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MAIN CONCLUSION: The SpHsfA8a upregulated expression can induce the expression of multiple heat-tolerance genes, and increase the tolerance of Arabidopsis thaliana to high-temperature stress. Sorbus pohuashanensis is an ornamental tree used in courtyards. However, given its poor thermotolerance, the leaves experience sunburn owing to high temperatures in summer, severely affecting its ornamental value. Heat-shock transcription factors play a critical regulatory role in the plant response to heat stress. To explore the heat-tolerance-related genes of S. pohuashanensis to increase the tree's high-temperature tolerance, the SpHsfA8a gene was cloned from S. pohuashanensis, and its structure and expression patterns in different tissues and under abiotic stress were analyzed, as well as its function in heat tolerance, was determined via overexpression in Arabidopsis thaliana. The results showed that SpHsfA8a encodes 416 amino acids with a predicted molecular weight of 47.18 kDa and an isoelectric point of 4.63. SpHsfA8a is a hydrophilic protein without a signal peptide and multiple phosphorylation sites. It also contains a typical DNA-binding domain and is similar to MdHsfA8a in Malus domestica and PbHsfA8 in Pyrus bretschneideri. In S. pohuashanensis, SpHsfA8a is highly expressed in the roots and fruits and is strongly induced under high-temperature stress in leaves. The heterologous expression of SpHsfA8a in A. thaliana resulted in a considerably stronger growth status than that of the wild type after 6 h of treatment at 45 °C. Its proline content, catalase and peroxidase activities also significantly increased, indicating that the SpHsfA8a gene increased the tolerance of A. thaliana to high-temperature stress. SpHsfA8a could induce the expression of multiple heat-tolerance genes in A. thaliana, indicating that SpHsfA8a could strengthen the tolerance of A. thaliana to high-temperature stress through a complex regulatory network. The results of this study lay the foundation for further elucidation of the regulatory mechanism of SpHsfA8a in response of S. pohuashanensis to high-temperature stress.
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Arabidopsis , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción del Choque Térmico , Respuesta al Choque Térmico , Proteínas de Plantas , Sorbus , Sorbus/genética , Sorbus/fisiología , Sorbus/metabolismo , Respuesta al Choque Térmico/genética , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción del Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismo , Plantas Modificadas Genéticamente , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Calor , Termotolerancia/genéticaRESUMEN
BACKGROUND: Indian jointvetch (Aeschynomene indica) is a common and pernicious weed found in the upland direct-seeding rice fields in the lower reaches of the Yangtze River in China. However, there are few reports on the degree of harm, genetic characteristics, and management methods of this weed. The purpose of this study is to clarify the harm of Indian jointvetch to upland direct-seeding rice, analyze the genetic characteristics of this weed based on chloroplast genomics and identify its related species, and screen herbicides that are effective in managing this weed in upland direct-seeding rice fields. RESULTS: In a field investigation in upland direct-seeding rice paddies in Shanghai and Jiangsu, we determined that the plant height and maximum lateral distance of Indian jointvetch reached approximately 134.2 cm and 57.9 cm, respectively. With Indian jointvetch present at a density of 4/m2 and 8/m2, the yield of rice decreased by approximately 50% and 70%, respectively. We further obtained the first assembly of the complete chloroplast (cp.) genome sequence of Indian jointvetch (163,613 bp). There were 161 simple sequence repeats, 166 long repeats, and 83 protein-encoding genes. The phylogenetic tree and inverted repeat region expansion and contraction analysis based on cp. genomes demonstrated that species with closer affinity to A. indica included Glycine soja, Glycine max, and Sesbania cannabina. Moreover, a total of 3281, 3840, and 3838 single nucleotide polymorphisms were detected in the coding sequence regions of the cp. genomes of S. cannabina voucher IBSC, G. soja, and G. max compared with the A. indica sequence, respectively. A greenhouse pot experiment indicated that two pre-emergence herbicides, saflufenacil and oxyfluorfen, and two post-emergence herbicides, florpyrauxifen-benzyl and penoxsulam, can more effectively manage Indian jointvetch than other common herbicides in paddy fields. The combination of these two types of herbicides is recommended for managing Indian jointvetch throughout the entire growth period of upland direct-seeding rice. CONCLUSIONS: This study provides molecular resources for future research focusing on the identification of the infrageneric taxa, phylogenetic resolution, and biodiversity of Leguminosae plants, along with recommendations for reliable management methods to control Indian jointvetch.
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Fabaceae , Genoma del Cloroplasto , Herbicidas , Oryza , Filogenia , China , Herbicidas/toxicidad , Oryza/genéticaRESUMEN
Ammannia arenaria and A. multifloras, morphologically similar at the seedling stage, are the most common broad-leaved weeds in paddy fields. Our study showed that A. arenaria occupied more space than A. multifloras when competing with rice. However, A. multifloras germination has lower temperature adaptability. No difference in sensitivity to common herbicides between two Ammannia species was observed. Chloroplast (cp) genomes could be conducive to clarify their genetic relationship. The complete cp genome sequences of A. arenaria (158,401 bp) and A. multiflora (157,900 bp) were assembled for the first time. In A. arenaria, there were 91 simple sequence repeats, 115 long repeats, and 86 protein-encoding genes, one, sixteen, and thirty more than those in A. multiflora. Inverted repeats regions expansion and contraction and the phylogenetic tree based on cp genomes demonstrated the closely relationship between the two species. However, in A. arenaria, 20 single nucleotide polymorphisms in the CDS region were detected compared to A. multiflora, which can be used to distinguish the two species. Moreover, there was one unique gene, infA, only in A. arenaria. This study provides reliable molecular resources for future research focusing on the infrageneric taxa identification, phylogenetic resolution, population structure, and biodiversity of Ammannia species.
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A novel 2-phenylquinoline-polyamine conjugate (QPC) was synthesized and characterized, its interaction with bovine serum albumin (BSA) was evaluated using UV-Vis, fluorescence and circular dichroism (CD) spectroscopy. The results showed that QPC caused a whole train of spectral variation, including enhancement of UV-vis absorption and reduction of fluorescence (FL), indicating QPC-BSA complex formed. FL results showed that the type of FL quenching waslarge static quenching, which was also accompanied with a process of dynamic quenching. Binding constants, thermodynamic parameters and docking results showed that the interaction between QPC and BSA was basically a Van der Waals, hydrogen bond and hydrophobic interaction. Synchronous and 3D-FL analysis revealed that QPC resulted in unapparent conformational alteration of BSA. The docking study suggested QPC was situated at the binding sites II of BSA, and 2-phenylquinoline moiety contributed to the hydrophobic interaction. The results of molecular dynamics revealed QPC altered the conformation of BSA, which showed that the inconsistency between experimental data and theoretical calculation results may be due to the instability of the compound.
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Poliaminas , Albúmina Sérica Bovina , Albúmina Sérica Bovina/química , Simulación del Acoplamiento Molecular , Sitios de Unión , Termodinámica , Espectrometría de Fluorescencia , Dicroismo Circular , Unión Proteica , Espectrofotometría UltravioletaRESUMEN
BACKGROUND: Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium-mesenchyme interactions. METHODS: Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp-dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests. RESULTS: The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-ß signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance. CONCLUSION: SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration.
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Pulpa Dental , Células Madre Mesenquimatosas , Animales , Humanos , Ratones , Desarrollo Embrionario , Regeneración , Diferenciación Celular , Odontoblastos , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismoRESUMEN
The ecological environment of Poyang Lake basin is an important part of the construction of ecological civilizations in the south of China. Based on the Landsat satellite remote sensing images, using the principal component analysis (PCA) method to construct the remote sensing ecological index (RSEI) as an evaluation index of ecological environment quality, introducing the Geodetector model to quantitatively detect the explanatory power of different influencing factors on the spatial divergence of the ecological environment, and exploring the changes in ecological environment quality in the Poyang Lake basin from 1990 to 2020 and the impact of different driving factors. The results of the study showed that there were obvious regional differences in the ecological environment quality in the basin. The areas with bad and poor ecological quality were mainly distributed in the central and northern plains; the areas with high and good quality grades were mainly distributed in the hilly and mountainous region of the southwestern part of the basin; the overall ecological environment of the Poyang Lake basin has been improving over the past 30 years; and the improved areas were mainly distributed in low-altitude areas. Geodetector results showed that population density was the factor with the highest explanatory power for the spatial divergence of ecological environment quality in the Poyang Lake basin. Among different natural factors, topographic factors (slope, aspect) had a higher driving force than meteorological factors (temperature, precipitation). The night light index factor showed an increasing yearly trend, indicating that the ecological environment quality of the Poyang Lake basin was gradually increased due to the influence of urbanization development. The construction of the RSEI model based on Google Earth Engine could not only effectively ensure the accuracy of ecological environment quality evaluation in different years but could also quickly realize image preprocessing and index calculations, which greatly improved the efficiency of ecological environment evaluation. These research results can provide a theoretical basis and scientific data support for the ecological environment protection work in the Poyang Lake basin.
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Microcystin-LR (MC-LR), one of aquatic environmental contaminants with reproductive toxicity produced by cyanobacterial blooms, but its toxic effects and mechanisms on the ovary are not fully understood. Here, proteomic techniques and molecular biology experiments were performed to study the potential mechanism of MC-LR-caused ovarian toxicity. Results showed that protein expression profile of ovarian granulosa cells (KK-1) was changed by 17 µg/mL MC-LR exposure. Comparing with the control group, 118 upregulated proteins as well as 97 downregulated proteins were identified in MC-LR group. Function of differentially expressed proteins was found to be enriched in pathways related to adherent junction, such as cadherin binding, cell-cell junction, cell adhesion and focal adherens. Furthermore, in vitro experiments, MC-LR significantly downregulated the expression levels of proteins associated with adherent junction (ß-catenin, N-cadherin, and α-catenin) as well as caused cytoskeletal disruption in KK-1 cells (P < 0.05), indicating that the adherent junction was damaged. Results of in vivo experiments have shown that after 14 days of acute MC-LR exposure (40 µg/kg), damaged adherent junction and an increased number of atretic follicles were observed in mouse ovaries. Moreover, MC-LR activated JNK, an upstream regulator of adherent junction proteins, in KK-1 cells and mouse ovarian tissues. In contrast, JNK inhibition alleviated MC-LR-induced adherent junction damage in vivo and in vitro, as well as the number of atretic follicles. Taken together, findings from the present study indicated that JNK is involved in MC-LR-induced granulosa cell adherent junction damage, which accelerated follicular atresia. Our study clarified a novel mechanism of MC-LR-caused ovarian toxicity, providing a theoretical foundation for protecting female reproductive health from environmental pollutants.
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Atresia Folicular , Proteómica , Animales , Femenino , Ratones , Células de la Granulosa , Microcistinas/toxicidad , MAP Quinasa Quinasa 4/metabolismoRESUMEN
Environmental cyanotoxin exposure may be a trigger of testicular cancer. Activation of PI3K/AKT/mTOR signaling pathway is the critical molecular event in testicular carcinogenesis. As a widespread cyanotoxin, microcystin-leucine arginine (MC-LR) is known to induce cell malignant transformation and tumorigenesis. However, the effects of MC-LR on the regulatory mechanism of PI3K/AKT/mTOR pathway in seminoma, the most common testicular tumor, are unknown. In this study, mouse spermatogonia cell line (GC-1) and nude mice were used to investigate the effects and mechanisms of MC-LR on the malignant transformation of spermatogonia by nude mouse tumorigenesis assay, cell migration invasion assay, western blot, and cell cycle assay, and so forth. The results showed that, after continuous exposure to environmentally relevant concentrations of MC-LR (20 nM) for 35 generations, the proliferation, migration, and invasion abilities of GC-1 cells were increased by 120%, 340%, and 370%, respectively. In nude mice, MC-LR-treated GC-1 cells formed tumors with significantly greater volume (0.998 ± 0.768 cm3 ) and weight (0.637 ± 0.406 g) than the control group (0.067 ± 0.039 cm3 ; 0.094 ± 0.087 g) (P < .05). Furthermore, PI3K inhibitor Wortmannin inhibited the PI3K/AKT/mTOR pathway and its downstream proteins (c-MYC, CDK4, CCND1, and MMP14) activated by MC-LR. Blocking PI3K alleviated MC-LR-induced cell cycle disorder and malignant proliferation, migration and invasive of GC-1 cells. Altogether, our findings suggest that MC-LR can induce malignant transformation of mouse spermatogonia, and the PI3K/AKT/mTOR pathway-mediated cell cycle dysregulation may be an important target for malignant proliferation. This study provides clues to further reveal the etiology and pathogenesis of seminoma.
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Ciclo Celular , Seminoma , Espermatogonias , Neoplasias Testiculares , Animales , Masculino , Ratones , Arginina/farmacología , Arginina/metabolismo , Carcinogénesis/metabolismo , División Celular , Proliferación Celular , Leucina , Ratones Desnudos , Microcistinas/toxicidad , Microcistinas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Seminoma/inducido químicamente , Seminoma/metabolismo , Seminoma/patología , Espermatogonias/metabolismo , Espermatogonias/patología , Neoplasias Testiculares/inducido químicamente , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Serina-Treonina Quinasas TOR/metabolismo , Transducción de SeñalRESUMEN
Automatic detection of retinal diseases based on deep learning technology and Ultra-widefield (UWF) images plays an important role in clinical practices in recent years. However, due to small lesions and limited data samples, it is not easy to train a detection-accurate model with strong generalization ability. In this paper, we propose a lesion attention conditional generative adversarial network (LAC-GAN) to synthesize retinal images with realistic lesion details to improve the training of the disease detection model. Specifically, the generator takes the vessel mask and class label as the conditional inputs, and processes the random Gaussian noise by a series of residual block to generate the synthetic images. To focus on pathological information, we propose a lesion feature attention mechanism based on random forest (RF) method, which constructs its reverse activation network to activate the lesion features. For discriminator, a weight-sharing multi-discriminator is designed to improve the performance of model by affine transformations. Experimental results on multi-center UWF image datasets demonstrate that the proposed method can generate retinal images with reasonable details, which helps to enhance the performance of the disease detection model.
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Generalización Psicológica , Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Networks are powerful tools to uncover functional roles of genes in phenotypic variation at a system-wide scale. Here, we constructed a maize network map that contains the genomic, transcriptomic, translatomic and proteomic networks across maize development. This map comprises over 2.8 million edges in more than 1,400 functional subnetworks, demonstrating an extensive network divergence of duplicated genes. We applied this map to identify factors regulating flowering time and identified 2,651 genes enriched in eight subnetworks. We validated the functions of 20 genes, including 18 with previously unknown connections to flowering time in maize. Furthermore, we uncovered a flowering pathway involving histone modification. The multi-omics integrative network map illustrates the principles of how molecular networks connect different types of genes and potential pathways to map a genome-wide functional landscape in maize, which should be applicable in a wide range of species.
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Proteómica , Zea mays , Zea mays/genética , Multiómica , Genómica , Genes de PlantasRESUMEN
OBJECTIVE: To observe the effect of navel acupuncture on bladder emptying function in patients with urinary retention after stroke based on the conventional treatment. METHODS: A total of 106 patients with urinary retention after stroke were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (53 cases, 3 cases dropped off). Patients in the control group were treated with drugs, catheterization and bladder function rehabilitation training. On the basis of the treatment in the control group, the observation group was treated with navel acupuncture, 30 min each time, once every other day, for 4 weeks. The bladder residual urine volume, spontaneous urination volume and catheterization times before and after treatment were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, in the two groups, the bladder residual urine volume and catheterization times were lower than those before treatment (P<0.01), and the spontaneous urination volume was higher than that before treatment (P<0.01); the bladder residual urine volume and catheterization times in the observation group were less than those in the control group (P<0.05, P<0.01), and the spontaneous urination volume was higher than that in the control group (P<0.01). The effective rate of the observation group was 90.0 % (45/50), which was higher than 72.0 % (36/50) in the control group (P<0.05). CONCLUSION: On the basis of conventional treatment, navel acupuncture can effectively improve the bladder emptying function of patients with urinary retention after stroke.
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Accidente Cerebrovascular , Retención Urinaria , Humanos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Vejiga Urinaria , Retención Urinaria/etiología , Retención Urinaria/terapiaRESUMEN
Echinochloa crus-galli var. crus-galli, E. crus-galli var. zelayensis, and E. glabrescens, morphologically similar at the seedling stage, are the most pernicious barnyard grass species in paddy fields worldwide. Chloroplast (cp) genomes could be conducive to their identification. In this study, we assembled the complete cp genome sequences of Echinochloa crus-galli var. crus-galli (139,856 bp), E. crus-galli var. zelayensis (139,874 bp), and E. glabrescens (139,874 bp), which exhibited a typical circular tetramerous structure, large and small single-copy regions, and a pair of inverted repeats. In Echinochloa crus-galli var. crus-galli, there were 136 simple sequence (SSRs) and 62 long (LRs) repeats, and in the other two species, 139 SSRs and 68 LRs. Each cp genome contains 92 protein-encoding genes. In Echinochloa crus-galli var. crus-galli and E. glabrescens, 321 and 1 single-nucleotide polymorphisms were detected compared to Echinochloa crus-galli var. zelayensis. IR expansion and contraction revealed small differences between the three species. The phylogenetic tree based on cp genomes demonstrated the phylogenetic relationship between ten barnyard grass species and other common Gramineae plants, showing new genetic relationships of the genus Echinochloa. This study provides valuable information on cp genomes, useful for identifying and classifying the genus Echinochloa and studying its phylogenetic relationships and evolution.
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Echinochloa , Genoma del Cloroplasto , Echinochloa/genética , FilogeniaRESUMEN
Microcystins (MCs) are widely distributed cyanobacterial toxins in eutrophic waters. At present, the endocrine-disrupting effects of MCs have been extensively studied, but whether MCs can be classified as environmental endocrine disruptors (EDCs) is still unclear. This review is aimed to evaluate the rationality for MCs as to be classified as EDCs based on the available evidence. It has been identified that MCs meet eight of ten key characteristics of chemicals that can be classified as EDCs. MCs interfere with the six processes, including synthesis, release, circulation, metabolism, binding and action of natural hormones in the body. Also, they are fit two other characteristics of EDC: altering the fate of producing/responding cells and epigenetic modification. Further evidence indicates that the endocrine-disrupting effect of MCs may be an important cause of adverse health outcomes such as metabolic disorders, reproductive disorders and effects on the growth and development of offspring. Generally, MCs have endocrine-disrupting properties, suggesting that it is reasonable for them to be considered EDCs. This is of great importance in understanding and evaluating the harm done by MCs on humans.
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Disruptores Endocrinos , Humanos , Disruptores Endocrinos/toxicidad , Microcistinas/farmacología , Sistema Endocrino , Hormonas , ReproducciónRESUMEN
The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9-12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.
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Pérdida de Hueso Alveolar , Modelos Animales de Enfermedad , Periodontitis , Ratas , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/patología , Animales , Humanos , Ligadura , Periodontitis/complicaciones , Periodontitis/patología , SedaRESUMEN
Thermo-mechanical process of nickel-based oxide dispersion strengthened (ODS) superalloys is critical to produce desired components. In this study, an efficient method of consolidating powder is introduced to optimize the preparation process, microstructure and properties of nickel-based ODS superalloys. The influences of consolidation temperature, strain rate and ball milling time on the hardness of nickel-based superalloys were studied. The relationship among process, microstructure and hardness was established, the nanoparticles strengthening and grain boundary strengthening in nickel-based ODS superalloys were discussed. The results indicate that long ball milling time, moderately low consolidation temperature and high strain rates are beneficial to improving properties of nickel-based superalloys. Moreover, dispersion strengthening of nanoparticles and grain boundary strengthening play important roles in enhancing nickel-based ODS superalloys.
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Point of interest (POI) recommendation is a popular personalized location-based service. This paper proposes a Geographic Personal Matrix Factorization (GPMF) model that makes effective use of geographic information from the perspective of the relationship between POIs and users. This model considers the role of geographic information from multiple perspectives based on the locational relationship among users, the distributional relationship between users and POIs, and the proximity and clustering relationship among POIs. The GPMF mines the influence of geographic information on different objects and carries out unique modeling through cosine similarity, non-linear function, and k nearest neighbor (KNN). This study explored the influence of geographic information on POI recommendation through extensive experiments with data from Foursquare. The result shows that GPMF performs better than the commonly used POI recommendation algorithm in terms of both precision and recall. Geographic information through proximity relations effectively improves the recommendation algorithm.
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Algoritmos , Insuficiencia Ovárica Primaria , Análisis por Conglomerados , Femenino , Humanos , SerogrupoRESUMEN
Microcystin-leucine arginine (MC-LR), an emerging water pollutant, produced by cyanobacteria, has an acute testicular toxicity. However, little is known about the chronic toxic effects of MC-LR exposure on the testis at environmental concentrations and the underlying molecular mechanisms. In this study, C57BL/6 J mice were exposed to different low concentrations of MC-LR for 6, 9 and 12 months. The results showed that MC-LR could cause testis structure loss, cell abscission and blood-testis barrier (BTB) damage. Long-term exposure of MC-LR also activated RhoA/ROCK pathway, which was accompanied by the rearrangement of α-Tubulin. Furthermore, MC-LR reduced the levels of the adherens junction proteins (N-cadherin and ß-catenin) and the tight junction proteins (ZO-1 and Occludin) in a dose- and time-dependent way, causing BTB damage. MC-LR also reduced the expressions of Occludin, ZO-1, ß-catenin, and N-cadherin in TM4 cells, accompanied by a disruption of cytoskeletal proteins. More importantly, the RhoA inhibitor Rhosin ameliorated these MC-LR-induced changes. Together, these new findings suggest that long-term exposure to MC-LR induces BTB damage through RhoA/ROCK activation: involvement of tight junction and adherens junction changes and cytoskeleton disruption. This study highlights a new mechanism for MC-LR-induced BTB disruption and provides new insights into the cause and treatment of BTB disruption.
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Barrera Hematotesticular , beta Catenina , Animales , Cadherinas , Masculino , Ratones , Ratones Endogámicos C57BL , Microcistinas/toxicidad , Ocludina/metabolismoRESUMEN
The NDVI (normalized difference vegetation index) was used as the vegetation coverage index. Based on the NDVI and weather data from 2000 to 2020, the characteristics of the spatiotemporal evolution and the driving mechanism of vegetation were investigated by using correlation analysis, the Theil-Sen estimator, the Mann-Kendall method, and multivariate residual trend analysis. The results showed that the growing season average NDVI in the Yellow River basin was a fluctuating upward trend of 0.005 a-1 from 2000 to 2020. Areas with significantly improved vegetation in the basin were mainly distributed in the Qinling Mountains, the Northern Shaanxi Plateau, and the Lvliang Mountains in the midstream. The average value of the partial correlation coefficient between the growing season average NDVI and rainfall in the Yellow River basin was 0.57, and the average value of the partial correlation coefficient between the growing season average NDVI and temperature was 0.49. The impact of rainfall on vegetation was higher than that of temperature. The areas where human activities significantly improved vegetation growth were mainly distributed in the northern Shaanxi Plateau, the Lvliang Mountains, and southern Ningxia. The areas where human activities inhibited vegetation growth were mainly distributed in cities with strong human activities such as Yinchuan, Baotou, Xi'an, Luoyang, Zhengzhou, and Taiyuan. Human activities and climate change contributed to 72% and 28% of the vegetation change in the Yellow River basin. Driven by human activities and climate change, the area where vegetation growth has improved in the Yellow River basin accounted for 96.4% of the basin area, of which the contribution rate of human activities greater than 80% of the area accounted for 34.3%, which was mainly distributed in the middle and southeast of the basin. The area with a contribution rate of climate change greater than 80% accounted for 4.2%, which was mainly distributed in the Sichuan-Tibet Plateau and Longzhong Loess Plateau in the basin. The results of this research can provide scientific support for the ecological protection and high-quality development of the Yellow River basin.
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Cambio Climático , Plantas/clasificación , Ríos , Efectos Antropogénicos , China , Ecosistema , Estaciones del Año , Análisis Espacio-Temporal , TemperaturaRESUMEN
Polyamine transporter (PAT) is a protein that can deliver "drug-polyamine" conjugates to tumor cells. 4-Chloro-naphthalimide- homospermidine (4-ClNAHSPD) displayed good antitumor activity and excellent cell selectivity via PAT pathway. In this paper, 4-ClNAHSPD and spermidine (SPD) were docked against PAT. The results showed that 4-ClNAHSPD could bind to PAT through hydrogen bond, Van der Waals, salt bridge or attractive charge and hydrophobic interaction. The interaction of SPD and PAT, however, was hydrogen bond and Van der Waals interaction. Moreover, their binding sites were also different. The primary binding sites of 4-ClNAHSPD with PAT are the residues of VAL59, HIS222, ASP61, ASP179 and GLU64, while SPD interacts with PAT in the sites of ASP37, ASP244, APS275 and SER36. The docked ligand-protein complexes were simulated for 5000ps. In simulations, various binding sites further resulted in the diverse root-mean-square deviation (RMSD) and root-mean-square deviation fluctuation (RMSF) values. The RMSD and RMSF values of 4-ClNAHSPD-PAT indicated that 4-ClNAHSPD caused a weak conformational change of PAT in a different style from SPD. More importantly, the interaction force numbers of 4-ClNAHSPD-PAT were also changed after the simulation. These results supported that 4-ClNAHSPD harnesses PAT pathway for cellular entrance.Communicated by Ramaswamy H. Sarma.
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Simulación de Dinámica Molecular , Naftalimidas , Ligandos , Simulación del Acoplamiento Molecular , PoliaminasRESUMEN
BACKGROUND: Despite advances in multiple disciplinary diagnoses and treatments, the prognosis of hepatocellular carcinoma (HCC) remains poor. Some evidence has identified that the aberrant expression of tropomyosins (TPMs) is involved with some cancers development. However, prognostic values of TPMs in HCC have not been thoroughly investigated. METHODS: Original TPM1-4 mRNA expression of TCGA HCC data and GTEx was downloaded from UCSC XENA. Oncomine database and GSE46408 were used for verification. Clinical stages and survival analysis of TPM1-4 in HCC were performed by GEPIA2. cBioPortal was utilized to assess TPM1-4 gene alteration in HCC. TIMER2.0 was used for investigating the relevance of TPM1-4 to tumor-infiltrating immune cells in HCC. Additionally, we constructed a TPM1-4 prognostic model to explore the value of TPM1-4 for prognostic evaluation in HCC. LinkedOmics was applied to elucidate TPM3 co-expression networks in HCC. RESULTS: This present study showed that TPM1-4 was upregulated in all HCC tissues, and TPM3 overexpression was correlated with poor survival outcomes in patients with HCC. Besides, TPM3 amplification was the main altered type in TPM1-4 genetic alteration, which affected the prognosis of HCC patients. The risk model revealed that TPM1, TPM2, and TPM3 were applied to risk assessment of HCC prognosis, among which TPM3 expression was significantly higher in the high-risk group than that in the low-risk group. Univariate and multivariate cox regression analyses indicated that TPM3 may be an independent prognostic factor of HCC prognosis. In addition, TPM3 co-expression genes mainly participated in the cell cycle by maintaining microtubule cytoskeleton in HCC progression. TPM1-4 was associated with some tumor-infiltrating immune cells in HCC. CONCLUSION: Our study detected that the expression level of TPM1-4 was all remarkably elevated in HCC, suggesting that TPM1-4 may serve an important role in HCC development. High TPM3 expression was found to be correlated with poor overall survival, and TPM3 may be an independent prognostic factor for HCC.