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1.
Nature ; 625(7993): 60-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38172363

RESUMO

Semiconducting graphene plays an important part in graphene nanoelectronics because of the lack of an intrinsic bandgap in graphene1. In the past two decades, attempts to modify the bandgap either by quantum confinement or by chemical functionalization failed to produce viable semiconducting graphene. Here we demonstrate that semiconducting epigraphene (SEG) on single-crystal silicon carbide substrates has a band gap of 0.6 eV and room temperature mobilities exceeding 5,000 cm2 V-1 s-1, which is 10 times larger than that of silicon and 20 times larger than that of the other two-dimensional semiconductors. It is well known that when silicon evaporates from silicon carbide crystal surfaces, the carbon-rich surface crystallizes to produce graphene multilayers2. The first graphitic layer to form on the silicon-terminated face of SiC is an insulating epigraphene layer that is partially covalently bonded to the SiC surface3. Spectroscopic measurements of this buffer layer4 demonstrated semiconducting signatures4, but the mobilities of this layer were limited because of disorder5. Here we demonstrate a quasi-equilibrium annealing method that produces SEG (that is, a well-ordered buffer layer) on macroscopic atomically flat terraces. The SEG lattice is aligned with the SiC substrate. It is chemically, mechanically and thermally robust and can be patterned and seamlessly connected to semimetallic epigraphene using conventional semiconductor fabrication techniques. These essential properties make SEG suitable for nanoelectronics.

2.
Nature ; 611(7937): 762-768, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36352228

RESUMO

The canonical model of striatal function predicts that animal locomotion is associated with the opposing regulation of protein kinase A (PKA) in direct and indirect pathway striatal spiny projection neurons (SPNs) by dopamine1-7. However, the precise dynamics of PKA in dorsolateral SPNs during locomotion remain to be determined. It is also unclear whether other neuromodulators are involved. Here we show that PKA activity in both types of SPNs is essential for normal locomotion. Using two-photon fluorescence lifetime imaging8-10 of a PKA sensor10 through gradient index lenses, we measured PKA activity within individual SPNs of the mouse dorsolateral striatum during locomotion. Consistent with the canonical view, dopamine activated PKA activity in direct pathway SPNs during locomotion through the dopamine D1 receptor. However, indirect pathway SPNs exhibited a greater increase in PKA activity, which was largely abolished through the blockade of adenosine A2A receptors. In agreement with these results, fibre photometry measurements of an adenosine sensor11 revealed an acute increase in extracellular adenosine during locomotion. Functionally, antagonism of dopamine or adenosine receptors resulted in distinct changes in SPN PKA activity, neuronal activity and locomotion. Together, our results suggest that acute adenosine accumulation interplays with dopamine release to orchestrate PKA activity in SPNs and proper striatal function during animal locomotion.


Assuntos
Adenosina , Corpo Estriado , Proteínas Quinases Dependentes de AMP Cíclico , Dopamina , Locomoção , Neurônios , Animais , Camundongos , Adenosina/metabolismo , Corpo Estriado/citologia , Corpo Estriado/enzimologia , Corpo Estriado/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dopamina/metabolismo , Locomoção/fisiologia , Neurônios/enzimologia , Neurônios/metabolismo , Receptores de Dopamina D1/metabolismo , Receptor A2A de Adenosina/metabolismo
3.
Proc Natl Acad Sci U S A ; 121(10): e2317026121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38408250

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.


Assuntos
COVID-19 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Peptidil Dipeptidase A/metabolismo , Ligação Proteica , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Nano Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607185

RESUMO

The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.

5.
BMC Plant Biol ; 24(1): 565, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879490

RESUMO

BACKGROUND: AP2/ERF is a large family of plant transcription factor proteins that play essential roles in signal transduction, plant growth and development, and responses to various stresses. The AP2/ERF family has been identified and verified by functional analysis in various plants, but so far there has been no comprehensive study of these factors in Chinese prickly ash. Phylogenetic, motif, and functional analyses combined with transcriptome analysis of Chinese prickly ash fruits at different developmental stages (30, 60, and 90 days after anthesis) were conducted in this study. RESULTS: The analysis identified 146 ZbAP2/ERF genes that could be classified into 15 subgroups. The motif analysis revealed the presence of different motifs or elements in each group that may explain the functional differences between the groups. ZbERF13.2, ZbRAP2-12, and ZbERF2.1 showed high levels of expression in the early stages of fruit development. ZbRAP2-4, and ZbERF3.1 were significantly expressed at the fruit coloring stage (R2 and G2). ZbERF16 were significantly expressed at fruit ripening and expression level increased as the fruit continued to develop. Relative gene expression levels of 6 representative ZbAP2/ERFs assessed by RT-qPCR agreed with transcriptome analysis results. CONCLUSIONS: These genes identified by screening can be used as candidate genes that affect fruit development. The results of the analysis can help guide future genetic improvement of Chinese prickly ash and enrich our understanding of AP2/ERF transcription factors and their regulatory functions in plants.


Assuntos
Frutas , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Fatores de Transcrição , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Genoma de Planta , Genes de Plantas , População do Leste Asiático
6.
Bioinformatics ; 39(8)2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37505461

RESUMO

MOTIVATION: Cell membrane segmentation in electron microscopy (EM) images is a crucial step in EM image processing. However, while popular approaches have achieved performance comparable to that of humans on low-resolution EM datasets, they have shown limited success when applied to high-resolution EM datasets. The human visual system, on the other hand, displays consistently excellent performance on both low and high resolutions. To better understand this limitation, we conducted eye movement and perceptual consistency experiments. Our data showed that human observers are more sensitive to the structure of the membrane while tolerating misalignment, contrary to commonly used evaluation criteria. Additionally, our results indicated that the human visual system processes images in both global-local and coarse-to-fine manners. RESULTS: Based on these observations, we propose a computational framework for membrane segmentation that incorporates these characteristics of human perception. This framework includes a novel evaluation metric, the perceptual Hausdorff distance (PHD), and an end-to-end network called the PHD-guided segmentation network (PS-Net) that is trained using adaptively tuned PHD loss functions and a multiscale architecture. Our subjective experiments showed that the PHD metric is more consistent with human perception than other criteria, and our proposed PS-Net outperformed state-of-the-art methods on both low- and high-resolution EM image datasets as well as other natural image datasets. AVAILABILITY AND IMPLEMENTATION: The code and dataset can be found at https://github.com/EmmaSRH/PS-Net.


Assuntos
Processamento de Imagem Assistida por Computador , Percepção , Humanos , Membrana Celular , Microscopia Eletrônica
7.
Magn Reson Med ; 91(3): 1149-1164, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37929695

RESUMO

PURPOSE: Preclinical MR fingerprinting (MRF) suffers from long acquisition time for organ-level coverage due to demanding image resolution and limited undersampling capacity. This study aims to develop a deep learning-assisted fast MRF framework for sub-millimeter T1 and T2 mapping of entire macaque brain on a preclinical 9.4 T MR system. METHODS: Three dimensional MRF images were reconstructed by singular value decomposition (SVD) compressed reconstruction. T1 and T2 mapping for each axial slice exploited a self-attention assisted residual U-Net to suppress aliasing-induced quantification errors, and the transmit-field (B1 + ) measurements for robustness against B1 + inhomogeneity. Supervised network training used MRF images simulated via virtual parametric maps and a desired undersampling scheme. This strategy bypassed the difficulties of acquiring fully sampled preclinical MRF data to guide network training. The proposed fast MRF framework was tested on experimental data acquired from ex vivo and in vivo macaque brains. RESULTS: The trained network showed reasonable adaptability to experimental MRF images, enabling robust delineation of various T1 and T2 distributions in the brain tissues. Further, the proposed MRF framework outperformed several existing fast MRF methods in handling the aliasing artifacts and capturing detailed cerebral structures in the mapping results. Parametric mapping of entire macaque brain at nominal resolution of 0.35 × $$ \times $$ 0.35 × $$ \times $$ 1 mm3 can be realized via a 20-min 3D MRF scan, which was sixfold faster than the baseline protocol. CONCLUSION: Introducing deep learning to MRF framework paves the way for efficient organ-level high-resolution quantitative MRI in preclinical applications.


Assuntos
Aprendizado Profundo , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodos
8.
Microb Pathog ; 190: 106629, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522492

RESUMO

Blastocystis sp. is a protozoan parasite that infects the intestines of humans and animals, causing chronic diseases such as skin rashes, abdominal pain, and irritable bowel syndrome. A survey was conducted to determine the prevalence and genetic diversity of Blastocystis sp. infection in cattle, in Hebei Province, China. 2746 cattle fecal samples were collected from 11 cities in Hebei Province and analyzed using polymerase chain reaction targeting the Blastocystis sp. barcoding gene. MEGA, PhyloSuite, and PopART were used to analyze the subtype, sequence signature, pairwise genetic distance, and genetic diversity indices. The results showed that the Blastocystis sp. detection rate was 12.60% (346/2746). The infection rate in different herds was affected by region, age, breeding mode, and variety; that is, the infection rates in areas of southern Hebei, cattle under one year old, intensive raising, and dairy cattle were higher than the infection rates in northern Hebei, cattle over one year old, scatter feeding, and beef cattle. Seven Blastocystis subtypes were identified, namely, ST1, ST2, ST5, ST10, ST14, ST21, and ST26; ST10 was the dominant subtype, and ST14 was the second most common subtype. A total of 374 polymorphic and conserved sites were obtained, including 273 invariable (monomorphic) sites and 101 variable (polymorphic) sites, accounting for 27.01% of all nucleotides. The nucleotide diversity index (Pi) was 0.07749, and the haplotype (gene) diversity index (Hd) was 0.946. This study provides the first comprehensive information on the epidemiological situation of Blastocystis sp. infection in cattle from Hebei Province, China, and revealed rich genetic diversity of Blastocystis sp.


Assuntos
Infecções por Blastocystis , Blastocystis , Doenças dos Bovinos , Fezes , Variação Genética , Filogenia , Animais , Bovinos , Blastocystis/genética , Blastocystis/classificação , Blastocystis/isolamento & purificação , China/epidemiologia , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/parasitologia , Infecções por Blastocystis/veterinária , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/epidemiologia , Fezes/parasitologia , Prevalência , DNA de Protozoário/genética , Genótipo , Reação em Cadeia da Polimerase
9.
Cancer Cell Int ; 24(1): 198, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835077

RESUMO

Translationally controlled tumor protein (TCTP), also known as histamine-releasing factor (HRF) or fortilin, is a highly conserved protein found in various species. To date, multiple studies have demonstrated the crucial role of TCTP in a wide range of cellular pathophysiological processes, including cell proliferation and survival, cell cycle regulation, cell death, as well as cell migration and movement, all of which are major pathogenic mechanisms of tumorigenesis and development. This review aims to provide an in-depth analysis of the functional role of TCTP in tumor initiation and progression, with a particular focus on cell proliferation, cell death, and cell migration. It will highlight the expression and pathological implications of TCTP in various tumor types, summarizing the current prevailing therapeutic strategies that target TCTP.

10.
Stress ; 27(1): 2357338, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38807493

RESUMO

Virtual reality based physical stress (VRPS) paradigms could eliminate the influence of social factors on participants, and it may be a desirable tool to explore the impact of personality traits on stress levels. In this study, we attempt to explore the effects of VRPS on stress response among individuals with different personality traits. Forty male participants with an average age of 22.79 ± 0.41 years were divided into two groups based on Harm Avoidance (HA) scores of Tridimensional Personality Questionnaire (TPQ), referred to as the Low-HA group and the High-HA group. The stress levels of the participants were assessed using salivary α-amylase (sAA) activity and heart rate variability (HRV) indices pre- and post-stress. The influence of personality traits on stress response among different groups was analyzed. VRPS significantly affected the sAA activity and HRV indicators of both groups. During and after stress, there were significant differences in sAA activity and HRV indicators between the two groups. The sAA levels and HRV indices of the Low-HA group were lower than those of the High-HA group. Furthermore, sAA levels and HRV indices were correlated with the scores of TPQ. VRPS scenarios elicit different stress responses on individuals with different harm avoidance personality traits. Stress evaluation based on VR scenarios presents potential in personality trait assessments, particularly for distinguishing between individuals with low and high HA tendencies.


Assuntos
Frequência Cardíaca , Personalidade , alfa-Amilases Salivares , Estresse Psicológico , Realidade Virtual , Humanos , Masculino , Personalidade/fisiologia , Frequência Cardíaca/fisiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Adulto Jovem , alfa-Amilases Salivares/metabolismo , alfa-Amilases Salivares/análise , Saliva/química , Adulto , Estresse Fisiológico/fisiologia , Inquéritos e Questionários , Redução do Dano
11.
Neurochem Res ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935224

RESUMO

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

12.
PLoS Biol ; 19(8): e3001348, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34351905

RESUMO

Beige fat dissipates energy and functions as a defense against cold and obesity, but the mechanism for its development is unclear. We found that interleukin (IL)-25 signaling through its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue after cold exposure and ß3-adrenoceptor agonist stimulation. IL-25 induced beige fat formation in white adipose tissue (WAT) by releasing IL-4 and IL-13 and promoting alternative activation of macrophages that regulate innervation and up-regulate tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine (NE). Blockade of IL-4Rα or depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the beige fat formation in WAT. Mice fed with a high-fat diet (HFD) were protected from obesity and related metabolic disorders when given IL-25 through a process that involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling in WAT may have therapeutic potential for controlling obesity and its associated metabolic disorders.


Assuntos
Adipócitos Bege/fisiologia , Tecido Adiposo Bege/crescimento & desenvolvimento , Resistência à Insulina , Interleucinas/metabolismo , Macrófagos/fisiologia , Agonistas de Receptores Adrenérgicos beta 3 , Animais , Temperatura Baixa , Homeostase , Interleucina-4/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Proteína Desacopladora 1/fisiologia
13.
Protein Expr Purif ; 215: 106392, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37952787

RESUMO

Cluster of differentiation 20 (CD20) is a nonglycosylated, multispanning transmembrane protein specifically integrated by B lymphocytes. Similar to CD20, another four-pass transmembrane protein, claudin 18.2, has attracted attention as an emerging therapeutic target for cancer. However, their poor solubility and toxic nature often hinder downstream applications, such as antibody drug development. Therefore, developing a cost-effective method for producing drug targets with multiple membrane-spanning domains is crucial. In this study, a high yield of recombinant CD20 was achieved through an E. coli-based in vitro coupled transcription-translation system. Surface plasmon resonance results showed that rituximab (an antileukemia drug) has nanomolar affinity with the CD20 protein, which aligns with published results. Notably, a previously hard-to-express claudin 18.2 recombinant protein was successfully expressed in the same reaction system by replacing its membrane-spanning domains with the transmembrane domains of CD20. The folding of the extracellular domain of the chimeric protein was verified using a commercial anti-claudin 18 antibody. This study provides a novel concept for promoting the expression of four-pass transmembrane proteins and lays the foundation for the large-scale industrial production of membrane-associated drug targets, similar to claudin 18.2.


Assuntos
Antígenos CD20 , Escherichia coli , Antígenos CD20/genética , Antígenos CD20/metabolismo , Escherichia coli/metabolismo , Rituximab/genética , Rituximab/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Claudinas/metabolismo
14.
Arterioscler Thromb Vasc Biol ; 43(10): 1887-1899, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37650330

RESUMO

BACKGROUND: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. METHODS: Primary microvessels were cultured in the TGM2D medium (tubular microvascular growth medium on 2-dimensional substrates). Stiff ECM was prepared by incubating ECM solution in regular culture dishes for 1 hour followed by PBS wash. Soft ECM with Young modulus of ≈6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, RT-qPCR (real-time quantitative polymerase chain reaction), Western blotting, and knockdown experiments were performed on the cells. RESULTS: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFß (transforming growth factor beta) signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined 2 pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As integrins are the major mechanosensor, we performed RT-qPCR screening of integrin family members and found Itgb1 (integrin ß1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF (connective tissue growth factor), to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. CONCLUSIONS: ECM stiffness and TGFß signaling cooperatively regulate microvascular stability and pericyte-myofibroblast differentiation. Stiff ECM promotes EC ITGB1 phosphorylation (Y783) and CTGF secretion, which induces pericyte-myofibroblast differentiation.


Assuntos
Comunicação Parácrina , Pericitos , Ratos , Animais , Pericitos/metabolismo , Células Endoteliais/metabolismo , Células Cultivadas , Fator de Crescimento Transformador beta/metabolismo , Fibrose , Matriz Extracelular/metabolismo , Miofibroblastos/metabolismo
15.
Bioorg Med Chem Lett ; 107: 129777, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38692522

RESUMO

Inflammation is the body's defense response to stimuli. When the homeostatic balance is disturbed, disease may result. Flavonoids have clear anti-inflammatory effects and the isopentenyl group significantly enhances the pharmacological activity of flavonoids. Therefore, isopentenyl flavonoids have the potential to serve as lead compounds for the development of anti-inflammatory drugs. Throughout this research, eight natural compounds were synthesized, including 5,7-dihydroxy-4'-methoxy-8-prenylflavonoid (1), 4'-O-Methylatalantoflavone (2), Kushenol W (3) and Racemoflavone (5), which were totally synthesized for the first time. Additionally, three flavonols: Licoflavonol (6), 3,5,7,3',4'-pentahydroxy-6-prenylflavonol (7) and Macarangin (8), can be one-step synthesized by direct C-isopentenylation. In the process, an economical and efficient C-isopentenylation method was also simultaneously explored that could facilitate the efficient synthesis of natural products. These compounds were evaluated for their potential anti-inflammatory activities via the NLRP3 signaling pathway. Notably, Macarangin (8) manifested the most potent inhibitory effect. The SAR (Structure-Activity Relationships) also showed the introduction of the isopentenyl group was determined to enhance these effects, whereas simple flavonoid frameworks or cyclization of isopentenyl groups all diminished anti-inflammatory activity.


Assuntos
Flavonoides , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/síntese química , Camundongos , Relação Dose-Resposta a Droga , Humanos
16.
Nanotechnology ; 35(17)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38266306

RESUMO

Atomically thin transition metal dichalcogenides (TMDs) exhibit rich excitonic physics, due to reduced dielectric screening and strong Coulomb interactions. Especially, some attractive topics in modern condensed matter physics, such as correlated insulator, superconductivity, topological excitons bands, are recently reported in stacking two monolayer (ML) TMDs. Here, we clearly reveal the tuning mechanism of tensile strain on interlayer excitons (IEXs) and intralayer excitons (IAXs) in WSe2/MoSe2heterostructure (HS) at low temperature. We utilize the cryogenic tensile strain platform to stretch the HS, and measure by micro-photoluminescence (µ-PL). The PL peaks redshifts of IEXs and IAXs in WSe2/MoSe2HS under tensile strain are well observed. The first-principles calculations by using density functional theory reveals the PL peaks redshifts of IEXs and IAXs origin from bandgap shrinkage. The calculation results also show the Mo-4d states dominating conduction band minimum shifts of the ML MoSe2plays a dominant role in the redshifts of IEXs. This work provides new insights into understanding the tuning mechanism of tensile strain on IEXs and IAXs in two-dimensional (2D) HS, and paves a way to the development of flexible optoelectronic devices based on 2D materials.

17.
Environ Sci Technol ; 58(1): 906-914, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38126778

RESUMO

Developing effective catalysts for N2O decomposition at low temperatures is challenging. Herein, the Cs-O-Co structure, as the active species fabricated by single-layer atoms of Cs over pure Co3O4, originally exhibited great catalytic activity of N2O decomposition in simulated vehicle exhaust and flue gas from nitric acid plants. A similar catalytic performance was also observed for Na, K, and Rb alkali metals over Co3O4 catalysts for N2O decomposition, illustrating the prevalence of alkali-metal-promotion over Co3O4 in practical applications. The catalytic results indicated that the TOF of Co3O4 catalysts loaded by 4 wt% Cs was nearly 2 orders of magnitude higher than that of pure Co3O4 catalysts at 300 °C. Interestingly, the conversions of N2O decomposition over Co3O4 catalysts doped by the same Cs loadings were significantly inhibited. Characterization results indicated that the primary active Cs-O-Co structure was formed by highly orbital hybridization between the Cs 6s and the O 2p orbital over the supported Co3O4 catalysts, where Cs could donate electrons to Co3+ and produce much more Co2+. In contrast, the doped Co3O4 catalysts were dominated by Cs2O2 species; meanwhile, CsOH species was generated by adsorbed water vapor led to a significant decrease in catalytic activity. In situ DRIFTS, rigorous kinetics, and DFT results elaborated the reaction mechanism of N2O decomposition, where the direct decomposition of adsorbed N2O was the kinetically relevant step over supported catalysts in the absence of O2. Meanwhile, the assistance of adsorbed N2O decomposition by activated oxygen was observed as the kinetically relevant step in the presence of O2. The results may pave a promising path toward developing alkali-metal-promotion catalysts for efficient N2O decomposition.


Assuntos
Cobalto , Óxidos , Óxidos/química , Cobalto/química , Álcalis
18.
Environ Sci Technol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934498

RESUMO

The elevation of the low-temperature oxidation activity for Pt/CeO2 catalysts is challenging to meet the increasingly stringent requirements for effectively eliminating carbon monoxide (CO) from automobile exhaust. Although reducing activation is a facile strategy for boosting reactivity, past research has mainly concentrated on applying H2 as the reductant, ignoring the reduction capabilities of CO itself, a prevalent component of automobile exhaust. Herein, atomically dispersed Pt/CeO2 was fabricated and activated by CO, which could lower the 90% conversion temperature (T90) by 256 °C and achieve a 20-fold higher CO consumption rate at 200 °C. The activated Pt/CeO2 catalysts showed exceptional catalytic oxidation activity and robust hydrothermal stability under the simulated working conditions for gasoline or diesel exhausts. Characterization results illustrated that the CO activation triggered the formation of a large portion of Pt0 terrace sites, acting as inherent active sites for CO oxidation. Besides, CO activation weakened the Pt-O-Ce bond strength to generate a surface oxygen vacancy (Vo). It served as the oxygen reservoir to store the dissociated oxygen and convert it into active dioxygen intermediates. Conversely, H2 activation failed to stimulate Vo, but triggered a deactivating transformation of the Pt nanocluster into inactive PtxOy in the presence of oxygen. The present work offers coherent insight into the upsurging effect of CO activation on Pt/CeO2, aiming to set up a valuable avenue in elevating the efficiency of eliminating CO, C3H6, and NH3 from automobile exhaust.

19.
Mol Biol Rep ; 51(1): 236, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285214

RESUMO

BACKGROUND: Early brain injury (EBI) is the vital factor in determining the outcome of subarachnoid hemorrhage (SAH). Schizandrin A (Sch A), the bioactive ingredient extracted from Schisandra chinensis, has been proved to exert beneficial effects in multiple human diseases. However, the effect of Sch A on SAH remains unknown. The current study was designed to explored role and mechanism of Sch A in the pathophysiological process of EBI following SAH. METHOD: A total of 74 male C57BL/6 J mice were subjected to endovascular perforation to establish the SAH model. Different dosages of Sch A were administrated post-modeling. The post-modeling assessments included neurological test, brain water content, RT-PCR, immunofluorescence, Nissl staining. Oxygenated hemoglobin was introduced into microglia to establish a SAH model in vitro. RESULT: Sch A significantly alleviated SAH-induced brain edema and neurological impairment. Moreover, application of Sch A remarkably inhibited SAH-induced neuroinflammation, evidenced by the decreased microglial activation and downregulated TNF-α, IL-1ß and IL-6 and expression. Additionally, Sch A, both in vivo and in vitro, protected neurons against SAH-induced inflammatory injury. Mechanismly, administration of Sch A inhibited miR-155/NF-κB axis and attenuated neuroinflammation, as well as alleviating neuronal injury. CONCLUSION: Our data suggested that Sch A could attenuated EBI following SAH via modulating neuroinflammation. The anti-inflammatory effect was exerted, at least partly through the miR-155/NF-κB axis, which may shed light on a possible therapeutic target for SAH.


Assuntos
Lesões Encefálicas , Ciclo-Octanos , Lignanas , MicroRNAs , Compostos Policíclicos , Hemorragia Subaracnóidea , Camundongos , Humanos , Animais , Masculino , Camundongos Endogâmicos C57BL , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , NF-kappa B , Doenças Neuroinflamatórias , Lesões Encefálicas/tratamento farmacológico , MicroRNAs/genética
20.
BMC Pulm Med ; 24(1): 312, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961438

RESUMO

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Fatores de Risco , Hospitalização/estatística & dados numéricos , Adulto , Prognóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fatores Etários , Modelos Logísticos , Neutrófilos , Nitrogênio da Ureia Sanguínea , L-Lactato Desidrogenase/sangue
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