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1.
Nature ; 582(7810): 55-59, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32494077

RESUMEN

The ability of superhydrophobic surfaces to stay dry, self-clean and avoid biofouling is attractive for applications in biotechnology, medicine and heat transfer1-10. Water droplets that contact these surfaces must have large apparent contact angles (greater than 150 degrees) and small roll-off angles (less than 10 degrees). This can be realized for surfaces that have low-surface-energy chemistry and micro- or nanoscale surface roughness, minimizing contact between the liquid and the solid surface11-17. However, rough surfaces-for which only a small fraction of the overall area is in contact with the liquid-experience high local pressures under mechanical load, making them fragile and highly susceptible to abrasion18. Additionally, abrasion exposes underlying materials and may change the local nature of the surface from hydrophobic to hydrophilic19, resulting in the pinning of water droplets to the surface. It has therefore been assumed that mechanical robustness and water repellency are mutually exclusive surface properties. Here we show that robust superhydrophobicity can be realized by structuring surfaces at two different length scales, with a nanostructure design to provide water repellency and a microstructure design to provide durability. The microstructure is an interconnected surface frame containing 'pockets' that house highly water-repellent and mechanically fragile nanostructures. This surface frame acts as 'armour', preventing the removal of the nanostructures by abradants that are larger than the frame size. We apply this strategy to various substrates-including silicon, ceramic, metal and transparent glass-and show that the water repellency of the resulting superhydrophobic surfaces is preserved even after abrasion by sandpaper and by a sharp steel blade. We suggest that this transparent, mechanically robust, self-cleaning glass could help to negate the dust-contamination issue that leads to a loss of efficiency in solar cells. Our design strategy could also guide the development of other materials that need to retain effective self-cleaning, anti-fouling or heat-transfer abilities in harsh operating environments.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , Incrustaciones Biológicas/prevención & control , Agua/química
2.
Cancer Sci ; 115(4): 1129-1140, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38351514

RESUMEN

Oncolytic viruses (OVs) possess the unique ability to selectively replicate within tumor cells, leading to their destruction, while also reversing the immunosuppression within the tumor microenvironment and triggering an antitumor immune response. As a result, OVs have emerged as one of the most promising approaches in cancer therapy. However, the effective delivery of intravenously administered OVs faces significant challenges imposed by various immune cells within the peripheral blood, hindering their access to tumor sites. Notably, neutrophils, the predominant white blood cell population comprising approximately 50%-70% of circulating white cells in humans, show phagocytic properties. Our investigation revealed that the majority of oncolytic vaccinia viruses (VV) are engulfed and degraded by neutrophils in the bloodstream. The depletion of neutrophils using the anti-LY6G Ab (1-A8) resulted in an increased accumulation of circulating oncolytic VV in the peripheral blood and enhanced deposition at the tumor site, consequently amplifying the antitumor effect. Neutrophils heavily rely on PI3K signaling to sustain their phagocytic process. Additionally, our study determined that the inhibition of the PI3Kinase delta isoform by idelalisib (CAL-101) suppressed the uptake of oncolytic VV by neutrophils. This inhibition led to a greater presence of oncolytic VV in both the peripheral blood and at the tumor site, resulting in improved efficacy against the tumor. In conclusion, our study showed that inhibiting neutrophil functions can significantly enhance the antitumor efficacy of intravenous oncolytic VV.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Virus Oncolíticos/fisiología , Virus Vaccinia/fisiología , Neutrófilos/patología , Viroterapia Oncolítica/métodos , Fosfatidilinositol 3-Quinasas , Neoplasias/patología , Microambiente Tumoral
3.
Environ Sci Technol ; 58(24): 10558-10566, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38833713

RESUMEN

Soot particles emitted from aircraft engines constitute a major anthropogenic source of pollution in the vicinity of airports and at cruising altitudes. This emission poses a significant threat to human health and may alter the global climate. Understanding the characteristics of soot particles, particularly those generated from Twin Annular Premixing Swirler (TAPS) combustors, a mainstream combustor in civil aviation engines, is crucial for aviation environmental protection. In this study, a comprehensive characterization of soot particles emitted from TAPS combustors was conducted using scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy. The morphology and nanostructure of soot particles were examined across three distinct fuel stage ratios (FSR), at 10%, 15%, and 20%. The SEM analysis of soot particle morphology revealed that coated particles constitute over 90% of the total particle sample, with coating content increasing proportionally to the fuel stage ratio. The results obtained from HRTEM indicated that average primary particle sizes increase with the fuel stage ratio. The results of HRTEM and Raman spectroscopy suggest that the nanostructure of soot particles becomes more ordered and graphitized with an increasing fuel stage ratio, resulting in lower oxidation activity. Specifically, soot fringe length increased with the fuel stage ratio, while soot fringe tortuosity and separation distance decreased. In addition, there is a prevalent occurrence of defects in the graphitic lattice structure of soot particles, suggesting a high degree of elemental carbon disorder.


Asunto(s)
Aeronaves , Hollín , Nanoestructuras/química , Tamaño de la Partícula , Emisiones de Vehículos , Espectrometría Raman , Contaminantes Atmosféricos
4.
Mol Ther ; 31(9): 2575-2590, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37408308

RESUMEN

Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells. And the supernatant of LIGHT CAR-T cells promoted T cell migration in a paracrine manner. Furthermore, LIGHT CAR-T cells showed superior anti-tumor efficacy and improved infiltration in comparison with conventional CAR-T cells in immunodeficient NSG mice. Accordingly, murine LIGHT-OT-1 T cells normalized tumor blood vessels and enforced intratumoral lymphoid structures in C57BL/6 syngeneic tumor mouse models, implying the potential of LIGHT CAR-T in clinical application. Taken together, our data revealed a straightforward strategy to optimize trafficking and cytotoxicity of CAR-T cells by redirecting TLSs through LIGHT expression, which has great potential to expand and optimize the application of CAR-T therapy in solid tumors.


Asunto(s)
Receptores Quiméricos de Antígenos , Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Animales , Ratones , Línea Celular Tumoral , Inmunoterapia Adoptiva , Ratones Endogámicos C57BL , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T , Microambiente Tumoral/genética
5.
Cell Mol Life Sci ; 80(3): 71, 2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36820986

RESUMEN

Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood-brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.


Asunto(s)
Barrera Hematoencefálica , Hipoxia-Isquemia Encefálica , Simportadores , Animales , Ratones , Transporte Biológico , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ratones Transgénicos , Simportadores/metabolismo , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología
6.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34035167

RESUMEN

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.


Asunto(s)
Vasos Sanguíneos/patología , Linfocitos T CD8-positivos/inmunología , Proteínas de Unión al Calcio/fisiología , Neoplasias/irrigación sanguínea , Neoplasias/patología , Animales , Femenino , Células HEK293 , Humanos , Inmunoterapia , Ratones , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/terapia , Microambiente Tumoral
7.
Mol Biol Evol ; 39(3)2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-35038730

RESUMEN

The spotted hyena (Crocuta crocuta) is a large and unique terrestrial carnivore. It is a particularly fascinating species due to its distinct phenotypic traits, especially its complex social structure and scavenging lifestyle, with associated high dietary exposure to microbial pathogens. However, the underlying molecular mechanisms related to these phenotypes remain elusive. Here, we sequenced and assembled a high-quality long-read genome of the spotted hyena, with a contig N50 length of ∼13.75 Mb. Based on comparative genomics, immunoglobulin family members (e.g., IGKV4-1) showed significant adaptive duplications in the spotted hyena and striped hyena. Furthermore, immune-related genes (e.g., CD8A, LAG3, and TLR3) experienced species-specific positive selection in the spotted hyena lineage. These results suggest that immune tolerance between the spotted hyena and closely related striped hyena has undergone adaptive divergence to cope with prolonged dietary exposure to microbial pathogens from scavenging. Furthermore, we provided the potential genetic insights underlying social complexity, hinting at social behavior and cognition. Specifically, the RECNE-associated genes (e.g., UGP2 and ACTR2) in the spotted hyena genome are involved in regulation of social communication. Taken together, our genomic analyses provide molecular insights into the scavenging lifestyle and societal complexity of spotted hyenas.


Asunto(s)
Hyaenidae , Animales , Secuencia de Bases , Genoma , Hyaenidae/genética , Conducta Social
8.
Small ; 19(29): e2300158, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37026682

RESUMEN

The non-contact and non-wetting droplet motion isolated from the solid surface has a high degree of freedom and thus can exhibit many peculiar interfacial phenomena. Here, an experimental phenomenon of spinning liquid metal droplets on an ice block is discovered, which adopts the dual solid-liquid phase transition of the liquid metal and the ice. The whole system is somewhat a variant of the classic Leidenfrost effect, which directly uses the latent heat released by the spontaneous solidification of the liquid metal droplet as a heat source to melt the ice and create an intervening lubricant water film. Interestingly, it is found that the droplets on ice become very mobile and undergo rapid spin as the solidification process proceeds. A series of comparative experiments clarify that the circumferential driving force comes from the escaping bubbles as the ice melts. Furthermore, by comparing the motion characteristics of different kinds of liquid metal droplets and solid balls on ice and investigating their physical properties and heat transfer, it is disclosed that the spin effect can be universal for objects of different materials, as long as the two necessary elements of rapid liquid film establishment and gas bubble release can be satisfied simultaneously.

9.
Metab Eng ; 78: 128-136, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37286072

RESUMEN

L-leucine is an essential amino acid widely used in food and pharmaceutical industries. However, the relatively low production efficiency limits its large-scale application. In this study, we rationally developed an efficient L-leucine-producing Escherichia coli strain. Initially, the L-leucine synthesis pathway was enhanced by overexpressing feedback-resistant 2-isopropylmalate synthase and acetohydroxy acid synthase both derived from Corynebacterium glutamicum, along with two other native enzymes. Next, the pyruvate and acetyl-CoA pools were enriched by deleting competitive pathways, employing the nonoxidative glycolysis pathway, and dynamically modulating the citrate synthase activity, which significantly promoted the L-leucine production and yield to 40.69 g/L and 0.30 g/g glucose, respectively. Then, the redox flux was improved by substituting the native NADPH-dependent acetohydroxy acid isomeroreductase, branched chain amino acid transaminase, and glutamate dehydrogenase with their NADH-dependent equivalents. Finally, L-leucine efflux was accelerated by precise overexpression of the exporter and deletion of the transporter. Under fed-batch conditions, the final strain LXH-21 produced 63.29 g/L of L-leucine, with a yield and productivity of 0.37 g/g glucose and 2.64 g/(L h), respectively. To our knowledge, this study achieved the highest production efficiency of L-leucine to date. The strategies presented here will be useful for engineering E. coli strains for producing L-leucine and related products on an industrial scale.


Asunto(s)
Corynebacterium glutamicum , Ingeniería Metabólica , Escherichia coli/genética , Escherichia coli/metabolismo , Leucina/genética , Leucina/metabolismo , Vías Biosintéticas , Glucosa/genética , Glucosa/metabolismo , Corynebacterium glutamicum/metabolismo
11.
Nanotechnology ; 33(29)2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35390780

RESUMEN

Carbon nanomaterials have become a promising anode material for potassium-ion batteries (KIBs) due to their abundant resources, low cost, and excellent conductivity. However, among carbon materials, the sluggish reaction kinetics and inferior cycle life severely restrict their commercial development as KIBs anodes. It is still a huge challenge to develop carbon materials with various structural advantages and ideal electrochemical properties. Therefore, it is imperative to find a carbon material with heteroatom doping and suitable nanostructure to achieve excellent electrochemical performance. Benefiting from a Na2SO4template-assisted method and KOH activation process, the KOH activated nitrogen and oxygen co-doped tubular carbon (KNOCTC) material with a porous structure exhibits an impressive reversible capacity of 343 mAh g-1at 50 mA g-1and an improved cyclability of 137 mAh g-1at 2 A g-1after 3000 cycles with almost no capacity decay. The kinetic analysis indicates that the storage mechanism in KNOCTC is attributed to the pseudocapacitive process during cycling. Furthermore, the new synthesis route of KNOCTC provides a new opportunity to explore carbon-based potassium storage anode materials with high capacity and cycling performance.

12.
J Nanobiotechnology ; 20(1): 166, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35346194

RESUMEN

The development of multidrug resistance (MDR) during cancer chemotherapy is a major challenge in current cancer treatment strategies. Numerous molecular mechanisms, including increased drug efflux, evasion of drug-induced apoptosis, and activation of DNA repair mechanisms, can drive chemotherapy resistance. Here we have identified the major vault protein (MVP) and the B-cell lymphoma-2 (BCL2) gene as two potential factors driving MDR in esophageal squamous cell carcinoma (ESCC). We have designed a novel and versatile self-assembling nanoparticle (NP) platform on a multifunctional carboxymethyl chitosan base to simultaneously deliver Adriamycin, and siRNAs targeting MVP and BCL2 (CEAMB NPs), thus reducing drug efflux and promoting apoptosis of esophageal cancer cells. To achieve effective delivery to tumor tissues and inhibit tumor growth in vivo, carboxymethyl chitosan was engineered to contain multiple histidines for enhanced cytosol delivery, cholesterol for improved self-assembly, and epidermal growth factor receptor (EGFR) antibodies to target cancer cells. Our results indicate that these nanoparticles are efficiently synthesized with the desired chemical composition to self-assemble into cargo-containing NPs. Furthermore, we have shown that the synthesized NPs will successfully inhibit cancer cells growth and tumor development when delivered to cultured ESCC cells or to in vivo mouse xenograft models. Our engineered NPs offer a potential novel platform in treating various types of chemotherapy-resistant tumors.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Nanopartículas Multifuncionales , Animales , Doxorrubicina/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Ratones , ARN Interferente Pequeño
13.
Curr Microbiol ; 79(2): 58, 2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-34982237

RESUMEN

The study aimed to evaluate the safety of copper ion sterilization based on copper ion residues in zebrafish (Brachydanio rerio), as well as bacterial community structure and diversity in recirculating aquaculture systems (RASs). The copper ion content was determined using national food safety standard GB 5009.13-2017. Bacterial community structures and alpha and beta diversity indexes were examined using the 16S rRNA gene sequences produced by Illumina HiSeq sequencing. The results revealed no significant copper ion enrichment in B. rerio when the copper ion concentration was 0.15 mg/L. The relative abundances of Erythrobacter, nitrite bacteria, and Flavanobacteria were clearly higher in the treatment group than in the control and differences in bacterial species richness and diversity were obvious. In addition, there was no sharp decrease in the microflora at the outflow of the copper ion generator. In conjunction with the changes in ammonia nitrogen, nitrate, and nitrite concentrations during the experiment, the results indicated that there were no significant effects on the purification efficacy of the biological filter, but the abundances of beneficial bacteria increased significantly. This is of great relevance in order to understand the response of bacterial communities affected by changing environmental conditions, such as copper ion sterilization.


Asunto(s)
Cobre , Pez Cebra , Animales , Acuicultura , Bacterias/genética , Cobre/farmacología , Agua Dulce , ARN Ribosómico 16S/genética , Esterilización
14.
BMC Genomics ; 22(1): 100, 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33530927

RESUMEN

BACKGROUND: Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or acquired (age-related) lesions. RESULTS: Here we used a functional candidate gene screening approach to identify mutations associated with cataracts in a captive giant panda (Ailuropoda melanoleuca). We screened 11 genes often associated with human cataracts and identified a novel missense mutation (c.686G > A) in the MIP gene encoding major intrinsic protein. This is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine (p.S229N) in the C-terminal tail of the protein, and modeling predicts that the mutation induces conformational changes that may interfere with lens permeability and cell-cell interactions. CONCLUSION: The c.686G > A mutation was found in a captive giant panda with a unilateral cataract but not in 18 controls from diverse regions in China, suggesting it is most likely a genuine disease-associated mutation rather than a single-nucleotide polymorphism. The mutation could therefore serve as a new genetic marker to predict the risk of congenital cataracts in captive giant pandas.


Asunto(s)
Catarata , Cristalino , Ursidae , Animales , Catarata/genética , Catarata/veterinaria , China , Humanos , Mutación Missense
15.
BMC Plant Biol ; 21(1): 264, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098903

RESUMEN

BACKGROUND: Prairie grass (Bromus catharticus) is a typical cool-season forage crop with high biomass production and fast growth rate during winter and spring. However, its genetic research and breeding has remained stagnant due to limited available genomic resources. The aim of this study was to generate large-scale genomic data using high-throughput transcriptome sequencing, and perform a preliminary validation of EST-SSR markers of B. catharticus. RESULTS: Eleven tissue samples including seeds, leaves, and stems were collected from a new high-yield strain of prairie grass BCS1103. A total of 257,773 unigenes were obtained, of which 193,082 (74.90%) were annotated. Comparison analysis between tissues identified 1803, 3030, and 1570 genes specifically and highly expressed in seed, leaf, and stem, respectively. A total of 37,288 EST-SSRs were identified from unigene sequences, and more than 80,000 primer pairs were designed. We synthesized 420 primer pairs and selected 52 ones with high polymorphisms to estimate genetic diversity and population structure in 24 B. catharticus accessions worldwide. Despite low diversity indicated by an average genetic distance of 0.364, the accessions from South America and Asia and wild accessions showed higher genetic diversity. Moreover, South American accessions showed a pure ancestry, while Asian accessions demonstrated mixed internal relationships, which indicated a different probability of gene flow. Phylogenetic analysis clustered the studied accessions into four clades, being consistent with phenotypic clustering results. Finally, Mantel analysis suggested the total phenotypic variation was mostly contributed by genetic component. Stem diameter, plant height, leaf width, and biomass yield were significantly correlated with genetic data (r > 0.6, P < 0.001), and might be used in the future selection and breeding. CONCLUSION: A genomic resource was generated that could benefit genetic and taxonomic studies, as well as molecular breeding for B. catharticus and its relatives in the future.


Asunto(s)
Bromus/genética , Perfilación de la Expresión Génica , Genes de Plantas , Proteínas de Plantas/genética , Transcripción Genética , Etiquetas de Secuencia Expresada , Marcadores Genéticos , Repeticiones de Microsatélite , Proteínas de Plantas/metabolismo
16.
BMC Cancer ; 21(1): 180, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33607955

RESUMEN

BACKGROUND: Aberrant activation of the Wnt/ß-catenin signaling pathway is one of the most frequent abnormalities in human cancer, including colorectal cancer (CRC). Previous studies revealed pivotal functions of WNT family members in colorectal cancer, as well as their prognostic values. Nevertheless, the prognostic role and mechanisms underlying WNT7b in colorectal cancer development remains unclear. METHODS: In this study, WNT7b expression was measured by immunohistochemical staining of 100 cases of surgically resected human colorectal cancerous tissues as well as matched adjacent normal tissues constructed as tissue microarrays. In vitro studies, we attempted to substantiate the WNT7b expressional pattern previously found in immunohistochemistry staining. We used the colorectal cancer cell-line HCT116 and normal colorectal cell-line FHC for immunofluorescence staining and nuclear/cytoplasmic separated western blotting. We measured epithelial-mesenchymal transition (EMT) markers and migration capacity of HCT116 in the context of WNT7b knocked-down using short interfering RNA. Finally, clinical and prognostic values of WNT7b activation levels were examined. RESULTS: WNT7b was expressed in the nucleus in adjacent normal tissues. In CRC tissues, nuclear expression of WNT7b was similar; however, membrane and cytoplasmic expression was strikingly enhanced. Consistently, in vitro analysis confirmed the same expression pattern of WNT7b. Compared with FHC cells, HCT116 cells displayed higher levels of WNT7b membrane and cytoplasmic enrichment, as well as higher migration capacity with a sensitized EMT process. Either partial knockdown of WNT7b or blockade of the Wnt/ß-catenin signaling pathway reversed EMT process and inhibited the migration of HCT116 cells. Finally, elevated secretion levels of WNT7b were significantly associated with lymphatic and remote metastasis and predicted worse prognosis in the CRC cohort. CONCLUSION: In summary, we demonstrated that the activation of WNT7b autocrine probably contributes to CRC metastasis by triggering EMT process through the Wnt/ß-catenin signaling pathway. High levels of WNT7b autocrine secretion predicts poor outcome in patients with CRC. This molecule is a promising candidate for clinical CRC treatments.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Proteínas Wnt/metabolismo , Vía de Señalización Wnt , Anciano , Anciano de 80 o más Años , Línea Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Tasa de Supervivencia
17.
Circ Res ; 125(8): 728-743, 2019 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-31455181

RESUMEN

Rationale: The constrained mitochondria in cardiomyocytes communicate with each other, through mitochondrial kissing or nanotunneling, forming a dynamically continuous network to share content and transfer signals. However, the molecular mechanism of cardiac inter-mitochondrial communication is unclear. Objective: To determine the molecular mechanism underlying the robust inter-mitochondrial communication and its pathophysiological relevance in the heart. Methods and Results: By mitochondria-targeted expressing the photoactivatable green fluorescent protein, we revealed that most mitochondrial nanotubes bridge communicating mitochondrial pairs were associated with microtubules. Miro2 (mitochondrial Rho GTPase), the outer mitochondrial membrane protein which usually mediates mitochondrial transport within cells, accompanied with mitochondrial nanotubes along microtubules in adult cardiomyocytes. Adenovirus mediated expression of Miro2 in cardiomyocytes accelerated inter-mitochondrial communication through increasing mitochondrial nanotunneling and mitochondrial kissing between adjacent mitochondrial pairs. In transverse aortic constriction-induced hypertrophic mouse hearts Miro2 protein was declined, accompanied with decreased inter-mitochondrial communication. Miro2 transgenic mice showed ameliorated cardiac function, increased mitochondrial nanotube formation and inter-mitochondrial communication, and improved mitochondrial function after transverse aortic constriction. E3 ubiquitin ligase Parkin was increased in transverse aortic constriction mouse hearts and phenylephrine stimulation-induced hypertrophic cardiomyocytes. Inhibition of proteasome blocked phenylephrine-induced decrease of Miro2, and Parkin overexpression led to the decrease of Miro2. Conclusions: Mitochondrial Miro2 expression levels regulate inter-mitochondrial communication along microtubules in adult cardiomyocytes, and degradation of Miro2 through Parkin-mediated ubiquitination contributes to impaired inter-mitochondrial communication and cardiac dysfunction during hypertrophic heart diseases.Visual Overview: An online visual overview is available for this article.


Asunto(s)
Cardiomegalia/metabolismo , Microtúbulos/metabolismo , Mitocondrias Cardíacas/metabolismo , Proteínas Mitocondriales/metabolismo , Transducción de Señal , Proteínas de Unión al GTP rho/metabolismo , Animales , Cardiomegalia/etiología , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Mitocondriales/genética , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fenilefrina/toxicidad , Proteolisis , Ratas , Ratas Sprague-Dawley , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Proteínas de Unión al GTP rho/genética
18.
Environ Res ; 197: 111129, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33839116

RESUMEN

The production of hydroxyl radicals has been demonstrated to improve the antifouling of marine through a photocatalytic strategy. However, only relying on the valence band of the photocatalyst to generate hydroxyl radicals is inefficient and limits the application of photocatalytic technology in the field of marine-antifouling coatings. Herein, we reported a new strategy in which Ag quantum dots are used to synthesize hydrogen peroxide (H2O2) by photocatalysis in seawater. The decomposition of the generated H2O2 to hydroxyl radicals improves the antifouling ability. Interestingly, the prominent size effect of Ag quantum dots is closely related to the yield of H2O2. We synthesized Ag quantum dots supported on ZnO and found that Ag quantum dots approximately 4 nm in size have the highest activity for H2O2 generation and undergo a 1 h photocatalytic reaction in which the concentration of H2O2 can reach 124 µg/mL. The efficiency of ZnO in inactivating marine microorganisms increased from 72.3% to 99.4% in seawater. The synthesis of H2O2 through photocatalysis based on the medium of seawater can expand the application of photocatalytic technology in the field of marine antifouling.


Asunto(s)
Puntos Cuánticos , Óxido de Zinc , Catálisis , Peróxido de Hidrógeno , Plata
19.
Environ Res ; 198: 111256, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33974844

RESUMEN

The use of photocatalytic technology to kill bacteria on marine vessel surface coatings has been paid more attention by research scholars. In this paper, petal-like microspheres with Ag nanoparticles were prepared by a simple one-step process combining the hydrothermal method and photodeposition. The 0.7% Ag/Bi2O2CO3 composite photocatalyst exhibited the highest photocatalytic efficiency for bacterial removal under visible light irradiation and had the highest photogenerated carrier separation efficiency, and the sterilization rate was doubled compared with that of pure Bi2O2CO3, reaching 95%. Using X-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron microscopy, the existence of Ag nanoparticles was confirmed, and their size was approximately 10 nm. The surface plasmon resonance (SPR) effect of Ag nanoparticles was investigated by ultraviolet-visible diffuse reflectance spectroscopy (DRS). It was shown that the surface plasmon resonance effect of Ag improved the spectral utilization of the Ag/Bi2O2CO3 composite photocatalyst and enhanced the stability of the catalyst. This caused the Ag/Bi2O2CO3 composite photocatalyst to have superior photocatalytic activity to pure Bi2O2CO3. The results of electrochemical impedance characterization and transient photocurrent response show that 0.7% Ag/Bi2O2CO3 has a high efficiency of photogenerated carrier separation. By the free radical capture test, hydroxyl radicals were the primary active substance, and Ag+ improved the photocatalytic sterilization activity.


Asunto(s)
Nanopartículas del Metal , Plata , Catálisis , Luz , Microscopía Electrónica de Transmisión
20.
Appl Microbiol Biotechnol ; 105(14-15): 5993-6005, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34272578

RESUMEN

Gut microbiota have a significant impact on host physiology and health, and host genetics and diet are considered as two important factors, but it is difficult to discriminate the influence of each single factor (host or diet) on gut microbiota under natural conditions. Moreover, current studies of avian microbiota mainly focus on domestic or captive birds, and it is still uncertain how host and diet take part in changing avian gut microbiota composition, diversity, and function in the wild. Here, high-throughput sequencing of 16S rRNA was used to identify the gut microbiota communities for sympatric wintering Great Bustards and Common Cranes at different diets. The results showed that 8.87% operational taxonomic units (OTUs) were shared among all sampling birds; in contrast, 39.43% of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were common among all individuals, indicating the existence of gut microbiota conservatism both in microbiota structure and function. Microbiota abundance and diversity differed between Great Bustards and Common Cranes in a specific wintering site, and microbiota variation was detected for the same host species under two different sites, suggesting that the change of gut microbiota was induced by both host and diet. Furthermore, we found that changes of both microbial communities and functional pathways were larger between hosts than those between diets, which revealed that host might be the dominant factor determining microbiota characteristics and function, while diet further drove the divergence of gut microbiota. Gut microbiota functions appeared to be more conserved than bacterial community structure, indicating that different bacteria may function in a similar way, while microbiota OTU diversity might not be necessarily associated with functional diversity. With diet shifting, gut microbiota changed both in terms of microbial communities and functional pathways for the sympatric birds, which implies that avian habitats and their physiological microbiota would be influenced by different farmland management regimes. KEY POINTS: • Gut microbiota can be shaped by both diets and hosts in sympatric species. • Host was the dominant factor shaping the gut microbiota communities and functional pathways. • Gut microbiota were conservative both in structure and in function, but more conservative in function.


Asunto(s)
Microbiota , Simpatría , Animales , Aves , Dieta , Humanos , ARN Ribosómico 16S/genética
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