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Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Proteínas Portadoras , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas de Microfilamentos , Sirtuinas , Humanos , Acetilación , Actinas/metabolismo , Línea Celular Tumoral , Neoplasias Esofágicas/patología , Histona Acetiltransferasas/metabolismo , Metástasis Linfática , Sirtuinas/metabolismoRESUMEN
BACKGROUND: Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. METHODS: SiRNA transfection, wound - healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. RESULTS: The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. CONCLUSION: In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNAâmiRNA-mRNA functional network and a new potential therapeutic target for SKCM.
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Secuencia de Bases , Movimiento Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Melanoma , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Técnicas de Silenciamiento del Gen , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismoRESUMEN
The trade-off between the lateral and vertical resolution has long posed challenges to the efficient and widespread application of Fourier light-field microscopy, a highly scalable 3D imaging tool. Although existing methods for resolution enhancement can improve the measurement result to a certain extent, they come with limitations in terms of accuracy and applicable specimen types. To address these problems, this paper proposed a resolution enhancement scheme utilizing data fusion of polarization Stokes vectors and light-field information for Fourier light-field microscopy system. By introducing the surface normal vector information obtained from polarization measurement and integrating it with the light-field 3D point cloud data, 3D reconstruction results accuracy is highly improved in axial direction. Experimental results with a Fourier light-field 3D imaging microscope demonstrated a substantial enhancement of vertical resolution with a depth resolution to depth of field ratio of 0.19%. This represented approximately 44 times the improvement compared to the theoretical ratio before data fusion, enabling the system to access more detailed information with finer measurement accuracy for test samples. This work not only provides a feasible solution for breaking the limitations imposed by traditional light-field microscope hardware configurations but also offers superior 3D measurement approach in a more cost-effective and practical manner.
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BACKGROUND: This study aims to assess the long-term trends in the burden of three major gynecologic cancers(GCs) stratified by social-demographic status across the world from 1990 to 2019. To assess the trends of risk factor attributed mortality, and to examine the specific effects of age, period, cohort behind them in different regions. METHODS: We extracted data on the mortality, disability-adjusted life years(DALYs), and age-standardized rates(ASRs) of cervical cancer(CC), uterine cancer(UC), and ovarian cancer(OC) related to risks from 1990 to 2019, as GCs burden measures. Age-period-cohort analysis was used to analyze trends in attributable mortality rates. RESULTS: The number of deaths and DALYs for CC, UC and OC increased since 1990 worldwide, while the ASDRs decreased. Regionally, the ASDR of CC was the highest in low SDI region at 15.05(11.92, 18.46) per 100,000 in 2019, while the ASDRs of UC and OC were highest in high SDI region at 2.52(2.32,2.64), and 5.67(5.16,6.09). The risk of CC death caused by unsafe sex increased with age and then gradually stabilized, with regional differences. The period effect of CC death attributed to smoking showed a downward trend. The cohort effect of UC death attributed to high BMI decreased in each region, especially in the early period in middle, low-middle and low SDI areas. CONCLUSIONS: Global secular trends of attributed mortality for the three GCs and their age, period, and cohort effects may reflect the diagnosis and treatment progress, rapid socioeconomic transitions, concomitant changes in lifestyle and behavioral patterns in different developing regions. Prevention and controllable measures should be carried out according to the epidemic status in different countries, raising awareness of risk factors to reduce future burden.
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Neoplasias de los Genitales Femeninos , Humanos , Femenino , Factores de Riesgo , Persona de Mediana Edad , Adulto , Anciano , Neoplasias de los Genitales Femeninos/epidemiología , Neoplasias de los Genitales Femeninos/mortalidad , Estudios de Cohortes , Años de Vida Ajustados por Discapacidad/tendencias , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/mortalidad , Salud Global/estadística & datos numéricos , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/epidemiología , Factores de Edad , Adulto Joven , Costo de EnfermedadRESUMEN
BACKGROUND: Modeling causality through graphs, referred to as causal graph learning, offers an appropriate description of the dynamics of causality. The majority of current machine learning models in clinical decision support systems only predict associations between variables, whereas causal graph learning models causality dynamics through graphs. However, building personalized causal graphs for each individual is challenging due to the limited amount of data available for each patient. METHOD: In this study, we present a new algorithmic framework using meta-learning for learning personalized causal graphs in biomedicine. Our framework extracts common patterns from multiple patient graphs and applies this information to develop individualized graphs. In multi-task causal graph learning, the proposed optimized initial guess of shared commonality enables the rapid adoption of knowledge to new tasks for efficient causal graph learning. RESULTS: Experiments on one real-world biomedical causal graph learning benchmark data and four synthetic benchmarks show that our algorithm outperformed the baseline methods. Our algorithm can better understand the underlying patterns in the data, leading to more accurate predictions of the causal graph. Specifically, we reduce the structural hamming distance by 50-75%, indicating an improvement in graph prediction accuracy. Additionally, the false discovery rate is decreased by 20-30%, demonstrating that our algorithm made fewer incorrect predictions compared to the baseline algorithms. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the effectiveness of meta-learning in personalized causal graph learning and cause inference modeling for biomedicine. In addition, the proposed algorithm can also be generalized to transnational research areas where integrated analysis is necessary for various distributions of datasets, including different clinical institutions.
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Algoritmos , Aprendizaje Automático , Humanos , CausalidadRESUMEN
Cultivated wheat is continually exposed to various pathogens. Blumeria graminis f. sp. tritici (Bgt) causes powdery mildew disease and significant yield loss. Pm60 was cloned from Triticum urartu and confers race-specific powdery mildew resistance in wheat. Pm60a and Pm60b are allelic variants of Pm60 and have two leucine-rich repeat motifs deletions and insertions, respectively, which were detected in other T. urartu accessions. Through map-based cloning, virus-induced gene silencing, and stable transformation assays, we demonstrated that Pm60a and Pm60b conferred Bgt E09 resistance resembling that provided by Pm60. However, the homozygous Pm60a (but not Pm60 or Pm60b) transformants driven by the native promoters lacked race-specific resistance when they were inoculated with Bgt E18. As all three T. urartu accessions contained the three foregoing alleles, they had high resistance to Bgt E18. Pyramiding Pm60a with either of the allelic genes in F1 plants did not cause mutual allele suppression or interference with Bgt E18 resistance. Deletion (but not insertion) of the two leucine-rich repeat motifs in Pm60a substantially narrowed the resistance spectrum. In T. urartu accession PI428210, we identified another locus adjacent to Pm60a and resistant to Bgt E18. Characterization of the alleles at the Pm60 locus revealed their diversity and similarity and may facilitate wheat breeding for resistance to powdery mildew disease caused by B. graminis f. sp. tritici.
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Resistencia a la Enfermedad , Triticum , Alelos , Ascomicetos , Resistencia a la Enfermedad/genética , Leucina , Fitomejoramiento , Enfermedades de las Plantas/genética , Triticum/genéticaRESUMEN
KEY MESSAGE: Two recessive powdery mildew resistance loci pmAeCIae8_2DS and pmAeCIae8_7DS from Aegilops tauschii were mapped and two synthesized hexaploid wheat lines were developed by distant hybridization. Wheat powdery mildew (Pm), one of the worldwide destructive fungal diseases, causes significant yield loss up to 30%. The identification of new Pm resistance genes will enrich the genetic diversity of wheat breeding for Pm resistance. Aegilops tauschii is the ancestor donor of sub-genome D of hexaploid wheat. It provides beneficial genes that can be easily transferred into wheat by producing synthetic hexaploid wheat followed by genetic recombination. We assessed the Pm resistance level of 35 Ae. tauschii accessions from different origins. Accession CIae8 exhibited high Pm resistance. Inheritance analysis and gene mapping were performed using F2 and F2:3 populations derived from the cross between CIae8 and a Pm susceptible accession PI574467. The Pm resistance of CIae8 was controlled by two independent recessive genes. Bulked segregate analysis using a 55 K SNP array revealed the SNPs were mainly enriched into genome regions, i.e. 2DS (13.5-20 Mb) and 7DS (4.0-15.5 Mb). The Pm resistance loci were named as pmAeCIae8_2DS and pmAeCIae8_7DS, respectively. By recombinant screening, we narrowed the pmAeCIae8_2DS into a 370-kb interval flanked by markers CINAU-AE7800 (14.89 Mb) and CINAU-AE20 (15.26 Mb), and narrowed the pmAeCIae8_7DS into a 260-kb interval flanked by markers CINAU-AE58 (4.72 Mb) and CINAU-AE25 (4.98 Mb). The molecular markers closely linked with the resistance loci were developed, and two synthesized hexaploid wheat (SHW) lines were produced. These laid the foundation for cloning of the two resistance loci and for transferring the resistance into common wheat.
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Aegilops , Genes Recesivos , Fitomejoramiento , Triticum , Mapeo Cromosómico , PoaceaeRESUMEN
Expert microscopic analysis of cells obtained from frequent heart biopsies is vital for early detection of pediatric heart transplant rejection to prevent heart failure. Detection of this rare condition is prone to low levels of expert agreement due to the difficulty of identifying subtle rejection signs within biopsy samples. The rarity of pediatric heart transplant rejection also means that very few gold-standard images are available for developing machine learning models. To solve this urgent clinical challenge, we developed a deep learning model to automatically quantify rejection risk within digital images of biopsied tissue using an explainable synthetic data augmentation approach. We developed this explainable AI framework to illustrate how our progressive and inspirational generative adversarial network models distinguish between normal tissue images and those containing cellular rejection signs. To quantify biopsy-level rejection risk, we first detect local rejection features using a binary image classifier trained with expert-annotated and synthetic examples. We converted these local predictions into a biopsy-wide rejection score via an interpretable histogram-based approach. Our model significantly improves upon prior works with the same dataset with an area under the receiver operating curve (AUROC) of 98.84% for the local rejection detection task and 95.56% for the biopsy-rejection prediction task. A biopsy-level sensitivity of 83.33% makes our approach suitable for early screening of biopsies to prioritize expert analysis. Our framework provides a solution to rare medical imaging challenges currently limited by small datasets.
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Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Niño , Diagnóstico por Imagen , Aprendizaje Automático , Medición de Riesgo , Complicaciones PosoperatoriasRESUMEN
Specular highlights present a challenge in light field microscopy imaging fields, leading to loss of target information and incorrect observation results. Existing highlight elimination methods suffer from computational complexity, false information and applicability. To address these issues, an adaptive multi-polarization illumination scheme is proposed to effectively eliminate highlight reflections and ensure uniform illumination without complex optical setup or mechanical rotation. Using a multi-polarized light source with hybrid modulated illumination, the system achieved combined multi-polarized illumination and physical elimination of specular highlights. This was achieved by exploiting the different light contributions at different polarization angles and by using optimal solution algorithms and precise electronic control. Experimental results show that the proposed adaptive illumination system can efficiently compute control parameters and precisely adjust the light source output in real time, resulting in a significant reduction of specular highlight pixels to less than 0.001% of the original image. In addition, the system ensures uniform illumination of the target area under different illumination configurations, further improving the overall image quality. This study presents a multi-polarization-based adaptive de-highlighting system with potential applications in miniaturization, biological imaging and materials analysis.
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Powdery mildew, a fungal disease caused by Blumeria graminis f. sp. tritici (Bgt), has a serious impact on wheat production. Loss of resistance in cultivars prompts a continuing search for new sources of resistance. Wild emmer wheat (Triticum turgidum ssp. dicoccoides, WEW), the progenitor of both modern tetraploid and hexaploid wheats, harbors many powdery mildew resistance genes. We report here the positional cloning and functional characterization of Pm41, a powdery mildew resistance gene derived from WEW, which encodes a coiled-coil, nucleotide-binding site and leucine-rich repeat protein (CNL). Mutagenesis and stable genetic transformation confirmed the function of Pm41 against Bgt infection in wheat. We demonstrated that Pm41 was present at a very low frequency (1.81%) only in southern WEW populations. It was absent in other WEW populations, domesticated emmer, durum, and common wheat, suggesting that the ancestral Pm41 was restricted to its place of origin and was not incorporated into domesticated wheat. Our findings emphasize the importance of conservation and exploitation of the primary WEW gene pool, as a valuable resource for discovery of resistance genes for improvement of modern wheat cultivars.
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Ascomicetos , Triticum , Ascomicetos/genética , Resistencia a la Enfermedad/genética , Genes de Plantas , Enfermedades de las Plantas , Triticum/genéticaRESUMEN
Bromus catharticus, rescuegrass, is a brome grass that has been cultivated for herbage production, and been widely naturalized in many provinces of China, including Henan province. During April and May 2020, powdery mildew was found on leaves of Br. catharticus on the campus of Henan Normal University, Xinxiang city (35.3°N; 113.9°E), Henan Province, China. Abundant white or grayish irregular or coalesced circular powdery colonies were scattered on the adaxial surface of leaves and 70% of the leaf areas were affected. Some of the infected leaves either were chlorotic or senescent. About 60% of the observed plants showed powdery mildew symptoms. Conidiophores (n = 25) were 32 to 45 µm × 7 to 15 µm and composed of foot cells and conidia (mostly 6 conidia) in chains. Conidia (n = 50) were 25 to 35 µm × 10 to 15 µm, on average 30 × 13 µm, with a length/width ratio of 2.3. Chasmothecia were not found. Based on these morphologic characteristics, the pathogen was initially identified as Blumeria graminis f. sp. bromi (Braun and Cook 2012; Troch et al. 2014). B. graminis mycelia and conidia were collected, and total genomic DNA was extracted (Zhu et al. 2019). The rDNA internal transcribed spacer (ITS) region was amplified with primer pairs ITS1/ITS4. The amplicon was cloned and sequenced. The sequence (574 bp) was deposited into GenBank under Accession No. MT892940. BLASTn analysis revealed that MT892940 was 100% identical to B. graminis f. sp. bromi on Br. catharticus (AB000935, 550 of 550 nucleotides) (Takamatsu et al. 1998). Phylogenetic analysis of MT892940 and ITS of other B. graminis ff. spp. clearly indicated least two phylogenetically distinct clades of B. graminis f. sp. bromi and that MT892940 clustered with the Takamatsu vouchers. Leaf surfaces of five healthy plants were fixed at the base of a settling tower and then inoculated by blowing conidia from diseased leaves using pressurized air. Five non-inoculated plants served as controls. The inoculated and non-inoculated plants were maintained separately in two growth chambers (humidity, 60%; light/dark, 16 h/8 h; temperature, 18â). Thirteen- to fifteen-days after inoculation, B. graminis signs and symptoms were visible on inoculated leaves, whereas control plants remained asymptomatic. The pathogenicity assays were repeated twice with the same results. The observed signs and symptoms were morphologically identical to those of the originally infected leaves. Accordingly, the causal organism of the powdery mildew was confirmed as B. graminis f. sp. bromi by morphological characteristics and ITS sequence data. B. graminis has been reported on Br. catharticus in the United States (Klingeman et al. 2018), Japan (Inuma et al. 2007) and Argentina (Delhey et al. 2003). To our best knowledge, this is the first report of B. graminis on Br. catharticus in China. Since hybridization of B. graminis ff. spp. is a mechanism of adaptation to new hosts, Br. catharticus may serve as a primary inoculum reservoir of B. graminis to infect other species (Menardo et al. 2016). This report provides fundamental information for the powdery mildew that can be used to develop control management of the disease in Br. catharticus herbage production.
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Poa pratensis, known as bluegrass, is a perennial grass and one of the best varieties with highly valued pasture and turf grass uses. It is widely grown on golf courses and used for lawns in squares and parks (Luo et al. 2020). During April and May 2020, powdery mildew-like signs and symptoms were observed on leaves of P. pratensis in Muye Park, Xinxiang city (35.3°N; 113.9°E), Henan Province, China. White or grayish powdery masses in spots- or coalesced lesions were abundant on the adaxial surfaces of leaves and covered up to 90 % of the leaf area. Some of the mildew-infested leaves appeared chlorotic or began senescence. Mildew-infested leaves were collected to microscopically observe the morphological characteristics of this pathogen. Conidiophores were composed of foot cells, followed by one or two cells, and conidia. The ellipsoid- shaped conidia (n = 50) were 25 - 36 × 10 - 15 µm (length × width), on average 30 × 13 µm, with a length/width ratio of 2.3. Foot-cells (n = 15) were 30 - 44 µm long and 7 - 15 µm wide. On leaf surfaces, germinated conidia produced a short primary germ tube and then a long secondary germ tube that finally differentiated into a hooked appressorium. Chasmothecia were not found. Based on these morphological characteristics, the pathogen was initially identified as B. graminis f. sp. poae, the known forma specialis (f. sp.) of B. graminis on P. pratensis (Braun and Cook 2012; Troch et al. 2014). Mycelia of the pathogen were scraped from infected leaves and total genomic DNA was isolated using the method described previously (Zhu et al. 2019). The rDNA internal transcribed spacer (ITS) region was amplified applying primer pairs ITS1/ITS4 (White et al. 1990). The amplicon was cloned and sequenced by Invitrogen (Shanghai, China). The obtained sequence for the pathogen was deposited into GenBank under Accession No. MT892956 and was 100 % identical (549/549 bp) to B. graminis on P. pratensis (AB273530) (Inuma et al. 2007). In addition, the phylogenetic analysis clearly showed that the identified fungus and B. graminis f. sp. poae were clustered in the same branch. To perform pathogenicity analysis, leaf surfaces of eight healthy plants were inoculated by dusting fungal conidia from diseased leaves. Eight non-inoculated plants served as a control. The non-inoculated and inoculated plants were separately maintained in two growth chambers (humidity, 60 %; light/dark, 16 h/8 h; temperature, 18 â). Twelve to fourteen days after inoculation, B. graminis signs were visible on inoculated leaves, while control plants remained healthy. The pathogenicity assays were repeated twice and showed same results. Therefore, based on the morphological characteristics and molecular analysis, the pathogen was identified and confirmed as B. graminis f. sp. poae. This pathogen has been reported on P. pratensis in Switzerland and Japan (Inuma et al. 2007). This is, to our best knowledge, the first disease note reporting B. graminis on P. pratensis in China. Because the hybridization of B. graminis formae speciales (ff. spp.). allow the pathogens to adapt to new hosts, P. pratensis may serve as a primary inoculum reservoir of B. graminis to threaten other species, including cereal crops (Klingeman et al. 2018; Menardo et al. 2016). In addition, powdery mildew may negatively affect the yield and quality of grasses. Our report expands the knowledge of B. graminis f. sp. poae and provides the fundamental information for future powdery mildew control.
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PURPOSE: Previous studies have suggested that serum carotenoids might be inversely associated with non-alcoholic fatty liver disease (NAFLD), but little data came from longitudinal studies. We prospectively examined the associations between serum-carotenoid levels and NAFLD severity and the intermediary effects of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR), body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese adults. METHODS: This prospective study included 3336 Chinese adults (40-75 years). We assessed serum concentrations of carotenoids at baseline and determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal ultrasonography was conducted to assess the presence and degree of NAFLD at years 3 and 6. RESULTS: The 2687 subjects who completed both NAFLD tests were classified into stable, improved and progressed groups according to changes in the degree of NAFLD between two visits. Analyses of covariance showed that ln-transformed serum concentrations of α-carotene, ß-cryptoxanthin, ß-carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively associated with NAFLD improvement (all p-trend < 0.05). After multivariable adjustment, mean differences in serum carotenoids were higher by 29.6% (ß-carotene), 18.2% (α-carotene), 15.6% (ß-cryptoxanthin), 11.5% (lycopene), 8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs. progressed subjects. Path analyses indicated the carotenoid-NAFLD association was mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were positively associated with the prevalence and progression of NAFLD. CONCLUSIONS: In middle-aged and elderly adults, higher serum-carotenoid concentrations were favorably associated with NAFLD improvement, mediated by reducing serum RBP4, triglycerides, HOMA-IR, and BMI. TRIAL REGISTRATIONS: This study has been registered at http://www.clinicaltrials.gov as NCT03179657.
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Carotenoides/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Adulto , Anciano , Índice de Masa Corporal , China , Femenino , Estudios de Seguimiento , Humanos , Resistencia a la Insulina , Hígado/diagnóstico por imagen , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Estudios Prospectivos , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Índice de Severidad de la Enfermedad , Triglicéridos/sangre , UltrasonografíaRESUMEN
BACKGROUND: Magnetic resonance (MR) spectroscopy (1H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported. PURPOSE: To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether 1H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs). MATERIAL AND METHODS: Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent 1H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan-Meier method and Cox regression were used for survival analysis. RESULTS: Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = -0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers. CONCLUSION: Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.
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Neoplasias Encefálicas/patología , Proliferación Celular/fisiología , Colina/metabolismo , Creatina/metabolismo , Glioma/patología , Espectroscopía de Resonancia Magnética/métodos , Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Adolescente , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Niño , Femenino , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética , Clasificación del Tumor , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. METHODS: Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. 1H NMR spectroscopy was employed to determine the Lac/Cr ratio. RESULTS: The DNA damage increased in a radiation dose-dependent manner (p < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-ι level decreased (C6, p < 0.01; U251, p < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level. CONCLUSION: The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.
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Apoptosis/efectos de la radiación , Creatina/análisis , Ácido Láctico/análisis , Rayos X , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Daño del ADN/efectos de la radiación , Electroforesis en Gel de Campo Pulsado , Glioma/metabolismo , Glioma/patología , Humanos , Isoenzimas/metabolismo , Espectroscopía de Resonancia Magnética , Proteína Quinasa C/metabolismo , Análisis de la Célula IndividualRESUMEN
Objective: To record the discovery of Culex inatomii in Chongming, Shanghai. Methods: Larvae and adult mosquitos of Cx. inatomii were collected in Dongtan of Chongming Island from May to November in 2015 and 2016, and their morphological characteristics were observed. The genomic DNA was extracted from adult mosquitos, PCR was performed to amplify the cytochrome c oxidaseâ (COâ ) gene. Multiple alignment of COâ sequence was conducted with ClustalW2. Pairwise distances within and between species were calculated using MEGA v5.10 based on COâ sequences of Cx. inatomii, Cx. modestus, Cx. pipiens pallens, and Cx. tritaeniorhynchus. The phylogenetic tree of the above four species was constructed using neighbor joining, maximum likelihood, and Bayesian methods. Results: One hundred and fifty-six adult female mosquitos and 36 larvae of Cx. inatomii were collected. Larvae were reared to adult stage in the laboratory (17 female, 19 male). Morphologically, the subapical lobe of the sidepiece in male genitalia was divided into two parts, the anterior part having 2 bladed setae, and the posterior part having 1 bladed setae and 1 lanceolar strong setae. This strucutre can be used to distinguish Cx. inatomii from Cx. modestus. PCR of COâ resulted in products of approximately 650 bp. They were sequenced and the sequencing result was submitted to GenBank (accession number, KX555565-KX555570). Multiple sequence alignment revealed a 96% sequence similarity of COâ between Cx. inatomii and Cx. modestus. The genetic distance between Cx. inatomii and Cx. modestus was 0.047, and that within them each was 0.003 and 0.011, respectively. The phylogenetic tree showed that the four species clustered as a monophyletic clade, and each formed an individual lineage. Cx. inatomii had a closer relationship with Cx. modestus, while distant from the other two species. Conclusion: We recorded the discovery of Cx. inatomii in Chongming, Shanghai.
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Culex , Animales , Teorema de Bayes , China , Femenino , Larva , Masculino , Filogenia , Alineación de SecuenciaRESUMEN
Previous studies have suggested that vitamin E (VE) may affect bone health, but the findings have been inconclusive. We examined the relationship between VE status (in both diet and serum) and bone mineral density (BMD) among Chinese adults. This community-based study included 3203 adults (2178 women and 1025 men) aged 40-75 years from Guangzhou, People's Republic of China. General and dietary intake information were collected using structured questionnaire interviews. The serum α-tocopherol (TF) level was quantified by reversed-phase HPLC. The BMD of the whole body, the lumbar spine and left hip sites (total, neck, trochanter, intertrochanter and Ward's triangle) were measured using dual-energy X-ray absorptiometry. In women, the dietary intake of VE was significantly and positively associated with BMD at the lumbar spine, total hip, intertrochanter and femur neck sites after adjusting for covariates (P(trend): 0·001-0·017). Women in quartile 3 of VE intake typically had the highest BMD; the covariate-adjusted mean BMD were 2·5, 3·06, 3·41 and 3·54% higher, respectively, in quartile 3 (v. 1) at the four above-mentioned sites. Similar positive associations were observed between cholesterol-adjusted serum α-TF levels and BMD at each of the studied bone sites (P(trend): 0·001-0·022). The covariate-adjusted mean BMD were 1·24-4·83% greater in quartile 4 (v. 1) in women. However, no significant associations were seen between the VE levels (dietary or serum) and the BMD at any site in men. In conclusion, greater consumption and higher serum levels of VE are associated with greater BMD in Chinese women but not in Chinese men.
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Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Dieta , Conducta Alimentaria , Osteoporosis/sangre , Vitaminas/farmacología , alfa-Tocoferol/farmacología , Absorciometría de Fotón , Anciano , Pueblo Asiatico , Huesos/metabolismo , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/prevención & control , Factores Sexuales , Encuestas y Cuestionarios , Vitaminas/sangre , Vitaminas/uso terapéutico , alfa-Tocoferol/sangre , alfa-Tocoferol/uso terapéuticoRESUMEN
Objective: The Anopheles hyrcanus group is widely distributed in the Palearctic and Oriental regions. Among the reported members, 25 species have definitive scientific names. Some are determined as vectors of malaria, lymphatic filariasis, and Japanese encephalitis. However, it is extremely difficult to morphologically discriminate the group members. With the development of techniques like crossing experiment, karyotype analysis, and molecular phylogeny, the classification of the Hyrcanus Group has been changed. In this review we update the list of the Hyrcanus Group, including addition of newly discovered species An. belenrae, An. kleini, An. xui, and An. hyrcanus spIR, and merges of An. junlianensis, An. yatsushiroensis, and An. kunmingensis as synonyms. We also discuss the relationships between An. hyrcanus and An. pseudopictus, An. lesteri and An. paraliae, as well as An. kleini and An. engarensis. This review will help to clearly define the relationships among the species.
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Anopheles , Mosquitos Vectores , Animales , Malaria , FilogeniaRESUMEN
The association between serum carotenoids and the metabolic syndrome (MetS) remains uncertain, and little is known about this relationship in the Chinese population. The present study examined the association between serum carotenoid concentrations and the MetS in Chinese adults. We conducted a community-based cross-sectional study in which 2148 subjects (1547 women and 601 men) aged 50-75 years were recruited in urban Guangzhou, China. Dietary data and other covariates were collected during face-to-face interviews. Blood pressure, waist circumference, blood lipids, glucose and serum carotenoids (α-, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin) were examined. We found dose-response inverse relationships between individual serum carotenoid concentrations and total carotenoids and the prevalence of the MetS after adjusting for potential confounders (P for trend < 0.001). The OR of the MetS for the highest (v. lowest) quartile were 0.31 (95% CI 0.20, 0.47) for α-carotene, 0.23 (95% CI 0.15, 0.36) for ß-carotene, 0.44 (95% CI 0.29, 0.67) for ß-cryptoxanthin, 0.39 (95% CI 0.26, 0.58) for lycopene, 0.28 (95% CI 0.18, 0.44) for lutein+zeaxanthin and 0.19 (95% CI 0.12, 0.30) for total carotenoids. Higher concentrations of each individual carotenoid and total carotenoids were significantly associated with a decrease in the number of abnormal MetS components (P for trend < 0.001-0.023). Higher serum carotenoid levels were associated with a lower prevalence of the MetS and fewer abnormal MetS components in middle-aged and elderly Chinese adults.
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Síndrome Metabólico/prevención & control , Xantófilas/sangre , beta Caroteno/sangre , Anciano , Pueblo Asiatico , Glucemia/metabolismo , Presión Sanguínea , Carotenoides/sangre , Carotenoides/uso terapéutico , China , Estudios Transversales , Criptoxantinas/sangre , Criptoxantinas/uso terapéutico , Dieta , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lípidos/sangre , Luteína/sangre , Luteína/uso terapéutico , Licopeno , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Circunferencia de la Cintura , Xantófilas/uso terapéutico , Zeaxantinas/sangre , Zeaxantinas/uso terapéutico , beta Caroteno/uso terapéuticoRESUMEN
Based on the variable part of mtDNA CO I gene sequence, a multiplex PCR method was developed for the identification of the three common sandflies (Phlebotomus longiductus, Ph. wui, and Ph. alexandri) in southern Xinjiang. The results demonstrated that this multiplex PCR method was reliable, and could be used to identify the three Phlebotomus species. The PCR product of CO I gene from Ph. longiductus, Ph. wui and Ph. alexandri was 248, 632, and 395 bp, respectively.