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1.
Nat Commun ; 15(1): 3925, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724512

RESUMO

Achieving a simple yet sustainable printing technique with minimal instruments and energy remains challenging. Here, a facile and sustainable 3D printing technique is developed by utilizing a reversible salting-out effect. The salting-out effect induced by aqueous salt solutions lowers the phase transition temperature of poly(N-isopropylacrylamide) (PNIPAM) solutions to below 10 °C. It enables the spontaneous and instant formation of physical crosslinks within PNIPAM chains at room temperature, thus allowing the PNIPAM solution to solidify upon contact with a salt solution. The PNIPAM solutions are extrudable through needles and can immediately solidify by salt ions, preserving printed structures, without rheological modifiers, chemical crosslinkers, and additional post-processing steps/equipment. The reversible physical crosslinking and de-crosslinking of the polymer through the salting-out effect demonstrate the recyclability of the polymeric ink. This printing approach extends to various PNIPAM-based composite solutions incorporating functional materials or other polymers, which offers great potential for developing water-soluble disposable electronic circuits, carriers for delivering small materials, and smart actuators.

2.
J Am Chem Soc ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768128

RESUMO

Chiral Pb-free metal-halide semiconductors (MHSs) have attracted considerable attention in the field of spintronics due to various interesting spin-related properties and chiral-induced spin selectivity (CISS) effect. Despite their excellent chemical and structural tunability, the material scope and crystal structure of Pb-free chiral MHSs exhibiting the CISS effect are still limited; chiral MHSs that have metal-halide structures of octahedra and tetrahedra are only reported. Here, we report a new class of chiral MHSs, of which palladium (Pd)-halides are formed in 1D square-pyramidal structures or 0D square-planar structures, with a general formula of ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x (MBA = methylbenzylammonium; x = 0, 0.25, 0.5, 0.75, and 1) for the first time. The crystals adopt the 1D helical chain of Pd-halide square-pyramid (for x = 0, 0.25, 0.5, and 0.75) and 0D structure of Pd-halide square-plane (for x = 1). All the Pd-halides are distorted by the interaction between the halide and the chiral organic ammonium and arranged in a noncentrosymmetric position. Circular dichroism (CD) for ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x indicates that chirality was transferred from chiral organic ammonium to Pd-halide inorganics. ((R-MBA)2PdBr4)1-x((R-MBA)2PdCl4)x (x = 0, 0.25, 0.5, and 0.75) shows a distortion index of 0.127-0.128, which is the highest value among the previously reported chiral MHSs to the best of our knowledge. We also find that (R/S-MBA)2Pd(Br1-xClx)4 crystals grow along the out-of-plane direction during spin coating and have high c-axis orientation and crystallinity, and (R/S-MBA)2Pd(Br1-xClx)4 (x = 0 and 0.5) crystals exhibit a CISS effect in polycrystalline bulk films. These results demonstrate the possibility of a new metal-halide series with square-planar structures or square-pyramidal structures for future spintronic applications.

3.
Dev Cell ; 59(9): 1210-1230.e9, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38569548

RESUMO

The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes. We discovered a glutamate receptor subunit required for basal neurotransmission and homeostasis at the larval neuromuscular junction. We describe larval glia and endorse the general view that glia perform consistent activities throughout development. This census represents an extensive resource and a powerful platform for future discoveries of cellular and molecular mechanisms in repair, regeneration, plasticity, homeostasis, and behavioral coordination.


Assuntos
Drosophila melanogaster , Larva , Neurônios Motores , Animais , Larva/genética , Larva/metabolismo , Neurônios Motores/metabolismo , Neurônios Motores/citologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Neuroglia/metabolismo , Neuroglia/citologia , Junção Neuromuscular/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , RNA-Seq/métodos , Análise da Expressão Gênica de Célula Única
4.
Exp Mol Med ; 56(1): 235-249, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38253797

RESUMO

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.


Assuntos
Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Animais , Humanos , Camundongos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Apoptose/genética , Citocromo-B(5) Redutase/metabolismo , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
5.
Adv Mater ; 36(7): e2309518, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38014492

RESUMO

Natural sharkskin features staggered-overlapped and multilayered architectures of riblet-textured anisotropic microdenticles, exhibiting drag reduction and providing a flexible yet strong armor. However, the artificial fabrication of three-dimensional (3D) sharkskin with these unique functionalities and mechanical integrity is a challenge using conventional techniques. In this study, it is reported on the facile microfabrication of multilayered 3D sharkskin through the magnetic actuation of polymeric composites and subsequent chemical shape fixation by casting thin polymeric films. The fabricated hydrophobic sharkskin, with geometric symmetry breaking, achieves anisotropic drag reduction in frontal and backward flow directions against the riblet-textured microdenticles. For mechanical integrity, hard-on-soft multilayered mechanical properties are realized by coating the polymeric sharkskin with thin layers of zinc oxide and platinum, which have higher hardness and recovery behaviors than the polymer. This multilayered hard-on-soft sharkskin exhibits friction anisotropy, mechanical robustness, and structural recovery. Furthermore, coating the MXene nanosheets provides the fabricated sharkskin with a low electrical resistance of ≈5.3 Ω, which leads to high Joule heating (≈229.9 °C at 2.75 V). The proposed magnetomechanical actuation-assisted microfabrication strategy is expected to facilitate the development of devices requiring multifunctional microtextures.

6.
Mater Horiz ; 10(11): 4892-4902, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37712182

RESUMO

Two-dimensional Ti3C2Tx MXenes are promising candidates for a wide range of film- or fiber-based devices owing to their solution processability, high electrical conductivity, and versatile surface chemistry. The surface terminal groups (Tx) of MXenes can be removed to increase their inherent electrical performance and ensure chemical stability. Therefore, understanding the chemical evolution during the removal of the terminal groups is crucial for guiding the production, processing, and application of MXenes. Herein, we investigate the effect of chemical modification on the electron-transfer behavior during the removal of the terminal groups by annealing Ti3C2Tx MXene single sheets under argon (Ar-MXene) and ammonia gas (NH3-MXene) conditions. Annealing in ammonia gas results in surface nitridation of MXenes and preserves the electron-abundant Ti3C2 structure, whereas annealing MXene single sheets in Ar gas results in the oxidation of the titanium layers. The surface-nitrided MXene film exhibits an electrical conductivity two times higher than that of the Ar-MXene film. The oxidation stability is quantified by calculating the oxidation rate constants for severe reactions with H2O2. The surface-nitrided MXene is 13 times more stable than Ar-MXene. The investigation of MXene single sheets provides fundamental insights that are valuable for designing electrically conductive and chemically stable MXenes.

7.
Cell Death Dis ; 14(8): 567, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633973

RESUMO

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Ferroptose/genética , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Neoplasias Pulmonares/genética , Fator 2 Relacionado a NF-E2/genética
8.
Small ; 19(44): e2301077, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37401792

RESUMO

A Joule heater made of emerging 2D nanosheets, i.e., MXene, has the advantage of low-voltage operation with stable heat generation owing to its highly conductive and uniformly layered structure. However, the self-heated MXene sheets easily get oxidized in warm and moist environments, which limits their intrinsic heating efficiencies. Herein, an ultrathin graphene skin is introduced as a surface-regulative coating on MXene to enhance its oxidative stability and Joule heating efficiency. The skin layer is deposited on MXene using a scalable solution-phased layer-by-layer assembly process without deteriorating the excellent electrical conductivity of the MXene. The graphene skin comprises narrow and hydrophobic channels, which results in ≈70 times higher water impermeability of the hybrid film of graphene and MXene (GMX) than that of the pristine MXene. A complementary electrochemical analysis confirms that the graphene skin facilitates longer-lasting protection than conventional polymer coatings owing to its tortuous pathways. In addition, the sp2 planar carbon surface with a low heat loss coefficient improves the heating efficiency of the GMX, indicating that this strategy is promising for developing adaptive heating materials with a tractable voltage range and high Joule heating efficiency.

9.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047042

RESUMO

Nitroreductase (NTR) has the ability to activate nitro group-containing prodrugs and decompose explosives; thus, the evaluation of NTR activity is specifically important in pharmaceutical and environmental areas. Numerous studies have verified effective fluorescent methods to detect and image NTR activity; however, near-infrared (NIR) fluorescence probes for biological applications are lacking. Thus, in this study, we synthesized novel NIR probes (NIR-HCy-NO2 1-3) by introducing a nitro group to the hemicyanine skeleton to obtain fluorescence images of NTR activity. Additionally, this study was also designed to propose a different water solubility and investigate the catalytic efficiency of NTR. NIR-HCy-NO2 inherently exhibited a low fluorescence background due to the interference of intramolecular charge transfer (ICT) by the nitro group. The conversion from the nitro to amine group by NTR induced a change in the absorbance spectra and lead to the intense enhancement of the fluorescence spectra. When assessing the catalytic efficiency and the limit of detection (LOD), including NTR activity imaging, it was demonstrated that NIR-HCy-NO2 1 was superior to the other two probes. Moreover, we found that NIR-HCy-NO2 1 reacted with type I mitochondrial NTR in live cell imaging. Conclusively, NIR-HCy-NO2 demonstrated a great potential for application in various NTR-related fields, including NTR activity for cell imaging in vivo.


Assuntos
Corantes Fluorescentes , Dióxido de Nitrogênio , Corantes Fluorescentes/farmacologia , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Nitrorredutases/metabolismo
10.
Nanoscale ; 15(17): 7710-7714, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37051888

RESUMO

Heterostructures of metal halide perovskites and TiOx are efficient photocatalytic materials owing to the combination of the advantages of each compound, specifically the high absorption coefficients and long charge-carrier lifetimes of perovskites, and efficient photocatalytic activity of TiOx. However, chemical reduction of CO2 using PNC/TiOx heterostructures without organic solvents has not been reported yet. Here, we report the first solvent-free reduction of CO2 using amorphous TiOx with embedded colloidal perovskite nanocrystals (PNCs). The combination was obtained by carrying out hydrolysis of titanium butoxide (TBOT) on the PNC surface without high-temperature calcination. We proposed a mechanism involving photoexcited electrons being transferred from PNCs to TBOT, enabling photocatalytic reactions using TiOx under visible-light excitation. We demonstrated efficient visible-light-driven photocatalytic reactions at PNC/TiOx interfaces, specifically with a CO production rate of 30.43 µmol g-1 h-1 and accelerated degradation of organic pollutants under natural sunlight. Our work has provided a simple path toward both efficient CO2 reduction and photocatalytic degradation of organic dyes.

11.
Langmuir ; 39(6): 2358-2367, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36734137

RESUMO

Surface modification to improve the oxidation stability and dispersibility of MXene in diverse organic media is a facile strategy for broadening its application. Among the various ligands that can be grafted on the MXene surface, oleylamine (OAm), with amine functionalities, is an advantageous candidate owing to its strong interactions and commercial viability. OAms are grafted onto MXene through covalent bonds induced by nucleophilic reactions and H bonds in liquid interface reactions at room temperature. In addition, this grafting behavior of the ligand was characterized by a reduction in the slope with an increase in the ligand concentration (Cl), confirming that the OAms were grafted via Langmuir-like behavior, and the monolayer of OAms was developed via two distinct steps (I: lying-down phase; II: ordered monolayer). MXene nanosheets modified by OAm (OAm-MX) are highly dispersible in a wide range of organic solvents owing to the alkyl chain of the OAms, which induces hydrophobic properties on the surface of MXene. The OAm-MX dispersion exhibits outstanding oxidation and dispersion stability and remarkable coating performance on a wide range of substrates owing to their excellent solution processability. Therefore, this study provides fundamental insights into the adsorption behavior and interaction between amine ligands and MXene nanosheets for the surface chemistry of MXene.

12.
Adv Mater ; 35(43): e2207454, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36300804

RESUMO

This review outlines problems and progress in development of solution-processed organic light-emitting diodes (SOLEDs) in industry and academia. Solution processing has several advantages such as low consumption of materials, low-cost processing, and large-area manufacturing. However, use of a solution process entails complications, such as the need for solvent resistivity and solution-processable materials, and yields SOLEDs that have limited luminous efficiency, severe roll-off characteristics, and short lifetime compared to OLEDs fabricated using thermal evaporation. These demerits impede production of practical SOLED displays. This review outlines the industrial demands for commercial SOLEDs and the current status of SOLED development in industries and academia, and presents research guidelines for the development of SOLEDs that have high efficiency, long lifetime, and good processability to achieve commercialization.

13.
Ecotoxicol Environ Saf ; 248: 114334, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36442398

RESUMO

Owing to their unique properties and biological activities, ionic liquids (ILs) have attracted research interest in pharmaceutics and medicine. Hypoxia-inducible factor (HIF)- 1α is an attractive cancer drug target involved in cancer malignancy in the hypoxic tumor microenvironment. Herein, we report the inhibitory activity of ILs on the HIF-1α pathway and their mechanism of action. Substitution of a dimethylamino group on pyridinium reduced hypoxia-induced HIF-1α activation. It selectively inhibited the viability of the human colon cancer cell line HCT116, compared to that of the normal fibroblast cell line WI-38. These activities were enhanced by increasing the alkyl chain length in the pyridinium. Under hypoxic conditions, dimethylaminopyridinium reduced the accumulation of HIF-1α and its target genes without affecting the HIF1A mRNA level in cancer cells. It suppressed the oxygen consumption rate and ATP production by directly inhibiting electron transfer chain complex I, which led to enhanced intracellular oxygen content and oxygen-dependent degradation of HIF-1α under hypoxia. These results indicate that dimethylaminopyridinium suppresses the mitochondria and HIF-1α-dependent glucose metabolic pathway in hypoxic cancer cells. This study provides insights into the anticancer activity of pyridinium-based ILs through the regulation of cancer metabolism, making them promising candidates for cancer treatment.


Assuntos
Neoplasias do Colo , Líquidos Iônicos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Líquidos Iônicos/toxicidade , Hipóxia , Oxigênio , Microambiente Tumoral
14.
Nat Mater ; 21(12): 1396-1402, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36396958

RESUMO

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

15.
Polymers (Basel) ; 14(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36297931

RESUMO

Increased demand for plastics leads to a large amount of plastic manufacturing, which is accompanied by inappropriate disposal of plastics. The by-products of these waste plastics are microplastics (MPs; less than 5 nm in size), which are produced because of various environmental and physicochemical factors, posing hazardous effects to the ecosystem, such as the death of marine organisms due to the swallowing of plastic specks of no nutritional value. Therefore, the collection, preparation, identification, and recycling of these microsized plastics have become imperative. The pretreatment of MPs requires numerous chemical agents comprising strong acids, bases, and oxidizing agents. However, there is limited research on the chemical resistance of various MPs to these substances to date. In this study, the chemical resistance of five species of MPs (high-density polyethylene, low-density polyethylene, polystyrene, polyethylene terephthalate, and polypropylene) to sulfuric acid, hydrochloric acid, hydrogen peroxide, potassium hydroxide, and sodium hydroxide was studied. The MPs were reacted with these chemical reagents at preset temperatures and durations, and variations in morphology and chemical structures were detected when the MPs were reacted with mineral acids, such as sulfuric acid. The data pertaining to these changes in MP properties could be a significant reference for future studies on MP pretreatment with strong acids, bases, and oxidizing agents.

16.
ACS Appl Mater Interfaces ; 14(26): 29867-29877, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35758035

RESUMO

Graphene-based fiber-shaped supercapacitors (FSSCs) have received considerable attention as potential wearable energy storage devices owing to their simple operating mechanism, flexibility, and long-term stability. To date, energy storage capacities of supercapacitors have been significantly improved via strategies such as heteroatom doping and the incorporation of pseudocapacitive metal oxides. Herein, we develop a novel and scalable direct-hybridization method that combines heteroatom doping and metal oxide hybridization for the fabrication of high-performance FSSCs. Using porous and highly conductive nitrogen and sulfur co-doped graphene fibers (NS-GFs) as self-heating units, we successfully convert ruthenium hydroxide anchored to the surface into ruthenium oxide nanoparticles after programmed sub-second electrothermal annealing without structural damage of the fibers. The resulting fibers show an increased gravimetric capacitance of 68.88 F g-1 compared to that of the pristine NS-GF (8.32 F g-1), excellent cyclic stability maintaining 96.67% of the initial capacitance after 20 000 continuous charging/discharging cycles, and good mechanical flexibility. The findings of this work advocate a successful Joule heating strategy for preparing high-performance graphene-based metal oxide hybrid FSSCs for use in energy storage applications.

17.
Biomed Pharmacother ; 146: 112500, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34891118

RESUMO

Hypoxia inducible factor (HIF)-1α is an important transcription factor regulating cancer metabolism in hypoxic environment. Capsaicin is known to inhibit hypoxia-induced HIF activity in lung cancer. Hence, in this study we tried to elucidate its inhibitory mechanism of action. In lung cancer cells, including H1299, H23, A549, and H2009 cells, capsaicin inhibited cell growth and HIF activation. Under hypoxic conditions, capsaicin reduced the accumulation of HIF-1α protein and the expression of its target genes, including pyruvate dehydrogenase kinase 1 (PDK1) and glucose transporter 1 (GLUT1), with no effect on overall HIF-1α mRNA levels in the H1299 cells. In addition, capsaicin increased intracellular oxygen levels by suppressing mitochondrial respiration, resulting in a reduction of HIF-1α accumulation. Furthermore, mitochondrial ATP production was reduced by capsaicin through the inhibition of mitochondrial respiration in the H1299, H23, A549, and H2009 cells. These results indicate that capsaicin potentially exhibits anticancer therapeutic effects in lung cancer under hypoxic conditions.


Assuntos
Capsaicina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/efeitos dos fármacos , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Transportador de Glucose Tipo 1/efeitos dos fármacos , Humanos
18.
BMB Rep ; 54(12): 620-625, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34814975

RESUMO

Microglia are known to be activated in the hypothalamic paraventricular nucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticity of presympathetic PVN neurons associated with the modulation of sympathetic outflow remains poorly investigated. In this study, we analyzed the direct link between microglial activation and spontaneous firing rate along with the underlying synaptic mechanisms in PVN neurons projecting to the rostral ventrolateral medulla (RVLM). Systemic injection of LPS induced microglial activation in the PVN, increased the frequency of spontaneous firing activity of PVN-RVLM neurons, reduced GABAergic inputs into these neurons, and increased plasma NE levels and heart rate. Systemic minocycline injection blocked all the observed LPS-induced effects. Our results indicate that LPS increases the firing rate and decreases GABAergic transmission in PVN-RVLM neurons associated with sympathetic outflow and the alteration is largely attributed to the activation of microglia. Our findings provide some insights into the role of microglial activation in regulating the activity of PVN-RVLM neurons associated with modulation of sympathetic outflow in cardiovascular diseases. [BMB Reports 2021; 54(12): 620-625].


Assuntos
Microglia , Núcleo Hipotalâmico Paraventricular , Animais , Lipopolissacarídeos/farmacologia , Vias Neurais/fisiologia , Neurônios , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Sprague-Dawley
19.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34799448

RESUMO

Circadian transcriptional timekeepers in pacemaker neurons drive profound daily rhythms in sleep and wake. Here we reveal a molecular pathway that links core transcriptional oscillators to neuronal and behavioral rhythms. Using two independent genetic screens, we identified mutants of Transport and Golgi organization 10 (Tango10) with poor behavioral rhythmicity. Tango10 expression in pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) is required for robust rhythms. Loss of Tango10 results in elevated PDF accumulation in nerve terminals even in mutants lacking a functional core clock. TANGO10 protein itself is rhythmically expressed in PDF terminals. Mass spectrometry of TANGO10 complexes reveals interactions with the E3 ubiquitin ligase CULLIN 3 (CUL3). CUL3 depletion phenocopies Tango10 mutant effects on PDF even in the absence of the core clock gene timeless Patch clamp electrophysiology in Tango10 mutant neurons demonstrates elevated spontaneous firing potentially due to reduced voltage-gated Shaker-like potassium currents. We propose that Tango10/Cul3 transduces molecular oscillations from the core clock to neuropeptide release important for behavioral rhythms.


Assuntos
Relógios Circadianos/fisiologia , Proteínas de Drosophila/metabolismo , Neuropeptídeos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Proteínas Culina/genética , Proteínas Culina/metabolismo , Drosophila , Proteínas de Drosophila/genética , Neurônios/metabolismo , Neuropeptídeos/genética , Proteômica , Sono
20.
Can J Anaesth ; 68(11): 1651-1658, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34405354

RESUMO

PURPOSE: Breaking of disposable blades during emergency endotracheal intubation has been reported. Breakage can cause serious injury and foreign body ingestion. We aimed to measure and analyze the strength characteristics of different disposable videolaryngoscope blades with the application of an upward-lifting force. METHODS: We measured the strength of four disposable videolaryngoscope blades (C-Mac® S Video laryngoscope MAC #3, Glidescope GVL® 3 stat, Pentax AWS® PBlade TL type, and King Vision® aBlade #3) using the fracture test. The strength of 12 samples of each type of disposable videolaryngoscope blade was measured using an Instron 5,966 tensile tester by applying an upward-lifting force. RESULTS: After the fracture test using C-Mac, Glidescope GVL, Pentax AWS, and King Vision, the number of deformed blades were 0, 12, 3, and 7, respectively, and the number of broken blades were 12, 0, 9, and 5, respectively. The mean (standard deviation) maximum force strengths of Pentax AWS, C-Mac, King Vision, and Glidescope GVL blades were 408.4 (27.4) N, 325.8 (26.5) N, 291.8 (39.3) N, and 262.7 (3.8) N, respectively (P < 0.001). CONCLUSION: Clinicians should be aware of the varied strength characteristics of the four types of disposable videolaryngoscope blades when they are used in endotracheal intubation.


RéSUMé: OBJECTIF: Des bris des lames jetables pendant l'intubation endotrachéale d'urgence ont été rapportés. Un bris peut causer des blessures graves et l'ingestion de corps étrangers. Nous avons cherché à mesurer et à analyser les caractéristiques de résistance de différentes lames de vidéolaryngoscope jetables en appliquant une force de traction vers le haut. MéTHODE: Nous avons mesuré la résistance de quatre lames de vidéolaryngoscope jetables (C-Mac® S Video laryngoscope MAC #3, Glidescope GVL® 3 stat, Pentax AWS® type PBlade TL, et King Vision® aBlade #3) en utilisant un test de rupture. La résistance de 12 échantillons de chaque type de lame de vidéolaryngoscope jetable a été mesurée à l'aide d'un dynamomètre Instron 5,966 en appliquant une force de traction vers le haut. RéSULTATS: Après le test de rupture sur les lames C-Mac, Glidescope GVL, Pentax AWS et King Vision, le nombre de lames déformées était de 0, 12, 3 et 7, respectivement, et le nombre de lames brisées était de 12, 0, 9 et 5, respectivement. Les forces de résistance maximales moyennes (écart type) des lames Pentax AWS, C-Mac, King Vision et Glidescope GVL étaient de 408,4 (27,4) N, 325,8 (26,5) N, 291,8 (39,3) N et 262,7 (3,8) N, respectivement (P < 0,001). CONCLUSION: Les cliniciens devraient être conscients des variations dans les caractéristiques de résistance de ces quatre types de lames de vidéolaryngoscope jetables lors de leur utilisation pour l'intubation endotrachéale.


Assuntos
Laringoscópios , Serviço Hospitalar de Emergência , Humanos , Intubação Intratraqueal , Laringoscopia , Gravação em Vídeo
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