RESUMEN
Invisibility, a fascinating ability of hiding objects within environments, has attracted broad interest for a long time. However, current invisibility technologies are still restricted to stationary environments and narrow band. Here, we experimentally demonstrate a Chimera metasurface for multiterrain invisibility by synthesizing the natural camouflage traits of various poikilotherms. The metasurface achieves chameleon-like broadband in situ tunable microwave reflection mimicry of realistic water surface, shoal, beach/desert, grassland, and frozen ground from 8 to 12 GHz freely via the circuit-topology-transited mode evolution, while remaining optically transparent as an invisible glass frog. Additionally, the mechanic-driven Chimera metasurface without active electrothermal effect, owning a bearded dragon-like thermal acclimation, can decrease the maximum thermal imaging difference to 3.1 °C in tested realistic terrains, which cannot be recognized by human eyes. Our work transitions camouflage technologies from the constrained scenario to ever-changing terrains and constitutes a big advance toward the new-generation reconfigurable electromagnetics with circuit-topology dynamics.
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Signaling by the evolutionarily conserved mitogen-activated protein kinase or extracellular signal-regulated kinase (MAPK/ERK) plays critical roles in converting extracellular stimuli into immune responses. However, whether MAPK/ERK signaling induces virus immunity by directly phosphorylating viral effectors remains largely unknown. Barley yellow striate mosaic virus (BYSMV) is an economically important plant cytorhabdovirus that is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a propagative manner. Here, we found that the barley (Hordeum vulgare) MAPK MPK3 (HvMPK3) and the planthopper ERK (LsERK) proteins interact with the BYSMV nucleoprotein (N) and directly phosphorylate N protein primarily on serine 290. The overexpression of HvMPK3 inhibited BYSMV infection, whereas barley plants treated with the MAPK pathway inhibitor U0126 displayed greater susceptibility to BYSMV. Moreover, knockdown of LsERK promoted virus infection in SBPHs. A phosphomimetic mutant of the N Ser290 (S290D) completely abolished virus infection because of impaired self-interaction of BYSMV N and formation of unstable N-RNA complexes. Altogether, our results demonstrate that the conserved MAPK and ERK directly phosphorylate the viral nucleoprotein to trigger immunity against cross-kingdom infection of BYSMV in host plants and its insect vectors.
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Hemípteros , Hordeum , Rhabdoviridae , Animales , Antivirales , Hordeum/genética , Insectos Vectores , Nucleoproteínas/genética , Rhabdoviridae/fisiologíaRESUMEN
The genetic basis of phenotypic variation is a long-standing concern of evolutionary biology. Coloration has proven to be a visual, easily quantifiable, and highly tractable system for genetic analysis and is an ever-evolving focus of biological research. Compared with the homogenized brown-yellow cocoons of wild silkworms, the cocoons of domestic silkworms are spectacularly diverse in color, such as white, green, and yellow-red; this provides an outstanding model for exploring the phenotypic diversification and biological coloration. Herein, the molecular mechanism underlying silkworm green cocoon formation was investigated, which was not fully understood. We demonstrated that five of the seven members of a sugar transporter gene cluster were specifically duplicated in the Bombycidae and evolved new spatial expression patterns predominantly expressed in silk glands, accompanying complementary temporal expression; they synergistically facilitate the uptake of flavonoids, thus determining the green cocoon. Subsequently, polymorphic cocoon coloring landscape involving multiple loci and the evolution of cocoon color from wild to domestic silkworms were analyzed based on the pan-genome sequencing data. It was found that cocoon coloration involved epistatic interaction between loci; all the identified cocoon color-related loci existed in wild silkworms; the genetic segregation, recombination, and variation of these loci shaped the multicolored cocoons of domestic silkworms. This study revealed a new mechanism for flavonoids-based biological coloration that highlights the crucial role of gene duplication followed by functional diversification in acquiring new genetic functions; furthermore, the results in this work provide insight into phenotypic innovation during domestication.
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Bombyx , Animales , Bombyx/genética , Bombyx/metabolismo , Seda/genética , Seda/metabolismo , Secuencia de Bases , Flavonoides/metabolismoRESUMEN
Plant rhabdoviruses heavily rely on insect vectors for transmission between sessile plants. However, little is known about the underlying mechanisms of insect attraction and transmission of plant rhabdoviruses. In this study, we used an arthropod-borne cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV), to demonstrate the molecular mechanisms of a rhabdovirus accessory protein in improving plant attractiveness to insect vectors. Here, we found that BYSMV-infected barley (Hordeum vulgare L.) plants attracted more insect vectors than mock-treated plants. Interestingly, overexpression of BYSMV P6, an accessory protein, in transgenic wheat (Triticum aestivum L.) plants substantially increased host attractiveness to insect vectors through inhibiting the jasmonic acid (JA) signaling pathway. The BYSMV P6 protein interacted with the constitutive photomorphogenesis 9 signalosome subunit 5 (CSN5) of barley plants in vivo and in vitro, and negatively affected CSN5-mediated deRUBylation of cullin1 (CUL1). Consequently, the defective CUL1-based Skp1/Cullin1/F-box ubiquitin E3 ligases could not mediate degradation of jasmonate ZIM-domain proteins, resulting in compromised JA signaling and increased insect attraction. Overexpression of BYSMV P6 also inhibited JA signaling in transgenic Arabidopsis (Arabidopsis thaliana) plants to attract insects. Our results provide insight into how a plant cytorhabdovirus subverts plant JA signaling to attract insect vectors.
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Arabidopsis , Hordeum , Rhabdoviridae , Animales , Arabidopsis/metabolismo , Complejo del Señalosoma COP9/metabolismo , Ciclopentanos/metabolismo , Hordeum/genética , Hordeum/metabolismo , Insectos Vectores , Oxilipinas/metabolismo , Proteínas/metabolismo , Rhabdoviridae/metabolismo , Transducción de Señal , Triticum/genética , Triticum/metabolismo , Ubiquitinas/metabolismoRESUMEN
Casein kinase 1 (CK1) family members are conserved Ser/Thr protein kinases that regulate important developmental processes in all eukaryotic organisms. However, the functions of CK1 in plant immunity remain largely unknown. Barley yellow striate mosaic virus (BYSMV), a plant cytorhabdovirus, infects cereal crops and is obligately transmitted by the small brown planthopper (SBPH; Laodelphax striatellus). The BYSMV phosphoprotein (P) exists as two forms with different mobilities corresponding to 42 kD (P42) and 44 kD (P44) in SDS-PAGE gels. Mass spectrometric analyses revealed a highly phosphorylated serine-rich (SR) motif at the C-terminal intrinsically disordered region of the P protein. The Ala-substitution mutant (PS5A) in the SR motif stimulated virus replication, whereas the phosphorylation-mimic mutant (PS5D) facilitated virus transcription. Furthermore, PS5A and PS5D associated preferentially with nucleocapsid protein-RNA templates and the large polymerase protein to provide optimal replication and transcription complexes, respectively. Biochemistry assays demonstrated that plant and insect CK1 protein kinases could phosphorylate the SR motif and induce conformational changes from P42 to P44. Moreover, overexpression of CK1 or a dominant-negative mutant impaired the balance between P42 and P44, thereby compromising virus infections. Our results demonstrate that BYSMV recruits the conserved CK1 kinases to achieve its cross-kingdom infection in host plants and insect vectors.
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Quinasa de la Caseína I/metabolismo , Interacciones Huésped-Patógeno/fisiología , Proteínas de Plantas/metabolismo , Rhabdoviridae/fisiología , Proteínas Virales/metabolismo , Secuencias de Aminoácidos , Quinasa de la Caseína I/genética , Genoma Viral , Proteínas de Insectos/metabolismo , Espectrometría de Masas , Mutación , Fosfoproteínas/metabolismo , Fosforilación , Enfermedades de las Plantas/virología , Rhabdoviridae/patogenicidad , Serina , Nicotiana/virología , Replicación Viral/fisiologíaRESUMEN
BACKGROUND: The continued rise of Klebsiella pneumoniae resistance to antibiotics is precipitating a medical crisis. Bacteriophages have been hailed as one possible therapeutic option to enhance the efficacy of antibiotics. This study describes the genomic characterization and biological property of a new bacteriophage vB_1086 and its potential for phage therapy application against Klebsiella pneumoniae. METHODS: In our study, the double-layer agar plate method isolated a lytic bacteriophage named vB_1086. Besides, we analyzed its biological characteristics and genetic background. Then the antibacterial ability of the bacteriophage vB_1086 combined with antibiotics were analyzed by the combined checkerboard method. The impact on the formation of biofilms was analyzed by crystal violet staining method. RESULTS: vB_1086 is a lytic bacteriophage with stable biological characteristics and clear genetic background, showing good antibacterial activity in combination with ceftriaxone, and the combination of phage and meropenem can effectively inhibit the formation of biofilm. Besides, the combination of bacteriophage and antimicrobials can effectively alleviate the generation of bacterial resistance and reduce the dosage of antimicrobials. CONCLUSION: vB_1086 is a novel phage. To some extent, these results provide valuable information that phage vB_1086 can be combined with antibiotics to reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance.
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Infecciones Bacterianas , Bacteriófagos , Agar/farmacología , Antibacterianos/farmacología , Bacteriófagos/genética , Ceftriaxona/farmacología , Violeta de Genciana , Humanos , Klebsiella pneumoniae , Meropenem/farmacologíaRESUMEN
AIMS: Quorum sensing (QS) is the intercellular communication used by bacteria to regulate collective behaviour. QS regulates the production of virulence factors in many bacterial species and is considered to be an attractive target for reducing bacterial pathogenicity. Chlorogenic acid (CA) is abundant in vegetables, fruits, and traditional Chinese medicine, and has multiple activities. This study aimed to investigate the QS quenching activity of CA against clinically isolated multidrug-resistant Pseudomonas aeruginosa. METHODS AND RESULTS: The results showed that CA inhibited the mobility of bacteria, reduced the production of pyocyanin, and inhibited the activity of elastase. Furthermore, crystal violet staining and scanning electron microscope experiments showed that CA inhibited the formation of multidrug-resistant P. aeruginosa biofilm. CA at or below the concentration of 2560 µg/mL exerted negligible cytotoxicity to RAW264.7 cells. The study also examined the expression of QS-related genes, including lasI, lasR, rhlI, rhlR, pqsA, and pqsR in P. aeruginosa and found that the expression of these genes was down-regulated under CA treatment. CONCLUSIONS: The study showed that CA could be used as an anti-virulence factor for treating clinical P. aeruginosa infection. SIGNIFICANCE AND IMPACT OF STUDY: For the first time, this study took clinically isolated multidrug-resistant P. aeruginosa as the experimental object, and suggested that CA might be an effective antimicrobial compound targeting QS in treating P. aeruginosa infection, thus providing a new therapeutic direction for treating bacterial infection and effectively alleviating bacterial resistance.
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Antibacterianos , Ácido Clorogénico , Pseudomonas aeruginosa , Animales , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Biopelículas , Ácido Clorogénico/farmacología , Ratones , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum , Células RAW 264.7 , Factores de Virulencia/genéticaRESUMEN
BACKGROUND: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections, such as diabetic foot infections, and further exacerbates the treatment options and cost of such conditions. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in wounds. However, the action of hypertonic glucose on bacterial pathogens that infect wounds is unclear. In this study, we investigated the inhibitory effects of hypertonic glucose on multidrug-resistant P. aeruginosa strains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused by P. aeruginosa. RESULTS: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the reference P. aeruginosa PAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa clinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors in P. aeruginosa. The expression of major quorum sensing genes (lasI, lasR, rhlI, and rhlR) in P. aeruginosa were all downregulated in response to hypertonic glucose treatment. In a Galleria mellonella larvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected by P. aeruginosa strains (3/5). CONCLUSIONS: Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa, as well as reduced the production of virulence factors and quorum sensing gene expression. Further studies that investigate hypertonic glucose therapy should be considered in treating chronic wound infections.
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Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Solución Hipertónica de Glucosa/farmacología , Pseudomonas aeruginosa/crecimiento & desarrollo , Factores de Virulencia/genética , Proteínas Bacterianas/genética , Biopelículas/efectos de los fármacos , China , Pie Diabético/microbiología , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Elastasa Pancreática/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/patogenicidad , Piocianina/genética , Percepción de Quorum , Centros de Atención TerciariaRESUMEN
Plant viruses have been used as rapid and cost-effective expression vectors for heterologous protein expression in genomic studies. However, delivering large or multiple foreign proteins in monocots and insect pests is challenging. Here, we recovered a recombinant plant cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV), for use as a versatile expression platform in cereals and the small brown planthopper (SBPH, Laodelphax striatellus) insect vector. We engineered BYSMV vectors to provide versatile expression platforms for simultaneous expression of three foreign proteins in barley plants and SBPHs. Moreover, BYSMV vectors could express the c. 600-amino-acid ß-glucuronidase (GUS) protein and a red fluorescent protein stably in systemically infected leaves and roots of cereals, including wheat, barley, foxtail millet, and maize plants. Moreover, we have demonstrated that BYSMV vectors can be used in barley to analyze biological functions of gibberellic acid (GA) biosynthesis genes. In a major technical advance, BYSMV vectors were developed for simultaneous delivery of CRISPR/Cas9 nuclease and single guide RNAs for genomic editing in Nicotiana benthamiana leaves. Taken together, our results provide considerable potential for rapid screening of functional proteins in cereals and planthoppers, and an efficient approach for developing other insect-transmitted negative-strand RNA viruses.
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Grano Comestible/genética , Grano Comestible/virología , Genoma de Planta , Genómica , Hemípteros/virología , Virus de Plantas/fisiología , Rhabdoviridae/fisiología , Animales , Secuencia de Bases , ADN Complementario/genética , Edición Génica , Vectores Genéticos/metabolismo , Glucuronidasa/metabolismo , Hordeum/ultraestructura , Hordeum/virología , Hojas de la Planta/virología , Virus de Plantas/ultraestructura , ARN Guía de Kinetoplastida/metabolismo , Rhabdoviridae/ultraestructura , Nicotiana/ultraestructura , Nicotiana/virologíaRESUMEN
As obligate parasites, plant viruses usually hijack host cytoskeletons for replication and movement. Rhabdoviruses are enveloped, negative-stranded RNA viruses that infect vertebrates, invertebrates, and plants, but the mechanisms of intracellular trafficking of plant rhabdovirus proteins are largely unknown. Here, we used Barley yellow striate mosaic virus (BYSMV), a plant cytorhabdovirus, as a model to investigate the effects of the actin cytoskeleton on viral intracellular movement and viral RNA synthesis in a mini-replicon (MR) system. The BYSMV P protein forms mobile inclusion bodies that are trafficked along the actin/endoplasmic reticulum network, and recruit the N and L proteins into viroplasm-like structures. Deletion analysis showed that the N terminal region (aa 43-55) and the remaining region (aa 56-295) of BYSMV P are essential for the mobility and formation of inclusions, respectively. Overexpression of myosin XI-K tails completely abolishes the trafficking activity of P bodies, and is accompanied by a significant reduction of viral MR RNA synthesis. These results suggest that BYSMV P contributes to the formation and trafficking of viroplasm-like structures along the ER/actin network driven by myosin XI-K. Thus, rhabdovirus P appears to be a dynamic hub protein for efficient recruitment of viral proteins, thereby promoting viral RNA synthesis.
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Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Hordeum/metabolismo , Hordeum/virología , ARN Viral/metabolismo , Rhabdoviridae/metabolismo , Rhabdoviridae/patogenicidad , Citoesqueleto de Actina/genética , Actinas/genética , Hordeum/genética , Transporte de Proteínas/genética , Transporte de Proteínas/fisiología , ARN Viral/genéticaRESUMEN
CONTEXT: ß-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. OBJECTIVE: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. MATERIALS AND METHODS: In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 µM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 106 BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. RESULTS: The phenotypes and function of BMDMs showed that 5, 25 and 50 µM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1ß, CD86 and MHCII in 25 µM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 µM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. CONCLUSIONS: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy.
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Artritis Experimental/tratamiento farmacológico , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Sitoesteroles/farmacología , Animales , Artritis Experimental/inmunología , Polaridad Celular/efectos de los fármacos , Polaridad Celular/inmunología , Citocinas/biosíntesis , Citocinas/sangre , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Interleucina-10/biosíntesis , Interleucina-10/inmunología , Activación de Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44+ CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth, and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro. Surprisingly, the combination with miR-5100 inhibitor significantly decreased the IC50 of LCSCs to cisplatin. Furthermore, miR-5100 increased CSC properties and cisplatin resistance by inhibiting Rab6, a direct target gene of miR-5100. We demonstrated that miR-5100 overexpression increases the cisplatin resistance of the LCSCs through the mitochondrial apoptosis pathway. In conclusion, our results suggest that miR-5100 increases the cisplatin resistance of the LCSCs by inhibiting the Rab6. This study provides novel insight into the regulation of LCSCs by miRNA.
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Antineoplásicos/farmacología , Cisplatino/farmacología , Resistencia a Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , MicroARNs/genética , Células Madre Neoplásicas/efectos de los fármacos , Proteínas de Unión al GTP rab/genética , Células A549 , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patologíaRESUMEN
P-type and n-type top-gate carbon nanotube thin-film transistors (TFTs) can be selectively and simultaneously fabricated on the same polyethylene terephthalate (PET) substrate by tuning the types of polymer-sorted semiconducting single-walled carbon nanotube (sc-SWCNT) inks, along with low temperature growth of HfO2 thin films as shared dielectric layers. Both the p-type and n-type TFTs show good electrical properties with on/off ratio of ≈105 , mobility of ≈15 cm2 V-1 s-1 , and small hysteresis. Complementary metal oxide semiconductor (CMOS)-like logic gates and circuits based on as-prepared p-type and n-type TFTs have been achieved. Flexible CMOS-like inverters exhibit large noise margin of 84% at low voltage (1/2 Vdd = 1.5 V) and maximum voltage gain of 30 at Vdd of 1.5 V and low power consumption of 0.1 µW. Both of the noise margin and voltage gain are one of the best values reported for flexible CMOS-like inverters at Vdd less than 2 V. The printed CMOS-like inverters work well at 10 kHz with 2% voltage loss and delay time of ≈15 µs. A 3-stage ring oscillator has also been demonstrated on PET substrates and the oscillation frequency of 3.3 kHz at Vdd of 1 V is achieved.
RESUMEN
BACKGROUND: microRNAs (miRNAs) are involved in the regulation of various cellular processes, such as differentiation, proliferation, metabolism, and apoptosis, and they have been implicated in several diseases, including cancers. METHODS: To assess the role of miRNA in the progression of breast cancer, we performed TaqMan-based miRNA profiling for plasma from patients with breast cancer (n = 53), unrelated diseases (n = 40), or matched healthy controls (n = 40), and for breast tumors or adjacent non-tumors (n = 41). RESULTS: We selected 18 miRNAs with predicted roles in breast cancer and demonstrated that let-7i (p = 0.019), let-7a (p = 0.02), and miR-650 (p = 0.008) were significantly up-regulated in plasma; miR-21 (p < 0.001) is up-regulated in breast cancer tissue, and miR-30e was down-regulated in both plasma (p < 0.001) and breast cancer tissues (p = 0.004). Plasma miR-30e expression was shown to be statistically associated with age (p = 0.0402) and clinical stage (p = 0.007). However, receiver-operating characteristic curve analyses suggested that miR-30e expression cannot significantly differentiate breast cancer from healthy tissue or plasma. Consistent with a potential role for miR-30e in breast cancer, three predicted targets of miR-30e (RAB11A, BNIP3L, and RAB32) are up-regulated in breast cancer tissue. CONCLUSIONS: These findings suggest that reduced miR-30e correlates with the clinical stage of breast cancer. It is worthwhile to further explore that the potential role of miR-30e as a tumor suppressor in breast cancer, as well as its potential therapeutic utility.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , MicroARNs/genética , Adulto , Factores de Edad , Área Bajo la Curva , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas/genética , Curva ROC , Factores de Riesgo , Proteínas Supresoras de Tumor/genética , Adulto Joven , Proteínas de Unión al GTP rab/genéticaRESUMEN
Kawasaki disease (KD) is a vasculitis disease in children that is associated with coronary artery ectasia (CAE). We investigated whether inducible nitric oxide synthase (i-NOS) and hydrogen sulfide (H2S) could be used to predict CAE secondary to KD. We enrolled 65 children with KD (35 cases with CAE and 30 cases without CAE), 33 healthy children, and 32 children with fever but without vasculitis disease (febrile group). We measured plasma nitric oxide (NO), total nitric oxide synthase (Total-NOS), i-NOS, constructive nitric oxide synthase (c-NOS) levels, and H2S content in all patients. Plasma NO, Total-NOS, i-NOS, and H2S were higher in KD children than in healthy and febrile children (P < 0.05). The i-NOS level was higher in KD children with CAE compared to those without CAE, while the H2S was lower (both P < 0.05). Using a combination of i-NOS (higher than 10 U/mL) and H2S (lower than 3.31 µmol/L) to predict CAE had 80 % sensitivity and 81 % specificity (P < 0.05). Elevated plasma i-NOS and decreased plasma H2S levels in the acute phase of KD have good predictive value for CAE and may be used to guide appropriate clinical treatment and prevent future cardiovascular complications.
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Vasos Coronarios/fisiopatología , Sulfuro de Hidrógeno/sangre , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Óxido Nítrico Sintasa/sangre , Óxido Nítrico/sangre , Estudios de Casos y Controles , Preescolar , China , Dilatación Patológica/etiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Curva ROCRESUMEN
The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we demonstrated that OGG1 could inhibit the generation of ROS and alleviate mitochondrial dysfunction and increased the expression of IL-1ß caused by PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'-tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1) staining using flow cytometry showed that PM2.5 induces the generation of ROS and leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells. Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP. Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1 inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the results of the comet assay showed that OGG1 had a significant repair effect on DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly suppressed the expression of IL-1ß caused by PM2.5. Together, these data suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL-1ß could be reversed by overexpression of OGG1. The mitochondrial dysfunction caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the expression of IL-1ß.
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Bronquios/efectos de los fármacos , Daño del ADN/efectos de los fármacos , ADN Glicosilasas/metabolismo , Células Epiteliales/efectos de los fármacos , Inflamación/prevención & control , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Material Particulado/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Apoptosis/efectos de los fármacos , Western Blotting , Bronquios/metabolismo , Bronquios/patología , ADN Glicosilasas/antagonistas & inhibidores , ADN Glicosilasas/genética , ADN Mitocondrial , Células Epiteliales/metabolismo , Células Epiteliales/patología , Técnica del Anticuerpo Fluorescente , Humanos , Inflamación/metabolismo , Inflamación/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND: E2F-1 is a transcription factor that stimulates cellular proliferation and cell cycle progression. E2F-1 alone is sufficient to stimulate cells to initiate DNA synthesis, and this unscheduled entry into S phase is a potent trigger of apoptosis. Gemcitabine, a novel pyrimidine analogue with structural and metabolic similarities to cytarabine, also can efficiently induce apoptosis, especially for cancer cells that are already in S phase. Gemcitabine has established antitumor activity against solid tumors, including head and neck, ovarian, and non-small cell lung cancers. Therefore, we hypothesized that exogenous E2F-1 expression could accumulate cells in the S phase and thus sensitize them to gemcitabine. METHODS: We constructed an adenoviral vector (AdCMVE2F-1) to transduce the exogenous E2F-1 gene into human cancer cells. Infection of human colon cancer cells with AdCMVE2F-1 resulted in the overexpression of E2F-1 mRNA and protein in a dose-dependent manner and consequently induced accumulation in S phase as measured by FACS analysis. To assess the synergistic antitumor effect of AdCMVE2F-1 and gemcitabine, the human colon cancer cel lines SW620, DLD-1, and LoVo were infected with AdCMVE2F-1 at various multiplicities of infection and then exposed to various concentrations of gemcitabine 24 hours after infection. RESULT: Isobologram analysis showed that E2F-1-transduced cancer cells exhibited higher sensitivity to gemcitabine treatment compared to control virus-infected cells. Treatment with AdCMVE2F-1 plus gemcitabine enhanced endogenous p53 expression in LoVo cells, which contain wild-type p53; however, the finding that the synergistic effect can also be observed in mutant p53-expressing SW620 and DLD-1 cells suggests that wild-type p53 function may not be necessary for the therapeutic effects of this drug combination. Conclusions: Our data demonstrate that overexpression of ectopic E2F-1 protein may render cels more sensitive to gemcitabine-mediated apoptosis, an outcome that has important general implications for the treatment of human cancer.
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Adenoviridae/metabolismo , Neoplasias del Colon/metabolismo , Desoxicitidina/análogos & derivados , Factor de Transcripción E2F1/metabolismo , Técnicas de Transferencia de Gen , Proteína p53 Supresora de Tumor/genética , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular , Neoplasias del Colon/genética , Fragmentación del ADN , Desoxicitidina/química , Humanos , Concentración 50 Inhibidora , Microscopía Fluorescente , Mutación , Proteína p53 Supresora de Tumor/metabolismo , GemcitabinaRESUMEN
The control of moisture content (MC) is essential in the drying of shrimp, directly impacting its quality and shelf life. This study aimed to develop an accurate method for determining shrimp MC by integrating hyperspectral imaging (HSI) with electronic nose (E-nose) technology. We employed three different data fusion approaches: pixel-, feature-, and decision-fusion, to combine HSI and E nose data for the prediction of shrimp MC. We developed partial least squares regression (PLSR) models for each method and compared their performance in terms of prediction accuracy. The decision fusion approach outperformed the other methods, producing the highest determination coefficients for both calibration (0.9595) and validation sets (0.9448). Corresponding root-mean square errors were the lowest for the calibration set (0.0370) and validation set (0.0443), indicating high prediction precision. Additionally, this approach achieved a relative percent deviation of 3.94, the highest among the methods tested. The findings suggest that the decision fusion of HSI and E nose data through a PLSR model is an effective, accurate, and efficient method for evaluating shrimp MC. The demonstrated capability of this approach makes it a valuable tool for quality control and market monitoring of dried shrimp products.
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Considering the increasing demand for high-resolution light-emitting diodes (LEDs), it is important that direct fine patterning technologies for LEDs be developed, especially for quantum-dot LEDs (QLEDs). Traditionally, the patterning of QLEDs relies on resin-based photolithography techniques, requiring multiple steps and causing performance deterioration. Nondestructive direct patterning may provide an easy and stepwise method to achieve fine-pixelated units in QLEDs. In this study, two isomeric tridentate cross-linkers (X8/X9) are presented and can be blended into the hole transport layer (HTL) and the emissive layer (EML) of QLEDs. Because of their photosensitivity, the in situ cross-linking process can be efficiently triggered by ultraviolet irradiation, affording high solvent resistance and nondestructive direct patterning of the layers. Red QLEDs using the cross-linked HTL demonstrate an impressive external quantum efficiency of up to 22.45%. Through lithographic patterning enabled by X9, line patterns of HTL and EML films exhibit widths as narrow as 2 and 4 µm, respectively. Leveraging the patterned HTL and EML, we show the successful fabrication of pixelated QLED devices with an area size of 3 × 3 mm2, alongside the successful production of dual-color pixelated QLED devices. These findings showcase the promising potential of direct patterning facilitated by engineered cross-linkers for the cost-effective fabrication of pixelated QLED displays.
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Postoperative complications of phacoemulsification, such as corneal edema caused by human corneal endothelial cell (CEC) injury, are still a matter of concern. Although several factors are known to cause CEC damage, the influence of ultrasound on the formation of free radicals during surgery should be considered. Ultrasound in aqueous humor induces cavitation and promotes the formation of hydroxyl radicals or reactive oxygen species (ROS). ROS-induced apoptosis and autophagy in phacoemulsification have been suggested to significantly promote CEC injury. CEC cannot regenerate after injury, and measures must be taken to prevent the loss of CEC after phacoemulsification or other CEC injuries. Antioxidants can reduce the oxidative stress injury of CEC during phacoemulsification. Evidence from rabbit eye studies shows that ascorbic acid infusion during operation or local application of ascorbic acid during phacoemulsification has a protective effect by scavenging free radicals or reducing oxidative stress. Both in experiments and clinical practice, hydrogen dissolved in the irrigating solution can also prevent CEC damage during phacoemulsification surgery. Astaxanthin (AST) can inhibit oxidative damage, thereby protecting different cells from most pathological conditions, such as myocardial cells, luteinized granulosa cells of the ovary, umbilical vascular endothelial cells, and human retina pigment epithelium cell line (ARPE-19). However, existing research has not focused on the application of AST to prevent oxidative stress during phacoemulsification, and the related mechanisms need to be studied. The Rho related helical coil kinase inhibitor Y-27632 can inhibit CEC apoptosis after phacoemulsification. Rigorous experiments are required to confirm whether its effect is realized through improving the ROS clearance ability of CEC.