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The study demonstrated that melatonin (MT) can induce the development of secondary hair follicles in Inner Mongolian cashmere goats through the Wnt10b gene, leading to secondary dehairing. However, the mechanisms underlying the expression and molecular function of Wnt10b in dermal papilla cells (DPC) remain unknown. This research aimed to investigate the impact of MT on DPC and the regulation of Wnt10b expression, function, and molecular mechanisms in DPC. The findings revealed that MT promotes DPC proliferation and enhances DPC activity. Co-culturing DPC with overexpressed Wnt10b and MT showed a significant growth promotion. Subsequent RNA sequencing (RNA-seq) of overexpressed Wnt10b and control groups unveiled the regulatory role of Wnt10b in DPC. Numerous genes and pathways, including developmental pathways such as Wnt and MAPK, as well as processes like hair follicle morphogenesis and hair cycle, were identified. These results suggest that Wnt10b promotes the growth of secondary hair follicles in Inner Mongolian cashmere goats by regulating crucial factors and pathways in DPC proliferation.
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Proliferación Celular , Cabras , Folículo Piloso , Melatonina , Proteínas Wnt , Animales , Folículo Piloso/metabolismo , Folículo Piloso/citología , Folículo Piloso/crecimiento & desarrollo , Cabras/genética , Cabras/metabolismo , Melatonina/farmacología , Melatonina/metabolismo , Proteínas Wnt/metabolismo , Proteínas Wnt/genética , Células CultivadasRESUMEN
Mammalian studies have demonstrated that B cell immune responses are regulated by mechanistic target of rapamycin complex 1 (mTORC1) signaling. Teleost fish represent the oldest living bony vertebrates that contain bona fide B cells. So far, whether the regulatory mechanism of mTORC1 signaling in B cells occurred in teleost fish is still unknown. In this study, we developed a fish model by using rapamycin (RAPA) treatment to inhibit mTORC1 signaling and demonstrated the role of mTORC1 signaling in teleost B cells. In support, we found inhibition of mTORC1 signaling by RAPA decreased the phagocytic capacity, proliferation, and Ig production of B cells. Critically, Flavobacterium columnare induced specific IgM binding in serum, and these titers were significantly inhibited by RAPA treatment, thus decreasing Ab-mediated agglutination of F. columnare and significantly increasing the susceptibility of fish upon F. columnare reinfection. Collectively, our findings elucidated that the mTORC1 pathway is evolutionarily conserved in regulating B cell responses, thus providing a new point for understanding the B cells functions in teleost fish.
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Linfocitos B , Transducción de Señal , Animales , Peces , Inmunoglobulina M , Mamíferos , Diana Mecanicista del Complejo 1 de la Rapamicina , Sirolimus/farmacologíaRESUMEN
The plant Goniothalamus leiocarpus of the Annonaceae family is used as an alternative medicine in tropical regions. Applying high-speed counter current chromatography (HSCCC), eight new bioactive styrylpyrone isomers, including 6R,7S,8R,2'S-goniolactone B (1), 6S,7S,8S,2'S-goniolactone B (2), 6R,7R,8R,2'S-goniolactone B (3), 6R,7S,8S,2'S-goniolactone C (4), 6R,7S,8R,2'S-goniolactone C (5), 6S,7R,8S,2'S-goniolactone C (6), and two positional isomers, 6R,7R,8R,2'S-goniolactone G (7) and 6S,7R,8R,2'S-goniolactone G (8), were isolated from a chloroform fraction (2.1 g) of G. leiocarpus, which had a prominent spot by TLC analysis. The structures of the new compounds were elucidated by MS, NMR, IR, and UV spectra, and their absolute configurations were determined by Mosher's method, ECD, and X-ray diffraction analysis. The isolates are characteristic components found in plants of the genus Goniothalamus and consist of two structural moieties: a styrylpyrone and a dihydroflavone unit. The isolation of the eight new compounds demonstrates the effectiveness of HSCCC in separating the isomers of natural styrylpyrone. In a bioactivity assessment, compounds 1 and 6 exhibited cytotoxic effects against the human colon carcinoma cell lines LS513 and SW620 with IC50 values ranging from 1.6 to 3.9 µM. Compounds 1, 2, 7, and 8 showed significant synergistic activity against antibiotic-resistant Staphylococcus aureus strains.
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Goniothalamus , Corteza de la Planta , Pironas , Goniothalamus/química , Pironas/química , Pironas/farmacología , Pironas/aislamiento & purificación , Estructura Molecular , Estereoisomerismo , Corteza de la Planta/química , Humanos , Distribución en Contracorriente/métodos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificaciónRESUMEN
Sorafenib was first approved as the standard treatment for advanced hepatocellular carcinoma (HCC). Despite providing an advantage in terms of patient survival, sorafenib has shown poor clinical efficacy and severe side effects after long-term treatment. Thus, combination treatment is a potential way to increase the effectiveness and reduce the dose-limiting toxicity of sorafenib. Extracts of the seeds of Annona montana have shown synergistic antitumor activity with sorafenib, and seven annonaceous acetogenins, including three new acetogenins, muricin P (2), muricin Q (3), and muricin R (4), were isolated from the extracts by bioguided fractionation and showed synergy with sorafenib. The structures of these compounds were determined using spectroscopic and chemical methods. Annonacin (1) and muricin P (2), which reduced intracellular ATP levels and promoted apoptosis, exhibited synergistic cytotoxicity with sorafenib in vitro. In vivo, annonacin (1) displayed synergistic antitumor activity by promoting tumor cell apoptosis. Moreover, the potential mechanism of annonacin (1) was predicted by transcriptomic analysis, which suggested that SLC33A1 is a potential target in HCC. Annonacin (1) might be a novel candidate for combination therapy with sorafenib against advanced HCC.
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Antineoplásicos Fitogénicos , Carcinoma Hepatocelular , Furanos , Lactonas , Neoplasias Hepáticas , Humanos , Acetogeninas/farmacología , Acetogeninas/química , Sorafenib/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Neoplasias Hepáticas/tratamiento farmacológico , Línea Celular Tumoral , ApoptosisRESUMEN
UPLC-TOF-MS/MDF directed phytochemical research of Chloranthus japonicus led to the isolation of 46 lindenane sesquiterpenoid dimers, which included 13 new analogs. Their structures with absolute configurations were elucidated by analysis of spectroscopic data. Fourteen compounds with ester chains significantly decreased PCSK9 protein level in medium of HepG2 cells, especially for compounds 14 and 29 (5 µM) with inhibition rates of 69.0% and 72.8%, respectively. Compound 14 in HepG2 cells was evaluated via DiI-LDL uptake assays and found to increase LDL uptake by upregulating LDLR mRNA and protein level. Meanwhile, 14 decreased the secretion of PCSK9 protein in medium and downregulated intracellular PCSK9 protein and mRNA level. The discovery of these natural small molecule compounds provides a novel structure basis for design PCSK9 regulators, making them a promising lead for development of new lipid-lowering agents.
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Proproteína Convertasa 9 , Sesquiterpenos , Humanos , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/metabolismo , Células Hep G2 , Sesquiterpenos/química , ARN MensajeroRESUMEN
BACKGROUND: Pulp regeneration is a novel approach for the treatment of immature permanent teeth with pulp necrosis. This technique includes the combination of stem cells, scaffolds, and growth factors. Recently, stem cell-derived extracellular vesicles (EVs) have emerged as a new methodology for pulp regeneration. Emerging evidence has proven that preconditioning is an effective scheme to modify EVs for better therapeutic potency. Meanwhile, proper scaffolding is of great significance to protect EVs from rapid clearance and destruction. This investigation aims to fabricate an injectable hydrogel loaded with EVs from pre-differentiated stem cells from human exfoliated deciduous teeth (SHEDs) and examine their effects on pulp regeneration. RESULTS: We successfully employed the odontogenic induction medium (OM) of SHEDs to generate functional EV (OM-EV). The OM-EV at a concentration of 20 µg/mL was demonstrated to promote the proliferation and migration of dental pulp stem cells (DPSCs). The results revealed that OM-EV has a better potential to promote odontogenic differentiation of DPSCs than common EVs (CM-EV) in vitro through Alizarin red phalloidin, alkaline phosphatase staining, and assessment of the expression of odontogenic-related markers. High-throughput sequencing suggests that the superior effects of OM-EV may be attributed to activation of the AMPK/mTOR pathway. Simultaneously, we prepared a photocrosslinkable gelatin methacryloyl (GelMA) to construct an OM-EV-encapsulated hydrogel. The hydrogel exhibited sustained release of OM-EV and good biocompatibility for DPSCs. The released OM-EV from the hydrogel could be internalized by DPSCs, thereby enhancing their survival and migration. In tooth root slices that were subcutaneously transplanted in nude mice, the OM-EV-encapsulated hydrogel was found to facilitate dentinogenesis. After 8 weeks, there was more formation of mineralized tissue, as well as higher levels of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1). CONCLUSIONS: The effects of EV can be substantially enhanced by preconditioning of SHEDs. The functional EVs from SHEDs combined with GelMA are capable of effectively promoting dentinogenesis through upregulating the odontogenic differentiation of DPSCs, which provides a promising therapeutic approach for pulp regeneration.
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Diferenciación Celular , Pulpa Dental , Vesículas Extracelulares , Gelatina , Metacrilatos , Odontogénesis , Regeneración , Células Madre , Diente Primario , Pulpa Dental/citología , Humanos , Vesículas Extracelulares/química , Gelatina/química , Gelatina/farmacología , Diferenciación Celular/efectos de los fármacos , Odontogénesis/efectos de los fármacos , Animales , Células Madre/efectos de los fármacos , Células Madre/citología , Células Madre/metabolismo , Regeneración/efectos de los fármacos , Diente Primario/citología , Metacrilatos/química , Metacrilatos/farmacología , Ratones , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Células Cultivadas , Hidrogeles/química , Hidrogeles/farmacología , Movimiento Celular/efectos de los fármacosRESUMEN
Myzus persicae is an important pest that has developed resistance to nearly all currently used insecticidal products. The employment of insecticide synergists is one of the effective strategies that need to be developed for the management of this resistance. Our study showed that treatment with a combination of the antibiotic, rifampicin, with imidacloprid, cyantraniliprole, or clothianidin significantly increased their toxicities against M. persicae, by 2.72, 3.59, and 2.41 folds, respectively. Rifampicin treatment led to a noteworthy reduction in the activities of multifunctional oxidases (by 32.64%) and esterases (by 23.80%), along with a decrease in the expression of the CYP6CY3 gene (by 58.57%) in M. persicae. It also negatively impacted the fitness of the aphids, including weight, life span, number of offspring, and elongation of developmental duration. In addition, bioassays showed that the combination of rifampicin and a detoxification enzyme inhibitor, piperonyl butoxide, or dsRNA of CYP6CY3 further significantly improved the toxicity of imidacloprid against M. persicae, by 6.19- and 7.55-fold, respectively. The present study suggests that development of active ingredients such as rifampicin as candidate synergists, show promise to overcome metabolic resistance to insecticides in aphids.
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Áfidos , Guanidinas , Insecticidas , Neonicotinoides , Nitrocompuestos , Butóxido de Piperonilo , Rifampin , Tiazoles , Animales , Rifampin/toxicidad , Rifampin/farmacología , Áfidos/efectos de los fármacos , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad , Tiazoles/toxicidad , Guanidinas/toxicidad , Butóxido de Piperonilo/toxicidad , Pirazoles/toxicidad , Sinergismo Farmacológico , Resistencia a los Insecticidas/genética , Sinergistas de Plaguicidas/toxicidad , ortoaminobenzoatos/toxicidad , Esterasas/metabolismoRESUMEN
Tomato yellow mottle-associated virus (TYMaV) belongs to the genus Cytorhabdovirus in the family Rhabdoviridae and has been reported to infect a variety of Solanaceae crops, such as Solanum lycopersicum, S. nigrum, Capsicum annuum and Nicotiana benthamiana (Li et al. 2022, Li et al. 2023, Xu et al. 2017, Zhou et al. 2019). In August 2022, about 500 out of 2000 tobacco (N. tabacum) plants showing leaf distortion, crinkling and mosaic symptoms were found in one tobacco growing field in Xingren City, Guizhou Province, China. To identify the causal pathogen(s), leaves from 20 symptomatic tobacco plants were collected and pooled to perform small RNA deep sequencing (sRNA-Seq) and assembly. Briefly, total RNA was extracted with TRIzol Reagent (Takara, Kusatsu, Japan). A small RNA cDNA library was constructed by the small RNA Sample Pre Kit. sRNA-Seq was performed with an Illumina NovaSeq 6000 platform. About 29 million reads were obtained and 334 contigs generated after removal of host-derived sequences. Among them, 31 unique contigs mapped to the TYMaV genome (NC_034240.1), covering 28.43% of the genome with the mean read coverage of 0.92%. Meanwhile, 226 contigs mapped to the genome of a potyvirus, chilli veinal mottle virus (ChiVMV, NC_005778.1), covering 88.79% of the genome with the mean read coverage of 0.83%. To verify the sRNA-Seq result for TYMaV identification, reverse transcription (RT)- PCR was performed with specific primers TYMaV-F (5'-CTGACGTAGTGTTGGCAGAT-3') and TYMaV-R (5'-AACCTCCATGCAGAACCATGG-3'). The expected-size 936-bp fragment was amplified from total RNA of all 20 samples. Dot enzyme-linked immunosorbent assays (Dot-ELISA) with antibody for TYMaV (kindly provided by Dr. Zhenggang Li from Guangdong Academy of Agricultural Sciences) were performed and further verified TYMaV infection. In addition, five asymptomatic tobacco plants from the same field as controls were used to detect TYMaV by RT-PCR and Dot-ELISA, and all samples showed negative test results. Subsequently, 17 primer pairs (Supplementary Table 1) were used to obtain the full-length sequence of TYMaV from a single positive tobacco sample by RT-PCR, followed by Sanger sequencing at Sangon Biotech (Shanghai, China). The resulting amplicon sequences were assembled into a nearly full-length genome sequence of a TYMaV isolate from tobacco in Guizhou (TYMaV-GZ). BLASTn analysis of the 13, 393 nt-long sequence (GeneBank accession number, PP444718) revealed 84.7% and 87.2% nt sequence identity with the TYMaV tomato isolate (KY075646.1) and the TYMaV S. nigrum isolate (MW527091.1), respectively. Moreover, five S. nigrum plants showing leaf crinkling and mosaic symptoms from tobacco fields tested positive for TYMaV by RT-PCR assay, suggesting a potential spread of TYMaV between tobacco and S. nigrum, which may serve as a reservoir for the virus in the tobacco fields. However, the transmission route of TYMaV remains unknown, and further verification is needed. To our knowledge, this is the first report of TYMaV infecting tobacco crop in China. It will be important to assess the potential economic importance of TYMaV to tobacco production in China and elsewhere, and to elucidate the respective roles of this virus and ChiVMV in the leaf distorting and yellowing symptoms.
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The substantial threat of concurrent air pollutants to public health is increasingly severe under climate change. To identify the common drivers and extent of spatiotemporal similarity of PM2.5 and ozone (O3), this paper proposed a log Gaussian-Gumbel Bayesian hierarchical model allowing for sharing a stochastic partial differential equation and autoregressive model of order one (SPDE-AR(1)) spatiotemporal interaction structure. The proposed model, implemented by the approach of integrated nested Laplace approximation (INLA), outperforms in terms of estimation accuracy and prediction capacity for its increased parsimony and reduced uncertainty, especially for the shared O3 sub-model. Besides the consistently significant influence of temperature (positive), extreme drought (positive), fire burnt area (positive), gross domestic product (GDP) per capita (positive), and wind speed (negative) on both PM2.5 and O3, surface pressure and precipitation demonstrate positive associations with PM2.5 and O3, respectively. While population density relates to neither. In addition, our results demonstrate similar spatiotemporal interactions between PM2.5 and O3, indicating that the spatial and temporal variations of these pollutants show relatively considerable consistency in California. Finally, with the aid of the excursion function, we see that the areas around the intersection of San Luis Obispo and Santa Barbara counties are likely to exceed the unhealthy O3 level for USG simultaneously with other areas throughout the year. Our findings provide new insights for regional and seasonal strategies in the co-control of PM2.5 and O3. Our methodology is expected to be utilized when interest lies in multiple interrelated processes in the fields of environment and epidemiology.
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Contaminantes Atmosféricos , Monitoreo del Ambiente , Ozono , Material Particulado , Ozono/análisis , California , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Teorema de Bayes , Análisis Espacio-Temporal , Cambio Climático , Contaminación del AireRESUMEN
Surface hydroxylation is the basis for material removal in chemical mechanical polishing (CMP) of monocrystalline silicon, diamond, and YAG crystals. Existing studies use experimental observations to investigate surface hydroxylation, but lack in-depth understanding of the hydroxylation process. In this paper, for the first time to the best of our knowledge, we analyze the surface hydroxylation process of YAG crystals in an aqueous solution using first-principle calculations. The presence of surface hydroxylation was verified by X-ray photoelectron spectroscopy (XPS) and thermogravimetric mass spectrometry (TGA-MS) detections. This study complements the existing research on the material removal mechanism of the CMP process of YAG crystals and provides theoretical support for the future improvement of the CMP technology.
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PURPOSE: Down syndrome (DS) is linked to a higher prevalence of obstructive sleep apnea (OSA) than in the general population, which in turn contributes to worse cognitive impairment in DS. However, the shared pathogenic mechanisms for DS and OSA remain incompletely illustrated. This study was designed to decipher the genetic cross-talk between DS and OSA by bioinformatics approach. METHODS: Transcriptomic datasets of DS (GSE59630) and OSA (GSE135917) were accessed from the Gene Expression Omnibus (GEO) repository. After screening out the common differentially expressed genes (DEGs) for DS and OSA, gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out. A protein-protein interaction (PPI) network was then constructed to determine essential modules and hub genes. Finally, based on hub genes, transcriptional factor (TF)-gene interaction and TF-miRNA regulatory networks were constructed. RESULTS: DS and OSA showed 229 DEGs. Functional analyses revealed how oxidative stress and inflammatory response were critical in the progression of DS and OSA. Ten significant hub genes were identified, including TLR4, SOD1, IGF1, FGF2, NFE2L2, PECAM1, S100A8, S100A9, FCGR3A, and KCNA1, which were candidate targets for DS and OSA. CONCLUSIONS: We found that DS and OSA display similarities in their pathogenesis. Key genes and signaling pathways revealed to be in common between the two conditions could lead us to new therapeutic targets for DS and OSA.
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Síndrome de Down , Apnea Obstructiva del Sueño , Humanos , Transcriptoma/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Perfilación de la Expresión Génica , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/diagnóstico , Cruzamientos GenéticosRESUMEN
Sorafenib (SF), a multi-kinase inhibitor, is the first FDA-approved systemic chemotherapy drug for advanced hepatocellular carcinoma (HCC). However, its clinical application is limited by severe toxicity and side effects associated with high applied doses. Sophora alopecuroides L. is traditionally used as Chinese herbal medicine for treating gastrointestinal diseases, bacillary dysentery, viral hepatitis, and other diseases, and exerts an important role in anti-tumor. Hence, we investigated the synergistic actions of seventeen flavonoids from this herb combined with SF against HCC cell lines and their primary mechanism. In the experiment, most compounds were found to prominently enhance the inhibitory effects of SF on HCC cells than their alone treatment. Among them, three compounds leachianone A (1), sophoraflavanone G (3), and trifolirhizin (17) exhibited significantly synergistic anticancer activities against MHCC97H cells at low concentration with IC50 of SF reduced by 5.8-fold, 3.6-fold, and 3.5-fold corresponding their CI values of 0.49, 0.66, and 0.46 respectively. Importantly, compounds 3 or 17 combined with SF could synergistically induce MHCC97H cells apoptosis via the endogenously mitochondrial-mediated apoptotic pathway, involving higher Bax/Bcl-2 expressions with the activation of caspase-9 and -3, and arrest the cell cycle in G1 phases. Strikingly, this synergistic effect was also closely related to the co-suppression of ERK and AKT signaling pathways. Furthermore, compound 3 significantly enhanced the suppression of SF on tumor growth in the HepG2 xenograft model, with a 79.3% inhibition ratio at high concentration, without systemic toxicity, compared to either agent alone. These results demonstrate that the combination treatment of flavonoid 3 and SF at low doses exert synergistic anticancer effects on HCC cells in vitro and in vivo.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Sophora , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/patología , Flavonoides/farmacología , Flavonoides/uso terapéutico , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Proliferación Celular , Compuestos de Fenilurea/farmacologíaRESUMEN
Exosomes are small nanovesicles with a size of approximately 40-120 nm that are secreted from cells. They are involved in the regulation of cell homeostasis and mediate intercellular communication. In addition, they carry proteins, nucleic acids, and lipids that regulate the biological activity of receptor cells. Recent studies have shown that exosomes perform important functions in liver diseases. This review will focus on liver diseases (drug-induced liver injury, hepatic ischemia-reperfusion injury, liver fibrosis, acute liver failure, and hepatocellular carcinoma) and summarize the therapeutic potential of exosomes from different cell sources in liver disease.
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Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , Carcinoma Hepatocelular/metabolismo , Exosomas/metabolismo , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/terapia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapiaRESUMEN
Surface plasmons usually take two forms: surface plasmon polaritons (SPP) and localized surface plasmons (LSP). Recent experiments demonstrate an interesting plasmon mode within plasmonic gaps, showing distinct characters from the two usual forms. In this investigation, by introducing a fundamental concept of SPP standing wave and an analytical model, we reveal the nature of the recently reported plasmon modes. The analytical model includes SPP propagating and SPP reflection within a metal-insulator-metal (MIM) cavity, which is rechecked and supplemented by numerical simulations. We systematically analyze SPP standing waves within various nanocavities. During the discussion, some unusual phenomena have been explained. For example, the hot spot of a nanodimer could be off-tip, depending on the order of standing wave mode; and that a nanocube on metal film can be viewed as a nanocube dimer with the same separation. And many other interesting phenomena have been discussed, such as dark mode of SPP standing wave and extraordinary optical transmission. The study gives a comprehensive understanding of SPP standing waves, and may promote the applications of cavity plasmons in ultrasensitive bio-sensings.
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BACKGROUND: Although several clinical studies have analysed the relationship between the levels of vascular endothelial growth factor (VEGF) and apelin-13 in venous blood and retinopathy of prematurity (ROP), no definitive conclusions have been reached. This study aimed to investigate the relationship between apelin-13 levels and VEGF levels and ROP. METHODS: Differences in plasma apelin-13 and VEGF levels were analysed in two groups of infants born with birth weight < 1500 g and gestational age < 32 weeks at Peking University People' s Hospital. One group comprised infants diagnosed with ROP and the other group was a control group comprising infants without ROP. RESULTS: Apelin-13 levels were significantly lower in the ROP group than in the control group, while VEGF levels showed the opposite result (both P < 0.001). Infants with severe ROP had lower apelin-13 levels and higher VEGF levels than with mild ROP (both P < 0.05).The receiver operating characteristic curve for apelin-13 level as the indicator of ROP showed that a cut-off value of 119.6 pg/mL yielded a sensitivity of 84.8% and a specificity of 63.6%, while for VEGF level, the cut-off value of 84.3 pg/mL exhibited a sensitivity of 84.8% and a specificity of 66.7%. CONCLUSIONS: Plasma apelin-13 and VEGF levels at 4-6 weeks of age may play a role in assisting the diagnosis of ROP.
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Retinopatía de la Prematuridad , Apelina , Estudios de Casos y Controles , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recién Nacido de muy Bajo Peso , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Down's syndrome (DS), a common chromosomal disease caused by chromosome 21 trisomy, is the main cause of cognitive impairment in children worldwide. Emerging evidence suggests that the microbiota-gut-brain axis plays a potential role in cognitive impairment. However, data regarding gut microbiota alterations in DS patients remain scarce, especially data from children with DS. This case-control study was conducted to explore the gut microbiota composition in Chinese DS children. Additionally, the potential association between gut microbiota and cognitive function in DS was evaluated. Microbiota communities in the feces of 15 DS subjects and 15 matched controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S rRNA gene. The relationships between gut microbiota composition and DS cognitive function scores were analyzed. The structure and richness of the gut microbiota differed between DS patients and healthy controls. The abundance of Acidaminococcaceae was decreased in DS patients. Moreover, the Kyoto Encyclopedia of Genes and Genomes analysis showed increased modules related to peptidases and pyrimidine metabolism. Overall, we confirmed that gut microbiota alterations occurred in Chinese patients with DS. Additionally, the fecal microbiota was closely related to DS cognitive impairment. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved. Elucidating these novel findings in the field of microbiota-gut-brain axis will provide a promising strategy for future studies of DS cognitive impairment.
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Disfunción Cognitiva , Síndrome de Down , Microbioma Gastrointestinal , Estudios de Casos y Controles , Niño , China , Disfunción Cognitiva/etiología , Humanos , ARN Ribosómico 16SRESUMEN
BACKGROUND: Early recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT. METHODS: A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram. RESULTS: There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model. CONCLUSIONS: Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Nomogramas , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVES: The objective of our study was to develop and validate a deep learning approach based on convolutional neural networks (CNNs) for automatic detection of the mandibular third molar (M3) and the mandibular canal (MC) and evaluation of the relationship between them on CBCT. MATERIALS AND METHODS: A dataset of 254 CBCT scans with annotations by radiologists was used for the training, the validation, and the test. The proposed approach consisted of two modules: (1) detection and pixel-wise segmentation of M3 and MC based on U-Nets; (2) M3-MC relation classification based on ResNet-34. The performances were evaluated with the test set. The classification performance of our approach was compared with two residents in oral and maxillofacial radiology. RESULTS: For segmentation performance, the M3 had a mean Dice similarity coefficient (mDSC) of 0.9730 and a mean intersection over union (mIoU) of 0.9606; the MC had a mDSC of 0.9248 and a mIoU of 0.9003. The classification models achieved a mean sensitivity of 90.2%, a mean specificity of 95.0%, and a mean accuracy of 93.3%, which was on par with the residents. CONCLUSIONS: Our approach based on CNNs demonstrated an encouraging performance for the automatic detection and evaluation of the M3 and MC on CBCT. Clinical relevance An automated approach based on CNNs for detection and evaluation of M3 and MC on CBCT has been established, which can be utilized to improve diagnostic efficiency and facilitate the precision diagnosis and treatment of M3.
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Aprendizaje Profundo , Tomografía Computarizada de Haz Cónico Espiral , Tomografía Computarizada de Haz Cónico , Canal Mandibular , Diente Molar , Tercer Molar/diagnóstico por imagenRESUMEN
Plant viruses are devastating plant pathogens that severely affect crop yield and quality. Plants have developed multiple lines of defense systems to combat viral infection. Gene silencing/RNA interference is the key defense system in plants that inhibits the virulence and multiplication of pathogens. The general mechanism of RNAi involves (i) the transcription and cleavage of dsRNA into small RNA molecules, such as microRNA (miRNA), or small interfering RNA (siRNA), (ii) the loading of siRNA/miRNA into an RNA Induced Silencing Complex (RISC), (iii) complementary base pairing between siRNA/miRNA with a targeted gene, and (iv) the cleavage or repression of a target gene with an Argonaute (AGO) protein. This natural RNAi pathway could introduce transgenes targeting various viral genes to induce gene silencing. Different RNAi pathways are reported for the artificial silencing of viral genes. These include Host-Induced Gene Silencing (HIGS), Virus-Induced Gene Silencing (VIGS), and Spray-Induced Gene Silencing (SIGS). There are significant limitations in HIGS and VIGS technology, such as lengthy and time-consuming processes, off-target effects, and public concerns regarding genetically modified (GM) transgenic plants. Here, we provide in-depth knowledge regarding SIGS, which efficiently provides RNAi resistance development against targeted genes without the need for GM transgenic plants. We give an overview of the defense system of plants against viral infection, including a detailed mechanism of RNAi, small RNA molecules and their types, and various kinds of RNAi pathways. This review will describe how RNA interference provides the antiviral defense, recent improvements, and their limitations.
Asunto(s)
MicroARNs , Virus de Plantas , Proteínas Argonautas/genética , Virus de Plantas/genética , Plantas/genética , Interferencia de ARN , ARN Bicatenario/genética , ARN Interferente Pequeño/genética , Complejo Silenciador Inducido por ARN/genéticaRESUMEN
BACKGROUND: Based on the interrelationship among photosynthesis (Pn), water consumption and drought resistance physiology under water changes, this study aimed to explore whether easily measured Pn could be used to reflect the physiological state of winter wheat and soil moisture. The study was a greenhouse pot experiment, with three growth periods and four gradients of moisture. RESULTS: The instantaneous water use efficiency of wheat improved significantly under short-term regulated deficit irrigation conditions. The photosynthetic parameters could effectively reflect the level of soil moisture (receiver operating characteristic curve analysis, area under the curve = 0.683-0.988). There was a significant correlation between Pn and yield under drought and rewatering (P < 0.05). The water consumption of winter wheat was significantly reduced by 15.5% to 47.6% (P < 0.05) during drought owing to the reduction of stomatal conductance and transpiration rate (Tr). There was a significant linear relationship between Tr and daily water consumption (R2 > 0.745, P< 0.05). There was a significant quadratic linear relationship (R2 > 0.600, P < 0.05) between Pn and the drought resistance indicators. The protective effect of drought resistance physiology on Pn was more significant during drought than during rewatering. Among the four physiological indicators of drought resistance, the relationship between peroxidase activity and Pn was relatively close (grey relational analysis, GRO = 1). CONCLUSIONS: The photosynthetic parameters during conditions of short-term water changes could effectively reflect the status of soil moisture, water consumption, yield and drought resistance. A focus on Pn and the rational use of related relationships are conducive to the selection of drought-resistant varieties and developing refined agricultural management. © 2021 Society of Chemical Industry.