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1.
Clin Immunol ; 263: 110226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663493

RESUMO

Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and innovative approach to address these infections. Synthetic or natural fungal, parasitic and viral components have been reported to induce trained immunity. However, it is not clear whether bacterial virulence proteins can induce protective trained immunity. Our research demonstrates Streptococcus pneumoniae virulence protein PepO, is a highly potent trained immunity inducer for combating broad-spectrum infection. Our findings showcase that rPepO training confers robust protection to mice against various pathogenic infections by enhancing macrophage functionality. rPepO effectively re-programs macrophages, re-configures their epigenetic modifications and bolsters their immunological responses, which is independent of T or B lymphocytes. In vivo and in vitro experiments confirm that trained macrophage-secreted complement C3 activates peritoneal B lymphocyte and enhances its bactericidal capacity. In addition, we provide the first evidence that granulocyte colony-stimulating factor (G-CSF) derived from trained macrophages plays a pivotal role in shaping central-trained immunity. In summation, our research demonstrates the capability of rPepO to induce both peripheral and central trained immunity in mice, underscoring its potential application in broad-spectrum anti-infection therapy. Our research provides a new molecule and some new target options for infectious disease prevention.


Assuntos
Macrófagos , Camundongos Endogâmicos C57BL , Streptococcus pneumoniae , Animais , Streptococcus pneumoniae/imunologia , Camundongos , Macrófagos/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Proteínas de Bactérias/imunologia , Linfócitos B/imunologia , Feminino , Imunidade Treinada
2.
Heart Fail Rev ; 29(1): 113-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37823952

RESUMO

The progression of heart failure is reported to be strongly associated with homeostatic imbalance, such as mitochondrial dysfunction and abnormal autophagy, in the cardiomyocytes. Mitochondrial dysfunction triggers autophagic and cardiac dysfunction. In turn, abnormal autophagy impairs mitochondrial function and leads to apoptosis or autophagic cell death under certain circumstances. These events often occur concomitantly, forming a vicious cycle that exacerbates heart failure. However, the role of the crosstalk between mitochondrial dysfunction and abnormal autophagy in the development of heart failure remains obscure and the underlying mechanisms are mainly elusive. The potential role of the link between mitochondrial dysfunction and abnormal autophagy in heart failure progression has recently garnered attention. This review summarized recent advances of the interactions between mitochondria and autophagy during the development of heart failure.


Assuntos
Insuficiência Cardíaca , Doenças Mitocondriais , Humanos , Insuficiência Cardíaca/metabolismo , Autofagia/fisiologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Doenças Mitocondriais/metabolismo
3.
Theor Appl Genet ; 137(7): 167, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909110

RESUMO

KEY MESSAGE: A large fragment deletion of CpAPRR2, encoding a two-component response regulator-like protein, which influences immature white rind color formation in zucchini (Cucurbita pepo). Fruit rind color is an important agronomic trait that affects commodity quality and consumer choice in zucchini (Cucurbita pepo). However, the molecular mechanism controlling rind color is unclear. We characterized two zucchini inbred lines: '19' (dark green rind) and '113' (white rind). Genetic analysis revealed white immature fruit rind color to be controlled by a dominant locus (CpW). Combining bulked segregant analysis sequencing (BSA-seq) and Kompetitive Allele-Specific PCR (KASP) markers, we mapped the CpW locus to a 100.4 kb region on chromosome 5 and then narrow down the candidate region to 37.5 kb using linkage analysis of 532 BC1 and 1613 F2 individuals, including 6 coding genes. Among them, Cp4.1LG05g02070 (CpAPRR2), encoding a two-component response regulator-like protein, was regarded to be a promising candidate gene. The expression level of CpAPRR2 in dark green rind was significantly higher than that in white rind and was induced by light. A deletion of 2227 bp at the 5' end of CpAPRR2 in '113' might explain the white phenotype. Further analysis of allelic diversity in zucchini germplasm resources revealed rind color to be associated with the deletion of CpAPRR2. Subcellular localization analysis indicated that CpAPRR2 was a nuclear protein. Transcriptome analysis using near-isogenic lines with dark green (DG) and white (W) rind indicated that genes involved in photosynthesis and porphyrin metabolism pathways were enriched in DG compared with W. Additionally, chlorophyll synthesis-related genes were upregulated in DG. These results identify mechanisms of zucchini rind color and provide genetic resources for breeding.


Assuntos
Mapeamento Cromossômico , Cucurbita , Frutas , Fenótipo , Pigmentação , Frutas/genética , Frutas/crescimento & desenvolvimento , Pigmentação/genética , Cucurbita/genética , Cucurbita/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Alelos , Genes de Plantas , Cor , Transcriptoma
4.
Toxicol Pathol ; 52(1): 35-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38385340

RESUMO

Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.


Assuntos
Dependovirus , Gânglios Espinais , Animais , Coelhos , Dependovirus/genética , Vetores Genéticos , Masculino , Humanos , Transgenes , Feminino , Células Receptoras Sensoriais
5.
J Nat Prod ; 87(4): 713-721, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38417168

RESUMO

PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-γ-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.


Assuntos
Antígeno B7-H1 , Interferon gama , Janus Quinases , Interferon gama/farmacologia , Humanos , Janus Quinases/metabolismo , Esteróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estrutura Molecular , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linhagem Celular Tumoral
6.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473740

RESUMO

The mottled leaf is one of the agronomic traits of zucchini and can be applied as a marker trait in aggregation breeding. However, the genetic mechanism responsible for mottled leaf has yet to be elucidated. In the present study, we used two inbred lines (line '19': silver mottled leaf; line '113': normal leaf) as parents for the physiological and genetic analysis of mottled leaf. The synthesis and net photosynthetic rate of chlorophyll were not significantly affected in the mottled areas of leaves. However, we detected a large space between the palisade parenchyma in the leaf mottle area of line '19', which may have caused the mottled leaf phenotype. Light also plays an important role in the formation of mottled leaf, and receiving light during the early stages of leaf development is a necessary factor. Genetic analysis has previously demonstrated that mottled leaf is a quantitative trait that is controlled by multiple genes. Based on the strategy of quantitative trait locus sequencing (QTL-seq), two QTLs were identified on chromosomes 1 and 17, named CpML1.1 and CpML17.1, respectively. Two major loci were identified using R/qtl software version 1.66 under greenhouse conditions in April 2019 (2019A) and April 2020 (2020A) and under open cultivation conditions in May 2020 (2020M). The major QTL, CpML1.1, was located in a 925.2-kb interval on chromosome 1 and explained 10.51%-24.15% of the phenotypic variation. The CpML17.1 was located in a 719.7-kb interval on chromosome 17 and explained 16.25%-38.68% of the phenotypic variation. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, the Cp4.1LG01g23790 at the CpML1.1 locus encoding a protein of the TPX2 family (target protein of Xklp2) may be a candidate gene for mottled leaf in zucchini. Our findings may provide a theoretical basis for the formation of mottled leaf and provide a foundation for the fine mapping of genes associated with mottled leaf. Molecular markers closely linked to mottled leaf can be used in molecular-assisted selection for the zucchini mottled leaf breeding.


Assuntos
Cucurbita , Cucurbita/genética , Melhoramento Vegetal , Mapeamento Cromossômico , Locos de Características Quantitativas , Folhas de Planta/genética
7.
Angew Chem Int Ed Engl ; 63(28): e202404398, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38698730

RESUMO

Catalyst deactivation by sintering and coking is a long-standing issue in metal-catalyzed harsh high-temperature hydrocarbon reactions. Ultrathin oxide coatings of metal nanocatalysts have recently appeared attractive to address this issue, while the porosity of the overlayer is difficult to control to preserve the accessibility of embedded metal nanoparticles, thus often leading to a large decrease in activity. Here, we report that a nanometer-thick alumina coating of MgAl2O4-supported metal catalysts followed by high-temperature reduction can transform a nonporous amorphous alumina overlayer into a porous Mg1-xAl2Oy crystalline spinel structure with a pore size of 2-3 nm and weakened acidity. The high porosity stems from the restrained Mg migration from the MgAl2O4 support to the alumina overlayer through solid-state reactions at high temperatures. The resulting Ni/MgAl2O4 and Pt/MgAl2O4 catalysts with a porous crystalline Mg1-xAl2Oy overlayer achieved remarkably high stability while preserving much higher activity than the corresponding alumina-coated Ni and Pt catalysts on MgO and Al2O3 supports in the reactions of dry reforming of methane and propane dehydrogenation, respectively.

8.
Opt Lett ; 48(21): 5471-5474, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910680

RESUMO

We have innovatively introduced the pulsated orifice ejection method into the preparation of glass fibers, successfully preparing high-purity Ge28Sb12Se60 glass fibers. These fibers have a smooth surface, uniform elemental distribution, and excellent bending properties, with a minimal bending radius of 2 mm. In the infrared spectrum from 2.5 to 13.5 µm, the fibers achieve 65% transmission. Additionally, the fibers possess a density of 4.586 g/cm3, a diameter of 35 µm, a glass transition temperature (Tg) of 369°C, and an onset crystallization temperature (Tx) of 557°C. We have also measured the surface tension of the glass fibers, finding values from 0.288 N/m to 0.124 N/m as temperatures rose from 450°C to 500°C. The POEM holds the potential to achieve fiber cores of lengths up to hundreds of meters in theory. Our work provides a distinctive perspective for the preparation of glass fibers.

9.
Chemistry ; 29(57): e202301968, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37486795

RESUMO

Self-assembly exploits noncovalent interaction to offer an effective method for the fabrication of materials. For Na9 [EuW10 O36 ] ⋅ 32H2 O (EuW10 ), the negative charges and abundant oxygen atoms on its surface provide a handle for static self-assembly. New properties are envisioned for EuW10 aggregates which are able to display such kinetics and time-programming characteristics, in order to satisfy more complex and intelligent application scenarios, such as DNA binding and information encryption. In this work, EuW10 coupling with stimuli-responsive dodecyl dimethylamine oxide (C12 DMAO) can generate versatile aggregates with pH-responsive properties. We demonstrated the temporal programming of the assembly and disassembly of EuW10 nanospheres using a pH clock reaction of acid/urease hydrolysis. The pH clock reaction endows EuW10 assemblies with dynamical properties, in which the charges and fluorescence changes are coded in this system. These fluorescent assemblies provide new application in time-programmed DNA capture and information encryption.

10.
Chemphyschem ; 24(24): e202300587, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37880197

RESUMO

Studying the characteristics and molecular mechanisms of liquid self-diffusion coefficient and viscosity changes is of great significance for, e. g., chemical and petroleum processing. As examples of highly complex liquid,an asphaltene-free high-acid and high-viscosity crude oil and its extracted fractions were studied by comparing their 1 H DOSY diffusion maps. The crude oil exhibited a polydisperse diffusion distribution, including multiple diffusion portions with diffusion coefficients much smaller than that of any single fraction in independent diffusion. The main mechanism that leads to the decreases in the diffusion coefficients of crude oil is attributed to diffusion resistance enhanced by Dynamical Molecular-Interaction Networks (DMINs), rather than by enlargement of the diffusion species caused by molecular aggregation. Constructed through the synergistic interactions of various polar molecules in crude oil, DMINs dynamically bind polar molecules, trap polarizable molecules, and spatially hinder the free motion of non-polar molecules. Overall, this reduces the mobility of all molecular species, as illustrated by the decreased diffusion coefficients. This study demonstrates that DOSY is a powerful NMR method to investigate molecular motion abilities also in complex mixtures. In addition, the insights in the influence of the interaction matrix on the molecular mobility also help to understand the contribution of "structural viscosity" to the viscosity of heavy oil.

11.
Langmuir ; 39(47): 16750-16759, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963300

RESUMO

Low-molecular-weight peptide hydrogels can be formed by self-assembly through weak interactions, but the application of the hydrogel is influenced by its weak mechanical properties. Therefore, it is important to construct low-molecular-weight peptide hydrogels with excellent mechanical properties. In this work, we designed the pentapeptide molecule Fmoc-FFCKK-OH (abbreviated as FFCKK) with a sulfhydryl group, and another low-molecular-weight cross-linker N,N'-methylenebis(acrylamide) (MBA) was introduced to construct a hydrogel with excellent mechanical properties. The secondary structure change process of FFCKK and the assembly mechanism of hydrogel were analyzed using theoretical calculations and experimental characterizations. The occurrence of thiol-ene click chemistry provides covalent interaction in the hydrogel, and the synergistic effect ofcovalent interaction and hydrogen bonding improves the mechanical properties of the hydrogel by nearly 10-fold. The hydrogel was observed to be able to withstand a stress of 368 Pa and to break in a layer-by-layer manner by compression testing. The micromechanics of the hydrogels were characterized, and the excellent mechanical properties of the hydrogels were confirmed. The synergistic approach provides a new idea for the preparation of low-molecular-weight peptide hydrogels and facilitates the expansion of their potential applications in biomedical fields.


Assuntos
Química Click , Hidrogéis , Hidrogéis/química , Compostos de Sulfidrila/química , Peptídeos/química
12.
Diabetes Obes Metab ; 25(3): 664-674, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36314246

RESUMO

AIM: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). METHODS: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non-T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. RESULTS: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta-analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = -0.72, 95% confidence interval (CI; -1.12, -0.33)], liver fat [SMD = -0.78, 95% CI (-1.24, -0.32)] and body mass index [weighted mean difference = -1.44, 95% CI (-1.95, -0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = -0.74, 95% CI (-1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. CONCLUSIONS: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured.


Assuntos
Diabetes Mellitus Tipo 2 , Liraglutida , Adulto , Humanos , Liraglutida/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Fígado , Índice de Massa Corporal , Tecido Adiposo , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Fish Shellfish Immunol ; 132: 108503, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36581255

RESUMO

In the present study, the polyimmunoglobulin receptor-like (pIgRL) of large yellow croaker (Larimichthys crocea) was first cloned and characterized. LcpIgRL's full-length cDNA was 1610 bp, encoding 377 amino acids, and the protein's predicted molecular weight was 41.9 kDa, containing two immunoglobulin-like structural domains. The transcript levels of LcpIgRL in different tissues of healthy large yellow croaker were examined by real-time fluorescence quantitative PCR, and the results showed that the gills and head kidney had the highest levels. Within 36 h of the large yellow croaker being infected with Vibrio harveyi, pIgRL mRNA first increased and then decreased in all determined tissues, with the highest expression in the skin and hindgut. Furthermore, a recombinant protein of the extracellular region of LcpIgRL was expressed in E. coli BL21, and a murine rLcpIgRL polyclonal antibody was prepared, which could react specifically with the natural LcpIgRL in skin mucus, but no natural LcpIgRL was detected in serum. Meanwhile, it was found that the rLcpIgRL could bind to the recombinant IgM and the natural IgM, indicating that LcpIgRL could mediate the transport of IgM in mucus. In addition, rLcpIgRL binds to Aeromonas hydrophila and V. harveyi, as well as lipopolysaccharide (LPS) and various saccharides, and reduced binding to bacteria was observed under LPS treatment, suggesting that LcpIgRL can bind to bacteria to prevent infection and that saccharide binding is an important mechanism of interaction between pIgRL and bacteria.


Assuntos
Perciformes , Receptores de Imunoglobulina Polimérica , Animais , Camundongos , Receptores de Imunoglobulina Polimérica/genética , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Escherichia coli/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Imunoglobulina M/genética , Proteínas de Peixes/química , Filogenia
14.
Fish Shellfish Immunol ; 135: 108631, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36907480

RESUMO

To investigate the effects of adding different concentrations of cup plant (Silphium perfoliatum L.) to the feed on the growth performance, hepatopancreas and intestinal microstructure, gene expression, enzyme activity, as well as intestinal microorganisms and resistance to Vibrio parahaemolyticus E1 and White spot syndrome virus (WSSV) infection of the shrimp, cup plant was added to the basal feed at 1%, 3%, 5% and 7% respectively, and fed the shrimp for 6 weeks. It was found that the addition of different concentrations of cup plant could significantly improve the specific growth rate and survival rate of shrimp, reduce the feed conversion rate, and improve the resistance to V. parahaemolyticus E1 and WSSV in shrimp, with the best effect of 5% addition. The tissue sections observations showed that the addition of cup plant significantly improved the hepatopancreas and intestinal tissues of shrimp, especially in alleviating the tissue damage caused by V. parahaemolyticus E1 and WSSV infection, but too high an addition (7%) could also cause side effects on the shrimp intestinal tract. Meantime, the addition of cup plant can also increase the activity of immunodigestive-related enzymes in the hepatopancreas and intestinal tissues of shrimp, and can significantly induce the up-regulation of immune-related genes expression, and it is positively correlated with the amount of addition in a certain range. In addition, it was found that the addition of cup plant has a significant regulating effect on the intestinal flora of shrimp, which can significantly promote the growth of beneficial bacteria such as Haloferula sp., Algoriphagus sp. and Coccinimonas sp., and inhibit pathogenic bacteria Vibrio sp., such as the number of Vibrionaceae_Vibrio and Pseudoalteromonadaceae_Vibrio in the experimental group were significantly reduced, and the lowest level in the 5% addition group. In summary, the study shows that cup plant can promote the growth of shrimp, improve the resistance of shrimp to disease, and is a potential green environmental feed additive that can replace antibiotics.


Assuntos
Asteraceae , Microbioma Gastrointestinal , Penaeidae , Vibrio parahaemolyticus , Vírus da Síndrome da Mancha Branca 1 , Animais , Resistência à Doença , Imunidade Inata/genética , Vibrio parahaemolyticus/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia
15.
Neurol Sci ; 44(8): 2985-2986, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37150792

RESUMO

Spinal dural arteriovenous fistula (SDAVF) is also known as a type 1 spinal arteriovenous malformation, representing the most frequent vascular malformation of the spine. A high suspicion index is often required for the initial diagnosis of SDAVF because of subtle magnetic resonance imaging signs. We present the case of a patient with SDAVF associated with syringomyelia of the thoracic spinal cord and hypothesize that a fistula might induce intramedullary fluid accumulation due to venous hypertension, which leads to syrinx formation.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Siringomielia , Humanos , Siringomielia/complicações , Siringomielia/diagnóstico por imagem , Coluna Vertebral , Medula Espinal/patologia , Imageamento por Ressonância Magnética/métodos , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Paraparesia/diagnóstico por imagem , Paraparesia/etiologia
16.
BMC Pulm Med ; 23(1): 210, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328853

RESUMO

BACKGROUND: RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics. METHODS: We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication. RESULTS: In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids. CONCLUSIONS: Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.


Assuntos
Hipersensibilidade , Transtornos Respiratórios , Hipersensibilidade Respiratória , Doenças Respiratórias , Humanos , Hipersensibilidade/genética , Adenosina , Glucocorticoides , Metiltransferases/genética
17.
J Stroke Cerebrovasc Dis ; 32(5): 107088, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36940566

RESUMO

OBJECTIVE: Elongated styloid process (ESP) and carotid web are rare etiologies of ischemic stroke. We report a rare case of ESP concomitant with carotid web as the cause of recurrent stroke. CASE PRESENTATION: A 59-year-old man was admitted to our hospital with recurrent numbness and weakness in the right upper extremity. The patient had a long-standing history of lightheadedness and left-side amaurosis with neck flexion. Magnetic resonance imaging (MRI) confirmed scattered infarctions in the left frontal and parietal lobes. After multi-modal imaging we determined that embolic cerebral infarction was most likely to be secondary to the carotid web. Moreover, ESP causes dynamic hypoperfusion during neck flexion. We believe that this is a good reason for dealing with both pathologies during the same surgery. Thus, carotid endarterectomy and styloid process resection were performed at the same time. The previous symptoms during the head position change did not recur, and the right hand weakness was resolved. CONCLUSION: ESP and carotid web are unusual mechanisms of ischemic stroke. Early diagnosis and timely treatment are essential to prevent subsequent severe strokes.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Artérias Carótidas , Infarto Cerebral/etiologia , Infarto Cerebral/complicações , Acidente Vascular Cerebral/etiologia , AVC Isquêmico/complicações
18.
Angew Chem Int Ed Engl ; 62(23): e202300110, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37026370

RESUMO

Increasing selectivity without the expense of activity is desired but challenging in heterogeneous catalysis. By revealing the molecule saturation and adsorption sensitivity on overlayer thickness, strain, and coordination of Pd-based catalysts from first-principles calculations, we designed a stable Pd monolayer (ML) catalyst on a Ru terrace to boost both activity and selectivity of acetylene semihydrogenation. The least saturated molecule is most sensitive to the change in catalyst electronic and geometric properties. By simultaneously compressing the Pd ML and exposing the high coordination sites, the adsorption of more saturated ethylene is considerably weakened to facilitate the desorption for high selectivity. The even stronger weakening to the least saturated acetylene drives its hydrogenation such that it is more exothermic, thereby boosting the activity. Tailoring the molecule saturation and its sensitivity to structure and composition provides a tool for rational design of efficient catalysts.

19.
Langmuir ; 38(2): 698-710, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34991310

RESUMO

Water security caused by heavy metals poses a deleterious hazard to public health and the ecological system. The construction of adsorbents by polyamidoamine (PAMAM) dendrimers for efficient removal of metal ions has attracted considerable interest. However, the general method for the fabrication of these adsorbents was achieved by the surface chemical modification of the substrates with PAMAM dendrimer, which usually causes the defects of low density and uneven distribution of the dendrimer, the blocking of pores, and reducing the adsorption performance. Hence, the development of a new method for preparation of PAMAM dendrimer-based adsorbent to realize the efficient and enhanced adsorption of metal ions is still a challenge. Herein, methylisothiocyanate decorated PAMAM dendrimer/mesoporous silica composites (G0-S-1/x, G1.0-S-1/x, G2.0-S-1/x, x = 2, 4, 6, 8, 10) were synthesized by the direct sol-gel reaction of alkoxysilyl-containing functional PAMAM dendrimer. The adsorbents display enhanced adsorption property for Hg(II) and Cd(II) as compared with the same adsorbents which were prepared by traditional chemical modification method. Take G2.0-S-1/2 as an example, the maximum adsorption capacities are 2.41 and 0.87 mmol·g-1 for Hg(II) and Cd(II), respectively . Moreover, the adsorbents show excellent selective adsorption and regeneration property. G2.0-S-1/2 displays distinct selectivity for Hg(II) with the presence of Co(II), Pb(II), Cd(II), and Cu(II). The regeneration percentage still maintains 95.2% after five adsorption-desorption cycles. The adsorption mechanism is also certified by the experimental method and theoretical calculation.


Assuntos
Mercúrio , Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio , Dendrímeros , Poliaminas , Dióxido de Silício , Enxofre , Poluentes Químicos da Água/análise
20.
Soft Matter ; 18(17): 3278-3290, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35437550

RESUMO

Human disorders associated with amyloid aggregation, such as Alzheimer's disease and Parkinson's disease, afflict the lives of millions worldwide. When peptides and proteins in the body are converted to amyloids, which have a tendency to aggregate, the toxic oligomers produced during the aggregation process can trigger a range of diseases. Nanoparticles (NPs) have been found to possess surface effects that can modulate the amyloid aggregation process and they have potential application value in the treatment of diseases related to amyloid aggregation and fibrillary tangles. In this review, we discuss recent progress relating to studies of nanoparticles that regulate amyloid aggregation. The review focuses on the factors influencing this regulation, which are important as guidelines for the future design of NPs for the treatment of amyloid aggregation. We describe the characterization methods that have been utilized so far in such studies. This review provides research information and characterization methods for the rational design of NPs, which should result in therapeutic strategies for amyloid diseases.


Assuntos
Doença de Alzheimer , Nanopartículas , Doença de Alzheimer/metabolismo , Amiloide/química , Peptídeos beta-Amiloides , Humanos , Nanopartículas/química , Peptídeos
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