2-2 (17.43%) and B6 (17.78%) for 25B-NBOH, E2-1 (42.81%), E2-2 (34.90%) and E8-2 (10.18%) for 25E-NBOH, H5 (49.28%), H2-1 (21.54%), and H1 (18.37%) for 25H-NBOH, P3-1 (10.94%), P3-2 (33.18%), P3-3 (14.85%) and P12-2 (23.00%) for 25iP-NBOMe. This is a study to evaluate their metabolic characteristics in detail. Comparative analysis of the N-benzyl derivatives of phenethylamines provided basic data for elucidating their pharmacology and toxicity. Timely analysis of the metabolic profiles of compounds with abuse potential will facilitate the early development of regulatory measures.

Asunto(s)

Drogas de Diseño , Alucinógenos , Humanos , Fenetilaminas/análisis , Cromatografía Líquida de Alta Presión , Microsomas Hepáticos/metabolismo , Drogas de Diseño/metabolismo

RESUMEN

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a crucial role in acute stress induced by bacterial infection and is strongly associated with reactive oxygen species (ROS) production. However, the role of IL-6 in the liver of fish after Aeromonas hydrophila infection remains unclear. Therefore, this study constructed a zebrafish (Danio rerio) il-6 knockout line by CRISPR/Cas9 to investigate the function of IL-6 in the liver post bacterial infection. After infection with A. hydrophila, pathological observation showed that il-6-/- zebrafish exhibited milder liver damage than wild-type (WT) zebrafish. Moreover, liver transcriptome sequencing revealed that 2432 genes were significantly up-regulated and 1706 genes were significantly down-regulated in il-6-/- fish compared with WT fish after A. hydrophila infection. Further, gene ontology (GO) analysis showed that differentially expressed genes (DEGs) were significantly enriched in redox-related terms, including oxidoreductase activity, copper ion transport, etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in pathways such as the PPAR signaling pathway, suggesting that il-6 mutation has a significant effect on redox processes in the liver after A. hydrophila infection. Additionally, il-6-/- zebrafish exhibited lower malondialdehyde (MDA) levels and higher superoxide dismutase (SOD) activities in the liver compared with WT zebrafish following A. hydrophila infection, indicating that IL-6 deficiency mitigates oxidative stress induced by A. hydrophila infection in the liver. These findings provide a basis for further studies on the role of IL-6 in regulating oxidative stress in response to bacterial infections.

Asunto(s)

Infecciones Bacterianas , Infecciones por Bacterias Gramnegativas , Interleucina-6 , Proteínas de Pez Cebra , Animales , Aeromonas hydrophila/fisiología , Infecciones Bacterianas/patología , Infecciones por Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/microbiología , Interleucina-6/genética , Hígado/patología , Mutación , Oxidación-Reducción , Estrés Oxidativo/genética , Pez Cebra/genética , Pez Cebra/microbiología , Proteínas de Pez Cebra/metabolismo , Modelos Animales de Enfermedad

RESUMEN

OBJECTIVES: To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood. METHODS: Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode. RESULTS: The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect. CONCLUSIONS: This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.

Asunto(s)

Dexmedetomidina , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Dexmedetomidina/análisis , Reproducibilidad de los Resultados , Cromatografía Liquida/métodos

RESUMEN

A rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the targeted analysis of 75 phenethylamines and their derivatives from the hair matrix. The monitored classes of phenethylamines included the 2C series, D series, N-benzyl derivatives, mescaline-derived compounds, MDMA analogs, and benzodifurans. Approximately 20 mg of hair was weighed and pulverized with 0.1% formic acid in methanol by cryogenic grinding. After ultrasonication, centrifugation, and filtration, the supernatant was analyzed by LC-MS/MS operating in the scheduled multiple reaction monitoring mode. Phenethylamines and their derivatives were separated in 13 min on a biphenyl column (2.6 µm, 100 Å, 100 × 3.0 mm) using a gradient eluting mobile phase composed of 0.1% formic acid in water and acetonitrile. The developed and validated method showed good selectivity, sensitivity (LOD: 0.5-10 pg/mg and LOQ: 1-20 pg/mg), linearity (R2 > 0.997), accuracy and precision (< 20%), and stability. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of phenethylamines in hair from authentic forensic cases.

Asunto(s)

Fenetilaminas , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Fenetilaminas/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Cabello/química

RESUMEN

Clonazolam is a designer benzodiazepine with strong sedative and amnesic effects. As we all know, the detection of metabolites is the key to confirming the use of substances in the field of forensic toxicology. In order to better describe clonazolam metabolism completely, we performed the two different experiments exploiting the unique characteristics of the models used. In this study, in vivo and in vitro samples were analyzed with liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. The results showed that seven Phase I metabolites and one Phase II metabolite were detected in zebrafish model. The remaining Phase I and II metabolites were also found in the incubation solution of pooled human liver microsomes. The main types of metabolic reactions of clonazolam included hydroxylation, dealkylation, nitroreduction, dechlorination, N-Acetylation, and O-glucuronidation. In this paper, the main metabolites and metabolic pathways of clonazolam are clarified in detail in order to further improve the metabolic rule of clonazolam. Based on these results, to better detect and judge the abuse of clonazolam, we suggest that M1, its nitro reduction product, is used as its biomarker. The results of this study provide a theoretical basis for the pharmacokinetics and forensic medicine of clonazolam.

Asunto(s)

Microsomas Hepáticos , Pez Cebra , Animales , Humanos , Microsomas Hepáticos/metabolismo , Pez Cebra/metabolismo , Benzodiazepinas/química , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión/métodos

RESUMEN

4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT, psilacetin, O-acetylpsilocin) is a synthetic tryptamine with psychedelic properties. Psilacetin may also act as precursor drug of psilocin, similar to psilocybin, but little is known about its metabolism. In this study, the phase I and phase II in vitro metabolism of 4-AcO-DMT was investigated with pooled human liver microsomes, and the reaction mixture was analyzed using liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry. Fifteen metabolites were formed after incubation of pooled human liver microsomes with 4-AcO-DMT (12 phase I metabolites and 3 phase II metabolites). The proposed metabolite structures were based on accurate mass analysis and MS/MS fragmentation patterns. The biotransformations included hydrolysis, hydroxylation, N-demethylation, oxidation, and conjugation with glucuronic acid. The hydrolysis metabolite was the most abundant compound. For the development of new methods for the identification of 4-AcO-DMT consumption, the beta-hydroxylation metabolite of 4-AcO-DMT (M2-1) is recommended as a biomarker. The data reported in this work might be applicable to metabolic transformation of 4-AcO-DMT in vivo and also forensically helpful.

Asunto(s)

Microsomas Hepáticos , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Humanos , Microsomas Hepáticos/metabolismo , Espectrometría de Masas en Tándem/métodos , Triptaminas/metabolismo

RESUMEN

The discovery of new semiconducting materials with low thermal conductivity is of vital importance in promoting thermal energy conversion and management. Herein, lattice dynamical and thermal transport mechanism of new energetically stable 2D Ga2O3(100) is presented using density functional theory. The results show that 2D Ga2O3(100) possesses an extremely low lattice thermal conductivity of ∼0.71 W mK-1 at 300 K. We find that 2D Ga2O3(100) possesses two intrinsic features that decrease the lattice thermal conductivity: (1) the existence of interspersed distorted tetrahedral and pentahedral coordination geometries, which improves the phonon anharmonicity of the system; (2) compared to bulk ß-Ga2O3, the reduced dimensionality suppresses heat transfer by introducing interfacial scattering in 2D Ga2O3(100). Additionally, the strong Ga-O covalent bond results in a low speed of sound, high phonon-phonon scattering rates, and thus low lattice thermal conductivity. Our finding is remarkable because ultralow thermal conductivity can be realized in a simple 2D oxide, which provides replaceable materials for further applications in the field of thermal management.

RESUMEN

Tissue engineering provides a powerful solution for current organ shortages, and researchers have cultured blood vessels, heart tissues, and bone tissues in vitro. However, traditional top-down tissue engineering has suffered two challenges: vascularization and reconfigurability of functional units. With the continuous development of micro-nano technology and biomaterial technology, bottom-up tissue engineering as a promising approach for organ and tissue modular reconstruction has gradually developed. In this article, relevant advances in living blocks fabrication and assembly techniques for creation of higher-order bioarchitectures are described. After a critical overview of this technology, a discussion of practical challenges is provided, and future development prospects are proposed.

RESUMEN

The Heusler alloys CoFeRGa (R = Ti, V, Cr, Mn, Cu, and Nb) have similar chemical compositions, but exhibit remarkably distinct electronic structures, magnetism and transport properties. These structures cover an extensive range of spin gapless semiconductors, half-metals, semiconductors and metals with either ferromagnetic, ferrimagnetic, antiferromagnetic, or nonmagnetic states. The Heusler alloys have three types of structures, namely, type-I, type-II, and type-III. By means of first-principles calculation combined with the Boltzmann equation within the consideration of spin-freedom, we explore the transport feature of the most stable structure (type-I). In addition, we provide evidence that all the considered materials are mechanically and dynamically stable, possessing high strength and toughness to resist compression and tensile strain. Moreover, the distinct electronic (metallic, insulating, and half-metallic) properties and magnetic behaviors originate mainly from a cooperative electron transfer and electronic structures have been verified by our calculation. Finally, we found that the tunable electronic structure with varied atomic numbers has significant influence on the spin-Seebeck effect. Correspondingly, the calculated spin-Seebeck coefficient of CoFeCrGa is -60.29 µV K-1 at 300 K, which is larger than that of other quaternary Heusler compounds. Our results provide a band-engineering platform to design Heusler structures with different electronic behaviors in isomorphic compounds, which provide the way for accelerating the pre-screening of materials to advance and for using the quaternary Heusler compounds for potential applications in spin caloritronic devices.

RESUMEN

Compositional tailoring externally enables the fine tuning of thermal transport parameters of materials using the dual modulation of electronic or thermal transport properties. Theoretically, we examined the lattice dynamics of three particularly ternary representatives with different stoichiometry, BaMgSi, Ba2Mg3Si4, and BaMg2Si2, and identified the inherent bonding hierarchy and rattling Ba atoms, which were responsible for reducing the lattice thermal conductivity. BaMgSi and Ba2Mg3Si4 exhibited inherently ultra-low lattice thermal conductivity of 1.27-0.37 W m-1 K-1 in the range of 300-1000 K due to the bonding hierarchy and rattling Ba atoms. The low-energy optical phonons are overlapping with the acoustic phonons. This is associated with the intrinsic rattler-like vibration of Ba cations and leads to the characteristic in the localization of the propagative phonons and large anharmonicity. Although BaMg2Si2 had a dumbbell-shaped Si-Si covalent and Ba-Si/Mg ionic bonding environment and intrinsic rattler-like vibration of Ba cations, the middle frequency optic phonon branches contribute considerably to the thermal conductivity of the lattice. At the same temperature, compared with BaMgSi and Ba2Mg3Si4, the lattice thermal conductivity of BaMg2Si2 almost doubles owing to the higher phonon lifetime and group velocities. Our findings highlight considerable potential for thermoelectric applications with a different stoichiometric ratio of Ba/Mg/Si systems due to their low lattice thermal conductivities via intrinsic modulating stoichiometry.