RESUMEN
Most of the state-of-the-art thermoelectric materials are inorganic semiconductors. Owing to the directional covalent bonding, they usually show limited plasticity at room temperature1,2, for example, with a tensile strain of less than five per cent. Here we discover that single-crystalline Mg3Bi2 shows a room-temperature tensile strain of up to 100 per cent when the tension is applied along the (0001) plane (that is, the ab plane). Such a value is at least one order of magnitude higher than that of traditional thermoelectric materials and outperforms many metals that crystallize in a similar structure. Experimentally, slip bands and dislocations are identified in the deformed Mg3Bi2, indicating the gliding of dislocations as the microscopic mechanism of plastic deformation. Analysis of chemical bonding reveals multiple planes with low slipping barrier energy, suggesting the existence of several slip systems in Mg3Bi2. In addition, continuous dynamic bonding during the slipping process prevents the cleavage of the atomic plane, thus sustaining a large plastic deformation. Importantly, the tellurium-doped single-crystalline Mg3Bi2 shows a power factor of about 55 microwatts per centimetre per kelvin squared and a figure of merit of about 0.65 at room temperature along the ab plane, which outperforms the existing ductile thermoelectric materials3,4.
RESUMEN
Unlike graphene derived from graphite, borophenes represent a distinct class of synthetic two-dimensional materials devoid of analogous bulk-layered allotropes, leading to covalent bonding within borophenes instead of van der Waals (vdW) stacking. Our investigation focuses on 665 vdW-stacking boron bilayers to uncover potential bulk-layered boron allotropes through vdW stacking. Systematic high-throughput screening and stability analysis reveal a prevailing inclination toward covalently bonded layers in the majority of boron bilayers. However, an intriguing outlier emerges in δ5 borophene, demonstrating potential as a vdW-stacking candidate. We delve into electronic and topological structural similarities between δ5 borophene and graphene, shedding light on the structural integrity and stability of vdW-stacked boron structures across bilayers, multilayers, and bulk-layered allotropes. The δ5 borophene analogues exhibit metallic properties and characteristics of phonon-mediated superconductors, boasting a critical temperature near 22 K. This study paves the way for the concept of "borophite", a long-awaited boron analogue of graphite.
RESUMEN
Spectrally stable pure-red perovskite quantum dots (QDs) with low lead content are essential for high-definition displays but are difficult to synthesize due to QD self-purification. Here, we make use of entropy-driven quantum-confined pure-red perovskite QDs to fabricate light-emitting diodes (LEDs) that have low toxicity and are efficient and spectrum-stable. Based on experimental data and first-principles calculations, multiple element alloying results in a 60% reduction in lead content while improving QD entropy to promote crystal stability. Entropy-driven QDs exhibit photoluminescence with 100% quantum yields and single-exponential decay lifetimes without alteration of their morphology or crystal structure. The pure-red LEDs utilizing entropy-driven QDs have spectrally stable electroluminescence, achieving a brightness of 4932 cd/m2, a maximum external quantum efficiency of over 20%, and a 15-fold longer operational lifetime than the CsPbI3 QD-based LEDs. These achievements demonstrate that entropy-driven QDs can mitigate local compositional heterogeneity and ion migration.
RESUMEN
Self-trapped exciton (STE) luminescence, typically associated with structural deformation of excited states, has attracted significant attention in metal halide materials recently. However, the mechanism of multiexciton STE emissions in certain metal halide crystals remains largely unexplored. This study investigates dual luminescence emissions in HCOO- doped Cs3Cu2I5 single crystals using transient and steady-state spectroscopy. The dual emissions are attributed to intrinsic STE luminescence originating from the host lattice and extrinsic STE luminescence induced by external dopants, respectively, each of which can be triggered independently at distinct energy levels. Theoretical calculations reveal that multiexciton emission originates from structural distortion of the host and dopant STEs within the 0D lattice in their respective excited states. By meticulously tuning the excitation wavelength and selectively exciting different STEs, the dynamic alteration of color change in Cs3Cu2I5:HCOO- crystals is demonstrated. Ultimately, owing to an extraordinarily high photoluminescence quantum yield (99.01%) and a diminished degree of self-absorption in Cs3Cu2I5:HCOO- crystals, they exhibit remarkable X-ray scintillation characteristics with light yield being improved by 5.4 times as compared to that of pristine Cs3Cu2I5 crystals, opening up exciting avenues for achieving low-dose X-ray detection and imaging.
RESUMEN
Ferroelectricity in CMOS-compatible hafnia (HfO_{2}) is crucial for the fabrication of high-integration nonvolatile memory devices. However, the capture of ferroelectricity in HfO_{2} requires the stabilization of thermodynamically metastable orthorhombic or rhombohedral phases, which entails the introduction of defects (e.g., dopants and vacancies) and pays the price of crystal imperfections, causing unpleasant wake-up and fatigue effects. Here, we report a theoretical strategy on the realization of robust ferroelectricity in HfO_{2}-based ferroelectrics by designing a series of epitaxial (HfO_{2})_{1}/(CeO_{2})_{1} superlattices. The designed ferroelectric superlattices are defects free, and most importantly, on the base of the thermodynamically stable monoclinic phase of HfO_{2}. Consequently, this allows the creation of superior ferroelectric properties with an electric polarization >25 µC/cm^{2} and an ultralow polarization-switching energy barrier at â¼2.5 meV/atom. Our work may open an avenue toward the fabrication of high-performance HfO_{2}-based ferroelectric devices.
RESUMEN
Compared with the ever-growing information about the anthropogenic discharge of nutrients, metals, and antibiotics on the disturbance of antibiotic resistance genes (ARGs), less is known about how the potential natural stressors drive the evolutionary processes of antibiotic resistance. This study examined how soil resistomes evolved and differentiated over 30 years in various land use settings with spatiotemporal homogeneity and minimal human impact. We found that the contents of soil organic carbon, nitrogen, soil microbial biomass, and bioavailable heavy metals, as well as related changes in the antibiotic resistome prevalence including diversity and abundance, declined in the order of grassland > cropland > bareland. Sixty-nine remaining ARGs and 14 mobile genetic elements (MGEs) were shared among three land uses. Multiple factors (i.e., soil properties, heavy metals, bacterial community, and MGEs) contributed to the evolutionary changes of the antibiotic resistome, wherein the resistome profile was dominantly driven by MGEs from both direct and indirect pathways, supported by a partial least-squares path model analysis. Our results suggest that pathways to mitigate ARGs in soils can coincide with land degradation processes, posing a challenge to the common goal of managing our environment sustainably.
Asunto(s)
Antibacterianos , Farmacorresistencia Microbiana , Microbiología del Suelo , Suelo , Suelo/química , Farmacorresistencia Microbiana/genética , Antibacterianos/farmacologíaRESUMEN
The continuous introduction of micropollutants into the environment through livestock farming, agricultural practices, and wastewater treatment is a major concern. Among these pollutants are synthetic sulfonamide antibiotics such as sulfamethoxazole, which are not always fully degraded and pose a risk of fostering antimicrobial resistance. It is challenging to assess the degradation of sulfonamides with conventional concentration measurements. This study introduces compound-specific isotope analysis of nitrogen isotope ratios at natural abundances by derivatization-gas chromatography hyphenated with isotope ratio mass spectrometry (derivatization-GC-IRMS) as a new and more precise method for tracing the origin and degradation of sulfonamides. Here, sulfamethoxazole was used as a model compound to develop and optimize the derivatization conditions using (trimethylsilyl)diazomethane as a derivatization reagent. With the optimized conditions, accurate and reproducible δ15N analysis of sulfamethoxazole by derivatization-GC-IRMS was achieved in two different laboratories with a limit for precise isotope analysis of 3 nmol N on column, corresponding to 0.253 µg non-derivatized SMX. Application of the method to four further sulfonamides, sulfadiazine, sulfadimethoxine, sulfadimidine, and sulfathiazole, shows the versatility of the developed method. Its benefit was demonstrated in a first application, highlighting the possibility of distinguishing sulfamethoxazole from different suppliers and pharmaceutical products.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Isótopos de Nitrógeno , Sulfonamidas , Sulfonamidas/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Isótopos de Nitrógeno/análisis , Contaminantes Químicos del Agua/análisis , Límite de Detección , Sulfametoxazol/análisisRESUMEN
Lighting accounts for one-fifth of global electricity consumption1. Single materials with efficient and stable white-light emission are ideal for lighting applications, but photon emission covering the entire visible spectrum is difficult to achieve using a single material. Metal halide perovskites have outstanding emission properties2,3; however, the best-performing materials of this type contain lead and have unsatisfactory stability. Here we report a lead-free double perovskite that exhibits efficient and stable white-light emission via self-trapped excitons that originate from the Jahn-Teller distortion of the AgCl6 octahedron in the excited state. By alloying sodium cations into Cs2AgInCl6, we break the dark transition (the inversion-symmetry-induced parity-forbidden transition) by manipulating the parity of the wavefunction of the self-trapped exciton and reduce the electronic dimensionality of the semiconductor4. This leads to an increase in photoluminescence efficiency by three orders of magnitude compared to pure Cs2AgInCl6. The optimally alloyed Cs2(Ag0.60Na0.40)InCl6 with 0.04 per cent bismuth doping emits warm-white light with 86 ± 5 per cent quantum efficiency and works for over 1,000 hours. We anticipate that these results will stimulate research on single-emitter-based white-light-emitting phosphors and diodes for next-generation lighting and display technologies.
RESUMEN
Application of biochar and inoculation with specific microbial strains offer promising approaches for addressing atrazine contamination in agricultural soils. However, determining the optimal method necessitates a comprehensive understanding of their effects under similar conditions. This study aimed to evaluate the effectiveness of biochar and Paenarthrobacter sp. AT5, a bacterial strain known for its ability to degrade atrazine, in reducing atrazine-related risks to soybean crops and influencing bacterial communities. Both biochar and strain AT5 significantly improved atrazine degradation in both planted and unplanted soils, with the most substantial reduction observed in soils treated with strain AT5. Furthermore, bioaugmentation with strain AT5 outperformed biochar in enhancing soybean growth, photosynthetic pigments, and antioxidant defenses. While biochar promoted higher soil bacterial diversity compared to strain AT5, the latter selectively enriched specific bacterial populations. Additionally, soil inoculated with strain AT5 displayed a notable increase in the abundance of key genes associated with atrazine degradation (trzN, atzB, and atzC), surpassing the effects observed with biochar addition, thus highlighting its effectiveness in mitigating atrazine risks in soil.
Asunto(s)
Atrazina , Biodegradación Ambiental , Carbón Orgánico , Glycine max , Herbicidas , Microbiología del Suelo , Contaminantes del Suelo , Atrazina/toxicidad , Glycine max/microbiología , Glycine max/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Herbicidas/toxicidad , Suelo/química , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismoRESUMEN
Atrazine, a widely used herbicide in modern agriculture, can lead to soil contamination and adverse effects on specific crops. To address this, we investigated the efficacy of biochar loaded with Paenarthrobacter sp. AT5 (an atrazine-degrading bacterial strain) in mitigating atrazine's impact on soybeans in black soil. Bacterially loaded biochar (BBC) significantly enhanced atrazine removal rates in both unplanted and planted soil systems. Moreover, BBC application improved soybean biomass, photosynthetic pigments, and antioxidant systems while mitigating alterations in metabolite pathways induced by atrazine exposure. These findings demonstrate the effectiveness of BBC in reducing atrazine-induced oxidative stress on soybeans in black soil, highlighting its potential for sustainable agriculture.
Asunto(s)
Atrazina , Carbón Orgánico , Glycine max , Estrés Oxidativo , Contaminantes del Suelo , Suelo , Atrazina/toxicidad , Glycine max/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Suelo/química , Carbón Orgánico/química , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Herbicidas/toxicidadRESUMEN
Tumor-associated calcium signal transducer 2 (Trop2) is highly specific expressed in gastric carcinoma (GC). The combination of Trop2 antibody and phototherapy agents could exhibit synergetic antitumor activity. Black phosphorus nanosheets (BP) are covalently modified with Trop2 IgG antibodies via heterobifunctional linker of polyethylene glycol (PEG). Then the Trop2 antibody was directionally conjugated to BP via Schiff base reaction between aldehyde group from oxidized Trop2 antibody and amino group of PEG. The Trop2-functionalzied BP can significantly increase the endocytosis of BP in Trop2-positive GC cells exhibiting a reinforced antitumor activity under near infrared (NIR) irradiation. More importantly, a murine orthotopic GC model demonstrates that Trop2 antibody modification can significantly promote the accumulation of BP at tumor tissues and strengthen antitumoral activity of phototherapy. Directional conjugation of Trop2 antibody to BP facilitates the BP with superior stability, tumor targeting ability and excellent anti-tumor activity under NIR irradiation without systemic toxicity.
Asunto(s)
Carcinoma , Neoplasias Gástricas , Humanos , Animales , Ratones , Fósforo , Fototerapia , Neoplasias Gástricas/terapia , Anticuerpos , Línea Celular TumoralRESUMEN
Almonertinib was included in the first-line treatment of non-small cell lung cancer with EGFR T790M mutations by the Chinese Society of Clinical Oncology in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra-performance liquid chromatography tandem mass spectrometry method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid-liquid extraction with tert-butyl methyl ether, an XSelect HSS T3 column (2.1 × 100 mm, 2.5 µm, Waters) was used for the chromatographic separation of almonertinib and sorafenib-D3 (internal standard). The analytes were detected using an AB Sciex Triple Quad 5,500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5-200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Ratas , Animales , Espectrometría de Masas en Tándem/métodos , Voriconazol , Fluconazol/farmacología , Cromatografía Liquida/métodos , Receptores ErbB , Inhibidores de Proteínas Quinasas , Mutación , Cromatografía Líquida de Alta Presión/métodos , Reproducibilidad de los ResultadosRESUMEN
Organic-inorganic hybrid semiconductors, of which organometal halide perovskites are representative examples, have drawn significant research interest as promising candidates for next-generation optoelectronic applications. This interest is mainly ascribed to the emergent optoelectronic properties of the hybrid semiconductors that are distinct from those of their purely inorganic and organic counterparts as well as different material fabrication strategies and the other material (e.g., mechanical) properties that combine the advantages of both. Herein, we present a high-throughput first-principles material screening study of the hybrid heterostructured semiconductors (HHSs) that differ entirely from organometal halide perovskite hybrid ion-substituting semiconductors. HHSs crystallize as superlattice structures composed of inorganic tetrahedrally coordinated semiconductor sublayers and organic sublayers made of bidentate chain-like molecules. By changing the composition (e.g., IV, III-V, II-VI, I-III-VI2 semiconductor) and polymorph (e.g., wurtzite and zinc-blende) of the inorganic components, the type of organic molecules (e.g., ethylenediamine, ethylene glycol, and ethanedithiol), and the thickness of the composing layers across 234 candidate HHSs, we investigated their thermodynamic, electronic structure, and optoelectronic properties. Thermodynamic stability analysis indicates the existence of 96 stable HHSs beyond the ZnTe/ZnSe-based ones synthesized experimentally. The electronic structure and optoelectronic properties of HHSs can be modulated over a wide range by manipulating their structural variants. A machine learning approach was further applied to the high-throughput calculated data to identify the critical descriptors determining thermodynamic stability and electronic band gap. Our results indicate promising prospects and provide valuable guidance for the rational design of organic-inorganic hybrid heterostructured semiconductors for potential optoelectronic applications.
RESUMEN
The contamination of soil with organic pollutants has been accelerated by agricultural and industrial development and poses a major threat to global ecosystems and human health. Various chemical and physical techniques have been developed to remediate soils contaminated with organic pollutants, but challenges related to cost, efficacy, and toxic byproducts often limit their sustainability. Fortunately, phytoremediation, achieved through the use of plants and associated microbiomes, has shown great promise for tackling environmental pollution; this technology has been tested both in the laboratory and in the field. Plant-microbe interactions further promote the efficacy of phytoremediation, with plant growth-promoting bacteria (PGPB) often used to assist the remediation of organic pollutants. However, the efficiency of microbe-assisted phytoremediation can be impeded by (i) high concentrations of secondary toxins, (ii) the absence of a suitable sink for these toxins, (iii) nutrient limitations, (iv) the lack of continued release of microbial inocula, and (v) the lack of shelter or porous habitats for planktonic organisms. In this regard, biochar affords unparalleled positive attributes that make it a suitable bacterial carrier and soil health enhancer. We propose that several barriers can be overcome by integrating plants, PGPB, and biochar for the remediation of organic pollutants in soil. Here, we explore the mechanisms by which biochar and PGPB can assist plants in the remediation of organic pollutants in soils, and thereby improve soil health. We analyze the cost-effectiveness, feasibility, life cycle, and practicality of this integration for sustainable restoration and management of soil.
Asunto(s)
Contaminantes Ambientales , Contaminantes del Suelo , Humanos , Suelo/química , Contaminantes del Suelo/análisis , Ecosistema , Biodegradación Ambiental , Plantas , BacteriasRESUMEN
BACKGROUND: Some studies suggested an increased risk of community-acquired pneumonia (CAP) among proton pump inhibitors (PPI) users. However, the published evidence is inadequate to define the association between PPI use and the risk of CAP. OBJECTIVE: The aims of our meta-analysis were to systematically assess the association between the risk of CAP and PPI use in adults to reduce the adverse effects of PPI and ensure the safety of medication for patients. METHODS: A comprehensive literature search was conducted, published between January 1, 2004, and February 1, 2021. The primary outcome was the incidence of CAP. This meta-analysis was performed using odds ratios (ORs) with 95% CIs as effective measures; 13 studies including 2 098 804 patients were enrolled in our meta-analysis. RESULTS: Our study revealed that the incidence of CAP was higher in PPI users than non -PPI users [OR = 1.37 (95% CI = 1.22-1.53)], especially for PPI duration < 30 days [OR = 1.49 (95% CI = 1.34-1.66)]. Compared with non-PPI use, PPI use increased the incidence of CAP in the stroke disease population [OR = 1.52 (95% CI = 1.33-1.75)], but not in the liver disease population [OR = 1.13 (95% CI = 0.98-1.30)]. CONCLUSIONS AND RELEVANCE: Using PPI could increase the risk of CAP when compared to not using PPI. PPI use increased the incidence of CAP in patients with stroke. Clinicians and clinical pharmacists should weigh the benefits before medication and strictly control the indication of the prescription, so as to reduce adverse reactions.
Asunto(s)
Infecciones Comunitarias Adquiridas , Neumonía , Accidente Cerebrovascular , Adulto , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Humanos , Oportunidad Relativa , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/epidemiología , Inhibidores de la Bomba de Protones/efectos adversos , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Recognition of structure prototypes from tremendous known inorganic crystal structures has been an important subject beneficial for materials science research and new materials design. The existing databases of inorganic crystal structure prototypes were mostly constructed by classifying materials in terms of the crystallographic space group information. Herein, we employed a distinct strategy to construct the inorganic crystal structure prototype database, relying on the classification of materials in terms of local atomic environments (LAEs) accompanied by unsupervised machine learning method. Specifically, we adopted a hierarchical clustering approach onto all experimentally known inorganic crystal structure data to identify structure prototypes. The criterion for hierarchical clustering is the LAE represented by the state-of-the-art structure fingerprints of the improved bond-orientational order parameters and the smooth overlap of atomic positions. This allows us to build up a LAE-based Inorganic Crystal Structure Prototype Database (LAE-ICSPD) containing 15,613 structure prototypes with defined stoichiometries. In addition, we have developed a Structure Prototype Generator Infrastructure (SPGI) package, which is a useful toolkit for structure prototype generation. Our developed SPGI toolkit and LAE-ICSPD are beneficial for investigating inorganic materials in a global way as well as accelerating the materials discovery process in the data-driven mode.
RESUMEN
Sorafenib (SOR), an inhibitor of multiple kinases, is a classic targeted drug for advanced hepatocellular carcinoma (HCC) which often coexists with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), is widely used in patients with T2DM. Notably, co-administration of SOR with DAPA is common in clinical settings. Uridine diphosphate-glucuronosyltransferase family 1 member A9 (UGT1A9) is involved in the metabolism of SOR and dapagliflozin (DAPA), and SOR is the inhibitor of UGT1A1 and UGT1A9 (in vitro). Therefore, changes in UGT1A9 activity caused by SOR may lead to pharmacokinetic interactions between the two drugs. The objective of the current study was to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of SOR and DAPA in plasma and to evaluate the effect of the co-administration of SOR and DAPA on their individual pharmacokinetic properties and the mechanism involved. The rats were divided into four groups: SOR (100 mg/kg) alone and co-administered with DAPA (1 mg/kg) for seven days, and DAPA (1 mg/kg) alone and co-administered with SOR (100 mg/kg) for seven days. Liquid-liquid extraction (LLE) was performed for plasma sample preparation, and the chromatographic separation was conducted on Waters XSelect HSS T3 column with a gradient elution of 0.1% formic acid and 5 mM ammonium acetate (Phase A) and acetonitrile (Phase B). The levels of Ugt1a7 messenger RNA (mRNA) were determined in rat liver and intestine using quantitative real-time polymerase chain reaction (qRT-PCR). The method was successfully applied to the study of pharmacokinetic interactions. DAPA caused a significant decrease in the maximum plasma concentrations (Cmax) and the area under the plasma concentration-time curves (AUC0-t) of SOR by 41.6% and 50.5%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) significantly increased 2.85- and 1.98-fold, respectively. When co-administering DAPA with SOR, the AUC0-t and the elimination half-life (t1/2Z) of DAPA significantly increased 1.66- and 1.80-fold, respectively, whereas the CLz/F significantly decreased by 40%. Results from qRT-PCR showed that, compared with control, seven days of SOR pretreatment decreased Ugt1a7 expression in both liver and intestine tissue. In contrast, seven days of DAPA pretreatment decreased Ugt1a7 expression only in liver tissue. Therefore, pharmacokinetic interactions exist between long-term use of SOR with DAPA, and UGT1A9 may be the targets mediating the interaction. Active surveillance for the treatment outcomes and adverse reactions are required.
Asunto(s)
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Acetonitrilos , Animales , Compuestos de Bencidrilo , Carcinoma Hepatocelular/tratamiento farmacológico , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Glucosa/uso terapéutico , Glucósidos , Glucuronosiltransferasa/genética , ARN Mensajero , Ratas , Reproducibilidad de los Resultados , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Sorafenib/farmacología , Espectrometría de Masas en Tándem/métodos , Uridina DifosfatoRESUMEN
Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis, but hypertension is the most common adverse reaction. Telmisartan is an angiotensin receptor blocker used to treat hypertension. In this study, a simple ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of lenvatinib and telmisartan, and it was applied to the pharmacokinetic drug interaction study. Plasma samples were treated with acetonitrile to precipitate protein. Water (containing 5 mM of ammonium acetate and 0.1% formic acid) and acetonitrile (0.1% formic acid) were used as the mobile phases to separate the analytes with gradient elution using a column XSelect HSS T3 (2.1 mm × 100 mm, 2.5 µm). Multiple reaction monitoring in the positive ion mode was used for quantification. The method was validated and the precision, accuracy, matrix effect, recovery, and stability of this method were reasonable. The determination of analytes was not interfered with by other substances in the blank plasma, and the calibration curves of lenvatinib and telmisartan were linear within the range of 0.2-1000 ng/mL and 0.1-500 ng/mL, respectively. The results indicate that lenvatinib decreased the systemic exposure of telmisartan. Potential drug interactions were observed between lenvatinib and telmisartan.
Asunto(s)
Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Compuestos de Fenilurea/farmacocinética , Quinolinas/farmacocinética , Espectrometría de Masas en Tándem , Telmisartán/farmacocinética , Animales , Monitoreo de Drogas , Estabilidad de Medicamentos , Estructura Molecular , Compuestos de Fenilurea/química , Quinolinas/química , Ratas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Telmisartán/químicaRESUMEN
Synthetically directing T-cells against tumors emerges as a promising strategy in immunotherapy, while it remains challenging to smartly engage T cells with tunable immune response. Herein, we report an intelligent molecular platform to engineer T-cell recognition for selective activation to potently kill cancer cells. To this end, we fabricated a hybrid conjugate that uses a click-type DNA-protein conjugation to equip the T cell-engaging antibody with two distinct programmable DNA nanoassemblies. By integrating multiple aptameric antigen-recognitions within a dynamic DNA circuit, we achieved combinatorial recognition of triple-antigens on cancer cells for selective T-cell activation after high-order logic operation. Moreover, by coupling a DNA nanostructure, we precisely defined the valence of the antigen-binding aptamers to tune avidity, realizing effective tumor elimination in vitro and in vivo. Together, we present a versatile and programmable strategy for synthetic immunotherapy.
Asunto(s)
Neoplasias , Linfocitos T , Anticuerpos , Antígenos , ADN/química , Humanos , Inmunoterapia , Neoplasias/terapiaRESUMEN
The quantum confinement effect resulting from size reduction drastically alters the electronic structure and optical properties of optoelectronic materials. Quantum confinement in nanomaterials can be efficiently controlled by morphology variation combined characteristics of nanomaterials, such as their size, shape, and spatial organization. In this study, considering indium arsenide (InAs) in tetrahedral semiconductors as an example, we demonstrated the controllable morphology evolution of InAs nanostructures by tuning the growth conditions. We used the atomistic pseudopotential method to investigate the morphology-dependent electronic and optical properties of InAs nanostructures: tapered and uniform nanostructures, including the absorption spectra, single-particle energy levels, distribution and overlap integral of band-edge states, and exciton binding energies. Compared with uniform nanomaterials, a weaker quantum confinement effect was observed in the tapered nanomaterials, because of which tapered InAs nanostructures have a smaller bandgap, larger separation of photoinduced carriers, and smaller exciton binding energy. The absorption spectra of InAs nanostructures also exhibit strong morphology dependence. Our results indicate that morphology engineering can be exploited as a potential approach for modulating the electronic and optoelectronic properties of nanomaterials.