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The plant cuticle, a structure primarily composed of wax and cutin, forms a continuous coating over most aerial plant surfaces. The cuticle plays important roles in plant tolerance to environmental stress, including stress imposed by drought. Some members of the 3-KETOACYL-COA SYNTHASE (KCS) family are known to act as metabolic enzymes involved in cuticular wax production. Here we report that Arabidopsis (Arabidopsis thaliana) KCS3, which was previously shown to lack canonical catalytic activity, instead functions as a negative regulator of wax metabolism by reducing the enzymatic activity of KCS6, a key KCS involved in wax production. We demonstrate that the role of KCS3 in regulating KCS6 activity involves physical interactions between specific subunits of the fatty acid elongation complex and is essential for maintaining wax homeostasis. We also show that the role of the KCS3-KCS6 module in regulating wax synthesis is highly conserved across diverse plant taxa from Arabidopsis to the moss Physcomitrium patens, pointing to a critical ancient and basal function of this module in finely regulating wax synthesis.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Mutação , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMO
Water-to-land transition is a hallmark of terrestrialization for land plants and requires molecular adaptation to resist water deficiency. Lineages- or species-specific genes are widespread across eukaryotes, and yet the majority of those are functionally unknown and not annotated. Recent studies have revealed that some of such genes could play a role in adapting to environmental stress responses. Here, we identified a novel gene PpBCG1 (Bryophyte Co-retained Gene 1) in the moss Physcomitrium patens that was responsive to dehydration and rehydration. Under de- and rehydration treatments, PpBCG1 was significantly co-expressed with the dehydrin-encoding gene PpDHNA. Microarray data revealed that PpBCG1 was highly expressed in tissues of spores, female organ archegonia, and mature sporophytes. In addition, the Ppbcg1 mutant showed reduced ability of dehydration tolerance, whose plants were accompanied by a relatively low level of chlorophyll content during recovery. Comprehensive transcriptomics uncovered a detailed set of regulatory processes that were affected by the PpBCG1 disruption. Moreover, experimental evidence showed that PpBCG1 might function in the antioxidant activity, abscisic acid (ABA) pathway, and intracellular calcium (Ca2+) homeostasis to resist desiccation. Together, our study provides insights into the roles of one bryophyte co-retained gene in the desiccation tolerance.
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OBJECTIVE: This study was designed to identify the role of circRNAs in tongue squamous cell carcinoma (TSCC) and discover novel circRNAs as potential diagnostic or therapeutic targets for TSCC. RESULTS: The circRNA expression profiles in TSCC were evaluated by high-throughput sequencing in 6 TSCC patients. Our data showed that 69 circRNAs were downregulated and 208 were upregulated significantly (fold change ≥2.0; p < 0.05). GO and KEGG analysis demonstrated that the parental genes of differentially expressed circRNAs were potentially implicated in TSCC pathogenesis. After bioinformatics analysis, 4 circRNAs (hsa_circ_0005035, hsa_circ_0002360, hsa_circ_0066251, and hsa_circ_0003161) were selected and successfully validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in 40 patients and 3 TSCC cell lines. The establishment and analysis of the circRNA-miRNA-mRNA network revealed the potential function and mechanism of these candidate circRNAs. CONCLUSION: Our study provided a comprehensive circRNAs expression profile of TSCC by RNA-seq and discovered 4 novel circRNAs with potential great diagnostic and therapeutic value. These findings provide new insights into the development of potential biomarkers and targets for TSCC treatment.
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Carcinoma de Células Escamosas , MicroRNAs , Neoplasias da Língua , Humanos , RNA Circular/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/genética , MicroRNAs/genética , Biologia Computacional , LínguaRESUMO
Isoprenoids are among the largest and most chemically diverse classes of organic compounds in nature and are involved in the processes of photosynthesis, respiration, growth, development, and plant responses to stress. The basic building block units for isoprenoid synthesis-isopentenyl diphosphate and its isomer dimethylallyl diphosphate-are generated by the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. Here, we summarize recent advances on the roles of the MEP and MVA pathways in plant growth, development and stress responses, and attempt to define the underlying gene networks that orchestrate the MEP and MVA pathways in response to developmental or environmental cues. Through phylogenomic analysis, we also provide a new perspective on the evolution of the plant isoprenoid pathway. We conclude that the presence of the MVA pathway in plants may be associated with the transition from aquatic to subaerial and terrestrial environments, as lineages for its core components are absent in green algae. The emergence of the MVA pathway has acted as a key evolutionary event in plants that facilitated land colonization and subsequent embryo development, as well as adaptation to new and varied environments.
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Ácido Mevalônico/metabolismo , Filogenia , Transdução de Sinais/fisiologia , Terpenos/metabolismoRESUMO
BACKGROUND: Autophagy is an evolutionarily conserved system for the degradation of intracellular components in eukaryotic organisms. Autophagy plays essential roles in preventing premature senescence and extending the longevity of vascular plants. However, the mechanisms and physiological roles of autophagy in preventing senescence in basal land plants are still obscure. RESULTS: Here, we investigated the functional roles of the autophagy-related gene PpATG3 from Physcomitrella patens and demonstrated that its deletion prevents autophagy. In addition, Ppatg3 mutant showed premature gametophore senescence and reduced protonema formation compared to wild-type (WT) plants under normal growth conditions. The abundance of nitrogen (N) but not carbon (C) differed significantly between Ppatg3 mutant and WT plants, as did relative fatty acid levels. In vivo protein localization indicated that PpATG3 localizes to the cytoplasm, and in vitro Y2H assays confirmed that PpATG3 interacts with PpATG7 and PpATG12. Plastoglobuli (PGs) accumulated in Ppatg3, indicating that the process that degrades damaged chloroplasts in senescent gametophore cells was impaired in this mutant. RNA-Seq uncovered a detailed, comprehensive set of regulatory pathways that were affected by the autophagy mutation. CONCLUSIONS: The autophagy-related gene PpATG3 is essential for autophagosome formation in P. patens. Our findings provide evidence that autophagy functions in N utilization, fatty acid metabolism and damaged chloroplast degradation under non-stress conditions. We identified differentially expressed genes in Ppatg3 involved in numerous biosynthetic and metabolic pathways, such as chlorophyll biosynthesis, lipid metabolism, reactive oxygen species removal and the recycling of unnecessary proteins that might have led to the premature senescence of this mutant due to defective autophagy. Our study provides new insights into the role of autophagy in preventing senescence to increase longevity in basal land plants.
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Autofagia/fisiologia , Bryopsida/fisiologia , Células Germinativas Vegetais/fisiologia , Proteínas de Plantas/fisiologia , Envelhecimento , Bryopsida/genética , Bryopsida/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Técnicas de Inativação de Genes , Células Germinativas Vegetais/metabolismo , Filogenia , Proteínas de Plantas/genética , TranscriptomaRESUMO
MAIN CONCLUSION: ß-carbonic anhydrases, which function in regulating plant growth, C/N status, and stomata number, showed functional redundancy and divergence in Physcomitrella patens. Carbonic anhydrases (CAs) catalyze the interconversion of CO2 and HCO3-. Plants have three evolutionarily unrelated CA families: α-, ß-, and γ-CAs. ßCAs are abundant in plants and are involved in CO2 assimilation, stress responses, and stomata formation. Recent studies of ßCAs have mainly examined C3 or C4 plants, whereas their functions in non-vascular plants are mostly unknown. In this study, phylogenetic analysis revealed that the evolution of ßCAs were conserved between subaerial green algae and bryophytes after terrestrialization event, and ßCAs from some cyanobacteria might begin evolving for the adaptation of terrestrial environment/habitat. In addition, we investigated the physiological roles of ßCAs in the basal land plant Physcomitrella patens. High PpßCA expression levels in different tissues suggest that PpßCAs play important roles in development in P. patens. Plants treated with 1-10 mM NaHCO3 had higher fresh and dry weight, PpßCA expression, total CA activity, and photosynthetic yield (Fv/Fm) compared with water-treated plants. However, treatment with 10 mM NaHCO3 influenced the C/N status. Further study of six Ppßca single-gene mutants revealed that PpßCAs have functional redundancy and divergence in regulating the C/N ratio of plants and stomatal formation. This study provides new insight into the physiological roles of ßCAs in basal land plants.
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Bryopsida/enzimologia , Carbono/metabolismo , Anidrases Carbônicas/metabolismo , Bryopsida/genética , Bryopsida/crescimento & desenvolvimento , Bryopsida/fisiologia , Dióxido de Carbono/metabolismo , Anidrases Carbônicas/genética , Fotossíntese , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estômatos de Plantas/enzimologia , Estômatos de Plantas/genética , Estômatos de Plantas/crescimento & desenvolvimentoRESUMO
MYB transcription factors (TFs) are one of the largest TF families in plants to regulate numerous biological processes. However, our knowledge of the MYB family in Physcomitrella patens is limited. We identified 116 MYB genes in the P. patens genome, which were classified into the R2R3-MYB, R1R2R3-MYB, 4R-MYB, and MYB-related subfamilies. Most R2R3 genes contain 3 exons and 2 introns, whereas R1R2R3 MYB genes contain 10 exons and 9 introns. N3R-MYB (novel 3RMYB) and NR-MYBs (novel RMYBs) with complicated gene structures appear to be novel MYB proteins. In addition, we found that the diversity of the MYB domain was mainly contributed by domain shuffling and gene duplication. RNA-seq analysis suggested that MYBs exhibited differential expression to heat and might play important roles in heat stress responses, whereas CCA1-like MYB genes might confer greater flexibility to the circadian clock. Some R2R3-MYB and CCA1-like MYB genes are preferentially expressed in the archegonium and during the transition from the chloronema to caulonema stage, suggesting their roles in development. Compared with that of algae, the numbers of MYBs have significantly increased, thus our study lays the foundation for further exploring the potential roles of MYBs in the transition from aquatic to terrestrial environments.
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Bryopsida/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Bryopsida/metabolismo , Duplicação Gênica , Filogenia , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismoRESUMO
MAIN CONCLUSION: Nuclear Factor-Y transcription factors, which function in regulating seed development (including storage reservoir accumulation) and responding to abiotic stresses, were identified and characterized in castor bean. Nuclear Factor-Y (NF-Y) transcription factors in plants contain three subunits (NF-YA, NF-YB and NF-YC), and function as a heterodimer or heterotrimer complex in regulating plant growth, development and response to stresses. Castor bean (Ricinus communis, Euphorbiaceae) one of the most economically important non-edible oilseed crops, able to grow in diverse soil conditions and displays high tolerance to abiotic stresses. Due to increasing demands for its seed oils, it is necessary to elucidate the molecular mechanism underlying the regulation of growth and development. Based on the available genome data, we identified 25 RcNF-Y members including six RcNF-YAs, 12 RcNF-YBs and seven RcNF-YCs, and characterized their gene structures. Yeast two-hybrid assays confirmed the protein-protein interactions among three subunits. Using transcriptomic data from different tissues, we found that six members were highly or specifically expressed in endosperms (in particular, two LEC1-type members RcNF-YB2 and RcNF-YB12), implying their involvement in regulating seed development and storage reservoir accumulation. Further, we investigated the expression changes of RcNF-Y members in two-week-old seedlings under drought, cold, hot and salt stresses. We found that the expression levels of 20 RcNF-Y members tested were changed and three RcNF-Y members might function in response to abiotic stresses. This study is the first reported on genomic characterization of NF-Y transcription factors in the family Euphorbiaceae. Our results provide the basis for improved understanding of how NF-Y genes function in the regulation of seed development and responses to abiotic stresses in both castor bean and other plants in this family.
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Fator de Ligação a CCAAT/metabolismo , Genes de Plantas/genética , Ricinus/genética , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/fisiologia , Regulação da Expressão Gênica de Plantas , Filogenia , Ricinus/metabolismo , Alinhamento de Sequência , Transcriptoma , Técnicas do Sistema de Duplo-HíbridoRESUMO
Plant-specific GRAS transcription factors play important roles in regulating growth, development, and stress responses. Castor beans (Ricinus communis) are important non-edible oilseed plants, cultivated worldwide for its seed oils and its adaptability to growth conditions. In this study, we identified and characterized a total of 48 GRAS genes based on the castor bean genome. Combined with phylogenetic analysis, the castor bean GRAS members were divided into 13 distinct groups. Functional divergence analysis revealed the presence of mostly Type-I functional divergence. The gene structures and conserved motifs, both within and outside the GRAS domain, were characterized. Gene expression analysis, performed in various tissues and under a range of abiotic stress conditions, uncovered the potential functions of GRAS members in regulating plant growth development and stress responses. The results obtained from this study provide valuable information toward understanding the potential molecular mechanisms of GRAS proteins in castor beans. These findings also serve as a resource for identifying the genes that allow castor beans to grow in stressful conditions and to enable further breeding and genetic improvements in agriculture.
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Evolução Molecular , Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Ricinus/genética , Estresse Fisiológico , Sequência Conservada , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo , Ricinus/classificação , Ricinus/metabolismoRESUMO
The transition from two-dimensional (2D) to 3D growth likely facilitated plants to colonize land, but its heterogeneity is not well understood. In this study, we utilized single-cell RNA sequencing to analyze the moss Physcomitrium patens, whose morphogenesis involves a transition from 2D to 3D growth. We profiled over 17,000 single cells covering all major vegetative tissues, including 2D filaments (chloronema and caulonema) and 3D structures (bud and gametophore). Pseudotime analyses revealed larger numbers of candidate genes that determine cell fates for 2D tip elongation or 3D bud differentiation. Using weighted gene co-expression network analysis, we identified a module that connects ß-type carbonic anhydrases (ßCAs) with auxin. We further validated the cellular expression patterns of ßCAs and demonstrated their roles in 3D gametophore development. Overall, our study provides insights into cellular heterogeneity in a moss and identifies molecular signatures that underpin the 2D-to-3D growth transition at single-cell resolution.
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Achieving uniform optical resolution for a large tissue sample is a major challenge for deep imaging. For conventional tissue clearing methods, loss of resolution and quality in deep regions is inevitable due to limited transparency. Here we describe the Transparent Embedding Solvent System (TESOS) method, which combines tissue clearing, transparent embedding, sectioning and block-face imaging. We used TESOS to acquire volumetric images of uniform resolution for an adult mouse whole-body sample. The TESOS method is highly versatile and can be combined with different microscopy systems to achieve uniformly high resolution. With a light sheet microscope, we imaged the whole body of an adult mouse, including skin, at a uniform 0.8 × 0.8 × 3.5 µm3 voxel resolution within 120 h. With a confocal microscope and a 40×/1.3 numerical aperture objective, we achieved a uniform sub-micron resolution in the whole sample to reveal a complete projection of individual nerve axons within the central or peripheral nervous system. Furthermore, TESOS allowed the first mesoscale connectome mapping of individual sensory neuron axons spanning 5 cm from adult mouse digits to the spinal cord at a uniform sub-micron resolution.
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Axônios , Imageamento Tridimensional , Camundongos , Animais , Solventes , Imageamento Tridimensional/métodos , Medula Espinal , Sistema Nervoso PeriféricoRESUMO
Pose registration is critical in vision and robotics. This article focuses on the challenging task of initialization-free pose registration up to 7DoF for homogeneous and heterogeneous measurements. While recent learning-based methods show promise using differentiable solvers, they either rely on heuristically defined correspondences or require initialization. Phase correlation seeks solutions in the spectral domain and is correspondence-free and initialization-free. Following this, we propose a differentiable solver and combine it with simple feature extraction networks, namely DPCN++. It can perform registration for homo/hetero inputs and generalizes well on unseen objects. Specifically, the feature extraction networks first learn dense feature grids from a pair of homogeneous/heterogeneous measurements. These feature grids are then transformed into a translation and scale invariant spectrum representation based on Fourier transform and spherical radial aggregation, decoupling translation and scale from rotation. Next, the rotation, scale, and translation are independently and efficiently estimated in the spectrum step-by-step. The entire pipeline is differentiable and trained end-to-end. We evaluate DCPN++ on a wide range of tasks taking different input modalities, including 2D bird's-eye view images, 3D object and scene measurements, and medical images. Experimental results demonstrate that DCPN++ outperforms both classical and learning-based baselines, especially on partially observed and heterogeneous measurements.
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Mosses are widely used in the establishment of greenery. However, little research has been conducted to choose a suitable species or improve their performance for this application. In our study, we examined Vesicularia montagnei (V. montagnei), a robust moss that is widely distributed in temperate, subtropical, and tropical Asia with varying environmental conditions. Axenic cultivation system of V. montagnei was developed on modified BCD medium, which enabled its propagation and multiplication in vitro. In this axenic cultivation environment, several diploid V. montagnei lines with enhancement of rhizoid system were generated through artificial induction of diploidization. Transcriptomic analysis revealed that several genes responsible for jasmonic acid (JA) biosynthesis and signaling showed significant higher expression levels in the diploid lines compared to the wild type. These results are consistent with the increasement of JA content in the diploid lines. Our establishment of the axenic cultivation method may provide useful information for further study of other Vesicularia species. The diploid V. montagnei lines with improved rhizoid system may hold promising potential for greenery applications. Additionally, our study sheds light on the biosynthesis and functions of JA in the early landed plants.
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Almost all genomes have orphan genes, the majority of which are not functionally annotated. There is growing evidence showed that orphan genes may play important roles in the environmental stress response of Physcomitrium patens. We identified PpARDT (ABA-responsive drought tolerance) as a moss-specific and ABA-responsive orphan gene in P. patens. PpARDT is mainly expressed during the gametophytic stage of the life cycle, and the expression was induced by different abiotic stresses. A PpARDT knockout (Ppardt) mutant showed reduced dehydration-rehydration tolerance, and the phenotype could be rescued by exogenous ABA. Meanwhile, transgenic Arabidopsis lines exhibiting heterologous expression of PpARDT were more sensitive to exogenous ABA than wild-type (Col-0) plants and showed enhanced drought tolerance. These indicate that PpARDT confers drought tolerance among land plants potentially by enhancing ABA response. Further, we identified genes encoding abscisic acid receptor PYR/PYL family proteins, and ADP-ribosylation factors (Arf) as hub genes associated with the Ppardt phenotype. Given the lineage-specific characteristics of PpARDT, our results provide insights into the roles of orphan gene in shaping lineage-specific adaptation possibly by recruiting common pre-existed pathway components.
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Arabidopsis , Bryopsida , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Bryopsida/genética , Secas , Estresse Fisiológico/genéticaRESUMO
Normal development of craniofacial sutures is crucial for cranial and facial growth in all three dimensions. These sutures provide a unique niche for suture stem cells (SuSCs), which are indispensable for homeostasis, damage repair, as well as stress balance. Expansion appliances are now routinely used to treat underdevelopment of the skull and maxilla, stimulating the craniofacial sutures through distraction osteogenesis. However, various treatment challenges exist due to a lack of full understanding of the mechanism through which mechanical forces stimulate suture and bone remodeling. To address this issue, we first identified crucial steps in the cycle of suture and bone remodeling based on the established standard suture expansion model. Observed spatiotemporal morphological changes revealed that the remodeling cycle is approximately 3 to 4 weeks, with collagen restoration proceeding more rapidly. Next, we traced the fate of the Gli1+ SuSCs lineage upon application of tensile force in three dimensions. SuSCs were rapidly activated and greatly contributed to bone remodeling within 1 month. Furthermore, we confirmed the presence of Wnt activity within Gli1+ SuSCs based on the high co-expression ratio of Gli1+ cells and Axin2+ cells, which also indicated the homogeneity and heterogeneity of two cell groups. Because Wnt signaling in the sutures is highly upregulated upon tensile force loading, conditional knockout of ß-catenin largely restricted the activation of Gli1+ SuSCs and suppressed bone remodeling under physiological and expansion conditions. Thus, we concluded that Gli1+ SuSCs play essential roles in suture and bone remodeling stimulated by mechanical force and that Wnt signaling is crucial to this process. © 2022 American Society for Bone and Mineral Research (ASBMR).
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Suturas Cranianas , Maxila , Células-Tronco , Suturas , Proteína GLI1 em Dedos de ZincoRESUMO
PURPOSE: To facilitate identification of clinical trial participation candidates, we developed a machine learning tool that automates the determination of a patient's metastatic status, on the basis of unstructured electronic health record (EHR) data. METHODS: This tool scans EHR documents, extracting text snippet features surrounding key words (such as metastatic, progression, and local). A regularized logistic regression model was trained and used to classify patients across five metastatic categories: highly likely and likely positive, highly likely and likely negative, and unknown. Using a real-world oncology database of patients with solid tumors with manually abstracted information as reference, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We validated the performance in a real-world data set, evaluating accuracy gains upon additional user review of tool's outputs after integration into clinic workflows. RESULTS: In the training data set (N = 66,532), the model sensitivity and specificity (% [95% CI]) were 82.4 [81.9 to 83.0] and 95.5 [95.3 to 96.7], respectively; the PPV was 89.3 [88.8 to 90.0], and the NPV was 94.0 [93.8 to 94.2]. In the validation sample (n = 200 from five distinct care sites), after user review of model outputs, values increased to 97.1 [85.1 to 99.9] for sensitivity, 98.2 [94.8 to 99.6] for specificity, 91.9 [78.1 to 98.3] for PPV, and 99.4 [96.6 to 100.0] for NPV. The model assigned 163 of 200 patients to the highly likely categories. The error prevalence was 4% before and 2% after user review. CONCLUSION: This tool infers metastatic status from unstructured EHR data with high accuracy and high confidence in more than 75% of cases, without requiring additional manual review. By enabling efficient characterization of metastatic status, this tool could mitigate a key barrier for patient ascertainment and clinical trial participation in community clinics.
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Registros Eletrônicos de Saúde , Neoplasias , Bases de Dados Factuais , Humanos , Aprendizado de Máquina , Neoplasias/terapia , Sensibilidade e EspecificidadeRESUMO
Treatments for infectious bone defects such as periodontitis require antibacterial and osteogenic differentiation capabilities. Nanotechnology has prompted the development of multifunctional material. In this research, we aim to synthesize a nanoparticle that can eliminate periodontal pathogenic microorganisms and simultaneously stimulate new bone tissue regeneration and mineralization. QAS-modified core-shell mesoporous silica containing Ag nanoparticles (Ag@QHMS) was successfully synthesized through the classic hydrothermal method and surface quaternary ammonium salt functionalization. The Ag@QHMS in vitro antibacterial activity was explored via coculture with Staphylococcus aureus, Escherichia coli, and Porphyromonas gingivalis biofilms. Bone mesenchymal stem cells (BMSCs) were selected for observing cytotoxicity, apoptosis, and osteogenic differentiation. Ag@QHMS showed a good sustained release profile of Ag+ and a QAS-grafted mesoporous structure. Compared with the single-contact antibacterial activity of QHMS, Ag@QHMS exhibited a more efficient and stable concentration-dependent antimicrobial efficacy; the minimum inhibitory concentration was within 100 µg/ml, which was below the BMSC biocompatibility concentration (200 µg/ml). Thus, apoptosis would not occur while promoting the increased expression of osteogenic-associated factors, such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), bone sialoprotein (BSP), and collagen type 1 (COL-1). A safe concentration of particles can stimulate cell alkaline phosphatase and matrix calcium salt deposition. The dual antibacterial effect from the direct contact killing of QAS and the sustained release of Ag nanoparticles, along with the Ag-promoted osteogenic differentiation, had been verified and utilized in Ag@QHMS. This system demonstrates the potential for utilizing pluripotent biomaterials to treat complex lesions.
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Antibacterianos/farmacologia , Nanopartículas Metálicas/administração & dosagem , Osteogênese/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Dióxido de Silício/química , Prata/química , Animais , Bactérias/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células-Tronco Mesenquimais/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Nanomedicina/métodos , Osteocalcina/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual/métodosRESUMO
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in tongue squamous cell carcinoma (TSCC) tumorigenesis. However, the comprehensive regulation of lncRNAs-transcription factors (TFs)-messenger RNAs (mRNAs) in TSCC remains largely unknown. The purpose of this study was to identify aberrantly expressed lncRNAs and the associated TF-mRNA network in TSCC. To explore lncRNA and mRNA expression profiles and their biological functions in TSCC, we surveyed the lncRNA and mRNA expression profiles of TSCC and adjacent tissues using next-generation RNA sequencing in six patients. Thousands of significantly differentially expressed lncRNAs (DELs) and mRNAs (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to demonstrate the principal functions of the significantly dysregulated lncRNAs and genes. A total of 40 DELs were screened between TSCC and adjacent non-cancerous tissues. Results obtained from GEPIA and StarBase confirmed the expression levels of nine pivotal DELs obtained in our study. Three of the nine deregulated DELs were identified to have a significant impact on the overall survival of TSCC patients, which were evaluated with GEPIA and StarBase. LncMAP was used to predict the lncRNA-TF-mRNA triplets in TSCC. Furthermore, based on these results, we established lncRNA-TF-mRNA coexpression networks for the up- and downregulated lncRNAs using Cytoscape. We also found that among the nine pivotal lncRNAs, there is limited research on the abnormally expressed lncRNAs, including RP11-54H7.4, CTD-2545M3.8, RP11-760H22.2, RP4-791M13.3, and LINC01405, in TSCC pathogenesis. This is the first study to show that RP11-54H7.4, LINC00152, and LINC01405 can be acted as a prognostic target for TSCC. Our findings provide a novel perspective and lay the foundation for future research on the potential roles of lncRNAs, TFs, and mRNAs in TSCC. Verification of the potential lncRNA-TF-mRNA regulatory networks will provide a more comprehensive understanding of the pathogenesis of TSCC.
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The coal-to-electricity project (CTEP) using electricity instead of coal for heating is a significant measure to cope with climate change and air pollution in China. After years of development, the CTEP has been implemented on a large scale of areas in Beijing. An evaluation model is proposed in this paper to analyze the environmental benefits and assist in determining whether the CTEP should be continued. Firstly, the heating system and framework of this paper are introduced. We also analyzed the feasibility of CTEP, illuminating how electric heating benefits the environment. Secondly, the evaluations models of CTEP are built, including reduction of coal, pollutant emission, and overall benefit. Finally, based on the models results are obtained and discussed and prove environmental benefits of CTEP. It is calculated that 18 kg of coal per unit heating area can be saved in the CTEP, which effectively reduces 98% of PM2.5, 95% of SO2, 44% of NOX, and 81% of CO2 emissions. The CTEP has increasing contribution to the reductions of atmospheric pollutants. The considerable environmental benefits demonstrate the significance of the CTEP in the north of China, which also facilitate its future development in areas outside of Beijing.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Pequim , China , Carvão Mineral/análise , Eletricidade , Monitoramento Ambiental , Material Particulado/análiseRESUMO
MicroRNA-375 is involved in many types of alimentary system cancers. Our previous studies showed that microRNA-375 was significantly down-regulated in carcinoma tissues compared with para-carcinoma tissues, which strongly indicates that microRNA-375 might suppress the occurrence and development of colorectal cancer. However, the mechanism underlying the microRNA-375 regulation in colorectal cancer remains unclear. In this study, we first sorted out jak2, map3k8 and atg7 as microRNA-375 targeted genes from multiple databases, and found that jak2, map3k8 and their downstream genes stat3 and erk were up-regulated in carcinoma tissues. Secondly, we over-expressed microRNA-375 in colorectal cancer cell lines (HCT116, Caco2 and HT29). Our results showed that in microRNA-375 over-expressing cells, JAK2/STAT3 and MAP3K8/ERK proteins were down-regulated, cell proliferation was inhibited, cell migration rate did not change. There was no significant difference on ATG7 expression between the control group and microRNA-375 over-expressing HT29/Caco2 cells, whereas microRNA-375 down-regulated ATG7 specifically in HCT116 cells. Finally, we demonstrated that expressing microRNA-375 suppressed tumor formation in nude mice. In conclusion, microRNA-375 might function as a tumor-repressive gene to inhibit cell proliferation, mainly through targeting both JAK2/STAT3 and MAP3K8/ERK signaling pathways in colorectal cancer. These findings suggest miR-375 as a promising diagnostic marker and a therapeutic drug for colorectal cancer.