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Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices1-4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (<5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA'-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field-effect devices that exhibit excellent performance at room temperature with mobilities of up to 4,600 cm2 V-1 s-1 and on-off ratios of up to 106. This paves the way for the bottom-up fabrication of high-performance electronic devices based on embedded layered materials.
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Bioluminescence in beetles has long fascinated biologists, with diverse applications in biotechnology. To date, however, our understanding of its evolutionary origin and functional variation mechanisms remains poor. To address these questions, we obtained high-quality reference genomes of luminous and nonluminous beetles in 6 Elateroidea families. We then reconstructed a robust phylogenetic relationship for all luminous families and related nonluminous families. Comparative genomic analyses and biochemical functional experiments suggested that gene evolution within Elateroidea played a crucial role in the origin of bioluminescence, with multiple parallel origins observed in the luminous beetle families. While most luciferase-like proteins exhibited a conserved nonluminous amino acid pattern (TLA346 to 348) in the luciferin-binding sites, luciferases in the different luminous beetle families showed divergent luminous patterns at these sites (TSA/CCA/CSA/LVA). Comparisons of the structural and enzymatic properties of ancestral, extant, and site-directed mutant luciferases further reinforced the important role of these sites in the trade-off between acyl-CoA synthetase and luciferase activities. Furthermore, the evolution of bioluminescent color demonstrated a tendency toward hypsochromic shifts and variations among the luminous families. Taken together, our results revealed multiple parallel origins of bioluminescence and functional divergence within the beetle bioluminescent system.
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Besouros , Animais , Humanos , Besouros/genética , Filogenia , Sequência de Aminoácidos , Luciferases/genética , Luciferases/química , Luciferases/metabolismo , Sítios de LigaçãoRESUMO
Two-dimensional materials have emerged as an important research frontier for overcoming the challenges in nanoelectronics and for exploring new physics. Among them, black phosphorus, with a combination of a tunable bandgap and high mobility, is one of the most promising systems. In particular, black phosphorus nanoribbons show excellent electrostatic gate control, which can mitigate short-channel effects in nanoscale transistors. Controlled synthesis of black phosphorus nanoribbons, however, has remained an outstanding problem. Here we report large-area growth of black phosphorus nanoribbons directly on insulating substrates. We seed the chemical vapour transport growth with black phosphorus nanoparticles and obtain uniform, single-crystal nanoribbons oriented exclusively along the [100] crystal direction. With comprehensive structural calculations, we discover that self-passivation at the zigzag edges holds the key to the preferential one-dimensional growth. Field-effect transistors based on individual nanoribbons exhibit on/off ratios up to ~104, confirming the good semiconducting behaviour of the nanoribbons. These results demonstrate the potential of black phosphorus nanoribbons for nanoelectronic devices and also provide a platform for investigating the exotic physics in black phosphorus.
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Graphene nanoribbons (GNRs), quasi one-dimensional (1D) narrow strips of graphene, have shown promise for high-performance nanoelectronics due to their exceptionally high carrier mobility and structurally tunable bandgaps. However, producing chirality-uniform GNRs on insulating substrates remains a big challenge. Here, we report the successful growth of bilayer GNRs with predominantly armchair chirality and ultranarrow widths (<5 nm) on insulating hexagonal boron nitride (h-BN) substrates using chemical vapor deposition (CVD). The growth of GNRs is catalyzed by transition metal nanoparticles, including Fe, Co, and Ni, through a unique tip-growth mechanism. Notably, GNRs catalyzed by Ni exhibit a high purity (97.3%) of armchair chirality. Electron transport measurements indicate that the ultrathin bilayer armchair GNRs exhibit quasi-metallic behavior. This quasi-metallicity is further supported by density functional theory (DFT) calculations, which reveal a significantly reduced bandgap in bilayer armchair GNRs. The chirality-specific GNRs reported here offer promising advancements for the application of graphene in nanoelectronics.
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BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Endostatinas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Endostatinas/administração & dosagem , Endostatinas/uso terapêutico , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Adulto , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
AXIN1, has been initially identified as a prominent antagonist within the WNT/ß-catenin signaling pathway, and subsequently unveiled its integral involvement across a diverse spectrum of signaling cascades. These encompass the WNT/ß-catenin, Hippo, TGFß, AMPK, mTOR, MAPK, and antioxidant signaling pathways. The versatile engagement of AXIN1 underscores its pivotal role in the modulation of developmental biological signaling, maintenance of metabolic homeostasis, and coordination of cellular stress responses. The multifaceted functionalities of AXIN1 render it as a compelling candidate for targeted intervention in the realms of degenerative pathologies, systemic metabolic disorders, cancer therapeutics, and anti-aging strategies. This review provides an intricate exploration of the mechanisms governing mammalian AXIN1 gene expression and protein turnover since its initial discovery, while also elucidating its significance in the regulation of signaling pathways, tissue development, and carcinogenesis. Furthermore, we have introduced the innovative concept of the AXIN1-Associated Phosphokinase Complex (AAPC), where the scaffold protein AXIN1 assumes a pivotal role in orchestrating site-specific phosphorylation modifications through interactions with various phosphokinases and their respective substrates.
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Via de Sinalização Wnt , beta Catenina , Animais , Ontologia Genética , Proteína Axina/genética , Proteína Axina/metabolismo , Via de Sinalização Wnt/genética , Fosforilação , Proteólise , beta Catenina/metabolismo , Mamíferos/metabolismoRESUMO
The influence of uranium (U) mining on the fungal diversity (FD) and communities (FC) structure was investigated in this work. Our results revealed that soil FC richness and FD indicators obviously decreased due to U, such as Chao1, observed OTUs and Shannon index (P<0.05). Moreover, the abundances of Mortierella, Gibberella, and Tetracladium were notably reduced in soil samples owing to U mining activities (P<0.05). In contrast, the abundances of Cadophora, Pseudogymnoascus, Mucor, and Sporormiella increased in all soil samples after U mining (P<0.05). Furthermore, U mining not only dramatically influenced the Plant_Pathogen guild and Saprotroph and Pathotroph modes (P<0.05), but also induced the differentiation of soil FC and the enrichment of the Animal_Pathogen-Soil_Saprotroph and Endophyte guilds and Symbiotroph and Pathotroph Saprotroph trophic modes. In addition, various fungal populations and guilds were enriched to deal with the external stresses caused by U mining in different U mining areas and soil depths (P<0.05). Finally, nine U-tolerant fungi were isolated and identified with a minimum inhibitory concentration range of 400-600â¯mg/L, and their adsorption efficiency for U ranged from 11.6% to 37.9%. This study provides insights into the impact of U mining on soil fungal stability and the response of fungi to U mining activities, as well as aids in the screening of fungal strains that can be used to promote remediation of U mining sites on plateaus.
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Fungos , Mineração , Microbiologia do Solo , Urânio , Urânio/toxicidade , Fungos/efeitos dos fármacos , Poluentes Radioativos do Solo/análise , Poluentes Radioativos do Solo/toxicidade , Solo/química , Testes de Sensibilidade MicrobianaRESUMO
Nuclear factor erythroid 2-like 3 (NFE2L3) is a member of the cap 'n' collar basic-region leucine zipper (CNC-bZIP) transcription factor family that plays a vital role in modulating oxidation-reduction steady-state and proteolysis. Accumulating evidence suggests that NFE2L3 participates in cancer development; however, little is known about the mechanism by which NFE2L3 regulates hepatocellular carcinoma (HCC) cell growth. Here, we confirmed that NFE2L3 promotes HCC cell proliferation by acting as a transcription factor, which directly induces the expression of proteasome and interferon-stimulated gene 15 (ISG15) to enhance the proteasome-dependent degradation of ISGylated p53. Post-translational ISGylation abated the stability of p53 and facilitated HCC cell growth. In summary, we uncovered the pivotal role of NFE2L3 in promoting HCC cell proliferation during proteostasis. This finding may provide a new target for the clinical treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
About 85% of patients with colorectal cancer (CRC) have the non-microsatellite instability-high (non-MSI-H) subtype, and many cannot benefit from immune checkpoint blockade. A potential reason for this is that most non-MSI-H colorectal cancers are immunologically "cold" due to poor CD8+ T cell infiltration. In the present study, we screened for potential cancer-testis antigens (CTAs) by comparing the bioinformatics of CD8+ T effector memory (Tem) cell infiltration between MSI-H and non-MSI-H CRC. Two ODF2-derived epitope peptides, P433 and P609, displayed immunogenicity and increased the proportion of CD8+ T effector memory (Tem) cells in vitro and in vivo. The adoptive transfer of peptide pool-induced CTLs inhibited tumor growth and enhanced CD8+ T cell infiltration in tumor-bearing NOD/SCID mice. The mechanistic study showed that knockdown of ODF2 in CRC cells promoted interleukin-15 expression, which facilitated CD8+ T cell proliferation. In conclusion, ODF2, a CTA, was negatively correlated with CD8+ T cell infiltration in "cold" non-MSI-H CRC and was selected based on the results of bioinformatics analyses. The corresponding HLA-A2 restricted epitope peptide induced antigen-specific CTLs. Immunotherapy targeting ODF2 could improve CTA infiltration via upregulating IL-15 in non-MSI-H CRC. This tumor antigen screening strategy could be exploited to develop therapeutic vaccines targeting non-MSI-H CRC.
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Neoplasias Colorretais , Linfócitos T Citotóxicos , Animais , Masculino , Camundongos , Neoplasias Colorretais/patologia , Epitopos , Proteínas de Choque Térmico , Interleucina-15 , Camundongos Endogâmicos NOD , Camundongos SCID , Peptídeos , Testículo/patologia , Vacinas de Subunidades Antigênicas , Vacinas AnticâncerRESUMO
Osteoarthritis (OA) is a prevalent degenerative joint disorder caused by the progressive destruction of cartilage and inflammation in the articular cavity. Studies have proved that the inhibition of articular cartilage destruction and generation of inflammatory factors can be effective strategies for treating OA. Notopterol (NOT) is a quality control index of Notopterygium incisum Ting ex H. T. Chang (N. incisum) with anti-inflammatory, antioxidant, and analgesic activities. Moreover, NOT has been used for many years to treat joint diseases. A study using human C28/I2 cells suggested that NOT down-regulated the hypersecretion of inflammatory mediators and alleviated the degradation of the extracellular matrix (ECM). In addition, NOT decreased the overproduction of reactive oxygen species (ROS) and chondrocyte apoptosis through the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. NOT exerted a chondroprotective effect by partly inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathways and regulating the nuclear factor Nrf2/heme oxygenase-1(HO-1) signaling pathway. In vivo, NOT improved the destruction of articular cartilage in a rat OA model, which may be related to the inhibition of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-12 expressions in synovial fluid. In summary, these results showed that NOT alleviated the progression of OA and is expected to become a new therapy for treating OA clinically.
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Cartilagem Articular , Osteoartrite , Humanos , Ratos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Osteoartrite/metabolismo , Inflamação/metabolismo , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Interleucina-1beta/metabolismoRESUMO
OBJECTIVES: To identify optimized MRI markers for evaluating chronic kidney disease (CKD) and renal interstitial fibrosis (IF). MATERIALS AND METHODS: This prospective study included 43 patients with CKD and 20 controls. The CKD group was divided into mild and moderate-to-severe subgroups based on pathological results. Scanned sequences included T1 mapping, R2* mapping, intravoxel incoherent motion imaging, and diffusion-weighted imaging. One-way analyses of variance were used to compare MRI parameters among groups. Correlations of MRI parameters with estimated glomerular filtration rate (eGFR) and renal IF were analyzed using age as covariates. The support vector machine (SVM) model was used to evaluate the diagnostic efficacy of multiparametric MRI. RESULTS: Compared to control values, renal cortical apparent diffusion coefficient (cADC), medullary ADC (mADC), cortical pure diffusion coefficient (cDt), medullary Dt (mDt), cortical shifted apparent diffusion coefficient (csADC), and medullary sADC (msADC) values gradually decreased in the mild and moderate-to-severe groups, while cortical T1 (cT1) and medullary T1 (mT1) values gradually increased. Values of cADC, mADC, cDt, mDt, cT1, mT1, csADC, and msADC were significantly associated with eGFR and IF (p < 0.001). The SVM model indicated that multiparametric MRI combining cT1 and csADC can distinguish patients with CKD from controls with high accuracy (0.84), sensitivity (0.70), and specificity (0.92) (AUC: 0.96). Multiparametric MRI combining cT1 and cADC exhibited high accuracy (0.91), sensitivity (0.95), and specificity (0.81) for evaluating IF severity (AUC: 0.96). CONCLUSION: Multiparametric MRI combining T1 mapping and diffusion imaging may be of clinical utility in non-invasive assessment of CKD and IF. CLINICAL RELEVANCE STATEMENT: This study shows that multiparametric MRI combining T1 mapping and diffusion imaging may be clinically useful in the non-invasive assessment of chronic kidney disease (CKD) and interstitial fibrosis; this could provide information for risk stratification, diagnosis, treatment, and prognosis. KEY POINTS: ⢠Optimized MRI markers for evaluating chronic kidney disease and renal interstitial fibrosis were investigated. ⢠Renal cortex/medullary T1 values increased as interstitial fibrosis increased; cortical shifted apparent diffusion coefficient (csADC) correlated significantly with eGFR and interstitial fibrosis. ⢠Support vector machine (SVM) combining cortical T1 (cT1) and csADC/cADC effectively identifies chronic kidney disease and accurately predicts renal interstitial fibrosis.
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Imageamento por Ressonância Magnética Multiparamétrica , Insuficiência Renal Crônica , Humanos , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/patologia , Rim/diagnóstico por imagem , Rim/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética/métodos , FibroseRESUMO
The functionalization of noble metals is an effective approach to lowering the sensing temperature and improving the sensitivity of metal oxide semiconductor (MOS)-based gas sensors. However, there is a dearth of comparative analyses regarding the differences in sensitization mechanisms between the two functionalization modes of noble metal loading and doping. In this investigation, we synthesized Pt-doped CuO gas-sensing materials using a one-pot hydrothermal method. And for Pt-loaded CuO, Pt was deposited on the synthesized pristine CuO surface by using a dipping method. We found that both functionalization methods can considerably enhance the response and selectivity of CuO toward NO2 at low temperatures. However, we observed that CuO with Pt loading had superior sensing performance at 25 °C, while CuO with Pt doping showed more substantial response changes with an increase in the operating temperature. This is mainly due to the different dominant roles of electron sensitization and chemical sensitization resulting from the different forms of Pt present in different functionalization modes. For Pt doping, electron sensitization is stronger, and for Pt loading, chemical sensitization is stronger. The results of this study present innovative ideas for understanding the optimization of noble metal functionalization for the gas-sensing performance of metal oxide semiconductors.
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The jasmonic acid (JA) signaling pathway plays important roles in plant defenses, development, and the synthesis of specialized metabolites synthesis. Transcription factor MYC2 is a major regulator of the JA signaling pathway and is involved in the regulation of plant physiological processes and specialized metabolite synthesis. Based on our understanding of the mechanism underlying the regulation of specialized metabolite synthesis in plants by the transcription factor MYC2, the use of synthetic biology approaches to design MYC2-driven chassis cells for the synthesis of specialized metabolites with high medicinal value, such as paclitaxel, vincristine, and artemisinin, seems to be a promising strategy. In this review, the regulatory role of MYC2 in JA signal transduction of plants to biotic and abiotic stresses, plant growth, development and specialized metabolite synthesis is described in detail, which will provide valuable reference for the use of MYC2 molecular switches to regulate plant specialized metabolite biosynthesis.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fenômenos Fisiológicos Vegetais , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Regeneration refers to the process by which organisms repair and replace lost tissues and organs. Regeneration is widespread in plants and animals; however, the regeneration capabilities of different species vary greatly. Stem cells form the basis for animal and plant regeneration. The essential developmental processes of animals and plants involve totipotent stem cells (fertilized eggs), which develop into pluripotent stem cells and unipotent stem cells. Stem cells and their metabolites are widely used in agriculture, animal husbandry, environmental protection, and regenerative medicine. In this review, we discuss the similarities and differences in animal and plant tissue regeneration, as well as the signaling pathways and key genes involved in the regulation of regeneration, to provide ideas for practical applications in agriculture and human organ regeneration and to expand the application of regeneration technology in the future.
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Células-Tronco Pluripotentes , Animais , Humanos , Medicina Regenerativa , Transdução de Sinais , Células-Tronco Totipotentes , PlantasRESUMO
Despite three decades of intense research efforts, the most fundamental question "why do carbon nanotubes grow?" remains unanswered. In fact, carbon nanotubes (CNTs) should not grow since the encapsulation of a catalyst with graphitic carbon is energetically more favorable than CNT growth in every aspect. Here, we answer this question using a theoretical model based on extensive first-principles and molecular dynamics calculations. We reveal a historically overlooked yet fundamental aspect of the CNT-catalyst interface, viz., that the interfacial energy of the CNT-catalyst edge is contact angle-dependent. The contact angle increases via graphitic cap lift-off, drastically decreasing the interfacial formation energy by up to 6-9 eV/nm, overcoming van der Waals cap-catalyst adhesion, and driving CNT growth. Mapping this remarkable and simple interplay allows us to understand, for the first time, why CNTs grow.
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Nanotubos de Carbono , Catálise , Simulação de Dinâmica MolecularRESUMO
Revealing a "true" picture of the carbon nanotube (CNT) growth front at the catalyst surface is critical to understanding the mechanism of CNT growth. If the CNT-catalyst interface is clean or messy, which will greatly affect the mechanism of controlled CNT growth, has never been properly solved either experimentally or theoretically. Here, this issue by ab initial calculation-based kinetic analysis and classical molecular dynamic (MD) simulations is revisited. It is found that the appearance of carbon chains at the CNT-catalyst interfaces or the "messy" interfaces in MD simulations is a consequence of the very short simulation time, and a "clean" CNT-catalyst interface will emerge if the simulation time is close to that in real experiments. This study reveals that, during real CNT experimental growth, a "clean" CNT-catalyst interface with zigzag, armchair, and/or kink sites dominates the growth kinetics, and therefore, the controllable CNT growth by tuning the CNT-catalyst interface is feasible.
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Nanotubos de Carbono , Cinética , Catálise , Simulação de Dinâmica MolecularRESUMO
Exosomes of different origins have been found to be protective against ischemic-induced myocardial injury. This study examined the protective effects of circulating exosomes in the mice model of acute myocardial infarction (AMI) and explored the underlying molecular mechanisms. The effects of exosomes on myocardial injury were assessed in the AMI mice model. The in vivo studies showed that circulating exosomes reduced the infarcted size, improved the morphology of heart tissues and also reduced apoptosis of the heart tissues. In addition, the model mice showed an increase in the CD34 + /VEGFR2 + cell population and CD31, CXCR4 and CXCL12 expression after exosomes treatment. MiR-190a-3p was significantly down-regulated in the exosomes derived from the culture medium of hypoxia-treated human cardiomyocytes (HCMs). Further analysis revealed that miR-190a-3p could physically interact with CXCR4/CXCL12 by targeting the respective 3'UTRs. These exosomes could up-regulated CXCR4 and CXCL12 expression in the EPCs; in addition, miR-190a-3p mimics repressed CXCR4/CXCL12 expression in EPCs, while its inhibitor had opposite effects. The in vitro functional assays showed that miR-190a-3p overexpression suppressed the cell viability, proliferation, migration, adhesion and tube formation of EPCs; while miR-190a-3p inhibitor had the opposite effects; exosomes derived from the culture medium of hypoxia-treated HCMs exhibited similar actions of miR-190a-3p inhibitor. Moreover, miR-190a-3p was down-regulated in exosomes from serum in the AMI group when compared to that from sham group. Treatment with exosomes from serum in the AMI group promoted cell proliferation, migration, adhesion and tube formation of EPCs when compared to that in the sham group. More importantly, IT1t attenuated the enhanced effects of miR-190a-3p inhibition on EPC proliferation, migration, adhesion and tube formation. In conclusion, circulating exosomes exerted protective effects on myocardial injury in the AMI mice model, and down-regulation of miR-190a-3p in the circulating exosomes may exert protective effects against myocardial injury. Hypoxia induced the downregulation of miR-190a-3p in the culture medium of HCMs, and the mechanistic investigations indicated that exosomes of hypoxia-conditioned HCM culture medium promoted the cell viability, proliferation, migration, adhesion and tube formation of EPCs via regulating miR-190a-3p/CXCR4/CXCL12 pathway.
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Exossomos , MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Camundongos , Regiões 3' não Traduzidas , Apoptose , Quimiocina CXCL12/metabolismo , Exossomos/metabolismo , Hipóxia/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Receptores CXCR4/metabolismoRESUMO
BACKGROUND: Bacillus subtilis, an important industrial microorganism, is commonly used in the production of industrial enzymes. Genome modification is often necessary to improve the production performance of cell. The dual-plasmid CRISPR-Cas9 system suitable for iterative genome editing has been applied in Bacillus subtilis. However, it is limited by the selection of knockout genes, long editing cycle and instability. RESULTS: To address these problems, we constructed an all-in-one plasmid CRISPR-Cas9 system, which was suitable for iterative genome editing of B. subtilis. The PEG4000-assisted monomer plasmid ligation (PAMPL) method greatly improved the transformation efficiency of B. subtilis SCK6. Self-targeting sgRNArep transcription was tightly controlled by rigorous promoter PacoR, which could induce the elimination of plasmids after genome editing and prepare for next round of genome editing. Our system achieved 100% efficiency for single gene deletions and point mutations, 96% efficiency for gene insertions, and at least 90% efficiency for plasmid curing. As a proof of concept, two extracellular protease genes epr and bpr were continuously knocked out using this system, and it only took 2.5 days to complete one round of genome editing. The engineering strain was used to express Douchi fibrinolytic enzyme DFE27, and its extracellular enzyme activity reached 159.5 FU/mL. CONCLUSIONS: We developed and applied a rapid all-in-one plasmid CRISPR-Cas9 system for iterative genome editing in B. subtilis, which required only one plasmid transformation and curing, and accelerated the cycle of genome editing. To the best of our knowledge, this is the rapidest iterative genome editing system for B. subtilis. We hope that the system can be used to reconstruct the B. subtilis cell factory for the production of various biological molecules.
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Bacillus subtilis , Edição de Genes , Bacillus subtilis/genética , Sistemas CRISPR-Cas , Edição de Genes/métodos , Técnicas de Inativação de Genes , Plasmídeos/genéticaRESUMO
BACKGROUND AND OBJECTIVES: To investigate the feasibility and safety of ultrasound-guided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) in pediatric patients. METHODS: A single-institute retrospective review was performed on 35 pediatric patients with predominantly hematological malignancies (88.6%) who underwent TIVAP implantation via ultrasound-guided right BCV approach from July 2018 to June 2021. The catheter tip was adjusted to be positioned at the cavoatrial junction under pulsed fluoroscopic guidance. Technical success rate, procedural information, and TIVAP-related complications were evaluated. RESULTS: All the pediatric TIVAP devices were successfully implanted via right BCV access. Venous access was successful by first attempt in 32 children (91%), two cases (5.7%) required a second attempt, and one patient (2.9%) required a third attempt. The mean procedural time was 44.6 ± 6.4 minutes (range: 34-62 minutes). No intraoperative complications occurred. The average TIVAP indwelling time was 564 ± 208 days (range: 193-1014 days), with a cumulative 19,723 catheter-days. Overall, three patients (8.6%) experienced four postoperative complications (two cases of local hematoma and two catheter dysfunctions) at a rate of 0.2 per 1000 catheter-days. No other complications such as wound dehiscence, delayed incision healing, catheter-related thrombosis (CRT), catheter malposition/fracture, surgical site infection, catheter-related bloodstream infection (CRBSI), pinch-off syndrome, and drug extravasation were observed during follow-up. CONCLUSIONS: Ultrasound-guided right BCV access for TIVAP placement in pediatric patients appears to be technically feasible, safe, and effective. Further large-sample, prospective studies are warranted.
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Cateterismo Venoso Central , Cateteres Venosos Centrais , Veias Braquiocefálicas/diagnóstico por imagem , Cateteres de Demora , Criança , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
The transmission of most respiratory pathogens, including SARS-CoV-2, occurs via virus-containing respiratory droplets, and thus, factors that affect virus viability in droplet residues on surfaces are of critical medical and public health importance. Relative humidity (RH) is known to play a role in virus survival, with a U-shaped relationship between RH and virus viability. The mechanisms affecting virus viability in droplet residues, however, are unclear. This study examines the structure and evaporation dynamics of virus-containing saliva droplets on fomites and their impact on virus viability using four model viruses: vesicular stomatitis virus, herpes simplex virus 1, Newcastle disease virus, and coronavirus HCoV-OC43. The results support the hypothesis that the direct contact of antiviral proteins and virions within the "coffee ring" region of the droplet residue gives rise to the observed U-shaped relationship between virus viability and RH. Viruses survive much better at low and high RH, and their viability is substantially reduced at intermediate RH. A phenomenological theory explaining this phenomenon and a quantitative model analyzing and correlating the experimentally measured virus survivability are developed on the basis of the observations. The mechanisms by which RH affects virus viability are explored. At intermediate RH, antiviral proteins have optimal influence on virions because of their largest contact time and overlap area, which leads to the lowest level of virus activity.