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The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.
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Since the pioneering work of Curtius and Fischer, chemical peptide synthesis has witnessed a century's development and evolved into a routine technology. However, it is far from perfect. In particular, it is challenged by sustainable development because the state-of-the-art of peptide synthesis heavily relies on legacy reagents and technologies developed before the establishment of green chemistry. Over the past three decades, a broad range of efforts have been made for greening peptide synthesis, among which peptide synthesis using unprotected amino acid represents an ideal and promising strategy because it does not require protection and deprotection steps. Unfortunately, C â N peptide synthesis employing unprotected amino acids has been plagued by undesired polymerization, while N â C inverse peptide synthesis with unprotected amino acids is retarded by severe racemization/epimerization owing to the iterative activation and aminolysis of high racemization/epimerization susceptible peptidyl acids. Consequently, there is an urgent need to develop innovative coupling reagents and strategies with novel mechanisms that can address the long-standing notorious racemization/epimerization issue of peptide synthesis.This Account will describe our efforts in discovery of ynamide coupling reagents and their application in greening peptide synthesis. Over an eight-year journey, ynamide coupling reagents have evolved into a class of general coupling reagents for both amide and ester bond formation. In particular, the superiority of ynamide coupling reagents in suppressing racemization/epimerization enabled them to be effective for peptide fragment condensation, and head-to-tail cyclization, as well as precise incorporation of thioamide substitutions into peptide backbones. The first practical inverse peptide synthesis using unprotected amino acids was successfully accomplished by harnessing such features and taking advantage of a transient protection strategy. Ynamide coupling reagent-mediated ester bond formation enabled efficient intermolecular esterification and macrolactonization with preservation of α-chirality and the configuration of the conjugated α,ß-C-C double bond. To make ynamide coupling reagents readily available with reasonable cost and convenience, we have developed a scalable one-step synthetic method from cheap starting materials. Furthermore, a water-removable ynamide coupling reagent was developed, offering a column-free purification of the target coupling product. In addition, the recycle of ynamide coupling reagent was accomplished, thereby paving the way for their sustainable industrial application.As such, this Account presents the whole story of the origin, mechanistic insights, preparation, synthetic applications, and recycle of ynamide coupling reagents with a perspective that highlights their future impact on peptide synthesis.
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Amidas , Peptídeos , Indicadores e Reagentes , Peptídeos/química , Amidas/química , Aminoácidos/química , ÉsteresRESUMO
TexSe1-x shortwave infrared (SWIR) photodetectors show promise for monolithic integration with readout integrated circuits (ROIC), making it a potential alternative to conventional expensive SWIR photodetectors. However, challenges such as a high dark current density and insufficient detection performance hinder their application in large-scale monolithic integration. Herein, we develop a ZnO/TexSe1-x heterojunction photodiode and synergistically address the interfacial elemental diffusion and dangling bonds via inserting a well-selected 0.3 nm amorphous TeO2 interfacial layer. The optimized device achieves a reduced dark current density of -3.5 × 10-5 A cm-2 at -10 mV, a broad response from 300 to 1700 nm, a room-temperature detectivity exceeding 2.03 × 1011 Jones, and a 3 dB bandwidth of 173 kHz. Furthermore, for the first time, we monolithically integrate the TexSe1-x photodiodes on ROIC (64 × 64 pixels) with the largest-scale array among all TexSe1-x-based detectors. Finally, we demonstrate its applications in transmission imaging and substance identification.
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Peptide therapeutics have experienced a rapid resurgence over the past three decades. While a few peptide drugs are biologically produced, most are manufactured via chemical synthesis. The cycle of prior protection of the amino group of an α-amino acid, activation of its carboxyl group, aminolysis with the free amino group of a growing peptide chain, and deprotection of the N-terminus constitutes the principle of conventional C â N peptide chemical synthesis. The mandatory use of the Nα-protecting group invokes two additional operations for incorporating each amino acid, resulting in poor step- and atom-economy. The burgeoning demand in the peptide therapeutic market necessitates cost-effective and environmentally friendly peptide manufacturing strategies. Inverse peptide chemical synthesis using unprotected amino acids has been proposed as an ideal and appealing strategy. However, it has remained unsuccessful for over 60 years due to severe racemization/epimerization during N â C peptide chain elongation. Herein, this challenge has been successfully addressed by ynamide coupling reagent employing a transient protection strategy. The activation, transient protection, aminolysis, and in situ deprotection were performed in one pot, thus offering a practical peptide chemical synthesis strategy formally using unprotected amino acids as the starting material. Its robustness was exemplified by syntheses of peptide active pharmaceutical ingredients. It is also amenable to fragment condensation and inverse solid-phase peptide synthesis. The compatibility to green solvents further enhances its application potential in large-scale peptide production. This study offered a cost-effective, operational convenient, and environmentally benign approach to peptides.
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Aminoácidos , Peptídeos , Aminoácidos/química , Peptídeos/química , Técnicas de Química Sintética , Peptídeo C , Biossíntese Peptídica , Técnicas de Síntese em Fase SólidaRESUMO
Solid-state Li-ion batteries have emerged as the most promising next-generation energy storage systems, offering theoretical advantages such as superior safety and higher energy density. However, polymer-based solid-state Li-ion batteries face challenges across wide temperature ranges. The primary issue lies in the fact that most polymer electrolytes exhibit relatively low ionic conductivity at or below room temperature. This sensitivity to temperature variations poses challenges in operating solid-state lithium batteries at sub-zero temperatures. Moreover, elevated working temperatures lead to polymer shrinkage and deformation, ultimately resulting in battery failure. To address this challenge of polymer-based solid-state batteries, this review presents an overview of various promising polymer electrolyte systems. The review provides insights into the temperature-dependent physical and electrochemical properties of polymers, aiming to expand the temperature range of operation. The review also further summarizes modification strategies for polymer electrolytes suited to diverse temperatures. The final section summarizes the performance of various polymer-based solid-state batteries at different temperatures. Valuable insights and potential future research directions for designing wide-temperature polymer electrolytes are presented based on the differences in battery performance. This information is intended to inspire practical applications of wide-temperature polymer-based solid-state batteries.
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Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC1 F1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding.
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Ascomicetos , Zea mays , Zea mays/genética , Ascomicetos/genética , Melhoramento Vegetal , Locos de Características Quantitativas/genética , Doenças das Plantas/genética , Resistência à Doença/genéticaRESUMO
Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.
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Inflamação , Microplásticos , Receptores Toll-Like , Animais , Camundongos , Receptores Toll-Like/metabolismo , Células RAW 264.7 , NF-kappa B/metabolismo , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , Macrófagos/efeitos dos fármacosRESUMO
In the field of armored vehicles, up to 70% of accidents are associated with low levels of situational awareness among the occupants, highlighting the importance of situational awareness in improving task performance. In this study, we explored the mechanisms influencing situational awareness by simulating an armored vehicle driving platform with 14 levels of experimentation in terms of five factors: experience, expectations, attention, the cueing channel, and automation. The experimental data included SART and SAGAT questionnaire scores, eye movement indicators, and electrocardiographic and electrodermal signals. Data processing and analysis revealed the following conclusions: (1) Experienced operators have higher levels of situational awareness. (2) Operators with certain expectations have lower levels of situational awareness. (3) Situational awareness levels are negatively correlated with information importance affiliations and the frequency of anomalous information in non-primary tasks. (4) Dual-channel cues lead to higher levels of situational awareness than single-channel cues. (5) Operators' situational awareness is lower at high automation levels.
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Condução de Veículo , Conscientização , Humanos , Conscientização/fisiologia , Adulto , Masculino , Feminino , Atenção/fisiologia , Movimentos Oculares/fisiologia , Eletrocardiografia/métodos , Inquéritos e Questionários , Adulto Jovem , Acidentes de Trânsito/prevenção & controle , Sinais (Psicologia) , Automação , Análise e Desempenho de Tarefas , AutomóveisRESUMO
Solution-processed colloidal quantum dot (CQD) photodiodes are compatible for monolithic integration with silicon-based readout circuitry, enabling ultrahigh resolution and ultralow cost infrared imagers. However, top-illuminated CQD photodiodes for longer infrared imaging suffer from mismatched energy band alignment between narrow-bandgap CQDs and the electron transport layer. In this work, we designed a new top-illuminated structure by replacing the sputtered ZnO layer with a SnO2 layer by atomic layer deposition. Benefiting from matched energy band alignment and improved heterogeneous interface, our top-illuminated CQD photodiodes achieve a broad-band response up to 1650 nm. At 220 K, these SnO2-based devices exhibit an ultralow dark current density of 3.5 nA cm-2 at -10 mV, reaching the noise limit for passive night vision. The detectivity is 4.1 × 1012 Jones at 1530 nm. These SnO2-based devices also demonstrate exceptional operation stability. By integrating with silicon-based readout circuitry, our CQD imager realizes water/oil discrimination and see-through smoke imaging.
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KEY MESSAGE: Here, we report that ZmAGO18b encoding an argonaute protein is a negative regulator of maize resistance against southern leaf blight. Southern leaf blight caused by fungal pathogen Cochliobolus heterostrophus is a destructive disease on maize throughout the world. Argonaute (AGO) proteins, key regulators in small RNA pathway, play important roles in plant defense. But whether they have function in maize resistance against C. heterostrophus is unknown. Association analysis between the nucleic variation of 18 ZmAGO loci with disease phenotype against C. heterostrophus was performed, and the ZmAGO18b locus was identified to be associated with resistance against C. heterostrophus. Overexpression of ZmAGO18b gene suppresses maize resistance against C. heterostrophus, and mutation of ZmAGO18b enhances maize resistance against C. heterostrophus. Further, we identified the resistant haplotype of ZmAGO18b by association analysis of natural variation in ZmAGO18b genomic DNA sequences with seedling resistance phenotypes against C. heterostrophus and confirmed the resistant haplotype is co-segregated with resistance phenotypes against C. heterostrophus in two F2 populations. In sum, this study reports that ZmAGO18b negatively regulates maize resistance against C. heterostrophus.
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Doenças das Plantas , Zea mays , Zea mays/genética , Zea mays/microbiologia , Mutação , Fenótipo , Doenças das Plantas/genética , Doenças das Plantas/microbiologiaRESUMO
BACKGROUND: This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms. MATERIAL/METHODS: Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples. RESULTS: A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied. CONCLUSIONS: This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.
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Aneurisma da Aorta Torácica , MicroRNAs , Humanos , Perfilação da Expressão Gênica , MicroRNAs/genética , Apoptose/genética , Redes Reguladoras de GenesRESUMO
BACKGROUND AND AIMS: Hyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients. METHODS AND RESULTS: A total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30-5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98-55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30-2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality. CONCLUSION: Hyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.
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Hiperuricemia , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , LDL-Colesterol , Biomarcadores , Alta do Paciente , Hiperuricemia/diagnóstico , Assistência ao Convalescente , Fatores de RiscoRESUMO
Efficient biosynthesis of microbial bioactive natural products (NPs) is beneficial for the survival of producers, while self-protection is necessary to avoid self-harm resulting from over-accumulation of NPs. The underlying mechanisms for the effective but tolerable production of bioactive NPs are not well understood. Herein, in the biosynthesis of two fungal polyketide mycotoxins aurovertinâ E (1) and asteltoxin, we show that the cyclases in the gene clusters promote the release of the polyketide backbone, and reveal that a signal peptide is crucial for their subcellular localization and full activity. Meanwhile, the fungus adopts enzymatic acetylation as the major detoxification pathway of 1. If intermediates are over-produced, the non-enzymatic shunt pathways work as salvage pathways to avoid excessive accumulation of the toxic metabolites for self-protection. These findings provided new insight into the interplay of efficient backbone release and multiple detoxification strategies for the production of fungal bioactive NPs.
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Micotoxinas , Policetídeos , Policetídeos/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Processamento de Proteína Pós-Traducional , Família MultigênicaRESUMO
BACKGROUND: Bursaphelenchus xylophilus is the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN). RESULTS: We cloned, characterized and functionally validated the B. xylophilus effector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 of B. xylophilus. An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine of B. xylophilus. Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number of B. xylophilus and morbidity of pine were significantly reduced in Pinus thunbergii infected with B. xylophilus when BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 in P. thunbergii. CONCLUSIONS: This study illustrated that BxML1 plays a critical role in the B. xylophilus-plant interaction and virulence of B. xylophilus.
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Pinus , Tylenchida , Animais , Ciclofilinas/genética , Pinus/parasitologia , Virulência , XylophilusRESUMO
Metal-halide perovskites have drawn profuse attention during the past decade, owing to their excellent electrical and optical properties, facile synthesis, efficient energy conversion, and so on. Meanwhile, the development of information storage technologies and digital communications has fueled the demand for novel semiconductor materials. Low-dimensional perovskites have offered a new force to propel the developments of the memory field due to the excellent physical and electrical properties associated with the reduced dimensionality. In this review, the mechanisms, properties, as well as stability and performance of low-dimensional perovskite memories, involving both molecular-level perovskites and structure-level nanostructures, are comprehensively reviewed. The property-performance correlation is discussed in-depth, aiming to present effective strategies for designing memory devices based on this new class of high-performance materials. Finally, the existing challenges and future opportunities are presented.
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Power generation by converting energy from the ambient environment has been considered a promising strategy for developing decentralized electrification systems to complement the electricity supply for daily use. Wet gases, such as water evaporation or moisture in the atmosphere, can be utilized as a tremendous source of electricity by emerging power generation devices, that is, moisture-enabled-electric nanogenerators (MEENGs). As a promising technology, MEENGs provided a novel manner to generate electricity by harvesting energy from moisture, originating from the interactions between water molecules and hydrophilic functional groups. Though the remarkable progress of MEENGs has been achieved, a systematic review in this specific area is urgently needed to summarize previous works and provide sharp points to further develop low-cost and high-performing MEENGs through overcoming current limitations. Herein, the working mechanisms of MEENGs reported so far are comprehensively compared. Subsequently, a systematic summary of the materials selection and fabrication methods for currently reported MEENG construction is presented. Then, the improvement strategies and development directions of MEENG are provided. At last, the demonstrations of the applications assembled with MEENGs are extracted. This work aims to pave the way for the further MEENGs to break through the performance limitations and promote the popularization of future micron electronic self-powered equipment.
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Fontes de Energia Elétrica , Eletricidade , Eletrônica , ÁguaRESUMO
Hybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed-halide hybrid perovskite single crystals of MAPbI3-x Brx (MA = CH3 NH3 + and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed-halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed-halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties.
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Background: Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitor is the cornerstone of acute coronary syndrome (ACS) management. Balancing the effects of different strategies of antiplatelet therapy including DAPT de-escalation, potent P2Y12 inhibitor monotherapy, and conventional DAPT is a hot topic. Methods: A systematic search was conducted from the MEDLINE, PubMed, and Embase through October 2021 to identify various DAPT strategies in randomized controlled trials (RCTs) for treatment of ACS patients after undergoing PCI with drug-eluting stent (DES). The network meta-analysis was performed to investigate the net clinic benefit of the DAPT de-escalation, potent P2Y12 inhibitor monotherapy, as well as conventional DAPT. The primary outcome was net adverse clinical events, defined as a composite of major bleeding and cardiac death, myocardial infarction, stroke, stent thrombosis, or target-vessel revascularization. The secondary outcomes include major adverse cardiac events and trial-defined major or minor bleeding. Results: A total of 14 RCTs with 63,982 patients were included. The DAPT de-escalation was associated with a lower risk of the primary outcome compared with potent P2Y12 inhibitor monotherapy (De-escalation vs monotherapy odds ratio (OR): 0.72 95% confidence interval (CI): 0.55-0.96), and other antiplatelet strategies (De-escalation vs clopidogrel + aspirin OR: 0.49 95% CI: 0.39-0.63; De-escalation vs prasugrel + aspirin OR: 0.76 95% CI: 0.59-0.98; De-escalation vs ticagrelor + aspirin OR: 0.76 95% CI: 0.55-0.90). There were no statistical differences in the incidence of bleeding (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.73 95% CI: 0.47-1.12) and major adverse cardiac events (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.79 95% CI: 0.59-1.08) between DAPT de-escalation and potent P2Y12 inhibitor monotherapy. Conclusions: This network meta-analysis showed that DAPT de-escalation would reduce the net adverse clinical events, compared with potent P2Y12 inhibitor monotherapy, for ACS patients undergone PCI treatment.
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Acyl-CoA thioesterase 9 (ACOT9) is a critical regulator of cellular utilization of fatty acids by catalysing the hydrolysis of acyl-CoA thioesters to non-esterified fatty acid and coenzyme A (CoA). Recently, ACOT9 was reported to participate in the pathogenesis of non-alcoholic liver disease (NAFLD), which arises from aberrant lipid metabolism and serves as a risk factor for hepatocellular carcinoma (HCC). However, the functions of ACOT9 in carcinogenesis and aberrant lipid metabolism in HCC remain unexplored. Here, we found that ACOT9 expression is significantly elevated in HCC at least partially due to the down-regulation of miR-449c-3p. Upregulation of ACOT9 is closely associated with poor prognosis for patients with HCC. Knockdown of ACOT9 expression in HCC cells significantly decreased cell proliferation, colony formation, migration and invasion, mainly through suppression of G1-to-S cell cycle transition and epithelial-to-mesenchymal transition (EMT). By contrast, forced ACOT9 expression promoted HCC growth and metastasis. In addition, we found that ACOT9 reprogrammed lipid metabolism in HCC cells by increasing de novo lipogenesis. Furthermore, we demonstrated that increased lipogenesis was involved in ACOT9-promoted HCC growth and metastasis. Altogether, we demonstrate that ACOT9 plays a critical oncogenic role in the promotion of tumour growth and metastasis by reprogramming lipid metabolism in HCC, indicating ACOT9 as a potential therapeutic target in treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Acil Coenzima A/metabolismo , Carcinogênese , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Ácidos Graxos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase NeoplásicaRESUMO
In order to meet the requirements of ultra-fast real-time monitoring of sarin simulator with high sensitivity and selectivity, it is of great significance to develop high performance dimethyl methylphonate (DMMP) sensor. Herein, we proposed a DMMP sensor based on p-hexafluoroisopropanol phenyl (HFIPPH) modified self-assembled single-walled carbon nanotubes (SWCNTs) with field effect transistor (FET) structure. The self-assembly method provides a 4 nanometres thick and micron sized SWCNT channel, with high selectivity to DMMP. The proposed SWCNTs-HFIPPH based sensor exhibits remarkably higher response to DMMP than bare SWCNT based gas sensor within only few seconds. The gas sensing response of SWCNTs-HFIPPH based sensor for 1 ppm DMMP is 18.2%, and the response time is about 10 s. What's more, the gas sensor we proposed here shows excellent selectivity and reproducibility, and the limitation of detection is as low as ppb level. The proposed method lays the foundation for miniaturization and integration of DMMP sensors, expecting to develop detection system for practical sarin sensing application.