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The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.
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Neoplasias Colorretais , Lipidômica , Fosfatidiletanolaminas , Espectrometria de Massas em Tandem , Língua , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Lipidômica/métodos , Masculino , Feminino , Língua/microbiologia , Língua/metabolismo , Língua/patologia , Língua/química , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Fosfatidiletanolaminas/metabolismo , Fosfatidiletanolaminas/análise , Idoso , Cromatografia Líquida , Lipídeos/análise , Lipídeos/química , Triglicerídeos/metabolismo , Triglicerídeos/análise , Adenoma/metabolismo , Adenoma/microbiologia , Esfingomielinas/análise , Esfingomielinas/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/química , Plasmalogênios/análise , Plasmalogênios/metabolismo , Plasmalogênios/química , Estudos de Casos e Controles , Etanolaminas/metabolismo , Etanolaminas/análise , Etanolaminas/química , Ceramidas/metabolismo , Ceramidas/análise , AdultoRESUMO
Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.
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Microplásticos , Poluentes Químicos da Água , Microplásticos/toxicidade , Plásticos/toxicidade , Água do Mar , Solo , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , AdsorçãoRESUMO
Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood-brain barrier. Moreover, preliminary structure-activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.
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Aminoquinolinas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Desenho de Fármacos , Glioblastoma/tratamento farmacológico , Aminoquinolinas/síntese química , Aminoquinolinas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
This study explored the possibility of incorporating extremophilic algal cultivation into dairy wastewater treatment by characterizing a unique algal strain. Results showed that extremophilic microalgae Chlorella vulgaris CA1 newly isolated from dairy wastewater tolerated a high level of ammonia nitrogen (2.7 g/L), which was over 20 times the ammonia nitrogen that regular Chlorella sp. could tolerate. The isolate was mixotrophically cultured in dairy effluent treated by anaerobic digestion (AD) for recycling nutrients and polishing the wastewater. The highest biomass content of 13.3 g/L and protein content of 43.4% were achieved in the culture in AD effluent. Up to 96% of the total nitrogen and 79% of the total phosphorus were removed from the dairy AD effluent. The ability of the algae to tolerate a high level of ammonia nitrogen suggests the potential for direct nutrient recycling from dairy wastewater while producing algal biomass and high value bioproducts.
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Chlorella vulgaris , Extremófilos , Microalgas , Amônia , Biomassa , Nitrogênio , Nutrientes , Fósforo , Águas ResiduáriasRESUMO
BACKGROUND: It has been reported that antagonistic microorganisms could effectively control the infection of Fusarium graminearum. However, there is limited information on the control of F. graminearum by Saccharomyces cerevisiae, while the possible control mechanisms involved through proteomic and transcriptomic techniques have also not been reported. RESULTS: The results of this study showed that S. cerevisiae Y-912 could significantly inhibit the growth of F. graminearum Fg1, and the spore germination rate and germ tube length of F. graminearum Fg1 were also significantly inhibited by S. cerevisiae Y-912. Proteomic analysis revealed that differentially expressed proteins which were made of some basic proteins and enzymes related to basal metabolism, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate mutase (PGAM), enolase (ENO), fructose diphosphate aldolase (FBA) and so on, were all down-regulated. The transcriptomics of F. graminearum control by S. cerevisiae was also analyzed. CONCLUSION: The control mechanism of S. cerevisiae Y-912 on F. graminearum Fg1 was a very complex material and energy metabolic process in which the related proteins and genes involved in the glycolytic pathway, tricarboxylic acid (TCA) cycle and amino acid metabolism were all down-regulated. © 2019 Society of Chemical Industry.
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Fusarium/genética , Saccharomyces cerevisiae/genética , Transcriptoma , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fusarium/crescimento & desenvolvimento , Fusarium/metabolismo , Proteoma/genética , Proteoma/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismoRESUMO
Graphene oxide nanosheets was prepared, modification with 3-aminopropyltriethoxysilane and used as the carrier for immobilization of NADH oxidase (NOX) from Streptococcus mutans. The prepared nanosheets were characterized with FTIR. A high immobilization yield of 92% and activity recovery of 91% were achieved at pH 7.0 and 25 °C. The thermostability of the immobilized NOX was improved about 60% compared with the free enzyme. And the immobilized NOX preserved about 92% of its initial activity after 500 h storage at 4 °C, while free NOX was totally denatured after 200 h at the same conditions. These results indicate that NH2-functionalized graphene oxide nanosheets has a good potential as carrier for immobilization of proteins, especially enzymes.
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Enzimas Imobilizadas , Grafite , Complexos Multienzimáticos , NADH NADPH Oxirredutases , Nanopartículas , ÓxidosRESUMO
Graphene oxide nanosheets was prepared, functionlized with 3-aminopropyltriethoxysilane and used as the carrier for immobilization of papain. A high immobilization yield and efficiency higher than 80% were achieved at pH 8.0 and 35 °C. The thermal stability of the immobilized papain was improved compared with the free enzyme. And the immobilized papain retained about 63% of its initial activity after 30 days storage at 4 °C, while free enzyme was only 41% at the same conditions. The immobilized enzyme displayed higher binding affinity to substrate because of the unique properties of GO. These results indicate that modified graphene oxide nanosheets has a good potential as carrier for immobilization of proteins, especially enzymes.
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Under solvothermal/surfactant-thermal conditions, two new open-framework borogermanate and galloborate, centrosymmetric (Hdima)2[Ge5B3O15(OH)] (1; dima = dimethylamine) and noncentrosymmetric Na4Ga3B4O12(OH) (2), were obtained and characterized. Compound 1 contains an unusual basket-shaped Ge5B3O18(OH) cluster and displays a 3D open-framework layered structure. Compound 2 shows an interrupted 3,4-connected network constructed by alternately linked BO3 units and Ga3+ ions and displays weak second-harmonic-generation response.
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Sewage sludge derived fertilizer is a promising solution for phosphorus (P) recovery from biowaste, however, the inherent iron content in the sludge ash (SSA) impedes the P availability of the fused calcium magnesium phosphate fertilizer (FCMP). To achieve the goal of iron removal during the process, carbothermal reduction was adopted for the first time and the performance of carbon addition was systematically evaluated. Results showed that carbon addition at 4.50 % significantly increased the P availability from 9.50 % to 11.00 % and decreased the required amounts of calcium/magnesium. Moreover, ferrophosphate with 20.20 % P can be produced and the melting point of the system can be reduced by manipulating carbon addition. Finally, a process design was provided for the co-production of FCMP and ferrophosphate. This study highlights the addition of carbon to facilitate iron removal in SSA for the production of FCMP with enhanced bioavailability at a reduced energy consumption scenario.
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Fertilizantes , Ferro , Fosfatos , Esgotos , Esgotos/química , Ferro/química , Fosfatos/química , Disponibilidade Biológica , Carbono/química , FósforoRESUMO
Chlorinated polyvinyl chloride (CPVC)-based activated carbon spheres with smooth surfaces, good sphericity, interconnected hierarchical porous structure and high porosity have been synthesized by non-solvent induced phase separation method, followed by successive treatments of stabilization, carbonization at 450 °C in N2 atmosphere, and activation with CO2 as an agent at 900-1000 °C. The effect of activation temperatures on the textural properties of activated carbon spheres and their adsorption potential for volatile organic compounds (VOCs) under dynamic conditions is investigated. CO2 activation improves the hierarchy in the microporous range by stimulating the formation of supermicropores and significantly expands the specific surface area and pore volume of activated carbon spheres. The textural properties of adsorbents play a vital role in the adsorption performance of different VOCs. The adsorption capacity of VOC molecules can be greatly promoted by elevating specific surface area and pore volume. Due to the compatibility difference between the VOC molecules and the pore structure of adsorbents, the adsorption capacity follows the order of toluene > m-xylene > n-hexane. The adsorption isotherm of toluene on CPVC-AC1000 can be generally expressed by the Langmuir model. The adsorbents with larger average pore diameters possess a lower activation energy of desorption, which is beneficial for desorption. The carbon sphere activated at 1000 °C is a high-performance adsorbent with good reusability. Thus, the present study provides a synthesis process to produce the activated carbon spheres with high porosity from low-cost CPVC for its application in VOC adsorption.
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Carvão Vegetal , Compostos Orgânicos Voláteis , Carvão Vegetal/química , Compostos Orgânicos Voláteis/química , Dióxido de Carbono , Adsorção , Porosidade , ToluenoRESUMO
Postharvest soft rot of eggplant fruits caused by Pectobacterium carotovorum is a bacterial disease with a high disease incidence and produces substantial economic losses. This study aimed to control postharvest soft rot of eggplant fruits by Bacillus velezensis and investigate the possible control mechanisms based on the effects of B. velezensis on P. carotovorum subsp. carotovorum (Pcc) and eggplant fruits, respectively. B. velezensis effectively controlled postharvest soft rot of eggplant fruits and directly inhibited Pcc growth in vitro. The volatile metabolites produced by B. velezensis showed no inhibition on Pcc. Whereas the cell-free filtrate of B. velezensis significantly inhibited the growth of Pcc in vitro and in vivo. Notably, methanol-soluble precipitates obtained from cell-free filtrate showed significant inhibition on Pcc, and the primary inhibitory substances were identified as surfactin isoforms. Besides, iturin and fengycin isoforms with much lower relative abundance were also detected in the methanol-soluble precipitates. Furthermore, B. velezensis enhanced the activities of reactive oxygen species (ROS) scavenging enzymes in eggplant fruits that alleviated ROS and oxidative damage; thereby, B. velezensis enhanced the fruits' disease resistance.
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Solanum melongena , Frutas , Metanol , Espécies Reativas de Oxigênio , Isoformas de ProteínasRESUMO
Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.
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BACKGROUND: Ovarian cancer is a significant public health concern with a poor prognosis for epithelial ovarian cancer. To explore the potential of immunotherapy in treating epithelial ovarian cancer, we investigated the immune microenvironments of 52 patients with epithelial ovarian cancer, including 43 with high-grade serous ovarian cancer and 9 with endometrioid ovarian cancer. RESULTS: Fresh tumor tissue was analyzed for genetic mutations and various parameters related to immune evasion and infiltration. The mean stromal score (stromal cell infiltration) in high-grade serous ovarian cancer was higher than in endometrioid ovarian cancer. The infiltration of CD8 T cells and exhausted CD8 T cells were found to be more extensive in high-grade serous ovarian cancer. Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and cancer-associated fibroblasts (CAF) scores were also higher in the high-grade serous ovarian cancer group, suggesting that the number of cytotoxic lymphocytes in the tumor microenvironment of high-grade serous ovarian cancer is likely lower compared to endometrioid ovarian cancer. CONCLUSIONS: The high mean stromal score and more extensive infiltration and exhaustion of CD8 T cells in high-grade serous ovarian cancer indicate that high-grade serous ovarian cancer exhibits a higher level of cytotoxic T cell infiltration, yet these T cells tend to be in a dysfunctional state. Higher Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and CAF scores in high-grade serous ovarian cancers suggest that immune escape is more likely to occur in high-grade serous ovarian cancer, thus endometrioid ovarian cancer may be more conducive to immunotherapy. Therefore, it is crucial to design immunotherapy clinical trials for ovarian cancer to distinguish between high-grade serous and endometrioid ovarian cancer from the outset. This distinction will help optimize treatment strategies and improve outcomes for patients with different subtypes.
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Carcinoma Endometrioide , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/patologia , Microambiente Tumoral , Neoplasias Ovarianas/genética , Carcinoma Endometrioide/terapia , Imunoterapia , Cistadenocarcinoma Seroso/patologiaRESUMO
Background: Lysosomes are instrumental in intracellular degradation and recycling, with their functional alterations holding significance in tumor growth. Nevertheless, the precise role of lysosome-related genes (LRGs) in breast cancer (BC) remains elucidated. This study aimed to establish a prognostic model for BC based on LRGs. Methods: Employing The Cancer Genome Atlas (TCGA) BC cohort as a training dataset, this study identified differentially expressed lysosome-related genes (DLRGs) through intersecting LRGs with differential expression genes (DEGs) between tumor and normal samples. A prognostic model of BC was subsequently developed using Cox regression analysis and validated within two Gene Expression Omnibus (GEO) external validation sets. Further analyses explored functional pathways, the immune microenvironment, immunotherapeutic responses, and sensitivity to chemotherapeutic drugs in different risk groups. Additionally, the mRNA and protein expression levels of genes within the risk model were examined by utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. Clinical tissue specimens obtained from patients were gathered to validate the expression of the model genes via Real-Time Polymerase Chain Reaction (RT-PCR). Results: We developed a risk model of BC based on five specific genes (ATP6AP1, SLC7A5, EPDR1, SDC1, and PIGR). The model was validated for overall survival (OS) in two GEO validation sets (p=0.00034 for GSE20685 and p=0.0095 for GSE58812). In addition, the nomogram incorporating clinical factors showed better predictive performance. Compared to the low-risk group, the high-risk group had a higher level of certain immune cell infiltration, including regulatory T cells (Tregs) and type 2 T helper cells (Th2). The high-risk patients appeared to respond less well to general immunotherapy and chemotherapeutic drugs, according to the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and drug sensitivity scores. The RT-PCR results validated the expression trends of some prognostic-related genes in agreement with the previous differential expression analysis. Conclusion: Our innovative lysosome-associated signature can predict the prognosis for BC patients, offering insights for guiding subsequent immunotherapeutic and chemotherapeutic interventions. Furthermore, it has the potential to provide a scientific foundation for identifying prospective therapeutic targets.
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In this paper, a high-order solver combining the flux reconstruction (FR) method and the thermal lattice Boltzmann flux solver (FRTLBFS) is developed for accurately and efficiently simulating incompressible thermal flows. The conservative differential equations recovered from Chapman-Enskog analysis of the thermal lattice Boltzmann equation are solved by the high-order FR method. The thermal lattice Boltzmann method is only applied to reconstruct the local solution used for evaluating fluxes at the solution and flux points. Unlike the traditional Navier-Stokes-Boussinesq (NSB) solvers where the inviscid and viscous terms are treated separately, the inviscid and viscous fluxes in the current FRTLBFS are coupled and computed uniformly. In comparison with the recently developed high-order flux reconstruction thermal lattice Boltzmann method, the FRTLBFS holds advantages such as high-order accuracy, good stability, and compactness but is more efficient and low storage, since only macroscopic flow variables including density, velocity, and temperature are stored and evolved. In addition, the physical boundary conditions in FRTLBFS can be directly implemented by using the same method as in conventional NSB solvers. Numerical validations of the proposed method are implemented by simulating (a) the porous plate problem, (b) natural convection in a square cavity, (c) unsteady natural convection in a tall cavity, and (d) thermal lid-driven cavity flow. Numerical results demonstrate that the present solver is an attractive tool to simulate incompressible thermal flows due to its high-order accuracy, stability, and low memory cost.
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BACKGROUND: The efficiency of biological systems as an option for pretreating lignocellulosic biomass has to be improved to make the process practical. Fungal treatment with manganese (Mn) addition for improving lignocellulosic biomass fractionation and enzyme accessibility were investigated in this study. The broad-spectrum effect was tested on two different types of feedstocks with three fungal species. Since the physicochemical and structural properties of biomass were the main changes caused by fungal degradation, detailed characterization of biomass structural features was conducted to understand the mechanism of Mn-enhanced biomass saccharification. RESULTS: The glucose yields of fungal-treated poplar and wheat straw increased by 2.97- and 5.71-fold, respectively, after Mn addition. Particularly, over 90% of glucose yield was achieved in Mn-assisted Pleurotus ostreatus-treated wheat straw. A comparison study using pyrolysis gas chromatography mass spectrometry (Py-GC/MS) and two-dimensional 1H-13C heteronuclear single quantum coherence (2D HSQC) nuclear magnetic resonance (NMR) spectroscopy was conducted to elucidate the role of Mn addition on fungal disruption of the cross-linked structure of whole plant cell wall. The increased Cα-oxidized products was consistent with the enhanced cleavage of the major ß-O-4 ether linkages in poplar and wheat straw lignin or in the wheat straw lignin-carbohydrate complexes (LCCs), which led to the reduced condensation degree in lignin and decreased lignin content in Mn-assisted fungal-treated biomass. The correlation analysis and principal component analysis (PCA) further demonstrated that Mn addition to fungal treatment enhanced bond cleavage in lignin, especially the ß-O-4 ether linkage cleavage played the dominant role in removing the biomass recalcitrance and contributing to the glucose yield enhancement. Meanwhile, enhanced deconstruction of LCCs was important in reducing wheat straw recalcitrance. The findings provided not only mechanistic insights into the Mn-enhanced biomass digestibility by fungus, but also a strategy for improving biological pretreatment efficiency of lignocellulose. CONCLUSION: The mechanism of enhanced saccharification of biomass by Mn-assisted fungal treatment mainly through Cα-oxidative cleavage of ß-O-4 ether linkages further led to the decreased condensation degree in lignin, as a result, biomass recalcitrance was significantly reduced by Mn addition.
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The general trend of automation is currently increasing in life science laboratories. The samples to be examined show a high diversity in their structures and composition as well as the determination methods. Complex automation lines such as those used in classic industrial automation are not a suitable solution with respect to the required flexibility of the systems due to changing application requirements. Rather, full automation requires the connection of several different subsystems, including manual process steps by the laboratory staff. This requires suitable workflow management systems that enable the planning and execution of complex process steps. The integration of mobile robots for transportation tasks is currently an important development trend for realizing full automation in life science laboratories. The article "Workflow Management System for the Integration of Mobile Robots in Future Labs of Life Sciences" presents the development and application of a hierarchical workflow management system (HWMS) as a top-level process management and control system. This concept combines the typical hierarchical automation structure with novel approaches for the integration of transportation tasks with variable degrees of automation. The aim is to create a general-purpose workflow management system that can be used in different areas of the life sciences, regardless of the specific device components and applications used.
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Disciplinas das Ciências Biológicas , Robótica , Automação , Humanos , Laboratórios , Fluxo de TrabalhoRESUMO
Overexpression of PTBP3, a factor involved in alternative splicing, may inhibit the differentiation of leukemia cells. However, its role in gastric cancer differentiation and the specific pathways involved are unclear. In this study, we found that PTBP3 was upregulated in the poorly differentiated gastric cancer tissues. Patients with high levels of PTBP3 expression had significantly shorter survival than those with low PTBP3 expression. In gastric cancer cells, the regulatory effect of PTBP3 on alternative splicing of the Id1 gene was investigated. Following sodium butyrate-induced differentiation of MKN45 cells, the expression of Id1a decreased, but the expression of Id1b increased. RNA interference and overexpression experiments showed that PTBP3 upregulated Id1a expression and downregulated Id1b expression. RNA immunoprecipitation (RIP) assays indicated PTBP3 could interact with Id1. UV cross-linking assays indicated that PTBP3 interacted with the CU rich region of the Id1 gene. Two-hybrid experiments and a gel mobility shift assays found that Id1b had a more potent affinity for Hes1 than Id1a. Chromatin immunoprecipitation (ChIP) assays verified the association of Hes1 and the promoter of PTBP3 gene. Luciferase assays revealed that Hes1 bound the N-box sequence in the PTBP3 promoter. After silencing or overexpression of Hes1, PTBP3 protein expression remained unchanged. Thus, the loss of feedback regulation among PTBP3, Id1, and Hes1 in gastric cancer cells may be one of the causes of inhibited differentiation and malignant proliferation of these cells.
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In this paper, we successfully constructed a ternary metal/non-metal nanomaterial which can synergize Z-scheme heterojunction and plasmonic metal/semiconductor for enhancing visible light photoreduction of aqueous Cr(VI). The as-formed ternary metal/non-metal nanomaterial was composed of g-C3N4 nanosheets mutual modified by Ag nanoparticles and Bi4O7. In the ternary nanomaterial, g-C3N4 nanosheets and Bi4O7 fabricated Z-scheme heterojunction, g-C3N4 nanosheets and Ag nanoparticles formed plasmonic metal/semiconductor system, synchronously. The photodeposition experiments were designed to indirect demonstrate the Z-scheme heterojunction via photocatalytic oxidation and reduction deposition reactions, AgNO3 was used as the electron acceptor and Pb(NO3)2 as the electron donor, photocatalytic reduction product and oxidation product were selectively deposited on g-C3N4 nanosheets and Bi4O7, respectively, revealing the Z-scheme heterojunction was definite formed. In addition, X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), UV-vis absorption, and Fourier-transform infrared spectroscopy (FTIR) were studied to indicate that the plasmonic metal/semiconductor system was existent in the ternary nanomaterial. The visible light photoreduction of ternary Ag/Bi4O7/g-C3N4 nanosheets was evaluated by photoreducing aqueous Cr(VI). The photoreduction results show that the ternary Ag/Bi4O7/g-C3N4 nanosheets is much higher than the pristine bulk g-C3N4 and g-C3N4 nanosheets.
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Breast cancer is one of the main diagnosis cancers annually worldwide. It is difficult to thorough cure due to drug resistance and the high possibility of metastasis. SM934 is a novel water-soluble artemisinin analog, and has been reported to have a promising therapeutic effect on multiple autoimmune diseases. In this study, SM934 was combined with Testosterone, which is related to prostate cancer, and the reaction product was SM934-Testosterone. We aimed to explore whether SM934, Testosterone and SM934-Testosterone could inhibit tumorigenesis and metastasis of breast cancer cells. Moreover, the mechanism also remains to be clarified. The results of our study showed that among the three compounds, only SM934-Testosterone treatment could lead to the suppression of cell proliferation and metastasis with IC50â¯=â¯30.66⯱â¯2.13⯵Mâ¯at 24â¯h in MDA-MB-231 and IC50â¯=â¯31.11⯱â¯1.79⯵Mâ¯at 24â¯h in SK-BR-3, where apoptosis was induced. But SM934-Testosterone showed little effects on breast cancer in vivo due to its poor water-solubility. Furthermore, computational target prediction and experimental validation demonstrated that Cathepsin K was the target of SM934-Testosterone. SM934-Testosterone inhibited the expression of Cathepsin K in breast cancer cells. Then, down-regulation of Cathepsin K in cancer cells by transfected with Cathepsin K shRNA inhibited cell proliferation and metastasis of breast cancer cells. Moreover, pathway enrichment was performed to understand the mechanism of action that Cathepsin K could adjust apoptosis regulator Bcl-X, and knockdown of Cathepsin K by SM934-Testosterone resulted in the reduction of Bcl-xL, which has been reported to be related to the proliferation and metastasis of cells. Collectively, SM934-Testosterone inhibited proliferation and metastasis ability of breast cancer cells via inhibiting the expression of Cathepsin K followed by the inhibition of Bcl-xL.