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Biomolecular condensation is a widespread mechanism of cellular compartmentalization. Because the "survival of motor neuron protein" (SMN) is implicated in the formation of three different membraneless organelles (MLOs), we hypothesized that SMN promotes condensation. Unexpectedly, we found that SMN's globular tudor domain was sufficient for dimerization-induced condensation in vivo, whereas its two intrinsically disordered regions (IDRs) were not. Binding to dimethylarginine (DMA) modified protein ligands was required for condensate formation by the tudor domains in SMN and at least seven other fly and human proteins. Remarkably, asymmetric versus symmetric DMA determined whether two distinct nuclear MLOs-gems and Cajal bodies-were separate or "docked" to one another. This substructure depended on the presence of either asymmetric or symmetric DMA as visualized with sub-diffraction microscopy. Thus, DMA-tudor interaction modules-combinations of tudor domains bound to their DMA ligand(s)-represent versatile yet specific regulators of MLO assembly, composition, and morphology.
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Arginina/análogos & derivados , Condensados Biomoleculares/metabolismo , Proteínas del Complejo SMN/química , Proteínas del Complejo SMN/metabolismo , Animales , Arginina/metabolismo , Núcleo Celular/metabolismo , Cuerpos Enrollados/metabolismo , Drosophila melanogaster/metabolismo , Células HEK293 , Células HeLa , Humanos , Ligandos , Metilación , Ratones , Modelos Biológicos , Células 3T3 NIH , Unión Proteica , Dominios Proteicos , Multimerización de Proteína , Ribonucleoproteínas Nucleares Pequeñas/metabolismoRESUMEN
The emergence of SARS-CoV-2, which is responsible for the COVID-19 pandemic, has highlighted the need for rapid characterization of viral mechanisms associated with cellular pathogenesis. Viral UTRs represent conserved genomic elements that contribute to such mechanisms. Structural details of most CoV UTRs are not available, however. Experimental approaches are needed to allow for the facile generation of high-quality viral RNA tertiary structural models, which can facilitate comparative mechanistic efforts. By integrating experimental and computational techniques, we herein report the efficient characterization of conserved RNA structures within the 5'UTR of the HCoV-OC43 genome, a lab-tractable model coronavirus. We provide evidence that the 5'UTR folds into a structure with well-defined stem-loops (SLs) as determined by chemical probing and direct detection of hydrogen bonds by NMR. We combine experimental base-pair restraints with global structural information from SAXS to generate a 3D model that reveals that SL1-4 adopts a topologically constrained structure wherein SLs 3 and 4 coaxially stack. Coaxial stacking is mediated by short linker nucleotides and allows SLs 1 to 2 to sample different cojoint orientations by pivoting about the SL3,4 helical axis. To evaluate the functional relevance of the SL3,4 coaxial helix, we engineered luciferase reporter constructs harboring the HCoV-OC43 5'UTR with mutations designed to abrogate coaxial stacking. Our results reveal that the SL3,4 helix intrinsically represses translation efficiency since the destabilizing mutations correlate with increased luciferase expression relative to wildtype without affecting reporter mRNA levels, thus highlighting how the 5'UTR structure contributes to the viral mechanism.
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Regiones no Traducidas 5' , Coronavirus Humano OC43 , ARN Viral , Coronavirus Humano OC43/genética , Luciferasas/genética , Dispersión del Ángulo Pequeño , Difracción de Rayos X , ARN Viral/genéticaRESUMEN
Beijing You Chicken, a valuable local chicken breed from Beijing, China, was once listed as an endangered breed. From the point of view of conservation, the preservation of this breed is an important task for the local researchers. Semen cryopreservation is a popular method to maintain valuable species. However, during cryopreservation, semen is susceptible to oxidative damage. Melatonin is a potent antioxidant and free radical scavenger, so it has been selected to improve the efficiency of sperm cryopreservation. In this study, the chicken semen was treated with different concentrations of melatonin in the cryopreservation solution. The results showed that melatonin at concentrations of 10-3 M and 10-5 M significantly improved sperm progressive motility and total motility, respectively, compared to the control (P < 0.05). Melatonin at 10-3 M also significantly improved the plasma membrane and acrosome integrity of spermatozoa compared to the control. The mechanisms are that melatonin significantly reduces the level of ROS and preserves sperm mitochondrial membrane potential. Most importantly, the melatonin-treated cryopreserved chicken sperm after artificial insemination significantly increased the hatching rate of chicks compared to the control (p < 0.05). The results show that melatonin has a positive effect on the quality of the cryopreserved spermatozoa. These results provide the theoretical and practical basis for using melatonin to improve Beijing You Chicken conservation, and they may also be applicable to poultry as a whole.
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Melatonina , Preservación de Semen , Masculino , Animales , Pollos , Melatonina/farmacología , Criopreservación/métodos , Semen , Beijing , Crioprotectores/farmacología , Crioprotectores/metabolismo , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides , Motilidad Espermática , Análisis de SemenRESUMEN
This study introduces a lightweight storage system for wearable devices, aiming to optimize energy efficiency in long-term and continuous monitoring applications. Utilizing Direct Memory Access and the Serial Peripheral Interface protocol, the system ensures efficient data transfer, significantly reduces energy consumption, and enhances the device autonomy. Data organization into Time Block Data (TBD) units, rather than files, significantly diminishes control overhead, facilitating the streamlined management of periodic data recordings in wearable devices. A comparative analysis revealed marked improvements in energy efficiency and write speed over existing file systems, validating the proposed system as an effective solution for boosting wearable device performance in health monitoring and various long-term data acquisition scenarios.
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Functionalized imidazo[1,2-α]pyridines are important scaffolds in pharmaceuticals. Herein, we present an efficient 3-sulfonylmethylation protocol for imidazo[1,2-α]pyridines by sodium sulfinates in DMA and H2O (2:1) via an FeCl3-catalyzed three-component coupling reaction. Various sulfonylmethyl imidazo[1,2-α]pyridines were thus afforded in high yields with excellent functional group tolerance. A plausible oxidation-addition mechanism was proposed.
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Effective density (ρeff) is one of the most important physical properties of atmospheric particles, providing important references in exploring the emissions and aging processes of fresh particles. In this study, a combined system of differential mobility analyzer, centrifugal particle mass analyzer, and condensation particle counter was used to periodically measure the ρeff of atmospheric particles in Shenzhen from Oct. 2021 to Jan. 2022. Results showed that the ρeff of particles with various size presented a bimodal distribution, which could be divided into main density (ρm, main peak, corresponding to relatively dense particles after aging) and sub density (ρs, sub peak, corresponding to fresh particles). The occurrence frequencies of ρs of particles with diameters of 50 and 80 nm were less than 20%, but were as high as about 40% of that with diameters from 120 to 350 nm. The ρm showed increasing trend with the size of particles, while ρs decreased as the increasing of the size of particles. The ρeff on pollution day varied significantly with chemical compositions. The increasing of the proportion of sulfate could promote the increasing of ρeff, while black carbon and organic matter caused opposite effects, which may be related to various factors, including the difference of the material density and morphology of various chemical components. The ρeff of 50, 80 and 120 nm particles decreased considerably during the new particle formation event, indicating that organic condensation was an important contributor to new particle growth.
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Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Tamaño de la Partícula , Aerosoles/análisis , Atmósfera , China , Monitoreo del Ambiente/métodosRESUMEN
Objective: To establish biological exposure index (BEI) of occupational exposure to arsenic and its inorganic compounds through occupational epidemiology and the regression analysis of internal and external exposure of workers. Methods: In November 2021, 125 workers with occupational exposure to arsenic and its inorganic compounds and 49 office administrators in a non-ferrous metal smelter in Yunnan Province were selected as the exposure group and control group, respectively. Air samples from the workplace of the study subjects on weekdays were collected and arsenic concentrations were determined. Urine samples were collected in end-of-work weekend and high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect the levels of trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , monomethyl arsenic (MMA) and dimethyl arsenic (DMA) in urine. The correlations between arsenic concentration in the workplace air and arsenic species in urine of workers were analyzed. Arsenic exposure concentration and the level of urinary arsenic (ΣiAs+MMA+DMA) of workers was analyzed by linear regression and the BEI of arsenic and its inorganic compounds in the workplace was proposed based on the results of micronucleus test. Results: The median of time-weighted average concentration (C(TWA)) of arsenic in the workplace air of the exposure group was 0.0116 mg/m(3), and the over-standard rate was 71.2% (89/125) . The concentrations of iAs(3+), iAs(5+), inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) ãMMAãDMA and urinary arsenic in the exposure group were higher than those in the control group at the end of shift, and the differences were statistically significant (P<0.05) . The concentration of arsenic in the workplace air had the strongest correlation with the concentration of urinary arsenic at the end of the shift (r(s)=0.909, P<0.001) . The regression equation was lg (y) =7.662+2.968lg (x) (r=0.821, P<0.05) . According to the occupational exposure limit (OEL) of arsenic in China, the concentration of urinary arsenic in the end-of-work weekend was calculated to be 53.2 µg/L. Combined with the results of micronucleus test, the BEI of occupational exposure to arsenic and its inorganic compounds in the workplace was proposed to be 50 µg/L. Conclusion: The urinary arsenic in the end-of-work weekend can be used as a biomarker of occupational exposure to arsenic, and its BEI is recommended to be 50 µg/L.
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Arsénico , Arsenicales , Exposición Profesional , Humanos , Arsénico/orina , China , Exposición Profesional/análisisRESUMEN
MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). RESULTS: Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. CONCLUSION: Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.
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Óxido Nítrico , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Biopsia , Área Bajo la Curva , ArgininaRESUMEN
Fungal pigments are characterized by a diverse set of chemical backbones, some of which present photosensitizer-like structures. From the genus Cortinarius, for example, several biologically active photosensitizers have been identified leading to the hypothesis that photoactivity might be a more general phenomenon in the kingdom Fungi. This paper aims at testing the hypothesis. Forty-eight fruiting body-forming species producing pigments from all four major biosynthetic pathways (i.e., shikimate-chorismate, acetate-malonate, mevalonate, and nitrogen heterocycles) were selected and submitted to a workflow combining in vitro chemical and biological experiments with state-of-the-art metabolomics. Fungal extracts were profiled by high-resolution mass spectrometry and subsequently explored by spectral organization through feature-based molecular networking (FBMN), including advanced metabolite dereplication techniques. Additionally, the photochemical properties (i.e., light-dependent production of singlet oxygen), the phenolic content, and the (photo)cytotoxic activity of the extracts were studied. Different levels of photoactivity were found in species from all four metabolic groups, indicating that light-dependent effects are common among fungal pigments. In particular, extracts containing pigments from the acetate-malonate pathway, e.g., extracts from Bulgaria inquinans, Daldinia concentrica, and Cortinarius spp., were not only efficient producers of singlet oxygen but also exhibited photocytotoxicity against three different cancer cell lines. This study explores the distribution of photobiological traits in fruiting body forming fungi and highlights new sources for phototherapeutics.
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Antineoplásicos , Oxígeno Singlete , Oxígeno Singlete/análisis , Extractos Vegetales , Cuerpos Fructíferos de los Hongos/químicaRESUMEN
Exposure to arsenic, an environmental contaminant, is known to cause arsenicosis and cancer. Although considerable research has been conducted to understand the underlying mechanism responsible for arsenic-induced cancers, the precise molecular mechanisms remain unknown, especially at the epigenetic regulation level. Long non-coding RNAs (LncRNAs) that have been shown to mediate various biological processes, including proliferation, apoptosis, necrosis, and mutagenesis. There are few studies on LncRNAs and biological damage caused by environmental pollutants. The LncRNAs taurine upregulated gene 1 (TUG1) regulates cell growth both in vitro and in vivo, and contributes its oncogenic role. However, the precise roles and related mechanisms of arsenic-induced cell apoptosis are still not fully understood owing to controversial findings in the literature. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed higher expression levels of TUG1 in people occupationally exposed to arsenic than in individuals living away from the source of arsenic exosure (N = 25). In addition, the results suggested that TUG1 was involved in arsenic-induced apoptosis. Furthermore, knockdown experiments showed that silencing of TUG1 markedly inhibited proliferation, whereas depletion of TUG1 led to increased apoptosis. The TUG1-small interfering RNA (siRNA) combination with arsenic (3 µM/L) slightly increased apoptosis compared with the TUG1-siRNA. Additionally, the knockdown experiments showed that the silencing of TUG1 by siRNA inhibited proliferation and promoted apoptosis by inducing p53, p-p53 (ser392), FAS, BCL2, MDM2, cleaved-caspase7 proteins in 16HBE cells. These results indicated that arsenic mediates the upregulation of TUG1 and induces cell apoptosis via activating the p53 signaling pathway.
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Arsénico , MicroARNs , ARN Largo no Codificante , Humanos , Regulación hacia Arriba , Arsénico/toxicidad , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Taurina , ARN Largo no Codificante/genética , Epigénesis Genética , Línea Celular Tumoral , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proliferación Celular , Células Epiteliales/metabolismo , Apoptosis , Transducción de Señal , MicroARNs/genéticaRESUMEN
The progressive trend of utilizing bioactive materials constitutes diverse materials exhibiting biocompatibility. The innovative aspect of this research is the tuning of the thermo-mechanical behavior of polyurethane (PU) composites with improved biocompatibility for vibrant applications. Polycaprolactone (CAPA) Mn = 2000 g-mol-1 was used as a macrodiol, along with toluene diisocyanate (TDI) and hexamethylene diisocyanate (HMDI), to develop prepolymer chains, which were terminated with 1,4 butane diol (BD). The matrix was reinforced with various concentrations of chitosan (1-5 wt %). Two series of PU composites (PUT/PUH) based on aromatic and aliphatic diisocyanate were prepared by varying the hard segment (HS) ratio from 5 to 30 (wt %). The Fourier-transformed infrared (FTIR) spectroscopy showed the absence of an NCO peak at 1730 cm-1 in order to confirm polymer chain termination. Thermal gravimetric analysis (TGA) showed optimum weight loss up to 500 °C. Dynamic mechanical analysis (DMA) showed the complex modulus (E*) ≥ 200 MPa. The scanning electron microscope (SEM) proved the ordered structure and uniform distribution of chain extender in PU. The hemolytic activities were recorded up to 15.8 ± 1.5% for the PUH series. The optimum values for the inhibition of biofilm formation were recorded as 46.3 ± 1.8% against E. coli and S. aureus (%), which was supported by phase contrast microscopy.
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Quitosano , Poliuretanos , Poliuretanos/química , Quitosano/química , Escherichia coli , Staphylococcus aureus , BioensayoRESUMEN
Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product N-nitrosamines without published AI information from animal carcinogenicity testing. Finally, a novel risk evaluation strategy for predicting and investigating the possible nitrosation of amine precursors and amine pharmaceuticals as powerful prevention of nitrosamine contamination is addressed.
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DNA double-strand breaks (DSBs) are among the deleterious lesions that are both endogenous and exogenous in origin and are repaired by nonhomologous end joining or homologous recombination. However, the molecular mechanisms responsible for maintaining genome stability remain incompletely understood. Here, we investigate the role of two E3 ligases, Dma1 and Dma2 (homologs of human RNF8), in the maintenance of genome stability in budding yeast. Using yeast spotting assays, chromatin immunoprecipitation and plasmid and chromosomal repair assays, we establish that Dma1 and Dma2 act in a redundant and a catalysis-dependent manner in the maintenance of genome stability, as well as localize to transcribed regions of the genome and increase in abundance upon phleomycin treatment. In addition, Dma1 and Dma2 are required for the normal kinetics of histone H4 acetylation under DNA damage conditions, genetically interact with RAD9 and SAE2, and are in a complex with Rad53 and histones. Taken together, our results demonstrate the requirement of Dma1 and Dma2 in regulating DNA repair pathway choice, preferentially affecting homologous recombination over nonhomologous end joining, and open up the possibility of using these candidates in manipulating the repair pathways toward precision genome editing.
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Biocatálisis , Proteínas de Ciclo Celular/metabolismo , Inestabilidad Genómica , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Reparación del ADNRESUMEN
Arsenic (As) accumulation in rice is of global concern for human health and international trade. Rice is typically reported to contain inorganic As (iAs) and dimethylated arsenate (DMA), with current food guidelines limiting toxic iAs but not less-toxic DMA. Here, we show that the highly toxic dimethylated monothioarsenate (DMMTA) is also found in rice worldwide and has been unknowingly determined as less-toxic DMA by previous routine analytical methods. Using enzymatic extraction followed by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) analysis with a C18 column, DMMTA was detected in rice grains (n = 103) from a field survey from China and in polished rice grains (n = 140) from a global market-basket survey. Concentration ranged from <0.20 to 34.8 µg/kg (median 10.3 µg/kg), accounting for 0 to 21% of total As. A strong linear correlation was observed in all rice samples between DMA and DMMTA (being 30 ± 8% of DMA) concentrations. This robust relationship allows an estimation of DMMTA in rice grains from the DMA data reported in previous market-basket surveys, showing a general global geographical pattern with DMMTA concentration increasing from the equator toward high-latitude regions. Based on the global occurrence and potential high toxicity, DMMTA in rice should be considered in health risk assessments and for setting food regulations.
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Arsénico , Arsenicales , Oryza , Arsenicales/química , Ácido Cacodílico , Cromatografía Líquida de Alta Presión , Comercio , Humanos , InternacionalidadRESUMEN
A straightforward approach for the construction of the new class of conjugated pyrans based on enamination of 2-methyl-4-pyrones with DMF-DMA was developed. 2-(2-(Dimethylamino)vinyl)-4-pyrones are highly reactive substrates that undergo 1,6-conjugate addition/elimination or 1,3-dipolar cycloaddition/elimination followed by substitution of the dimethylamino group without ring opening. This strategy includes selective transformations leading to conjugated and isoxazolyl-substituted 4-pyrone structures. The photophysical properties of the prepared 4-pyrones were determined in view of further design of novel merocyanine fluorophores. A solvatochromism was found for enamino-substituted 4-pyrones accompanied by a strong increase in fluorescence intensity in alcohols. The prepared conjugated structures demonstrated valuable photophysical properties, such as a large Stokes shift (up to 204 nm) and a good quantum yield (up to 28%).
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Piranos , Pironas , Piranos/química , Pironas/químicaRESUMEN
BACKGROUND: Freshness is an important quality of squid with respect to determining the market price. The methods of evaluation of freshness fail to be widely used as a result of the lack of rapidity and quantitation. In the present study, a rapid and non-destructive quantification of squid freshness by Fourier transform infrared spectroscopy (FTIR) spectra combined with chemometric techniques was performed. RESULTS: The relatively linear content change of trimethylamine (TMA-N) and dimethylamine (DMA-N) of squid during storage at 4 °C indicated their feasibility as a freshness indicator, as also confirmed by sensory evaluation. The spectral changes were mainly caused by the degradation of proteins and the production of amines by two-dimensional infrared correlation spectroscopy, among which TMA-N, DMA-N and putrescine were the main amines. The successive projections algorithm (SPA) was employed to select the sensitive wavenumbers to freshness for modeling prediction including partial least-squares regression, support vector regression (SVR) and back-propagation artificial neural network. Generally, the SPA-SVR model of the selected characteristic wavenumber showed a higher prediction accuracy for DMA-N (R2 P = 0.951; RMSEP = 0.218), whereas both SPA-SVR (R2 P = 0.929; RMSEP = 2.602) and Full-SVR (R2 P = 0.941; RMSEP = 2.492) models had a higher predictive ability of TMA-N. CONCLUSION: The results of the present study demonstrate that FTIR spectroscopy coupled with multivariate calibration shows significant potential for the prediction of freshness in squid. © 2021 Society of Chemical Industry.
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Decapodiformes , Alimentos Marinos , Algoritmos , Animales , Análisis de los Mínimos Cuadrados , Alimentos Marinos/análisis , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Objective: To investigate the effect of arsenic and its main metabolites on the apoptosis of human lung adenocarcinoma cell line A549 and the expression of pro-apoptotic genes Bad and Bik. Methods: In October 2020, A549 cells were recovered and cultured, and the cell viability was detected by the cell counting reagent CCK-8 to determine the concentration and time of sodium arsenite exposure to A549. The study was divided into NaAsO(2) exposure groups and metobol: le expoure groups: the metabolite comparison groups were subdivided into the control group, the monomethylarsinic acid exposure group (60 µmol/L) , and the dimethylarsinic acid exposure group (60 µmol/L) ; sodium arsenite dose groups were subdivided into 4 groups: control group (0) , 20, 40, 60 µmol/L sodium arsenite NaAsO(2). Hoechst 33342/propidium iodide double staining (Ho/PI) was used to observe cell apoptosis and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of Bad and Bik mRNA in cells after exposure. Western blotting was used to detect the protein expressions of Bad, P-Bad-S112, Bik, cleaved Bik and downstream proteins poly ADP-ribose polymerase PARP1 and cytochrome C (Cyt-C) , using spectrophotometry to detect the activity changes of caspase 3, 6, 8, 9. Results: Compared with the control group, the proportion of apoptotic cells in the 20, 40, and 60 µmol/L NaAsO(2) dose groups increased significantly (P<0.01) , and the expression levels of Bad, Bik mRNA, the protein expression levels of Bad, P-Bad-S112, Bik, cleaved Bik, PARP1, Cyt-C were increased (all P<0.05) , and the activities of Caspase 3, 6, 8, and 9 were significantly increased with significantly differences (P<0.05) . Compared with the control group, the expression level of Bad mRNA in the DMA exposure group (1.439±0.173) was increased with a significant difference (P=0.024) , but there was no significant difference in the expression level of Bik mRNA (P=0.788) . There was no significant differences in the expression levels of Bad and Bik mRNA in the poison groups (P=0.085, 0.063) . Compared with the control group, the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to MMA were 0.696±0.023, 0.707±0.014, 0.907±0.031, 1.032±0.016, and there was no significant difference between the two groups (P=0.469, 0.669, 0.859, 0.771) ; the gray values of proteins Bad, Bik, PARP1 and Cyt-C exposed to DMA were 0.698±0.030, 0.705±0.022, 0.908±0.015, 1.029±0.010, and there was no difference between the two groups (P=0.479, 0.636, 0.803, 0.984) . Conclusion: Sodium arsenite induces the overexpression of Bad and Bik proteins, initiates the negative feedback regulation of phosphorylated Bad and the degradation of Bik, activates the downstream proteins PARP1, Cyt-C and Caspase pathways, and mediates the apoptosis of A549 cells.
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Arsénico , Venenos , Células A549 , Adenosina Difosfato Ribosa/farmacología , Apoptosis , Proteínas Reguladoras de la Apoptosis , Arsenitos , Ácido Cacodílico/farmacología , Caspasa 3 , Caspasas/farmacología , Citocromos c/farmacología , Humanos , Proteínas Mitocondriales/farmacología , Propidio/farmacología , ARN Mensajero , Sincalida/farmacología , Compuestos de Sodio , Proteína Letal Asociada a bcl/metabolismoRESUMEN
Progress in metal-organic frameworks (MOFs) has advanced from fundamental chemistry to engineering processes and applications, resulting in new industrial opportunities. The unique features of MOFs, such as their permanent porosity, high surface area, and structural flexibility, continue to draw industrial interest outside the traditional MOF field, both to solve existing challenges and to create new businesses. In this context, diverse research has been directed toward commercializing MOFs, but such studies have been performed according to a variety of individual goals. Therefore, there have been limited opportunities to share the challenges, goals, and findings with most of the MOF field. In this review, we examine the issues and demands for MOF commercialization and investigate recent advances in MOF process engineering and applications. Specifically, we discuss the criteria for MOF commercialization from the views of stability, producibility, regulations, and production cost. This review covers progress in the mass production and formation of MOFs along with future applications that are not currently well known but have high potential for new areas of MOF commercialization.
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Gas-phase electrophoresis yields size distributions of polydisperse, aerosolized analytes based on electrophoretic principles. Nanometer-sized, surface-dry, single-charged particles are separated in a high laminar sheath flow of particle-free air and an orthogonal tunable electric field. Additionally, nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyzer (nES GEMMA) data are particle-number based. Therefore, small particles can be detected next to larger ones without a bias, for example, native proteins next to their aggregates. Analyte transition from the liquid to the gas phase is a method inherent prerequisite. In this context, nonvolatile sample buffers influence results. In the worst case, the (bio-)nanoparticle signal is lost due to an increased baseline and unspecific clustering of nonvolatile components. We present a novel online hyphenation of liquid chromatography and gas-phase electrophoresis, coupling a size-exclusion chromatography (SEC) column to an advanced nES GEMMA. Via this novel approach, it is possible to (i) separate analyte multimers already present in liquid phase from aggregates formed during the nES process, (ii) differentiate liquid phase and spray-induced multimers, and (iii) to remove nonvolatile buffer components online before SEC-nES GEMMA analysis. Due to these findings, SEC-nES GEMMA has the high potential to help to understand aggregation processes in biological buffers adding the benefit of actual size determination for noncovalent assemblies formed in solution. As detection and characterization of protein aggregation in large-scale pharmaceutical production or sizing of noncovalently bound proteins are findings directly related to technologically and biologically relevant situations, we proposed the presented method to be a valuable addition to LC-MS approaches.
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Cromatografía en Gel , Electroforesis , Agregado de Proteínas , ProteínasRESUMEN
Purpose: Even though differences between deciduous and permanent dentin have been widely studied, their dynamic mechanical behavior has never been compared. The objective of the present study was to quantify the differences between deciduous and permanent dentin under cyclic mechanical loading, which is similar to masticatory stress.Materials and Methods: Deciduous and permanent teeth, respectively from children (9 ~ 12 years old) and young people (18 ~ 25 years old), were wet-sectioned perpendicular to the longitudinal axis and the central specimens of coronal dentin were evaluated by nanoscopic dynamic mechanical analysis (nanoDMA).Results: The average storage, loss, and complex moduli, as well as the hardness of deciduous dentin were signiï¬cantly (p < 0.05) lower than those of permanent dentin. Moreover, the tan δ value of permanent dentin was significantly (p < 0.05) lower than that of deciduous dentin across the loading frequency range, indicating that viscoelastic behavior and loss of elastic energy were significantly reduced in the stiffer permanent dentin. All the nanoDMA responses showed a significant influence of the dynamic loading frequency (p < 0.05): Both deciduous and permanent dentin showed reduced viscoelasticty with increased loading frequencies.Conclusions: Compared with deciduous dentin, permanent dentin exhibits higher stiffness with reduced energy loss during deformation, and therefore superior mechanical characteristics for the mastication process.