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The proliferation and apoptosis of ovarian granulosa cells are important for folliculogenesis. As a transcription factor, SRY-box transcription factor 4 (SOX4) has important roles in regulating cellular proliferation and apoptosis. Nonetheless, the regulatory mechanisms of SOX4 on proliferation and apoptosis of granulosa cells remain elusive. Therefore, a stably overexpressed SOX4 ovarian granulosa cell line KGN was generated by lentivirus encapsulation. We observed that overexpression of SOX4 inhibits apoptosis, promotes proliferation and migration of KGN cells. Comparative analysis of the transcriptome revealed 868 upregulated and 696 downregulated DEGs in LV-SOX4 in comparison with LV-CON KGN cell lines. Afterward, further assessments were performed to explore the possible functions about these DEGs. The data showed their involvement in many biological processes, particularly the Hippo signaling pathway. Moreover, the expression levels of YAP1, WWTR1, WTIP, DLG3, CCN2, and AMOT, which were associated with the Hippo signaling pathway, were further validated by qRT-PCR. In addition, the protein expression levels of YAP1 were markedly elevated, while p-YAP1 were notably reduced after overexpression of SOX4 in KGN cells. Thus, these results suggested that SOX4 regulates apoptosis, proliferation and migration of KGN cells, at least partly, through activation of the Hippo signaling pathway, which might be implicated in mammalian follicle development.
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Células de la Granulosa , Vía de Señalización Hippo , Femenino , Animales , Humanos , Línea Celular Tumoral , Células de la Granulosa/metabolismo , Proliferación Celular , Apoptosis , Mamíferos/metabolismo , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas Co-Represoras/metabolismoRESUMEN
Carbon materials hold significant promise in electrocatalysis, particularly in electrochemical CO2 reduction reaction (eCO2 RR) and two-electron oxygen reduction reaction (2e- ORR). The pivotal factor in achieving exceptional overall catalytic performance in carbon catalysts is the strategic design of specific active sites and nanostructures. This work presents a comprehensive overview of recent developments in carbon electrocatalysts for eCO2 RR and 2e- ORR. The creation of active sites through single/dual heteroatom doping, functional group decoration, topological defect, and micro-nano structuring, along with their synergistic effects, is thoroughly examined. Elaboration on the catalytic mechanisms and structure-activity relationships of these active sites is provided. In addition to directly serving as electrocatalysts, this review explores the role of carbon matrix as a support in finely adjusting the reactivity of single-atom molecular catalysts. Finally, the work addresses the challenges and prospects associated with designing and fabricating carbon electrocatalysts, providing valuable insights into the future trajectory of this dynamic field.
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Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.
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A new direction for China in exploring sustainable development is the Innovative City Pilot Policy (ICPP), which provides policy guidance for accelerating carbon peaking and carbon neutrality by reducing carbon emissions. With data from 282 cities spanning 2006-2018, this paper examines ICPP's effect on carbon intensity (CI) through a multi-period difference-in-differences (DID) model, as well as exploring the mediating effect, moderating effect, heterogeneity, and spatial spillover effects. The results show that ICPP reduces CI significantly by enhancing technology innovation (TI), and when industrial structure (IS) is added, the effect of ICPP is expanded. The ICPP gains additional advantages in reducing CI by optimizing the efficiency of resource allocation (ERA). Compared with the concentration of human capital (HCL), the amount of scientific research institutes (SRI) has a slightly greater moderating effect. ICPP impacts considering location, size, and hierarchy heterogeneity. ICPP has a greater impact on mitigating CI in the western, larger size, and provincial capital cities. There are positive spillover effects of the ICPP on neighboring CI. To support the idea that ICPP can effectively contribute to CI reduction, this paper provides empirical evidence and theoretical guidelines.
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Objective: Adolescence is a high-risk period for traffic injury. One factor that may impact adolescent safety in traffic is the presence of peers. We conducted a quasi-experimental research study to examine the impact of peer presence, peer familiarity, and peer group size on adolescent pedestrian risk-taking intentions in both sidewalk and street-crossing settings. Methods: 607 students aged 12-18 years from Nantong city, China, completed a questionnaire that presented 20 traffic scenarios. The scenarios varied based on a 3 (peer group size: no peer vs. one peer vs. multiple peers) x 2 (peer familiarity: familiar vs. unfamiliar) x 2 (traffic setting: crossing the street vs. walking on the roadside) experimental design. Adolescents' responses indicated safer vs riskier intentions in each situation. Results: Results found that: (1) Adolescents were safer when walking on the sidewalk than when crossing the street; (2) Whether crossing the street or walking on the sidewalk, adolescents' behavioral intentions were safer when there were peers present than when there were no peers present; (3) Adolescents' safety tended to be higher overall with unfamiliar peers than with familiar peers; (4) Adolescents were less safe when crossing the street with familiar peer(s) than with unfamiliar peer(s), but no differences emerged when walking on the sidewalk. Conclusions: Adolescents report safer behavior when walking with a peer or peers compared with walking alone. Familiar peers reduce adolescents' safety of behavior intentions in traffic, especially when crossing the street.
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Acquired drug resistance occurred in the treatment of non-small-cell lung cancer is a persistent challenge, especially in EGFR mutant type. In this study, we present design, synthesis and biological evaluation of novel quinazoline and pyrrolopyrimidine derivatives that simultaneously occupy the orthosteric and allosteric sites of EGFR. Among them, compound A-7 was confirmed as a potential EGFRL858R/T790M/C797S and EGFRDel19/T790M/C797S inhibitor. Docking study indicated that compound A-7 could simultaneously occupy two binding sites of EGFR and form three key H-bonds with the residues Met793, Lys745 and Met766 in two regions.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB , Sitio Alostérico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Inhibidores de Proteínas Quinasas/química , Resistencia a AntineoplásicosRESUMEN
BACKGROUND: In recent years, there has been an increasing demand for plant-based cheese analogues, however, the protein content of plant-based cheeses currently on the market is generally low and cannot meet the nutritional needs of consumers. RESULTS: Based on the ideal value similarity method (TOPSIS) analysis the best recipe for plant-based cheese was 15% tapioca starch, 20% soy protein isolate, 7% gelatine as a quality enhancer and 15% coconut oil. The protein content of this plant-based cheese was170.1 g kg-1 , which was close to commercial dairy-based cheese and significantly higher than commercial plant-based cheese, The fat content was 114.7 g kg-1 , lower than that of commercial dairy-based cheese. The rheology properties show that the viscoelasticity of the plant-based cheese is higher than that of dairy-based cheese and commercial plant-based. The microstructure results show that the type and content of protein has a significant impact on its microstructure. The Fourier-transform infrared (FTIR) spectrum of the microstructure shows a characteristic value at 1700 cm-1 , because the starch was heated and leached to form a complex with lauric acid under the action of hydrogen bond. It can be inferred that in the interaction between plant-based cheese raw materials, fatty acids serve as a bridge between starch and protein. COUCLUSION: This study described the formula of plant-based cheese and the interaction mechanism between the ingredients, providing a basis for the development of subsequent plant-based cheese related products. © 2023 Society of Chemical Industry.
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Queso , Queso/análisis , Proteínas , Reología , Viscosidad , AlmidónRESUMEN
Melanoma belongs to cutaneous malignancy. Long non-coding RNAs (lncRNAs) have been suggested as crucial effectors in modulating progression of different malignancies, including melanoma. However, novel lncRNA solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) was not reported in melanoma. Herein, SLCO4A1-AS1 was detected to be up-regulated in melanoma cell lines compared with human normal melanocytes (HEM-a). Additionally, proliferation, migration and invasion of melanoma cells were weakened but apoptosis was facilitated due to SLCO4A1-AS1 down-regulation. Subsequently, miR-1306-5p was revealed to be sequestered by SLCO4A1-AS1 and down-regulated in melanoma cells. Functional assays further sustained that overexpressed miR-1306-5p had inhibitory influence on proliferation, migration and invasion and promoting influence on apoptosis of melanoma cells. Polycomb group ring finger 2 (PCGF2) was predicted as the downstream of miR-1306-5p, displaying aberrantly high expression in melanoma cell lines. Furthermore, PCGF2 expression was negatively modulated by miR-1306-5p and positively regulated by SLCO4A1-AS1. Finally, rescue assays demonstrated melanoma cell malignant behaviours suppressed by SLCO4A1-AS1 knockdown could be reversed by overexpressed PCGF2. Our study suggested that SLCO4A1-AS1 promoted the melanoma cell malignant behaviours via targeting miR-1306-5p/PCGF2, which might facilitate the discovery of novel biomarkers for melanoma treatment.
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Melanoma , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Melanoma/genética , MicroARNs/genética , MicroARNs/metabolismo , Complejo Represivo Polycomb 1 , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Oxygen species functionalized graphene (O-G) is an effective electrocatalyst for electrochemically synthesizing hydrogen peroxide (H2 O2 ) by a 2 e- oxygen reduction reaction (ORR). The type of oxygen species and degree of carbon crystallinity in O-G are two key factors for the high catalytic performance of the 2 e- ORR. However, the general preparing method of O-G by the precursor of graphite has the disadvantages of consuming massive strong oxidant and washing water. Herein, the biomass-based graphene with tunable oxygen species is rapidly fabricated by a CO2 laser. In a flow cell setup, the laser-induced graphene (LIG) with abundant active oxygen species and graphene structure shows high catalytic performance including high Faraday efficiency (over 78 %) and high mass activity (814â mmolgcatalyst -1 â h-1 ), superior to most of the reported carbon-based electrocatalysts. Density function theory demonstrates the meta-C atoms at nearby C-O, O-C=O species are the key catalytic sites. Therefore, we develop one facile method to rapidly convert biomass to graphene electrocatalyst used for H2 O2 synthesis.
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Based on the obtained SARs, further structural optimisation of compound BC2021-104511-15i was conducted in this investigation, and totally ten novel quinoline derivates were designed, synthesised and optimised for biological activity. Among them, compound 10a displayed significant in vitro anticancer activity against COLO 205 cells with an IC50 value of 0.11 µM which was over 90-fold more potent than that of Regorafenib (IC50>10.0 µM) and Fruquintinib (IC50>10.0 µM). Furthermore, compound 10a exhibited over 90-fold selectivity towards COLO 205 relative to human normal colorectal mucosa epithelial cell FHC cells. Flow cytometry study demonstrated that compound 10a could induce apoptosis in COLO 205 cells, however, it could not induce cell cycle arrest in COLO 205 cells. The results of preliminary kinase profile study showed that compound 10a was a potential HGFR and MST1R dual inhibitor, with IC50 values of 0.11 µM and 0.045 µM, respectively.
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Antineoplásicos , Neoplasias , Quinolinas , Antineoplásicos/química , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/tratamiento farmacológico , Quinolinas/farmacología , Relación Estructura-Actividad , Urea/farmacologíaRESUMEN
Single atom catalysts (SACs) are widely researched in various chemical transformations due to the high atomic utilization and catalytic activity. Carbon-supported SACs are the largest class because of the many excellent properties of carbon derivatives. The single metal atoms are usually immobilized by doped N atoms and in some cases by C geometrical defects on carbon materials. To explore the catalytic mechanisms and improve the catalytic performance, many efforts have been devoted to modulating the electronic structure of metal single atomic sites. Doping with polynary metals and heteroatoms has been recently proposed to be a simple and effective strategy, derived from the modulating mechanisms of metal alloy structure for metal catalysts and from the donating/withdrawing heteroatom doping for carbon supports, respectively. Polynary metals SACs involve two types of metal with atomical dispersion. The bimetal atom pairs act as dual catalytic sites leading to higher catalytic activity and selectivity. Polynary heteroatoms generally have two types of heteroatoms in which N always couples with another heteroatom, including B, S, P, etc. In this Review, the recent progress of polynary metals and heteroatoms SACs is summarized. Finally, the barriers to tune the activity/selectivity of SACs are discussed and further perspectives presented.
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The accelerating research interest in graphene involving the use of Hummers method has generated non-negligible amount of wastewater containing residual graphite as well as Mn2+ . In this paper, we report the first example of using this wastewater as precursor to prepare Mn3 O4 /N-doped graphite (NG) composites through a facile solvothermal process. The mass fraction of Mn3 O4 in the composites was manipulated by adding various amounts of extra Mn2+ . The conversion of Mn2+ to Mn3 O4 nanoparticles and the N atoms doping were achieved by adding hydrazine hydrate and ammonia into the system. The as-obtained Mn3 O4 /NG composites were well characterized by SEM, TEM, EDS, Raman, XPS, TGA, XRD and N2 adsorption-desorption experiments and showed excellent catalytic performances as well as stability in the degradation of a model organic pollutant methylene blue (MB). Theoretical simulation was also carried out to illustrate the structural features of the Mn3 O4 /NG composite. This work presents a novel idea of designing functional materials from waste precursors.
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The large-scale, low-cost preparation of Pt-based catalysts with high activity and durability for the methanol oxidation reaction is still challenging. The key to achieving this aim is finding suitable supporting materials. In this paper, N-doped carbon nanofibrous networks are prepared by annealing a gel containing two inexpensive and ecofriendly precursors, that is, bacterial cellulose and urea, for the loading of Pt nanoparticles. An undoped analogue is also prepared for comparison. Meanwhile, the effect of the annealing temperature on the performance of the catalysts is evaluated. The results show that the N doping and higher annealing temperature can improve the electron conductivity of the catalyst and provide more active sites for the loading of ultrafine Pt nanoparticles with a narrow size distribution. The best catalyst exhibits a remarkably high electrocatalytic activity (627â mA mg-1 ), excellent poison tolerance, and high durability. This work demonstrates an ideal Pt supporting material for the methanol oxidation reaction.
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Celulosa/química , Nanopartículas del Metal/química , Metanol/química , Nanofibras/química , Platino (Metal)/química , Carbono/química , Catálisis , Microscopía Electrónica de Rastreo , Nitrógeno/química , Oxidación-Reducción , Espectroscopía de FotoelectronesRESUMEN
BACKGROUND: Pemetrexed (PEM) is an anti-cancer agent targeting DNA and RNA synthesis, and clinically in use for mesothelioma and non-small cell lung carcinoma. A mechanism of resistance to PEM is associated with elevated activities of several enzymes involved in nucleic acid metabolism. METHODS: We established two kinds of PEM-resistant mesothelioma cells which did not show any increase of the relevant enzyme activities. We screened genes enhanced in the PEM-resistant cells with a microarray analysis and confirmed the expression levels with Western blot analysis. A possible involvement of the candidates in the PEM-resistance was examined with a WST assay after knocking down the expression with si-RNA. We also analyzed a mechanism of the up-regulated expression with agents influencing AMP-activated protein kinase (AMPK) and p53. RESULTS: We found that expression of cardiac ankyrin repeat protein (CARP) was elevated in the PEM-resistant cells with a microarray and Western blot analysis. Down-regulation of CARP expression with si-RNA did not however influence the PEM resistance. Parent and PEM-resistant cells treated with PEM increased expression of CARP, AMPK, p53 and histone H2AX. The CARP up-regulation was however irrelevant to the p53 genotypes and not induced by an AMPK activator. Augmented p53 levels with nutlin-3a, an inhibitor for p53 degradation, and DNA damages were not always associated with the enhanced CARP expression. CONCLUSIONS: These data collectively suggest that up-regulated CARP expression is a potential marker for development of PEM-resistance in mesothelioma and that the PEM-mediated enhanced expression is not directly linked with immediate cellular responses to PEM.
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Fabrication of sustainable bio-based malleable thermosets (BMTs) with excellent mechanical properties and reprocessing ability for applications in electronic devices has attracted more and more attention but remains significant challenges. Herein, the BMTs with excellent mechanical robustness and reprocessing ability were fabricated via integrating with radical polymerization and Schiff-base chemistry, and employed as the flexible substrate to prepare the capacitive sensor. To prepare the BMTs, an elastic bio-copolymer derived from plant oil and 5-hydroxymethylfurfural was first synthesized, and then used to fabricate the dynamic crosslinked BMTs through Schiff-base chemistry with the amino-modified cellulose and polyether amine. The synergistic effect of rigid cellulose backbone and the construction of dynamic covalent crosslinking network not only achieved high tensile strength (8.61 MPa) and toughness (3.77 MJ/m3) but also endowed the BMTs with excellent reprocessing ability with high mechanical toughness recovery efficiency of 104.8 %. More importantly, the BMTs were used as substrates to fabricate the capacitive sensor through the CO2-laser irradiation technique. The resultant capacitive sensor displayed excellent and sensitive humidity sensing performance, which allowed it to be successfully applied in human health monitoring. This work paved a promising way for the preparation of mechanical robustness malleable bio-thermosets for electronic devices.
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Celulosa , Furaldehído , Aceites de Plantas , Celulosa/química , Furaldehído/química , Furaldehído/análogos & derivados , Aceites de Plantas/química , Capacidad Eléctrica , Temperatura , Resistencia a la Tracción , HumanosRESUMEN
Serine/arginine repetitive matrix 2 (SRRM2) has been implicated in tumorigenesis, cancer development, and drug resistance through aberrant splicing; however, its correlation with multiple myeloma (MM) has not been reported. We investigated the potential of SRRM2 as a biomarker and immunotherapeutic target in MM by examining its expression in MM cells using flow cytometry. Our study included 95 patients with plasma cell disease, including 80 MM cases, and we detected SRRM2 expression on plasma cells and normal blood cells to analyze its relationship with clinical profiles. We found widespread positive expression of SRRM2 on plasma cells with little expression on normal blood cells, and its expression on abnormal plasma cells was higher than that on normal plasma cells. Comparative analysis with clinical data suggests that SRRM2 expression on plasma cells correlates with MM treatment response. MM patients with high SRRM2 expression had higher levels of serum ß2-mg and LDH, ISS staging, and plasma cell infiltration, as well as high-risk mSMART 3.0 stratification and cytogenetic abnormalities, particularly 1q21 amplification. In patients with previous MM, high SRRM2 expression on plasma cells was associated with higher plasma cell infiltration, high-risk mSMART 3.0 risk stratification, cytogenetic abnormalities, more relapses, and fewer autologous stem cell transplant treatments. In summary, SRRM2 may serve as a novel biomarker and immunotherapeutic target for MM. Its expression level on plasma cells can help in risk stratification of MM and monitoring of treatment response.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Citometría de Flujo , Inmunoterapia , Biomarcadores , Aberraciones Cromosómicas , Proteínas de Unión al ARNRESUMEN
Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) patients usually have very poor prognoses, and drug-resistance is one of the major limiting factors. In this study, we aimed to explore the functions of Transforming Growth Factor-ß1 (TGFB1) in AML drug-resistance. First, TGFB1 levels in serum and bone marrow are higher in R/R patients compared with newly diagnosed patients, this phenomenon could be due to different sources of secreted TGFB1 according to immunohistochemistry of marrow biopsies. Similarly, TGFB1 expression in AML drug-resistant cell lines is higher than that in their parental cell lines, and blocking the TGFB signaling pathway by specific inhibitors decreased resistance to chemotherapeutic agents. On the other hand, exogenous TGFB1 can also promote AML parental cells senescence and chemotherapy resistance. Next, we found SOX4 level is upregulated in drug-resistant cells, and parental cells treated with exogenous TGFB1 induced upregulation of SOX4 levels. Interference of SOX4 expression by siRNA diminished the TGFB1-induced sensitivity to chemotherapeutic agents. Finally, we conduct metabolomic analysis and find Alanine, aspartate and glutamate metabolism pathway, and Glycerophospholipid metabolism pathway are decreased after inhibiting TGFB signaling pathway or interfering SOX4 expression. This study concludes that TGFB1 level in R/R AML patients and drug-resistant strains is significantly increased. Blocking the TGFB signaling pathway can enhance the chemosensitivity of drug-resistant cells by suppressing SOX4 expression and metabolic reprogramming.
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Leucemia Mieloide Aguda , Factor de Crecimiento Transformador beta1 , Humanos , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda/tratamiento farmacológico , Transducción de Señal , Alanina , Factores de Transcripción SOXCRESUMEN
STUDY OBJECTIVES: Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. METHODS: Diffusion tensor imaging was conducted for people with narcolepsy (nâ =â 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. RESULTS: A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). CONCLUSIONS: People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.
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Encéfalo , Imagen de Difusión Tensora , Narcolepsia , Humanos , Narcolepsia/fisiopatología , Narcolepsia/genética , Narcolepsia/diagnóstico por imagen , Masculino , Adulto , Femenino , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/patología , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatología , Sustancia Blanca/patología , Trastorno de la Conducta del Sueño REM/fisiopatología , Trastorno de la Conducta del Sueño REM/diagnóstico por imagen , Trastorno de la Conducta del Sueño REM/genética , Estudios de Casos y Controles , Persona de Mediana EdadRESUMEN
OBJECTIVE: To study the effects of umbilical cord blood monocytes (UCBMC) transplantation on erythropoietin (EPO) protein and oligodendrocyte progenitor cells in hypoxia-ischemia (HI) neonatal rats. METHODS: Forty seven-day-old Sprague-Dawley rats were randomly divided into normal control (N), HI, UCBMC and HI+UCBMC groups (n=10 each). Hypoxic-ischemic brain damage (HIBD) model was prepared according to the Rice method. Twenty-four hours after hypoxia, the N and HI groups were injected with 2 µL phosphate buffered saline (PBS), and the UCBMC and HI+UCBMC groups were injected with 3×10(6) UCBMC via the lateral ventricle. EPO protein and oligodendrocyte progenitor cells in the subventricular zone of the injured brain were observed by EPO/DAPI and NG2/DAPI immunofluorescence double staining, and their correlation was analyzed. RESULTS: Seven days after transplantation, there were more NG2(+)DAPI(+) and EPO(+)DAPI(+) cells in the HI+UCBMC group than in the UCBMC (P<0.05), N and HI groups (P<0.01). More NG2(+)DAPI(+) and EPO(+)DAPI(+) cells were observed in the UCBMC group compared with the N and HI groups (P<0.01). There were more NG2(+)DAPI(+) cells in the N group than in the HI group (P<0.01). The number of NG2(+)DAPI(+) cells was correlated with the number of EPO(+)DAPI(+) cells in the HI+UCBMC group (r=0.898, ß=1.4604, P<0.01). CONCLUSIONS: UCBMC can promote expression of oligodendrocyte progenitor cells, which is correlated with an increase in EPO protein and thus repairs brain white matter damage in neonatal rats with HIBD.
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Eritropoyetina/biosíntesis , Sangre Fetal/citología , Hipoxia-Isquemia Encefálica/terapia , Monocitos/trasplante , Oligodendroglía/patología , Células Madre/patología , Animales , Animales Recién Nacidos , Eritropoyetina/análisis , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Ratas , Ratas Sprague-DawleyRESUMEN
The secretory proteome plays an important role in the pathogenesis of phytopathogenic fungi. However, the relationship between the large-scale secretome of phytopathogenic fungi and their lifestyle is not fully understood. In the present study, the secretomes of 150 plant pathogenic fungi were predicted and the characteristics associated with different lifestyles were investigated. In total, 94,974 secreted proteins (SPs) were predicted from these fungi. The number of the SPs ranged from 64 to 1,662. Among these fungi, hemibiotrophic fungi had the highest number (average of 970) and proportion (7.1%) of SPs. Functional annotation showed that hemibiotrophic and necrotroph fungi, differ from biotrophic and symbiotic fungi, contained much more carbohydrate enzymes, especially polysaccharide lyases and carbohydrate esterases. Furthermore, the core and lifestyle-specific SPs orthogroups were identified. Twenty-seven core orthogroups contained 16% of the total SPs and their motif function annotation was represented by serine carboxypeptidase, carboxylesterase and asparaginase. In contrast, 97 lifestyle-specific orthogroups contained only 1% of the total SPs, with diverse functions such as PAN_AP in hemibiotroph-specific and flavin monooxygenases in necrotroph-specific. Moreover, obligate biotrophic fungi had the largest number of effectors (average of 150), followed by hemibiotrophic fungi (average of 120). Among these effectors, 4,155 had known functional annotation and pectin lyase had the highest proportion in the functionally annotated effectors. In addition, 32 sets of RNA-Seq data on pathogen-host interactions were collected and the expression levels of SPs were higher than that of non-SPs, and the expression level of effector genes was higher in biotrophic and hemibiotrophic fungi than in necrotrophic fungi, while secretase genes were highly expressed in necrotrophic fungi. Finally, the secretory activity of five predicted SPs from Setosphearia turcica was experimentally verified. In conclusion, our results provide a foundation for the study of pathogen-host interaction and help us to understand the fungal lifestyle adaptation.