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Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint inhibitors (ICIs) that may facilitate HER2-positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen-enhanced photodynamic therapy (PDT) increases immunogenic cell death (ICD), providing a promising strategy to render the tumor microenvironment more sensitive to the ICIs. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) obtained using nanobubbles (NBs) water for oxygen delivery in vivo can facilitate enhanced PDT. Here, dual-receptor targeted Lipo-NBs-O2 (DRT@Lipo-NBs-O2) is prepared by modifying Lipo-NBs-O2 with anti-PDL1 scFv and the fusion protein anti-HER2 scFv-tandem-repeat cytochrome c (anti-HER2-nCytc). Copper phthalocyanine is the photosensitizer (PS). DRT@Lipo-PS-NBs-O2 plus near-infrared irradiation leads to robust ICD induction, increasing DC activation and CD8+ T-cell numbers. Modification with anti-PDL1 scFv improves tumor distribution of DRT@Lipo-PS-NBs-O2 and plays the ICI role, invigorating CD8+ T cells and boosting the effects of immunotherapy. Oxygen supplied through DRT@Lipo-PS-NBs-O2 reduces P-glycoprotein expression. Enhanced PDT and Cytc can cause tumor cell death, thereby reducing the immune burden. Under dual receptor targeting and laser local irradiation, tumor cells become subject to the combination effects of PDT, ICD, ICIs, and apoptosis; this effectively suppresses tumor growth and metastasis. Lipo-NBs-O2 affords a combination of oxygen delivery and multidrug therapy to alleviate HER2-positive breast cancer.
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The subfamily Agavoideae comprises crassulacean acid metabolism (CAM), C3, and C4 plants with a young age of speciation and slower mutation accumulation, making it a model crop for studying CAM evolution. However, the genetic mechanism underlying CAM evolution remains unclear because of lacking genomic information. This study assembled the genome of Agave hybrid NO.11648, a constitutive CAM plant belonging to subfamily Agavoideae, at the chromosome level using data generated from high-throughput chromosome conformation capture, Nanopore, and Illumina techniques, resulting in 30 pseudo-chromosomes with a size of 4.87 Gb and scaffold N50 of 186.42 Mb. The genome annotation revealed 58 841 protein-coding genes and 76.91% repetitive sequences, with the dominant repetitive sequences being the I-type repeats (Copia and Gypsy accounting for 18.34% and 13.5% of the genome, respectively). Our findings also provide support for a whole genome duplication event in the lineage leading to A. hybrid, which occurred after its divergence from subfamily Asparagoideae. Moreover, we identified a gene duplication event in the phosphoenolpyruvate carboxylase kinase (PEPCK) gene family and revealed that three PEPCK genes (PEPCK3, PEPCK5, and PEPCK12) were involved in the CAM pathway. More importantly, we identified transcription factors enriched in the circadian rhythm, MAPK signaling, and plant hormone signal pathway that regulate the PEPCK3 expression by analysing the transcriptome and using yeast one-hybrid assays. Our results shed light on CAM evolution and offer an essential resource for the molecular breeding program of Agave spp.
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Aging is a multifactorial biological process involving chronic diseases that manifest from the molecular level to the systemic level. From its inception to 31 May 2022, this study searched the PubMed, Web of Science, EBSCO, and Cochrane library databases to identify relevant research from 15,983 articles. Multiple approaches have been employed to combat aging, such as dietary restriction (DR), exercise, exchanging circulating factors, gene therapy, and anti-aging drugs. Among them, anti-aging drugs are advantageous in their ease of adherence and wide prevalence. Despite a shared functional output of aging alleviation, the current anti-aging drugs target different signal pathways that frequently cross-talk with each other. At present, six important signal pathways were identified as being critical in the aging process, including pathways for the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), nutrient signal pathway, silent information regulator factor 2-related enzyme 1 (SIRT1), regulation of telomere length and glycogen synthase kinase-3 (GSK-3), and energy metabolism. These signal pathways could be targeted by many anti-aging drugs, with the corresponding representatives of rapamycin, metformin, acarbose, nicotinamide adenine dinucleotide (NAD+), lithium, and nonsteroidal anti-inflammatory drugs (NSAIDs), respectively. This review summarized these important aging-related signal pathways and their representative targeting drugs in attempts to obtain insights into and promote the development of mechanism-based anti-aging strategies.
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BACKGROUND: Purple curl leaf disease brings a significant threat to the development of agave industry, the underlying mechanism of disease-resistant Agave sisalana. hybrid 11648 (A. H11648R) is still unknown. RESULTS: To excavate the crucial disease-resistant genes against purple curl leaf disease, we performed an RNA-seq analysis for A.H11648R and A.H11648 during different stages of purple curl leaf disease. The DEGs (differentially expressed genes) were mainly enriched in linolenic acid metabolism, starch and sucrose mechanism, phenylpropanoid biosynthesis, hypersensitive response (HR) and systemic acquired resistance. Further analysis suggested that eight candidate genes (4'OMT2, ACLY, NCS1, GTE10, SMO2, FLS2, SQE1 and RCOM) identified by WGCNA (weighted gene co-expression network analysis) may mediate the resistance to agave purple curl disease by participating the biosynthesis of benzylisoquinoline alkaloids, steroid, sterols and flavonoids, and the regulation of plant innate immunity and systemic acquired resistance. After qPCR verification, we found that AsRCOM, coding a glycosyltransferase and relevant to the regulation of plant innate immunity and systemic acquired resistance, may be the most critical disease-resistant gene. Finally, the overexpression of AsRCOM gene in agave could significantly enhance the resistance to purple curl disease with abundant reactive oxygen species (ROS) accumulations. CONCLUSIONS: Integrative RNA-seq analysis found that HR may be an important pathway affecting the resistance to purple curl leaf disease in agave, and identified glycosyltransferase AsRCOM as the crucial gene that could significantly enhance the resistance to purple curl leaf disease in agave, with obvious ROS accumulations.
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Agave , Agave/genética , Especies Reactivas de Oxígeno , Perfilación de la Expresión Génica , Inmunidad de la Planta/genética , Hojas de la Planta/genética , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genéticaRESUMEN
BACKGROUND: Glutamate stimuli and hyperactivation of its receptor are predominant determinants of ischemia-induced cytotoxic cerebral edema, which is closely associated with protein nanoparticle (PN)-induced increases in osmotic pressure. Herein, we investigated the electrochemical and mechanical mechanisms underlying the neuron swelling induced by PNs via the co-activation of N-methyl-D-aspartate receptor subunit (NMDAR) and excitatory metabotropic glutamate receptors (mGluRs). RESULTS: We observed that co-activation of ionic glutamate receptor NMDAR and Group I metabotropic mGluRs promoted alteration of PN-induced membrane potential and increased intracellular osmosis, which was closely associated with calcium and voltage-dependent ion channels. In addition, activation of NMDAR-induced calmodulin (CaM) and mGluR downstream diacylglycerol (DAG)/protein kinase C α (PKCα) were observed to play crucial roles in cytotoxic hyperosmosis. The crosstalk between CaM and PKCα could upregulate the sensitivity and sustained opening of sulfonylurea receptor 1 (SUR1)-transient receptor potential cation channel subfamily M member 4 (TRPM4) and transmembrane protein 16 A (TMEM16A) channels, respectively, maintaining the massive Na+/Cl- influx, and the resultant neuron hyperosmosis and swelling. Intracellular PNs and Na+/Cl- influx were found to be as potential targets for cerebral edema treatment, using the neurocyte osmosis system and a cerebral ischemic rat model. CONCLUSIONS: This study highlights PNs as a key factor in "electrochemistry-tension" signal transduction controlling Na+/Cl- ion channels and increased osmotic pressure in ischemia-induced cytotoxic edema. Moreover, enhanced sensitivity in both Na+ and Cl- ion channels also has a crucial role in cerebral edema.
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Edema Encefálico , Nanopartículas , Receptores de Glutamato Metabotrópico , Canales Catiónicos TRPM , Ratas , Animales , Receptores de N-Metil-D-Aspartato/fisiología , Receptores de Glutamato Metabotrópico/metabolismo , Presión Osmótica , Proteína Quinasa C-alfa/metabolismo , Edema , Isquemia , Canales Catiónicos TRPM/metabolismoRESUMEN
Ecological water resources occupy a vital position in the national economy; without sufficient ecological water resources, the construction and economic development of sponge cities would be seriously restricted. Appropriately, the Chinese government proposed that sponge city planning should be carried out in accordance with the number of available ecological water resources. The government therefore put forward the method of conservation and intensification to solve the problem of water shortage. This paper highlights the interactions between ecological water resources, sponge cities, and economic development in northern China, starting with the interaction and mechanism of action that concerns ecological water resource utilization, sponge cities, and economic development. In the empirical test, the dynamic changes of the three indicators were analyzed empirically using the panel data vector autoregression method, and the dynamic relationship of each factor was measured using generalized moment estimation. It was found that ecological water resources are a key factor in promoting regional economic development, and the relationship between ecological water resources and sponge cities is both supportive and constraining; therefore, the constraints that ecological water resources place on sponge cities also indirectly affects economic development. To disconnect the use of water and ecological resources from economic development, it is necessary to note the following: the feedback effect of economic development and the resolution of the contradiction between sponge cities, water, and ecological resource use.
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Ecosistema , Agua , Ciudades , Recursos Hídricos , Planificación de Ciudades , Desarrollo Económico , China , Conservación de los Recursos Naturales/métodos , EcologíaRESUMEN
Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan-Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610-2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325-2.104). It also suggests the metabolic specificity of this population.
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Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Índice de Masa Corporal , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Rodents, such as mice, are vulnerable targets, and potential intermediate hosts, of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, and Omicron. N501Y in the receptor-binding domain (RBD) of Spike protein is the key mutation dictating the mouse infectivity, on which the neighboring mutations within RBD have profound impacts. However, the impacts of mutations outside RBD on N501Y-mediated mouse infectivity remain to be explored. RESULTS: Herein, we report that two non-RBD mutations derived from mouse-adapted strain, Ins215KLRS in the N-terminal domain (NTD) and H655Y in the subdomain linking S1 to S2, enhance mouse infectivity in the presence of N501Y mutation, either alone or together. This is associated with increased interaction of Spike with mouse ACE2 and mutations-induced local conformation changes in Spike protein. Mechanistically, the H655Y mutation disrupts interaction with N657, resulting in a less tight loop that wraps the furin-cleavage finger; and the insertion of 215KLRS in NTD increases its intramolecular interaction with a peptide chain that interfaced with the RBD-proximal region of the neighboring protomer, leading to a more flexible RBD that facilitates receptor binding. Moreover, the Omicron Spike that contains Ins214EPE and H655Y mutations confer mouse infectivity > 50 times over the N501Y mutant, which could be effectively suppressed by mutating them back to wild type. CONCLUSIONS: Collectively, our study sheds light on the cooperation between distant Spike mutations in promoting virus infectivity, which may undermine the high infectiousness of Omicron variants towards mice.
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COVID-19 , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/genética , Animales , Ratones , Mutación , Unión Proteica , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
The Fas-associated death domain (FADD) has long been regarded as a crucial adaptor protein in the extrinsic apoptotic pathway. Despite the non-apoptotic function of FADD is gradually being discovered and confirmed, its corresponding physiological and pathological significance is still unclear. Based on the database of GWAS catalog and GTEx Portal, 17 SNPs associated with leukemia susceptibility were found to be linked to FADD expression. We then investigated a regulatory role of FADD in T-acute lymphoblastic leukemia (T-ALL) using Jurkat cells as a model. Jurkat cells stably depleted of FADD (FADD-/- Jurkat) expression exhibited dampened proliferation, hypersensitivity to Etoposide-induced intrinsic apoptosis whereas near total resistance to TRAIL-induced extrinsic apoptosis. Comparison between wild type and FADD-/- Jurkat cells using iTRAQ-based proteomics revealed considerably altered expression spectrum of genes, and led us to focus on metabolic pathways. Investigation of glycolytic and mitochondrial pathways and relevant enzymes revealed that FADD knockout triggered a metabolic shift from glycolysis to mitochondrial respiration in Jurkat cells. Re-expression of FADD in FADD-/- Jurkat cells partially rescued glycolytic capacity. FADD loss triggers global metabolic reprogramming in Jurkat cells and therefore remains as a potential druggable target for ALL treatment.
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Apoptosis , Proteína de Dominio de Muerte Asociada a Fas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Apoptosis/genética , Proteína de Dominio de Muerte Asociada a Fas/genética , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Glucólisis/genética , Humanos , Células Jurkat , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
Direct quantitative analysis of soil polypropylene microplastics (MPs) via thermal method is still a challenge due to its sensitivity to the soil matrix during the thermal decomposition. In this work, the impact of soil organic matter (SOM) on MPs decomposition in real soil was estimated, and high SOM contents was found have significantly negative effect on the qualitative and quantitative analysis of PP. To solve this problem, a salt crust-assisted thermal decomposition method was developed to reduce the soil matrix effect. By adding salt solution and heating in appropriate temperature program, salt crust can be formed between MPs and soil matrix to isolate PP MPs and soils during the heating process, and thereby to avoid the influence of SOM. Thermal desorption/decomposition coupling with headspace solid phase microextraction (HS-SPME) was used extraction of MPs decomposition products. All the thermal decomposition products of PP were identified, several alkenes and dialkenes were selected as candidates for quantitative analysis, and 2,4,6,8,10-pentamethyltridec-1-ene with optimal linearity was finally established for quantification. Besides, this method was also established for simultaneous determination of PP MPs and organic contaminants (OCs) including PCBs and PAHs, since it is capable of providing a new approach for investigation of their interaction in real soil environment. A theoretical LOD of 0.002 wt% was obtained for PP MPs, and the LOD of OCs ranges from 0.05 to 1.87 ng/g. Determination of aged soil samples reveal that adsorption of OCs is not a predominating effect of MPs in soil environment, and MPs contaminants may reduce the soil retention capacity. This method provides a new approach for direct quantification of soil PP MPs, and applicable for investigation of the interactions between MPs and OCs in real soils.
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Microplásticos , Contaminantes del Suelo , Plásticos , Polipropilenos , Suelo , Contaminantes del Suelo/análisisRESUMEN
The review aimed to investigate the accuracy of breath tests in the diagnosis of diabetes mellitus, identify exhaled volatile organic compounds with the most evidence as potential biomarkers, and summarize prospects and challenges in diabetic breath tests. Databases including Medline, PubMed, EMBASE, Cochrane Library and Science Citation Index Expanded were searched. Human studies describing diabetic breath analysis with more than 10 subjects as controls and patients were included. Population demographics, breath test conditions, biomarkers, analytical techniques and diagnostic accuracy were extracted. Quality assessment was performed with the Standards for Reporting Diagnostic Accuracy and a modified QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Forty-four research with 2699 patients with diabetes were included for qualitative data analysis and 14 eligible studies were used for meta-analysis. Pooled analysis of type 2 diabetes breath test exhibited sensitivity of 91.8% (95% CI 83.6% to 96.1%), specificity of 92.1% (95% CI 88.4% to 94.7%) and area under the curve (AUC) of 0.96 (95% CI 0.94 to 0.97). Isotopic carbon dioxide (CO2) showed the best diagnostic accuracy with pooled sensitivity of 0.949 (95% CI 0.870 to 0.981), specificity of 0.946 (95% CI 0.891 to 0.975) and AUC of 0.98 (95% CI 0.97 to 0.99). As the most widely reported biomarker, acetone showed moderate diagnostic accuracy with pooled sensitivity of 0.638 (95% CI 0.511 to 0.748), specificity of 0.801 (95% CI 0.691 to 0.878) and AUC of 0.79 (95% CI 0.75 to 0.82). Our results indicate that breath test is a promising approach with acceptable diagnostic accuracy for diabetes mellitus and isotopic CO2 is the optimal breath biomarker. Even so, further validation and standardization in subject control, breath sampling and analysis are still required.
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Pruebas Respiratorias , Diabetes Mellitus Tipo 2 , Biomarcadores , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Estándares de ReferenciaRESUMEN
Breath analysis is a promising method for metabolomics studies and clinical diagnosis, as it enables the observation of metabolites in a convenient and noninvasive way. In this work, an atmospheric pressure photoionization (APPI) source was modified for online analysis of exhaled breath by coupling with quadrupole time-of-flight mass spectrometry (QTOFMS). Three parameters, namely, the capillary voltage, the sampling flow and the curtain gas flow of the APPI source, were optimized. Five healthy volunteers, three males and two females, were enrolled to test the performance of modified APPI-QTOFMS by analyzing their exhaled breath. A total of 21 compounds were tentatively identified, and four metabolites, namely, dimethyl selenoxide, δ-valerolactam, hydroxymandelic acid and palmitic amide were detected in the exhaled breath for the first time. The result shows that modified APPI-QTOFMS can be used for the online study of exhaled breath. Graphical abstract.
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Pruebas Respiratorias/instrumentación , Espectrometría de Masas/instrumentación , Presión Atmosférica , Diseño de Equipo , Espiración , Femenino , Humanos , Lactamas/análisis , Masculino , Metabolómica/instrumentación , Compuestos de Organoselenio/análisis , Óxidos/análisisRESUMEN
To investigate pollution from phthalate esters (PAEs) in the soils of the West Lake Scenic Area, Hangzhou, Zhejiang province, a total of 42 samples were collected from 4 species of soil with different uses. The concentrations and composition of 6 PAEs were analyzed by gas chromatography triple quadrupole mass spectrometry (GC-MS/MS). The sources and spatial distribution of PAEs in the different soil species were analyzed using Principal Component Analysis (PCA) and Ordinary Kriging (OK) methods. It was found that the total concentrations of the 6 PAEs (ΣPAEs) ranged from 597.6 µg·kg-1 to 7360.1 µg·kg-1, of which Dimethyl Phthalate (DMP), Di-n-buthyl Phthalate (DBP), and Di-(2-ethylhexyl) Phthalate (DEHP) were most abundant (98.43% of ΣPAEs). As major pollutant, DEHP contributed as much as 66.28% to ΣPAEs. The composition of PAEs in different soil species differed due to source differences; transportation and tourist activities were the main sources of these PAEs. The 6 PAEs were mainly distributed in the northwestern portion of the West Lake Scenic Area, decreasing from north to south and from east to west.
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Lacking macroscopic plasticity severely limits structure applications of bulk metallic glasses (BMGs). In general, particle-reinforced BMGs have an enhanced ductility but show reduced strength, whereas body-centered-cubic CuZr phase (B2 phase)-reinforced bulk MGs display improved ductility and strength. The underlying reason for the improvement in B2 phase-reinforced BMGs is still ambiguous. Herein, the atomic arrangement in Cu48Zr48Al4 BMGs with and without the B2 phase under tensile deformation is studied using molecular dynamics simulation. Different from pure MG where shear transformation zones (STZs) are activated along the same direction to form the domain shear band, STZs in the B2 phase-reinforced MG are activated along different directions disturbing the formation of a domain shear band. More plastic deformation and increased stress are allowed because of the phase transformations of B2 phases. The revealed deformation mechanism of B2 phase-reinforced MGs enables us to design heterogeneous structures with excellent strength and toughness.
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Direct analysis and identification of biological tissue is significant for clinical applications. In this study, porcine liver and kidney have been analyzed using laser ablation electrospray ionization time-of-flight mass spectrometry (LAESI-TOFMS). This method showed good reproducibility for the same types of tissue and is capable of distinguishing different tissue species. The margin assessment was also performed using porcine renal tissue, and the response time was less than 6 s. Furthermore, human hepatocarcinoma tissue and normal tissue were identified using this method. Our results indicate that LAESI-TOFMS is a feasible approach for direct identification of tumor tissue and potential for assessment of the resection margin.
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A solvent-assisted vacuum desorption method is developed and combined with gas chromatography-tandem mass spectrometry (GC-MS/MS) for quick determination of soil PAHs. With the assistance of a reduced pressure of 0.0001â¯kPa and the DMSO/acetone (1:1) mixed solvent, this method allows desorption of PAHs in a moderate temperature of 160 °C. Analytes were trapped in a collection tube and eluted with n-hexan for GC-MS/MS analysis. The entire procedure can be completed within 20 min. In order to validate this method for determining soil PAHs, the solvent-assisted vacuum desorption method, Soxhlet extraction and ASE extraction were applied in different samples of real contaminated soils. Most HMW PAHs showed similar concentrations, yet LMW PAHs with solvent-assisted vacuum desorption presented significantly higher concentrations than those with conventional methods, such as NAP, ANY, ANA and FLU. Further investigation revealed that solvent-assisted vacuum desorption is capable of improving both the extractability and collection efficiency of those four LMW PAHs in real contaminated soil. This method enables desorption of HMW PAHs and provides the additional benefit of improved extractability and collection efficiency for LMW PAHs.
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Monitoreo del Ambiente/métodos , Cromatografía de Gases y Espectrometría de Masas , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/análisis , Suelo/química , Solventes/química , VacioRESUMEN
In this study, we identified a "black dot"-like cell culture contaminant as a species belonging to the genus of Pusillimonas using 16S rDNA sequencing. Among all antibiotics tested, a combinatorial treatment of ampicillin and gentamicin both at 100 µg/mL was able to eliminate this contaminant. The contaminant was then visualized by fluorescence microscopy using propidium iodide staining and was found inside the cytosol of contaminated A549 cells. To characterize the efficacy of antibiotics for contaminant removal, we devised a quantitative method to determine the average number of 16S rDNA copies associated with a single A549 cell, which is directly proportional to the average number of contaminant per A549 cell. By using primers specific to the 16S rDNA sequence of the contaminant, we were able to estimate contaminants per single contaminated cell using both qPCR-based relative and absolute quantification.
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Técnicas de Cultivo de Célula , ARN Ribosómico 16S/análisis , Células A549 , Humanos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Nitrogen-containing compounds are important components in human breath. However, their origins have not yet been clearly understood. In this study, a modified electrospray ionization (ESI) source coupling with quadrupole time-of-flight mass spectrometry has been used for breath analysis. Fourteen nitrogen-containing compounds were identified in mouth-exhaled breath, and 10 of them were from the oral cavity and oropharynx. Moreover, 8 of these nitrogen-containing compounds were recognized as endogenous metabolites. This result provides important clues for exploring the biological origins of these nitrogen-containing compounds. Observation of the ion suppression phenomenon also indicates that breath analysis should be carried out after clearing of the oral cavity and oropharynx, or directly through nose-breathing to eliminate the influence of those nitrogen-containing compounds from the oral cavity.
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Pruebas Respiratorias/métodos , Espiración , Boca , Compuestos de Nitrógeno/análisis , Espectrometría de Masa por Ionización de Electrospray , Humanos , Compuestos de Nitrógeno/químicaRESUMEN
A highly sensitive portable piezoresistive sensor with a fast response time in an extended linear working range is urgently needed to meet the rapid development of artificial intelligence, interactive human-machine interfaces, and ubiquitous flexible electronics. However, it is a challenge to rationally couple these figures of merit (sensitivity, response time, and working range) together as they typically show functionally correlative behavior in the sensor. Here, we aim at introducing the hierarchical pores across several size orders from micro- to larger scale into the intrinsically flexible graphene-based electrode materials that overcome this limitation of the sensor. We achieved a flexible sensor with a prominent sensitivity of 11.9 kPa-1 in the linear range of 3 Pa to â¼21 kPa and a rapid response time of 20 ms to positively monitor the pulse rate, voice recognition, and true force value for biomedical and interactive human-machine interface application assisted by an analog-digital converter. More interesting is the carbon-nanotube-doped graphene that also served as the electrode in the waterproof supercapacitor to actively drive the sensor as a whole flexible system. We believe our findings not only offer a general strategy for the graphene-based platform in flexible electronics but also possess other intriguing potential in functional application such as the heat dissipation component in electron devices or seawater filtration in environment application.
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In this study, we explored the therapeutic potential of microRNA (miR) analogs against non-small-cell lung cancer (NSCLC) using lentiviral delivery of short hairpin RNA (shRNA). By using A549 as a model cell line, we used analogs and mimics of miR-4319/miR-125-5p to target the tumorigenic RAF1 gene. Lentiviral vectors carrying shRNA of a highly efficient miRNA analog of miR-4319/miR-125-5p, Analog2, were constructed to infect A549 cells. Our results showed that, compared with the noncancerous bronchial epithelial cell line 16HBE, lentivirus delivering Analog2 shRNA induced significant G2/M arrest and subsequent apoptosis in A549 cells, but not in 16HBE cells. Western blot analysis revealed that key factors regulating cell cycle were downregulated following RAF1 inhibition. In vivo xenograft experiments showed that lentivirus carrying Analog2 shRNA markedly decreased tumor size. Therefore, lentiviral delivery of Analog2 shRNA is a valid RNA interference-based treatment against NSCLC with high potency and specificity.