RESUMEN
In this work, we demonstrate how the ion association constant can be attributed to the difference between the full Poisson-Boltzmann equation and its linearized version in very dilute solutions. We follow a pragmatic approach first by deriving an analytical approximated solution to the Poisson-Boltzmann equation, then calculating its respective Helmholtz free energy and activity coefficient, and then finally comparing it to the contribution from the mass action law principle. The final result is the Ebeling association constant. We conclude that electrostatic ion-ion interaction models miss the ion association contribution naturally introduced in higher-order electrostatic theories. We also demonstrate how the negative deviations from the Debye-Hückel limiting law can be physically attributed to the ion association phenomenon.
RESUMEN
Water is one of the most abundant substances on earth, but it is still not entirely understood. It shows unusual behavior, and its properties present characteristic extrema unlike any other fluid. This unusual behavior has been linked to the two-state theory of water, which proposes that water forms different clusters, one with a high density and one with a low density, which may even form two distinct phases at low temperatures. Models incorporating the two-state theory manage to capture the unusual extrema of water, unlike traditional equations of state, which fail. In this work, we have derived the framework to incorporate the two-state theory of water into the Statistical-Associating-Fluid-Theory (SAFT). More specifically, we have assumed that water is an ideal solution of high density water molecules and low density water molecules that are in chemical equilibrium. Using this assumption, we have generalized the association term SAFT to allow for the simultaneous existence of the two water types, which have the same physical parameters but different association properties. We have incorporated the newly derived association term in the context of the Perturbed Chain-SAFT (PC-SAFT). The new model is referred to as PC-SAFT-Two-State (PC-SAFT-TS). Using PC-SAFT-TS, we have succeeded in predicting the characteristic extrema of water, such as its density and speed of sound maximum, etc., without loss of accuracy compared to the original PC-SAFT. This new framework is readily extended to mixtures, and PC-SAFT-TS manages to capture the solubility minimum of hydrocarbons in water in a straightforward manner.
RESUMEN
Thermodynamic and dynamic anomalies of water play a crucial role in supporting life on our planet. The two-state theory attributes these anomalies to a dynamic equilibrium between locally favored tetrahedral structures (LFTSs) and disordered normal liquid structures. This theory provides a straightforward, phenomenological explanation for water's unique thermodynamic and dynamic characteristics. To validate this two-state feature, it is critical to unequivocally identify these structural motifs in a dynamically fluctuating disordered liquid. In this study, we employ a recently introduced structural parameter (θavg) that characterizes the local angular order within the first coordination shell to identify these LFTSs through molecular dynamics simulations. We employ both realistic water models with a liquid-liquid critical point (LLCP) and a coarse-grained water model without an LLCP to study water's anomalies in low-pressure regions below 2 kbar. The two-state theory consistently describes water's thermodynamic anomalies in these models, both with and without an LLCP. This suggests that the anomalies predominantly result from the two-state features rather than criticality, particularly within experimentally accessible temperature-pressure regions.
RESUMEN
Microwave photonic phase detectors (MPPDs) can extract ultrastable microwaves from a mode-locked laser (MLL), but their frequencies are often limited by the pulse repetition rate. Few works studied methods to break the frequency limitation. Here, a setup based on an MPPD and an optical switch is proposed to synchronize an RF signal from a voltage-controlled oscillator (VCO) to an interharmonic of an MLL and to realize the pulse repetition rate division. The optical switch is employed to realize pulse repetition rate division, and the MPPD is followed to detect the phase difference between the frequency-divided optical pulse and the microwave signal from the VCO, which is then fed back to the VCO via a proportional-integral (PI) controller. Both the optical switch and the MPPD are driven by the signal from the VCO. When the system reaches its steady state, the synchronization and repetition rate division are achieved simultaneously. An experiment is conducted to verify the feasibility. The 80½th, 80â rd, and 80â rd interharmonics are extracted, and pulse repetition rate division factors of two and three are realized. The phase noises at offset frequency of 10â kHz are improved by more than 20â dB.
RESUMEN
The occurrence and progression of colorectal cancer (CRC) are closely related to intestinal microecological disorders. Butyrate, the representative of short chain fatty acids, possess anti-inflammatory and antioxidant effects, and its antitumor effect has been gradually paid attention to. In this study, azoxymethane/dextran sodium sulfate induced mouse CRC model was used to explore the role and mechanism of butyrate in regulating colon cancer and its intestinal microecological balance. Outcomes exhibited that butyrate alleviated weight loss, disease activity index, and survival in CRC mice and inhibited tumor number and progression. Further research revealed that butyrate restrained the aggregation of harmful while promoting the colonization of beneficial flora, such as Actinobacteriota, Bifidobacteriales and Muribaculacea through 16S rDNA sequence analysis. This study confirmed that butyrate can ameliorate CRC by repairing intestinal microecology, providing ideas and evidence for chemical prophylactic agents, such as butyrate to remedy tumors and regulate tumor microbiota.
Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Ratones , Animales , Butiratos/efectos adversos , Modelos Animales de Enfermedad , Azoximetano/efectos adversos , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Neoplasias Colorrectales/patologíaRESUMEN
[Figure: see text].
Asunto(s)
Transición Epitelial-Mesenquimal , Enfermedades de las Válvulas Cardíacas/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína 28 que Contiene Motivos Tripartito/metabolismo , Animales , Endocardio/metabolismo , Endocardio/patología , Epigénesis Genética , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/patología , Válvulas Cardíacas/metabolismo , Válvulas Cardíacas/patología , Código de Histonas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Proteínas de Unión al ARN/genética , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Proteína 28 que Contiene Motivos Tripartito/genéticaRESUMEN
Retinoblastoma (RB) constitutes a prevalent malignancy in clinic and usually occurs in children under the age of 5 years old. The increased frequency of malignant tumor metastases and the delayed diagnosis and treatment caused unsatisfactory therapeutic efficiency. Quercetin was formerly identified to impede tumor growth in certain malignancies. Our study attempted to investigate the effects and mechanisms of quercetin in Rb development, in order to provide an effective clinical therapeutic approach. Rb cell lines (WER1-RB1 and Y79) were incubated with different concentrations of quercetin, and then cell proliferation, invasion, apoptosis, and oxidative stress were determined. It was showed that quercetin restrained Rb cell proliferation and invasion, and induced cell apoptosis and oxidative stress in a dose dependent manner. Moreover, we found that quercetin incubation upregulated miR-137 expression in Rb cells. MiR-137 inhibition abrogated quercetin-mediated inhibition of Rb cell progression. Furthermore, dual-luciferase reporter gene assay validated that fibronectin type III domain-containing protein 5 (FNDC5) was a target for miR-137. MiR-137 overexpression restrained proliferation and invasion, and enhanced apoptosis and oxidative stress in Rb cells, whereas FNDC5 overexpression abrogated these effects. Additionally, nude mice were injected with WER1-RB1 cells to establish a xenograft tumor model, and then treated with 50 or 100 mg/kg quercetin. Quercetin treatment mitigated xenograft tumor growth in nude mice. In conclusion, quercetin restrained proliferation and invasion, and induced apoptosis and oxidative stress in Rb cells through regulating the miR-137/FNDC5 pathway. We expected that our study could provide an effective approach for Rb treatment. However, quercetin and miR-137 may have off-target effects in Rb cells, and our study still has certain limitations. Therefore, we will investigate the effects of quercetin on other signaling pathways in Rb cells and explore the application of combination therapy in follow-up experiments, in order to provide a rigorous research basis for the treatment of Rb with quercetin.
RESUMEN
The online and offline blended learning mode based on SPOC has gradually become a popular teaching mode in higher institutions due to COVID-19 pandemic. However, students of English as a Foreign Language (EFL) in SPOC-based blended learning environments continue facing problems of low participation and persistent intention. In order to explore the influencing factors of EFL students' continuance intentions to learn under the SPOC blended learning environment, this study recruits 48 EFL students from three higher vocational colleges based on the grounded theory. Through the triple coding method of open, axis, and selective coding based on the grounded theory and the used of software Nvivo to conduct a triple coding analysis of the text data obtained from the in-depth interviews and focus group interviews, a theoretical model of the influencing factors of EFL students' continuous learning intention (pre-influencing factors, external situational factors, and continuance intention) is proposed. Besides, a systematic framework based on stakeholders response to improve EFL students' continuance learning intentions in SPOC-based blended learning environments is constructed accordingly. This study can provide reference for basic theory and variable selection for subsequent research on the influencing factors of EFL students' continuance learning intentions in China and elsewhere.
RESUMEN
Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations. VEGFA-responsive genes were associated with active promoters, but changes in promoter histone marks were not tightly linked to gene expression changes. VEGFA altered transcription factor occupancy and the distal epigenetic landscape, which profoundly contributed to VEGFA-dependent changes in gene expression. Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network, which revealed that the small MAF transcription factors are master regulators of the VEGFA transcriptional program and angiogenesis. Collectively these results revealed that extracellular stimuli rapidly reconfigure the chromatin landscape to coordinately regulate biological responses.
Asunto(s)
Epigénesis Genética , Neovascularización Fisiológica/genética , Transcripción Genética , Factor A de Crecimiento Endotelial Vascular/fisiología , Animales , Células Cultivadas , Cromatina/metabolismo , Elementos de Facilitación Genéticos , Humanos , Factores de Transcripción Maf/metabolismo , Masculino , Ratones , Ratones Desnudos , Regiones Promotoras Genéticas , Factores de Transcripción/metabolismoRESUMEN
Classical swine fever virus (CSFV), a member of the genus Pestivirus of the family Flaviviridae, relies on host machinery to complete its life cycle. Previous studies have shown a close connection between virus infection and fatty acid biosynthesis, mainly regulated by fatty acid synthase (FASN). However, the molecular action of how FASN participates in CSFV replication remains to be elucidated. In this study, two chemical inhibitors of the fatty acid synthesis pathway [5-(tetradecyloxy)-2-furoic acid (TOFA) and tetrahydro-4-methylene-2R-octyl-5-oxo-3S-furancarboxylic acid (C75)] significantly impaired the late stage of viral propagation, suggesting CSFV replication required fatty acid synthesis. We next found that CSFV infection stimulated the expression of FASN, whereas knockdown of FASN inhibited CSFV replication. Furthermore, confocal microscopy showed that FASN participated in the formation of replication complex (RC), which was associated with the endoplasmic reticulum (ER). Interestingly, CSFV NS4B interacted with FASN and promoted overexpression of FASN, which is regulated by functional Rab18. Moreover, we found that FASN regulated the formation of lipid droplets (LDs) upon CSFV infection, promoting virus proliferation. Taken together, our work provides mechanistic insight into the role of FASN in the viral life of CSFV, and it highlights the potential antiviral target for the development of therapeutics against pestiviruses. IMPORTANCE Classical swine fever, caused by classical swine fever virus (CSFV), is one of the notifiable diseases by the World Organization for Animal Health (OIE) and causes significant financial losses to the pig industry globally. CSFV, like other (+)-strand RNA viruses, requires lipid and sterol biosynthesis for efficient replication. However, the role of lipid metabolism in CSFV replication remains unknown. Here, we found that fatty acid synthase (FASN) was involved in viral propagation. Moreover, FASN is recruited to CSFV replication sites in the endoplasmic reticulum (ER) and interacts with NS4B to regulate CSFV replication that requires Rab18. Furthermore, we speculated that lipid droplet (LD) biosynthesis, indirectly regulated by FASN, ultimately promotes CSFV replication. Our results highlight a critical role for de novo fatty acid synthesis in CSFV infection, which might help control this devastating virus.
Asunto(s)
4-Butirolactona/análogos & derivados , Virus de la Fiebre Porcina Clásica/fisiología , Peste Porcina Clásica/virología , Ácido Graso Sintasas/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo , Replicación Viral , Proteínas de Unión al GTP rab/metabolismo , 4-Butirolactona/farmacología , Animales , Peste Porcina Clásica/enzimología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/virología , Ácido Graso Sintasas/metabolismo , Interacciones Huésped-Patógeno , Porcinos , Proteínas no Estructurales Virales/genética , Proteínas de Unión al GTP rab/genéticaRESUMEN
Cytoskeleton, as a ubiquitous structure in the cells, plays an important role in the process of virus entry, replication, and survival. However, the action mechanism of cytoskeleton in the invasion of Pestivirus into host cells remains unclear. In this study, we systematically dissected the key roles of the main cytoskeleton components, microfilaments and microtubules in the endocytosis of porcine Pestivirus, Classical swine fever virus (CSFV). We observed the dynamic changes of actin filaments in CSFV entry. Confocal microscopy showed that CSFV invasion induced the dissolution and aggregation of stress fibers, resulting in the formation of lamellipodia and filopodia. Chemical inhibitors and RNA interference were used to find that the dynamic changes of actin were caused by EGFR-PI3K/MAPK-RhoA/Rac1/Cdc42-cofilin signaling pathway, which regulates the microfilaments to help CSFV entry. Furthermore, co-localization of the microfilaments with clathrin and Rab5 (early endosome), as well as microtubules with Rab7 (late endosome) and Lamp1 (lysosome) revealed that microfilaments were activated and rearranged to help CSFV trafficking to early endosome after endocytosis. Subsequently, recruitment of microtubules by CSFV also assisted membrane fusion of the virions from late endosome to lysosome with the help of a molecular motor, dynein. Unexpectedly, vimentin, which is an intermediate filament, had no effect on CSFV entry. Taken together, our findings comprehensively revealed the molecular mechanisms of cytoskeletal components that regulated CSFV endocytosis and facilitated further understanding of Pestivirus entry, which would be conducive to explore antiviral molecules to control classical swine fever.IMPORTANCEEndocytosis, an essential biological process mediating cellular internalization events, is often exploited by pathogens for their entry into target cells. Previously, we have reported different mechanisms of CSFV endocytosis into the porcine epithelial cells (PK-15) and macrophages (3D4/21); however, the details of microfilaments/microtubules mediated virus migration within the host cells remained to be elucidated. In this study, we found that CSFV infection induced rearrangement of actin filaments regulated by cofilin through EGFR-PI3K/MAPK-RhoA/Rac1/Cdc42 pathway. Furthermore, we found that CSFV particles were trafficked along actin filaments in early and late endosomes, and through microtubules in lysosomes after entry. Here, we provide for the first time a comprehensive description of the cytoskeleton that facilitates entry and intracellular transport of highly pathogenic swine virus. Results from this study will greatly contribute to the understanding of virus-induced early and complex changes in host cells that are important in CSFV pathogenesis.
RESUMEN
Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly contagious disease of swine with high morbidity and mortality that negatively affects the pig industry worldwide, in particular in China. Soon after the endocytosis of CSFV, the virus makes full use of the components of host cells to complete its life cycle. The endocytosis sorting complex required for transport (ESCRT) system is a central molecular machine for membrane protein sorting and scission in eukaryotic cells that plays an essential role in many physiological metabolic processes, including invasion and egress of envelope viruses. However, the molecular mechanism that ESCRT uses to regulate the replication of CSFV is unknown. In this study, we demonstrated that the ESCRT-I complex Tsg101 protein participates in clathrin-mediated endocytosis of CSFV and is also involved in CSFV trafficking. Tsg101 assists the virus in entering the host cell through the late endosome (Rab7 and Rab9) and finally reaching the lysosome (Lamp-1). Interestingly, Tsg101 is also involved in the viral replication process by interacting with nonstructural proteins 4B and 5B of CSFV. Finally, confocal microscopy showed that the replication complex of Tsg101 and double-stranded RNA (dsRNA) or NS4B and NS5B protein was close to the endoplasmic reticulum (ER), not the Golgi, in the cytoplasm. Collectively, our finding highlights that Tsg101 regulates the process of CSFV entry and replication, indicating that the ESCRT plays an important role in the life cycle of CSFV. Thus, ESCRT molecules could serve as therapeutic targets to combat CSFV infection.IMPORTANCE CSF, caused by CSFV, is a World Organization for Animal Health (OIE) notifiable disease and causes significant financial losses to the pig industry globally. The ESCRT machinery plays an important regulatory role in several members of the genera Flavivirus and Hepacivirus within the family Flaviviridae, such as hepatitis C virus, Japanese encephalitis virus, and dengue virus. Previous reports have shown that assembling and budding of these viruses require ESCRT. However, the role of ESCRT in Pestivirus infection remains to be elucidated. We determined the molecular mechanisms of the regulation of CSFV infection by the major subunit Tsg101 of ESCRT-I. Interestingly, Tsg101 plays an essential regulatory role in both clathrin-mediated endocytosis and genome replication of CSFV. Overall, the results of this study provide further insights into the molecular function of ESCRT-I complex protein Tsg101 during CSFV infection, which may serve as a molecular target for pestivirus inhibitors.
Asunto(s)
Virus de la Fiebre Porcina Clásica/fisiología , Proteínas de Unión al ADN/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Factores de Transcripción/metabolismo , Internalización del Virus , Replicación Viral , Animales , Línea Celular , Peste Porcina Clásica/metabolismo , Peste Porcina Clásica/virología , Proteínas de Unión al ADN/genética , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/virología , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Endosomas/metabolismo , Endosomas/virología , Interacciones Huésped-Patógeno , Lisosomas/metabolismo , Lisosomas/virología , ARN Viral/metabolismo , Porcinos , Factores de Transcripción/genética , Proteínas no Estructurales Virales/metabolismo , Compartimentos de Replicación Viral/metabolismoRESUMEN
Directly modulated vector beam lasers are increasingly desirable for wide applications ranging from optical manipulation to optical communications. We report the first, to our knowledge, high-speed directly modulated vector beam laser with azimuthally polarized emission. It is a microcylinder cavity interacted with a proper second-order grating on top, which enables single mode lasing and efficient surface emission. Through theoretical and numerical analysis, the laser is designed in detail. With an optimized top grating, the emission of the laser is an azimuthally polarized vector beam. With high-differential-gain material and a small active region, the laser can be directly modulated with a high 3 dB bandwidth reach of 40 GHz in simulation. The proposed high-speed directly modulated semiconductor laser with an azimuthally polarized vector beam is promising for applications in fiber space communications or quantum information.
RESUMEN
The monopolar spindle 1 ((hMps1/TTK) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To explore the possible relationship between TTK inhibition and radiosensitivity, we examined whether TTK inhibition influences cellular susceptibility of radiation. And we further revealed its mechanisms. We found that the expression of TTK was obviously higher in liver cancer tissues compared to the normal liver tissues. Kaplan-Meier Plotter demonstrated that patients with low TTK expression levels had a longer overall survival than patients with high TTK expression levels. TTK inhibitor AZ3146 could simulated liver cancer cells to accumulate in the G2/M phase, which ultimately enhances DNA damage with more γ-H2AX foci and more apoptosis and necrosis induced by radiation, which prompted that TTK inhibition sensitized liver cancer cells to radiation. In addition, TTK inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced mitotic catastrophe (MC) induced by radiation in a p21-mediated manner. In this study, we present evidences that the TTK inhibitor promotes the radiosensitivity of liver cancer cells through regulating cell cycle in p21-mediated manner in vitro, indicating that TTK inhibitor may be an attractive radiosensitizer for the patients with liver cancer.
Asunto(s)
Proteínas de Ciclo Celular/antagonistas & inhibidores , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Proteínas Oncogénicas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Tolerancia a Radiación/efectos de los fármacos , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Centrosoma/efectos de los fármacos , Centrosoma/metabolismo , Centrosoma/efectos de la radiación , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de la radiación , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/patología , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase M del Ciclo Celular/efectos de la radiación , Necrosis/tratamiento farmacológico , Necrosis/radioterapia , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Análisis de SupervivenciaRESUMEN
MAIN CONCLUSION: A Populus euphratica NAC gene regulates (1,3; 1,4)-ß-D-glucan content in oat developing seed and improves the spikelet number and grain number per spike in transgenic oat under salinity conditions Salinity is the major factor affecting the production and quality of oat, and improving oat salt tolerance to increase yield and quality is vital. (1,3;1,4)-ß-D-glucan in Gramineae is the key component in response to various environmental signals, and it is the most important functional ingredient in oat grain. The NAC transcription factors are important candidate genes used in genetic engineering to improve plant abiotic stress tolerance. In this study, we introduced Populus euphratica PeNAC1, controlled by its own promoter, into hexaploid cultivated oat and produced six transgenic lines. Compared to the non-transgenic control, the expression of PeNAC1 significantly improved the seed germination rate, seedling survival rate, and leaf chlorophyll content in the transgenic plants under salt stress. These physiological changes increased the spikelet number and grain number per spike in the transgenic oat under salinity conditions and reduced the yield loss per plant. The results indicated that the heterologous expression of PeNAC1 plays an effective role in improving the salt tolerance in transgenic oat. In addition, overexpressing PeNAC1 significantly increased the (1,3;1,4)-ß-D-glucan content as well as the expression level of the (1,3;1,4)-ß-D-glucan biosynthetic genes AsCslF3, AsCslF6, and AsCslF9 in the transgenic lines under salt stress, which suggested that PeNAC1 regulates the synthesis of (1,3;1,4)-ß-D-glucan. Our research should assist in the discovery of the diverse action modes of NAC proteins, while PeNAC1 will be useful for improving the salt tolerance and quality of oat through molecular breeding.
Asunto(s)
Tolerancia a la Sal , Factores de Transcripción , Avena/genética , Avena/metabolismo , Regulación de la Expresión Génica de las Plantas , Glucanos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Salinidad , Tolerancia a la Sal/genética , Estrés Fisiológico/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The long noncoding RNA DANCR (differentiation antagonizing non-protein coding RNA) displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in nasopharyngeal carcinoma (NPC) remain poorly understood. We found that DANCR is dramatically up-regulated in human NPC, and that it is an indicator for poor survival prognosis. DANCR knockdown suppressed cell proliferation, colony formation in vitro, and tumorigenicity in vivo. Mechanistic analyses demonstrated that DANCR could bind to RNA-binding protein 3 (RBM3) protein and stabilize SOX2 mRNA, resulting in NPC cell proliferation. Our findings indicate that DANCR functions as an oncogene and a potential therapeutic target for NPC.
Asunto(s)
Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , ARN Largo no Codificante/genética , Factores de Transcripción SOXB1/genética , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Proteínas de Unión al ARN/metabolismoRESUMEN
Cerebrovascular diseases have a high mortality and disability rate in developed countries. Endothelial cell injury is the main cause of atherosclerosis and cerebrovascular disease. Long non-coding RNA (lncRNA) has been proved to participate in the progression of endothelial cell. Our study aimed to develop the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury. The expression of OIP5-AS1, miR-98-5p and High-mobility group protein box-1 (HMGB1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect the cell proliferation and apoptosis. The levels of cyclinD1, Bcl-2 Associated X Protein (Bax), Cleaved-caspase-3, Toll like receptors 4 (TLR4), phosphorylation of p65 (p-P65), phosphorylation of nuclear factor-kappa B inhibitor α (p-IκB-α) and HMGB1 were measured by Western blot. The concentrations of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The production of Reactive oxygen species (ROS), Superoxide Dismutase (SOD) and malondialdehyde (MDA) was detected by the corresponding kit. The targets of OIP5-AS and miR-98-5p were predicted by starBase 3.0 and TargetScan and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression of OIP5-AS1 was upregulated, while miR-98-5p was downregulated in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, inflammatory injury and oxidative stress injury in ox-LDL-induced HUVEC cells. Interestingly, miR-98-5p was a target of OIP5-AS1 and miR-98-5p inhibition abolished the effects of OIP5-AS1 downregulation on ox-LDL-induced HUVECs injury. More importantly, miR-98-5p directly targeted HMGB1, and OIP5-AS1 regulated the expression of HMGB1 by sponging miR-98-5p. Finally, OIP5-AS1 regulated the TLR4/nuclear factor-kappa B (NF-κB) signaling pathway through miR-98-5p/HMGB1 axis. LncRNA OIP5-AS1 accelerates ox-LDL-induced endothelial cell injury through regulating HMGB1 mediated by miR-98-5p via the TLR4/NF-κB signaling pathway.
Asunto(s)
Células Endoteliales/metabolismo , Proteína HMGB1/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Apoptosis , Proliferación Celular , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación , Lipoproteínas LDL/metabolismo , Estrés Oxidativo , Fosforilación , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Reducing carbon dioxide emissions is one of the possible solutions to prevent global climate change, which is urgently needed for the sustainable development of our society. In this work, easily available, biodegradable amino acid ionic liquids (AAILs) with great potential for CO2 absorption in the manned closed space such as spacecraft, submarines and other manned devices are used as the basic material. Molecular dynamics simulations and ab initio calculations were performed for 12 AAILs ([P4444][X] and [P66614][X], [X] = X = [GLy]-, [Im]-, [Pro]-, [Suc]-, [Lys]-, [Asp]2-), and the dynamic characteristics and the internal mechanism of AAILs to improve CO2 absorption capacity were clarified. Based on structural analysis and the analysis of interaction energy including van der Waals and electrostatic interaction energy, it was revealed that the anion of ionic liquids dominates the interaction between CO2 and AAILs. At the same time, the CO2 absorption capacity of AAILs increases in the order [Asp]2- < [Suc]- < [Lys]- < [Pro]- < [Im]- < [Gly]-. Meanwhile, the synergistic absorption of CO2 by multiple-sites of amino and carboxyl groups in the anion was proved by DFT calculations. These findings show that the anion of AAILs can be an effective factor to regulate the CO2 absorption process, which can also provide guidance for the rational and targeted molecular design of AAILs for CO2 capture, especially in the manned closed space.
Asunto(s)
Aminoácidos/química , Dióxido de Carbono/química , Líquidos Iónicos/química , Teoría Funcional de la Densidad , Modelos Químicos , Simulación de Dinámica MolecularRESUMEN
Pancreatic cancer is one of the most fatal malignancies with high mortality. Gemcitabine (GEM)-based chemotherapy is the most important treatment. However, the development of GEM resistance leads to chemotherapy failure. Previous studies demonstrated the anticancer activity of ginsenoside Rg3 in a variety of carcinomas through modulating multiple signaling pathways. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, flow cytometry apoptosis assay, Western blotting assay, xenograft experiment, and immunohistochemistry assay were performed in GEM-resistant pancreatic cancer cell lines. Ginsenoside Rg3 inhibited the viability of GEM-resistant pancreatic cancer cells in a time-dependent and concentration-dependent manner through induction of apoptosis. The level of long noncoding RNA cancer susceptibility candidate 2 (CASC2) and PTEN expression was upregulated by the ginsenoside Rg3 treatment, and CASC2/PTEN signaling was involved in the ginsenoside Rg3-induced cell growth suppression and apoptosis in GEM-resistant pancreatic cancer cells. Ginsenoside Rg3 could be an effective anticancer agent for chemoresistant pancreatic cancer.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos/efectos de los fármacos , Ginsenósidos/farmacología , Fosfohidrolasa PTEN/metabolismo , Neoplasias Pancreáticas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Supresoras de Tumor/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Desoxicitidina/farmacología , Ginsenósidos/uso terapéutico , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Transfección , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genética , Proteínas Supresoras de Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina , Neoplasias PancreáticasRESUMEN
Discoid lupus erythematosus (DLE) is a chronic autoimmune skin disease that usually causes disfiguring scarring, dyspigmentation, and atrophy. Despite a range of available topical and systemic therapies, the treatment of DLE remains a therapeutic challenge, especially in some refractory cases. Here, we reported three male patients with long-term chronic lesions of unilateral facial localized DLE, who failed to have their disease controlled with many previous topical/systemic treatments, showed rapid and well response to intralesional injections of betamethasone (2 mg/mL, 0.2 mL/site) monotherapy once every 2 weeks for two, two, and four times of treatment, respectively. Intralesional betamethasone may provide a safe and effective alternative in the management of refractory localized DLE skin lesions.