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1.
Cell ; 187(15): 3936-3952.e19, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936359

RESUMEN

Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.


Asunto(s)
Duplicación de Gen , Edición Génica , Genoma Humano , Humanos , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , ADN/genética , Animales , Células Madre Embrionarias/metabolismo , Cromosomas Humanos/genética
2.
Nature ; 610(7930): 74-80, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36163287

RESUMEN

The adverse impact of particulate air pollution on human health1,2 has prompted the development of purification systems that filter particulates out of air3-5. To maintain performance, the filter units must inevitably be replaced at some point, which requires maintenance, involves costs and generates solid waste6,7. Here we show that an ion-doped conjugated polymer-coated matrix infiltrated with a selected functional liquid enables efficient, continuous and maintenance-free air purification. As the air to be purified moves through the system in the form of bubbles, the functional fluid provides interfaces for filtration and for removal of particulate matter and pollutant molecules from air. Theoretical modelling and experimental results demonstrate that the system exhibits high efficiency and robustness: its one-time air purification efficiency can reach 99.6%, and its dust-holding capacity can reach 950 g m-2. The system is durable and resistant to fouling and corrosion, and the liquid acting as filter can be reused and adjusted to also enable removal of bacteria or odours. We anticipate that our purification approach will be useful for the development of specialist air purifiers that might prove useful in a settings such as hospitals, factories and mines.


Asunto(s)
Absorción Fisicoquímica , Contaminantes Atmosféricos , Filtración , Material Particulado , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/aislamiento & purificación , Bacterias/aislamiento & purificación , Polvo/prevención & control , Filtración/instrumentación , Filtración/métodos , Humanos , Odorantes/prevención & control , Material Particulado/química , Material Particulado/aislamiento & purificación , Polímeros/química , Residuos Sólidos
3.
Mol Cell ; 80(1): 87-101.e5, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32931746

RESUMEN

Studies in three mouse models of breast cancer identified profound discrepancies between cell-autonomous and systemic Akt1- or Akt2-inducible deletion on breast cancer tumorigenesis and metastasis. Although systemic Akt1 deletion inhibits metastasis, cell-autonomous Akt1 deletion does not. Single-cell mRNA sequencing revealed that systemic Akt1 deletion maintains the pro-metastatic cluster within primary tumors but ablates pro-metastatic neutrophils. Systemic Akt1 deletion inhibits metastasis by impairing survival and mobilization of tumor-associated neutrophils. Importantly, either systemic or neutrophil-specific Akt1 deletion is sufficient to inhibit metastasis of Akt-proficient tumors. Thus, Akt1-specific inhibition could be therapeutic for breast cancer metastasis regardless of primary tumor origin. Systemic Akt2 deletion does not inhibit and exacerbates mammary tumorigenesis and metastasis, but cell-autonomous Akt2 deletion prevents breast cancer tumorigenesis by ErbB2. Elevated circulating insulin level induced by Akt2 systemic deletion hyperactivates tumor Akt, exacerbating ErbB2-mediated tumorigenesis, curbed by pharmacological reduction of the elevated insulin.


Asunto(s)
Neoplasias Mamarias Animales/enzimología , Neoplasias Mamarias Animales/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Carcinogénesis/patología , Femenino , Eliminación de Gen , Humanos , Insulina/metabolismo , Isoenzimas/metabolismo , Metástasis de la Neoplasia , Neutrófilos/metabolismo , Receptor ErbB-2/metabolismo
4.
FASEB J ; 38(6): e23559, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38502020

RESUMEN

Articular cartilage injury is one of the most common diseases in orthopedic clinics. Following an articular cartilage injury, an inability to resist vascular invasion can result in cartilage calcification by newly formed blood vessels. This process ultimately leads to the loss of joint function, significantly impacting the patient's quality of life. As a result, developing anti-angiogenic methods to repair damaged cartilage has become a popular research topic. Despite this, tissue engineering, as an anti-angiogenic strategy in cartilage injury repair, has not yet been adequately investigated. This exhaustive literature review mainly focused on the process and mechanism of vascular invasion in articular cartilage injury repair and summarized the major regulatory factors and signaling pathways affecting angiogenesis in the process of cartilage injury. We aimed to discuss several potential methods for engineering cartilage repair with anti-angiogenic strategies. Three anti-angiogenic tissue engineering methods were identified, including administering angiogenesis inhibitors, applying scaffolds to manage angiogenesis, and utilizing in vitro bioreactors to enhance the therapeutic properties of cultured chondrocytes. The advantages and disadvantages of each strategy were also analyzed. By exploring these anti-angiogenic tissue engineering methods, we hope to provide guidance for researchers in related fields for future research and development in cartilage repair.


Asunto(s)
Cartílago Articular , Calidad de Vida , Humanos , Inmunoterapia , Inhibidores de la Angiogénesis , Calcificación Fisiológica
5.
Mol Psychiatry ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654124

RESUMEN

Pathogenic mutant huntingtin (mHTT) infiltrates the adult Huntington's disease (HD) brain and impairs fetal corticogenesis. However, most HD animal models rarely recapitulate neuroanatomical alterations in adult HD and developing brains. Thus, the human cortical organoid (hCO) is an alternative approach to decode mHTT pathogenesis precisely during human corticogenesis. Here, we replicated the altered corticogenesis in the HD fetal brain using HD patient-derived hCOs. Our HD-hCOs had pathological phenotypes, including deficient junctional complexes in the neural tubes, delayed postmitotic neuronal maturation, dysregulated fate specification of cortical neuron subtypes, and abnormalities in early HD subcortical projections during corticogenesis, revealing a causal link between impaired progenitor cells and chaotic cortical neuronal layering in the HD brain. We identified novel long, oriented, and enriched polyQ assemblies of HTTs that hold large flat Golgi stacks and scaffold clathrin+ vesicles in the neural tubes of hCOs. Flat Golgi stacks conjugated polyQ assemblies by ADP-ribosylation factor 1 (ARF1). Inhibiting ARF1 activation with Brefeldin A (BFA) disassociated polyQ assemblies from Golgi. PolyQ assembles with mHTT scaffolded fewer ARF1 and formed shorter polyQ assembles with fewer and shorter Golgi and clathrin vesicles in neural tubes of HD-hCOs compared with those in hCOs. Inhibiting the activation of ARF1 by BFA in healthy hCOs replicated impaired junctional complexes in the neural tubes. Together, endogenous polyQ assemblies with mHTT reduced the Golgi recruiting ARF1 in the neuroepithelium, impaired the Golgi structure and activities, and altered the corticogenesis in HD-hCO.

6.
PLoS Biol ; 20(11): e3001868, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36395338

RESUMEN

The striatum links neuronal circuits in the human brain, and its malfunction causes neuronal disorders such as Huntington's disease (HD). A human striatum model that recapitulates fetal striatal development is vital to decoding the pathogenesis of striatum-related neurological disorders and developing therapeutic strategies. Here, we developed a method to construct human striatal organoids (hStrOs) from human pluripotent stem cells (hPSCs), including hStrOs-derived assembloids. Our hStrOs partially replicated the fetal striatum and formed striosome and matrix-like compartments in vitro. Single-cell RNA sequencing revealed distinct striatal lineages in hStrOs, diverging from dorsal forebrain fate. Using hStrOs-derived assembloids, we replicated the striatal targeting projections from different brain parts. Furthermore, hStrOs can serve as hosts for striatal neuronal allografts to test allograft neuronal survival and functional integration. Our hStrOs are suitable for studying striatal development and related disorders, characterizing the neural circuitry between different brain regions, and testing therapeutic strategies.


Asunto(s)
Organoides , Células Madre Pluripotentes , Humanos , Cuerpo Estriado , Neostriado , Prosencéfalo
7.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35173045

RESUMEN

We develop a high-throughput technique to relate positions of individual cells to their three-dimensional (3D) imaging features with single-cell resolution. The technique is particularly suitable for nonadherent cells where existing spatial biology methodologies relating cell properties to their positions in a solid tissue do not apply. Our design consists of two parts, as follows: recording 3D cell images at high throughput (500 to 1,000 cells/s) using a custom 3D imaging flow cytometer (3D-IFC) and dispensing cells in a first-in-first-out (FIFO) manner using a robotic cell placement platform (CPP). To prevent errors due to violations of the FIFO principle, we invented a method that uses marker beads and DNA sequencing software to detect errors. Experiments with human cancer cell lines demonstrate the feasibility of mapping 3D side scattering and fluorescent images, as well as two-dimensional (2D) transmission images of cells to their locations on the membrane filter for around 100,000 cells in less than 10 min. While the current work uses our specially designed 3D imaging flow cytometer to produce 3D cell images, our methodology can support other imaging modalities. The technology and method form a bridge between single-cell image analysis and single-cell molecular analysis.


Asunto(s)
Citometría de Flujo/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Citometría de Flujo/instrumentación , Humanos , Imagenología Tridimensional/instrumentación , Imagenología Tridimensional/métodos , Programas Informáticos
8.
Proc Natl Acad Sci U S A ; 119(29): e2206462119, 2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35858305

RESUMEN

Emulsification is a crucial technique for mixing immiscible liquids into droplets in numerous areas ranging from food to medicine to chemical synthesis. Commercial emulsification methods are promising for high production, but suffer from high energy input. Here, we report a very simple and scalable emulsification method that employs the drag-reducing liquid gating structure to create a smooth liquid-liquid interface for the reduction of resistance and tunable generation of droplets with good uniformity. Theoretical modeling and experimental results demonstrate that our method exhibits ultrahigh efficiency, which can reach up to more than 4 orders of magnitude greater energy-saving compared to commercial methods. For temperature-sensitive biological components, such as enzymes, proteins, and bacteria, it can offer a comfortable environment to avoid exposure to high temperatures during emulsifying, and the interface also enables the suppression of fouling. This unique drag-reducing liquid gating interfacial emulsification mechanism promotes the efficiency of droplet generation and provides fresh insight into the innovation of emulsifications that can be applied in many fields, including the food industry, the daily chemical industry, biomedicine, material fabrication, the petrochemical industry, and beyond.

9.
Cancer Sci ; 115(8): 2738-2750, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38888048

RESUMEN

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.


Asunto(s)
Neoplasias Pancreáticas , ARN Ribosómico 16S , Humanos , Neoplasias Pancreáticas/microbiología , Neoplasias Pancreáticas/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Anciano , ARN Ribosómico 16S/genética , Metaboloma , Microbiota , Metabolómica/métodos , Páncreas/metabolismo , Páncreas/microbiología , Corynebacterium/metabolismo , Corynebacterium/genética
10.
Anal Chem ; 96(15): 6037-6044, 2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38560885

RESUMEN

Dopamine (DA), an essential neurotransmitter, is closely associated with various neurological disorders, whose real-time dynamic monitoring is significant for evaluating the physiological activities of neurons. Electrochemical sensing methods are commonly used to determine DA, but they mostly rely on the redox reaction of its o-phenolic hydroxyl group, which makes it difficult to distinguish it from substances with this group. Here, we design a biomimetic nanozyme inspired by the coordination structure of the copper-based active site of dopamine ß-hydroxylase, which was successfully synthesized via a urea-mediated MOF pyrolysis reconstruction strategy. Experimental studies and theoretical calculations revealed that the nanozyme with Cu-N3 coordination could hydroxylate the carbon atom of the DA ß-site at a suitable potential and that the active sites of this Cu-N3 structure have the lowest binding energy for the DA ß-site. With this property, the new oxidation peak achieves the specific detection of DA rather than the traditional electrochemical signal of o-phenol hydroxyl redox, which would effectively differentiate it from neurotransmitters, such as norepinephrine and epinephrine. The sensor exhibited good monitoring capability in DA concentrations from 0.05 to 16.7 µM, and its limit of detection was 0.03 µM. Finally, the sensor enables the monitoring of DA released from living cells and can be used to quantitatively analyze the effect of polystyrene microplastics on the amount of DA released. The research provides a method for highly specific monitoring of DA and technical support for initial screening for neurocytotoxicity of pollutants.


Asunto(s)
Dopamina , Oxigenasas de Función Mixta , Dopamina/química , Fenol , Biomimética , Cobre , Plásticos , Pirólisis , Electrodos , Neurotransmisores , Técnicas Electroquímicas/métodos
11.
Anal Chem ; 96(4): 1515-1521, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38232235

RESUMEN

Pure shift nuclear magnetic resonance (NMR) spectroscopy presents a promising solution to provide sufficient spectral resolution and has been increasingly applied in various branches of chemistry, but the optimal resolution is generally accompanied by long experimental times. We present a proof of concept of deep learning for fast, high-quality, and reliable pure shift NMR reconstruction. The deep learning (DL) protocol allows one to eliminate undersampling artifacts, distinguish peaks with close chemical shifts, and reconstruct high-resolution pure shift NMR spectroscopy along with accelerated acquisition. More meaningfully, the lightweight neural network delivers satisfactory reconstruction performance on personal computers by several hundred simulated data learning, which somewhat lifts the prohibiting demand for a large volume of real training samples and advanced computing hardware generally required in DL projects. Additionally, an M-to-S strategy applicable to common DL cases is further exploited to boost the network generalization capability. As a result, this study takes a meaningful step toward deep learning protocols for broad chemical applications.

12.
Anal Chem ; 96(33): 13742-13748, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39115999

RESUMEN

As one of the commonly used intact detection techniques, liquid NMR spectroscopy offers unparalleled insights into the chemical environments, structures, and dynamics of molecules. However, it generally encounters the challenges of crowded or even overlapped spectra, especially when probing complex sample systems containing numerous components and complicated molecular structures. Herein, we exploit a general NMR protocol for efficient NMR analysis of complex systems by combining fast pure shift NMR and GEMSTONE-based selective TOCSY. First, this protocol enables ultrahigh-selective observation on the coupling networks that are totally correlated with targeted resonances or components, even where they are situated in severely overlapped spectral regions. Second, pure shift simplification is introduced to enhance the spectral resolution and further resolve the subspectra containing spectral congestion, thus facilitating the dissection of overlapped spectra. Additionally, sparse sampling accompanied by spectral reconstruction is adopted to significantly accelerate acquisition and improve spectral quality. The advantages of this protocol were demonstrated on different complex sample systems, including a challenging compound of estradiol, a mixture of sucrose and d-glucose, and natural grape juice, verifying its feasibility and power, and boosting the potential application landscapes in various chemical fields.

13.
Anal Chem ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172624

RESUMEN

Activatable photosensitizers (PSs) generating 1O2 only under specific conditions can minimize concomitant injury to normal tissues. Heavy-atom-free PSs hold the merits of low dark toxicity, long triplet-state lifetimes, good photostability, and relatively low cost. PSs with emission in the second near-infrared (NIR-II) window are highly valuable for deep-tissue, high-contrast imaging. Herein, we have designed and synthesized a series of heavy-atom-free PSs by a one-step reaction between an easily accessible rhodamine derivative and commercially available thiophene aldehydes. One of the as-prepared PSs, 2b-3T, exhibits emission maxima at 810 nm and tails to the NIR-II region at 1140 nm, together with large Stokes shift (178 nm). Importantly, the newly developed PSs, featuring functional carboxylic acid groups, present promising opportunities as versatile platforms for creating activatable PSs. To validate our concept, we developed Cu2+/pH-activatable PSs using the spirocyclization mechanism of rhodamine. Ultimately, we showcased the effectiveness of these innovative PSs in photodynamic therapy through in vitro experiments.

14.
Small ; : e2404552, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106240

RESUMEN

Oxygen evolution reaction is the essential anodic reaction for water splitting. Designing tunable electronic structures to overcome its slow kinetics is an effective strategy. Herein, the molecular ammonium iron sulfate dodecahydrate is employed as the precursor to synthesize the C, N, S triatomic co-doped Fe(Al)OOH on Ni foam (C,N,S-Fe(Al)OOH-NF) with asymmetric electronic structure. Both in situ oxygen vacancies and their special electronic configuration enable the electron transfer between the d-p orbitals and get the increase of OER activity. Density functional theory calculation further indicates the effect of electronic structure on catalytic activity and stability at the oxygen vacancies. In alkaline solution, the catalyst C,N,S-Fe(Al)OOH-NF shows good catalytic activity and stability for water splitting. For OER, the overpotential of 10 mA cm-2 is 264 mV, the tafel slope is 46.4 mV dec-1, the HER overpotential of 10 mA cm-2 is 188 mV, the tafel slope is 59.3 mV dec-1. The stability of the catalyst can maintain ≈100 h. This work has extraordinary implications for understanding the mechanistic relationship between electronic structure and catalytic activity for designing friendly metal (oxy)hydroxide catalysts.

15.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34718395

RESUMEN

Since the first report of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, over 100 million people have been infected by COVID-19, millions of whom have died. In the latest year, a large number of omics data have sprung up and helped researchers broadly study the sequence, chemical structure and function of SARS-CoV-2, as well as molecular abnormal mechanisms of COVID-19 patients. Though some successes have been achieved in these areas, it is necessary to analyze and mine omics data for comprehensively understanding SARS-CoV-2 and COVID-19. Hence, we reviewed the current advantages and limitations of the integration of omics data herein. Firstly, we sorted out the sequence resources and database resources of SARS-CoV-2, including protein chemical structure, potential drug information and research literature resources. Next, we collected omics data of the COVID-19 hosts, including genomics, transcriptomics, microbiology and potential drug information data. And subsequently, based on the integration of omics data, we summarized the existing data analysis methods and the related research results of COVID-19 multi-omics data in recent years. Finally, we put forward SARS-CoV-2 (COVID-19) multi-omics data integration research direction and gave a case study to mine deeper for the disease mechanisms of COVID-19.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Genómica , SARS-CoV-2 , Antivirales/química , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/genética , Humanos , SARS-CoV-2/química , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
16.
Nat Mater ; 22(11): 1324-1331, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37770676

RESUMEN

Two-dimensional (2D) semiconductors, such as transition metal dichalcogenides, provide an opportunity for beyond-silicon exploration. However, the lab to fab transition of 2D semiconductors is still in its preliminary stages, and it has been challenging to meet manufacturing standards of stability and repeatability. Thus, there is a natural eagerness to grow wafer-level, high-quality films with industrially acceptable scale-cost-performance metrics. Here we report an improved chemical vapour deposition synthesis method in which the controlled release of precursors and substrates predeposited with amorphous Al2O3 ensure the uniform synthesis of monolayer MoS2 as large as 12 inches while also enabling fast and non-toxic growth to reduce manufacturing costs. Transistor arrays were fabricated to further confirm the high quality of the film and its integrated circuit application potential. This work achieves the co-optimization of scale-cost-performance metrics and lays the foundation for advancing the integration of 2D semiconductors in industry-standard pilot lines.

17.
Plant Cell Environ ; 47(5): 1452-1470, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38233741

RESUMEN

MicroRNAs (miRNAs) are small noncoding RNAs that play a vital role in plant responses to abiotic and biotic stresses. Recently, it has been discovered that some primary miRNAs (pri-miRNAs) encode regulatory short peptides called miPEPs. However, the presence of miPEPs in rice, and their functions in response to abiotic stresses, particularly stress induced by heavy metals, remain poorly understood. Here, we identified a functional small peptide (miPEP156e) encoded by pri-miR156e that regulates the expression of miR156 and its target SPL genes, thereby affecting miR156-mediated cadmium (Cd) tolerance in rice. Overexpression of miPEP156e led to decreased uptake and accumulation of Cd and reactive oxygen species (ROS) levels in plants under Cd stress, resulting in improved rice Cd tolerance, as observed in miR156-overexpressing lines. Conversely, miPEP156e mutants displayed sensitivity to Cd stress due to the elevated accumulation of Cd and ROS. Transcriptome analysis further revealed that miPEP156e improved rice Cd tolerance by modulating Cd transporter genes and ROS scavenging genes. Our study provides insights into the regulatory mechanism of miPEP156e in rice response to Cd stress and demonstrates the potential of miPEPs as an effective tool for improving crop abiotic stress tolerance.


Asunto(s)
MicroARNs , Oryza , MicroARNs/genética , MicroARNs/metabolismo , Cadmio/metabolismo , Oryza/fisiología , Especies Reactivas de Oxígeno/metabolismo , Péptidos/metabolismo , Regulación de la Expresión Génica de las Plantas
18.
Chemistry ; : e202402199, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117600

RESUMEN

Isoindigo, an electron-withdrawing building block for polymeric field-effect transistors, has long been considered to be non-fluorescent. Moreover, using electron-deficient heterocycle to replace the phenyl ring in the isoindigo core for better electron transport behaviour is synthetically challenging. Here we report the syntheses of a series of tetraazaisoindigos, including pyrazinoisoindigo (PyrII), pyrimidoisoindigo (PymII) and their hybrid (PyrPymII), and the investigation on their photophysical and electric properties. Proper flanking groups need to be chosen to stabilize these highly electron-deficient bislactams. Both PyrII and PymII derivatives show lower LUMO energy levels than that of naphthalene bisimide (NDI). Interestingly, PyrII is instinctively unstable and can be easily reduced, while both PymII derivatives are stable. More surprisingly, PymII derivatives are highly fluorescent and their photoluminescence quantum yields are around 40%, 133 times higher than that of reported isoindigo derivatives. UV-vis spectroscopic results and theoretical calculations show that strong intramolecular hydrogen-bond exists in PymII, which prohibits it from non-radiative decay and accounts for its fluorescent behaviour.  PymII deriviatives are n-type semiconductors, while Ph-PyrII and the hybrid show balanced ambipolar charge transport behaviour, all among the best isoindigo derivatives. Our study not only discloses the structure-property relationship of tetraazaisoindigos, but also provides electron-deficient monomers for conjugated polymers.

19.
Langmuir ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39024471

RESUMEN

Fe3O4 nanoparticles occupy a pivotal position in the realm of nanobiology due to their nontoxic, biocompatible, and superparamagnetic properties. This study examines the influence of surface modifiers on the properties of magnetic nanoparticles. Poly(methacrylic acid) (PMAA), poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSM), trisodium citrate (TSC), carboxymethylcellulose (CMC), and carboxymethylated-dextran 40 (CMD40) were introduced into a one-pot solvothermal method to synthesize magnetic nanoparticles. TEM, the 4-(bromomethyl)-6,7-dimethoxy coumarin (BMMC) absorption assay, and the Bradford method were employed to characterize the diameter, carboxyl content, and protein immobilization ability of the nanoparticles, respectively. The findings revealed that CMD40-modified magnetic nanoparticles (CMD40-MNPs) exhibited the highest carboxyl content and streptavidin (SA) immobilization content, reaching 6.5 × 10-7 mol/mg and 375 µg/mg, respectively. In contrast, CMC-modified magnetic nanoparticles displayed opposite trends. This is primarily attributed to dextran's unique molecular structure, which enhances its water solubility and biocompatibility, thereby facilitating contact with Fe3O4 nanoparticles in aqueous solutions. CMD40-MNPs possess a saturation magnetization value of 60.90 emu/g and can be collected within (60 ± 5) s using a standard magnetic separator. Cytotoxicity assays demonstrated that CMD40-MNPs are nontoxic to cells. A cell sorting strategy utilizing the binding of SA-CMD40-MNPs and biotin antihuman CD3 antibody-modified cell suspensions was employed to isolate CD3+T cells. The results indicate that the purity and efficiency of targeted CD3+T cells are 85.2% and 61.5%, respectively.

20.
Inorg Chem ; 63(28): 13059-13067, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38937959

RESUMEN

Type I photosensitizers offer an advantage in photodynamic therapy (PDT) due to their diminished reliance on oxygen levels, thus circumventing the challenge of hypoxia commonly encountered in PDT. In this study, we present the synthesis and comprehensive characterization of a novel type I photosensitizer derived from a cyclometalated Ir(III)-rhodamine complex. Remarkably, the complex exhibits a shift in absorption and fluorescence, transitioning from "off" to "on" states in aprotic and protic solvents, respectively, contrary to initial expectations. Upon exposure to light, the complex demonstrates the effective generation of O2- and ·OH radicals via the type I mechanism. Additionally, it exhibits notable photodynamic antibacterial activity against both Gram-positive and Gram-negative bacteria, demonstrated through in vitro and in vivo experiments. This research offers valuable insights for the development of novel type I photosensitizers.


Asunto(s)
Antibacterianos , Bacterias Gramnegativas , Bacterias Grampositivas , Iridio , Pruebas de Sensibilidad Microbiana , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rodaminas , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Bacterias Gramnegativas/efectos de los fármacos , Rodaminas/química , Rodaminas/farmacología , Iridio/química , Iridio/farmacología , Bacterias Grampositivas/efectos de los fármacos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Animales , Rayos Infrarrojos , Estructura Molecular , Ratones
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