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1.
Mol Cell ; 84(4): 776-790.e5, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38211588

RESUMO

TANK-binding kinase 1 (TBK1) is a potential therapeutic target in multiple cancers, including clear cell renal cell carcinoma (ccRCC). However, targeting TBK1 in clinical practice is challenging. One approach to overcome this challenge would be to identify an upstream TBK1 regulator that could be targeted therapeutically in cancer specifically. In this study, we perform a kinome-wide small interfering RNA (siRNA) screen and identify doublecortin-like kinase 2 (DCLK2) as a TBK1 regulator in ccRCC. DCLK2 binds to and directly phosphorylates TBK1 on Ser172. Depletion of DCLK2 inhibits anchorage-independent colony growth and kidney tumorigenesis in orthotopic xenograft models. Conversely, overexpression of DCLK2203, a short isoform that predominates in ccRCC, promotes ccRCC cell growth and tumorigenesis in vivo. Mechanistically, DCLK2203 elicits its oncogenic signaling via TBK1 phosphorylation and activation. Taken together, these results suggest that DCLK2 is a TBK1 activator and potential therapeutic target for ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinogênese/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Quinases Semelhantes a Duplacortina , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
2.
Nature ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914114

RESUMO

Further improvements in perovskite solar cells (PSCs) require better control of ionic defects in the perovskite photoactive layer during the manufacturing stage and their usage1-5. Here, we report a living passivation strategy using a hindered urea/thiocarbamate bond6-8 Lewis acid-base material (HUBLA), where dynamic covalent bonds with water and heat-activated characteristics can dynamically heal the perovskite to ensure device performance and stability. Upon exposure to moisture or heat, HUBLA generates new agents and further passivates defects in the perovskite. This passivation strategy achieved high-performance devices with a power conversion efficiency (PCE) of 25.1%. HUBLA devices retained 94% of their initial PCE for approximately 1500 hours of aging at 85 °C in N2 and maintained 88% of their initial PCE after 1000 hours of aging at 85 °C and 30% relative humidity (RH) in air.

3.
Nature ; 615(7950): 56-61, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36859579

RESUMO

Correlating atomic configurations-specifically, degree of disorder (DOD)-of an amorphous solid with properties is a long-standing riddle in materials science and condensed matter physics, owing to difficulties in determining precise atomic positions in 3D structures1-5. To this end, 2D systems provide insight to the puzzle by allowing straightforward imaging of all atoms6,7. Direct imaging of amorphous monolayer carbon (AMC) grown by laser-assisted depositions has resolved atomic configurations, supporting the modern crystallite view of vitreous solids over random network theory8. Nevertheless, a causal link between atomic-scale structures and macroscopic properties remains elusive. Here we report facile tuning of DOD and electrical conductivity in AMC films by varying growth temperatures. Specifically, the pyrolysis threshold temperature is the key to growing variable-range-hopping conductive AMC with medium-range order (MRO), whereas increasing the temperature by 25 °C results in AMC losing MRO and becoming electrically insulating, with an increase in sheet resistance of 109 times. Beyond visualizing highly distorted nanocrystallites embedded in a continuous random network, atomic-resolution electron microscopy shows the absence/presence of MRO and temperature-dependent densities of nanocrystallites, two order parameters proposed to fully describe DOD. Numerical calculations establish the conductivity diagram as a function of these two parameters, directly linking microstructures to electrical properties. Our work represents an important step towards understanding the structure-property relationship of amorphous materials at the fundamental level and paves the way to electronic devices using 2D amorphous materials.

4.
Plant Cell ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819320

RESUMO

The brassinosteroid (BR) receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) plays a critical role in plant growth and development. Although much is known about how BR signaling regulates growth and development in many crop species, the role of StBRI1 in regulating potato (Solanum tuberosum) tuber development is not well understood. To address this question, a series of comprehensive genetic and biochemical methods were applied in this investigation. It was determined that StBRI1 and Solanum tuberosum PLASMA MEMBRANE (PM) PROTON ATPASE2 (PHA2), a PM-localized proton ATPase, play important roles in potato tuber development. The individual overexpression of StBRI1 and PHA2 led to a 22% and 25% increase in tuber yield per plant, respectively. Consistent with the genetic evidence, in vivo interaction analysis using double transgenic lines and PM H+-ATPase activity assays indicated that StBRI1 interacts with the C-terminus of PHA2, which restrains the intramolecular interaction of the PHA2 C-terminus with the PHA2 central loop to attenuate autoinhibition of PM H+-ATPase activity, resulting in increased PHA2 activity. Furthermore, the extent of PM H+-ATPase autoinhibition involving phosphorylation-dependent mechanisms corresponds to phosphorylation of the penultimate Thr residue (Thr-951) in PHA2. These results suggest that StBRI1 phosphorylates PHA2 and enhances its activity, which subsequently promotes tuber development. Altogether, our results uncover a BR-StBRI1-PHA2 module that regulates tuber development and suggest a prospective strategy for improving tuberous crop growth and increasing yield via the cell surface-based BR signaling pathway.

5.
Nature ; 579(7798): 219-223, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132712

RESUMO

Ultrathin two-dimensional (2D) semiconducting layered materials offer great potential for extending Moore's law of the number of transistors in an integrated circuit1. One key challenge with 2D semiconductors is to avoid the formation of charge scattering and trap sites from adjacent dielectrics. An insulating van der Waals layer of hexagonal boron nitride (hBN) provides an excellent interface dielectric, efficiently reducing charge scattering2,3. Recent studies have shown the growth of single-crystal hBN films on molten gold surfaces4 or bulk copper foils5. However, the use of molten gold is not favoured by industry, owing to its high cost, cross-contamination and potential issues of process control and scalability. Copper foils might be suitable for roll-to-roll processes, but are unlikely to be compatible with advanced microelectronic fabrication on wafers. Thus, a reliable way of growing single-crystal hBN films directly on wafers would contribute to the broad adoption of 2D layered materials in industry. Previous attempts to grow hBN monolayers on Cu (111) metals have failed to achieve mono-orientation, resulting in unwanted grain boundaries when the layers merge into films6,7. Growing single-crystal hBN on such high-symmetry surface planes as Cu (111)5,8 is widely believed to be impossible, even in theory. Nonetheless, here we report the successful epitaxial growth of single-crystal hBN monolayers on a Cu (111) thin film across a two-inch c-plane sapphire wafer. This surprising result is corroborated by our first-principles calculations, suggesting that the epitaxial growth is enhanced by lateral docking of hBN to Cu (111) steps, ensuring the mono-orientation of hBN monolayers. The obtained single-crystal hBN, incorporated as an interface layer between molybdenum disulfide and hafnium dioxide in a bottom-gate configuration, enhanced the electrical performance of transistors. This reliable approach to producing wafer-scale single-crystal hBN paves the way to future 2D electronics.

6.
Nano Lett ; 24(25): 7672-7680, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38869481

RESUMO

Kagome materials have recently garnered substantial attention due to the intrinsic flat band feature and the stimulated magnetic and spin-related many-body physics. In contrast to their bulk counterparts, two-dimensional (2D) kagome materials feature more distinct kagome bands, beneficial for exploring novel quantum phenomena. Herein, we report the direct synthesis of an ultrathin kagome-structured Co-telluride (Co9Te16) via a molecular beam epitaxy (MBE) route and clarify its formation mechanism from the Co-intercalation in the 1T-CoTe2 layers. More significantly, we unveil the flat band states in the ultrathin Co9Te16 and identify the real-space localization of the flat band states by in situ scanning tunneling microscopy/spectroscopy (STM/STS) combined with first-principles calculations. A ferrimagnetic order is also predicted in kagome-Co9Te16. This work should provide a novel route for the direct synthesis of ultrathin kagome materials via a metal self-intercalation route, which should shed light on the exploration of the intriguing flat band physics in the related systems.

7.
Small ; 20(7): e2306132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37800612

RESUMO

Epitaxy growth and mechanical transfer of high-quality III-nitrides using 2D materials, weakly bonded by van der Waals force, becomes an important technology for semiconductor industry. In this work, wafer-scale transferrable GaN epilayer with low dislocation density is successfully achieved through AlN/h-BN composite buffer layer and its application in flexible InGaN-based light-emitting diodes (LEDs) is demonstrated. Guided by first-principles calculations, the nucleation and bonding mechanism of GaN and AlN on h-BN is presented, and it is confirmed that the adsorption energy of Al atoms on O2 -plasma-treated h-BN is over 1 eV larger than that of Ga atoms. It is found that the introduced high-temperature AlN buffer layer induces sufficient tensile strain during rapid coalescence to compensate the compressive strain generated by the heteromismatch, and a strain-relaxation model for III-nitrides on h-BN is proposed. Eventually, the mechanical exfoliation of single-crystalline GaN film and LED through weak interaction between multilayer h-BN is realized. The flexible free-standing thin-film LED exhibits ≈66% luminescence enhancement with good reliability compared to that before transfer. This work proposes a new approach for the development of flexible semiconductor devices.

8.
Small ; : e2401770, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764303

RESUMO

Ultrathin PtSe2 ribbons can host spin-polarized edge states and distinct edge electrocatalytic activity, emerging as a promising candidate for versatile applications in various fields. However, the direct synthesis is still challenging and the growth mechanism is still unclear. Herein, the arrayed growth of ultrathin PtSe2 ribbons on bunched vicinal Au(001) facets, via a facile chemical vapor deposition (CVD) route is reported. The ultrathin PtSe2 flakes can transform from traditional irregular shapes to desired ribbon shapes by increasing the height of bunched and unidirectionally oriented Au steps (with step height hstep) is found. This crossover, occurring at hstep ≈ 3.0 nm, defines the tailored growth from step-flow to single-terrace-confined modes, as validated by density functional theory calculations of the different system energies. On the millimeter-scale single-crystal Au(001) films with aligned steps, the arrayed ultrathin PtSe2 ribbons with tunable width of ≈20-1000 nm, which are then served as prototype electrocatalysts for hydrogen evolution reaction (HER) is achieved. This work should represent a huge leap in the direct synthesis and the mechanism exploration of arrayed ultrathin transition-metal dichalcogenides (TMDCs) ribbons, which should stimulate further explorations of the edge-related physical properties and practical applications.

9.
New Phytol ; 241(4): 1510-1524, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38130037

RESUMO

Brassinosteroids (BRs) are plant hormones that are essential in plant growth and development. BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1 ASSOCIATED RECEPTOR KINASE 1 (BAK1), which are located on the plasma membrane, function as co-receptors that accept and transmit BR signals. PROHIBITIN 3 (PHB3) was identified in both BRI1 and BAK1 complexes by affinity purification and LC-MS/MS analysis. Biochemical data showed that BRI1/BAK1 interacted with PHB3 in vitro and in vivo. BRI1/BAK1 phosphorylated PHB3 in vitro. When the Thr-80 amino acid in PHB3 was mutated to Ala, the mutant protein was not phosphorylated by BRI1 and the mutant protein interaction with BRI1 was abolished in the yeast two-hybrid assay. BAK1 did not phosphorylate the mutant protein PHB3T54A . The loss-of-function phb3 mutant showed a weaker BR signal than the wild-type. Genetic analyses revealed that PHB3 is a BRI1/BAK1 downstream substrate that participates in BR signalling. PHB3 has five homozygous in tomato, and we named the closest to AtPHB3 as SlPHB3.1. Biochemical data showed that SlBRI1/SlSERK3A/SlSERK3B interacted with SlPHB3.1 and SlPHB3.3. The CRISPR-Cas9 method generated slphb3.1 mutant led to a BR signal stunted relatively in tomatoes. PHB3 is a new component of the BR signal pathway in both Arabidopsis and tomato.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Arabidopsis/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Brassinosteroides/metabolismo , Solanum lycopersicum/genética , Proteínas Quinases/metabolismo , Fosforilação , Proteínas de Arabidopsis/metabolismo , Cromatografia Líquida , Proibitinas , Espectrometria de Massas em Tandem , Transdução de Sinais/fisiologia , Proteínas Mutantes
10.
Opt Lett ; 49(12): 3336-3339, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875614

RESUMO

We demonstrate a circulator-free thin-film lithium niobate (TFLN) dispersion compensator based on the cascading 2 × 2 multimode interferometer (MMI) and two identical chirped Bragg gratings (CBGs). The cascaded MMI-CBG structure provides a dispersion value of 920 ps/nm/m over a 20 nm bandwidth covering 1537 to 1557 nm, featuring a compact footprint of 1 mm × 0.7 mm. Utilizing this device within a TFLN electro-optic time-lens system, we successfully generate 863-fs pulses at a 37 GHz repetition rate. Our compact, scalable, low-loss, and circulator-free dispersion compensator is the building block for the efficient generation of high-peak-power femtosecond laser pulses.

11.
Biomacromolecules ; 25(5): 3153-3162, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38693895

RESUMO

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 µm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.


Assuntos
Técnicas Fotoacústicas , Polímeros , Semicondutores , Técnicas Fotoacústicas/métodos , Animais , Camundongos , Polímeros/química , Quinoxalinas/química , Feminino , Humanos , Tiadiazóis/química , Raios Infravermelhos , Camundongos Nus , Camundongos Endogâmicos BALB C , Meios de Contraste/química
12.
Environ Sci Technol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934536

RESUMO

Understanding the bioavailability of per- and polyfluoroalkyl substances (PFAS) in food is essential for accurate human health risk assessment. Given the rising incidence of inflammatory bowel disease (IBD), this study aimed to investigate the impacts of IBD on the bioavailability of PFAS in food using mice models. The relative bioavailability (RBA) of PFAS was the highest in the chronic IBD mice (64.3-144%), followed by the healthy (60.8-133%) and acute IBD mice (41.5-121%), suggesting that chronic IBD enhanced the PFAS exposure risk. In vitro tests showed that the intestinal micelle stability increased as a result of reduced content of short-chain fatty acids, thus promoting the PFAS bioaccessibility in the digestive fluid of chronic IBD. Additionally, increased pathogenic and decreased beneficial bacteria in the gut of IBD groups facilitated the intestinal permeability, thus enhancing PFAS absorption. These together explained the higher RBA of PFAS in the chronic IBD. However, remarkably lower enzymatic activities suggested severely impaired digestive ability in the acute IBD, which facilitated the excretion of PFAS from feces, thus lowering the RBA. Conversely, PFAS exposure might exacerbate IBD by changing the gut microbiota structures. This study hints that individuals with chronic intestinal inflammation might have higher PFAS exposure risk than the healthy population.

13.
Macromol Rapid Commun ; : e2300737, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38521991

RESUMO

Near-infrared (NIR)-triggered shape memory hydrogels with promising mechanical strength hold immense potential in the field of biomedical applications and soft actuators. However, the optical and mechanical properties of currently reported hydrogels usually suffer from limited solubility and dispersion of commonly used photothermal additives in hydrogels, thus restricting their practical implementations. Here,, a set of NIR-responsive shape memory hydrogels synthesized by polyaddition of diisocyanate-terminated poly(ethylene glycol), imidazolidinyl urea (IU), and p-benzoquinone dioxime (BQDO) is reported. The introduction of IU, a hydrogen bond reinforcing factor, significantly enhances the mechanical properties of the hydrogels, allowing for their tunable ranges of the ultimate tensile strength (0.4-2.5 MPa), elongation at break (210-450%), and Young's modulus (190-850 kPa). The unique hydrogels exhibit an intrinsic photothermal effect because of the covalently incorporated photothermal moiety (BQDO), and the photothermal supramolecular hydrogel shows controllable shape memory capabilities characterized by rapid recovery speed and high recovery ratio (>90%). This design provides new possibilities for applying shape memory hydrogels in the field of soft actuators.

14.
Macromol Rapid Commun ; 45(11): e2400036, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453138

RESUMO

Preparation of materials that possess highly strong and tough properties simultaneously is a great challenge. Thermosetting resins as a type of widely used polymeric materials without synergistic strength and toughness limit their applications in some special fields. In this report, an effective strategy to prepare thermosetting resins with synergistic strength and toughness, is presented. In this method, the soft and rigid microspheres with dynamic hemiaminal bonds are fabricated first, followed by hot-pressing to crosslink at the interfaces. Specifically, the rigid or soft microspheres are prepared via precipitation polymerization. After hot-pressing, the resulting rigid-soft blending materials exhibit superior strength and toughness, simultaneously. As compared with the precursor rigid or soft materials, the toughness of the rigid-soft blending films (RSBFs) is improved to 240% and 2100%, respectively, while the strength is comparable to the rigid precursor. As compared with the traditional crushing, blending, and hot-pressing of rigid or soft materials to get the nonuniform materials, the strength and toughness of the RSBFs are improved to 168% and 255%, respectively. This approach holds significant promise for the fabrication of polymer thermosets with a unique combination of strength and toughness.


Assuntos
Polimerização , Resinas Sintéticas/química , Microesferas , Polímeros/química , Temperatura , Teste de Materiais , Propriedades de Superfície , Tamanho da Partícula
15.
Environ Res ; 251(Pt 2): 118707, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490632

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are recognized as emerging environmental pollutants due to their high persistence and toxicities to humans and animals. Understanding the temporal trend of PFAS in the environment is important for their pollution control and making appropriate policies. Many studies have reported the PFAS concentrations in Taihu Lake, the third largest lake in China, while their temporal trend during the years was seldom investigated. This study summarizes the PFAS concentrations in the water, sediment and organisms in Taihu Lake from 2009 to 2020 to depict their temporal trends. Meanwhile, the ecological model of AQUATOX was applied to evaluate and predict the potential risks of PFAS from 2012 to 2030. The results showed that the total PFAS concentrations varied but without distinct increase or decrease in both water and sediment during the years, while PFAS concentrations in organisms significantly decreased. The yearly mean concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in the water were 21.7-25.4 ng/L and 9.7-26.5 ng/L respectively, lower than the Standards for Drinking Water Quality of China and the suggested water quality criteria to protect the aquatic organisms. In sediment, PFOA and PFOS concentrations were 0.16-0.69 ng/g and 0.15-0.82 ng/g respectively, much lower than the recommended sediment quality guideline values. Based on the AQUATOX prediction, there will be no major threats caused by PFAS to the growth of biota in Taihu Lake in the near future, while the biomass of some species (e.g. carp) will be affected under the perturbation of PFAS. Both field investigation and AQUATOX simulation showed that PFOS concentrations in invertebrates and fish descend steadily, while no remarkable decrease in PFOA concentrations was expected. This study suggests a decreasing ecological risk of PFAS in Taihu Lake, while highlights the necessity of continuous monitoring of PFAS contamination.


Assuntos
Ácidos Alcanossulfônicos , Monitoramento Ambiental , Fluorocarbonos , Sedimentos Geológicos , Lagos , Poluentes Químicos da Água , Fluorocarbonos/análise , China , Lagos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Medição de Risco , Ácidos Alcanossulfônicos/análise , Animais , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Caprilatos/análise
16.
Curr Microbiol ; 81(4): 104, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393394

RESUMO

A Gram-stain-negative, non-flagellated, aerobic, ovoid or rod-shaped bacterium with motility, designated B8T, was isolated from the sediment of Clam Island beach, Liaoning province, China. The optimum growth of strain B8T occurred at 35 oC, pH 7.0, and in the presence of 4.0-5.0% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain B8T formed a distinct lineage within the genus Sphingomicrobium and was closely related to Sphingomicrobium nitratireducens O-35T (98.3% sequence similarity), Sphingomicrobium aestuariivivum KCTC 42286T (96.9%), and Sphingomicrobium astaxanthinifaciens JCM 18551T (96.5%). The digital DNA-DNA hybridization and average nucleotide identity values between strain B8T and closely related strains were lower than 21.0% and 78.0%, much lower than the cutoff values of 70.0% and 95.0%, respectively, for bacterial species delineation. The dominant respiratory quinone of strain B8T was ubiquinone-10. The major fatty acids were Sum In Feature 8 (C18:1ω7c and/or C18:1ω6c), Sum In Feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C17:1ω6c, C18:1 2-OH, and C16:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, glycolipids, and four unknown polar lipids. The DNA G + C content of strain B8T was 63.9%. Based on the phenotypic, phylogenetic, and chemotaxonomic analyses, strain B8T is considered a new species of Sphingomicrobium, for which the name Sphingomicrobium clamense sp. nov. is proposed. The type strain is B8T (= CGMCC 1.19486T = KCTC 92052T).


Assuntos
Fosfolipídeos , Água do Mar , Fosfolipídeos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/química , Ubiquinona/química , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA
17.
BMC Pediatr ; 24(1): 96, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310242

RESUMO

BACKGROUND: NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy. CASE PRESENTATION: Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later. CONCLUSION: We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.


Assuntos
Aspartato-tRNA Ligase , Epilepsia Resistente a Medicamentos , Epilepsia , Estado Epiléptico , Feminino , Humanos , Estado Epiléptico/diagnóstico , Estado Epiléptico/genética , Epilepsia Resistente a Medicamentos/genética , Mutação de Sentido Incorreto , RNA de Transferência , Mutação , Aspartato-tRNA Ligase/genética
18.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443220

RESUMO

Sugar transport across tonoplasts is essential for maintaining cellular sugar homeostasis and metabolic balance in plant cells. It remains unclear, however, how this process is regulated among different classes of sugar transporters. Here, we identified a tonoplast H+/glucose symporter, MdERDL6-1, from apples, which was highly expressed in fruits and exhibited expression patterns similar to those of the tonoplast H+/sugar antiporters MdTST1 and MdTST2. Overexpression of MdERDL6-1 unexpectedly increased not only glucose (Glc) concentration but also that of fructose (Fru) and sucrose (Suc) in transgenic apple and tomato leaves and fruits. RNA sequencing (RNA-seq) and expression analyses showed an up-regulation of TST1 and TST2 in the transgenic apple and tomato lines overexpressing MdERDL6-1 Further studies established that the increased sugar concentration in the transgenic lines correlated with up-regulation of TST1 and TST2 expression. Suppression or knockout of SlTST1 and SlTST2 in the MdERDL6-1-overexpressed tomato background reduced or abolished the positive effect of MdERDL6-1 on sugar accumulation, respectively. The findings demonstrate a regulation of TST1 and TST2 by MdERDL6-1, in which Glc exported by MdERDL6-1 from vacuole up-regulates TST1 and TST2 to import sugars from cytosol to vacuole for accumulation to high concentrations. The results provide insight into the regulatory mechanism of sugar accumulation in vacuoles mediated by the coordinated action of two classes of tonoplast sugar transporters.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , Malus/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Vacúolos/metabolismo , Citosol/metabolismo , Frutose/metabolismo , Frutas/metabolismo , Técnicas de Inativação de Genes , Inativação Gênica , Glucose/metabolismo , Solanum lycopersicum/genética , Malus/genética , Proteínas de Transporte de Monossacarídeos/genética , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , RNA-Seq , Sacarose/metabolismo , Regulação para Cima
19.
Sensors (Basel) ; 24(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610294

RESUMO

The rapid development of the Internet of Things (IoT) has brought many conveniences to our daily life. However, it has also introduced various security risks that need to be addressed. The proliferation of IoT botnets is one of these risks. Most of researchers have had some success in IoT botnet detection using artificial intelligence (AI). However, they have not considered the impact of dynamic network data streams on the models in real-world environments. Over time, existing detection models struggle to cope with evolving botnets. To address this challenge, we propose an incremental learning approach based on Gradient Boosting Decision Trees (GBDT), called GBDT-IL, for detecting botnet traffic in IoT environments. It improves the robustness of the framework by adapting to dynamic IoT data using incremental learning. Additionally, it incorporates an enhanced Fisher Score feature selection algorithm, which enables the model to achieve a high accuracy even with a smaller set of optimal features, thereby reducing the system resources required for model training. To evaluate the effectiveness of our approach, we conducted experiments on the BoT-IoT, N-BaIoT, MedBIoT, and MQTTSet datasets. We compared our method with similar feature selection algorithms and existing concept drift detection algorithms. The experimental results demonstrated that our method achieved an average accuracy of 99.81% using only 25 features, outperforming similar feature selection algorithms. Furthermore, our method achieved an average accuracy of 96.88% in the presence of different types of drifting data, which is 2.98% higher than the best available concept drift detection algorithms, while maintaining a low average false positive rate of 3.02%.

20.
Nano Lett ; 23(10): 4617-4626, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37161990

RESUMO

Light filters are ubiquitous in projection and display techniques, illumination engineering, image sensing, photography, etc., while those enabling wide-gamut dynamic light color tuning are still lacking. Herein, by combining the electro-heating capability of graphene and unique optical properties (thermochromism and circular dichroism) of small-molecule-weight cholesteric liquid crystal (ChLC), a brand-new thermochromic light modulator is constructed as actively tunable color filter. Transparent graphene/glass hybrid with reasonably high conductivity serves both as a high-performance heater for actuating the thermochromism of temperature-responsive ChLC and as neutral light attenuator for brightness control. Thanks to the temperature- and polarization-dependent spectral properties of the ChLC, widely tunable hue and saturation properties of transmission light color are achieved, respectively. Several intriguing applications, e.g., color-variable smart windows for backlight color tuning and color-variable filters for photography, are also demonstrated. This work hereby provides new paradigms for promoting the applications of graphene/ChLC-based light modulators in next-generation light-management-related scenarios.

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