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1.
Nano Lett ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985501

RESUMO

Stationary energy storage infrastructure based on zinc-ion transport and storage chemistry is attracting more attention due to favorable metrics, including cost, safety, and recycling feasibility. However, splitting water and liquid electrolyte fluidity lead to cathode dissolution and Zn corrosion, resulting in rapid attenuation of the capacity and service life. Herein, a new architecture of solid-state electrolytes with high zinc ionic conductivity at room temperature was prepared via solidification of deep eutectic solvents utilizing MXene as nucleation additives. The ionic conductivity of MXene/ZCEs reached 6.69 × 10-4 S cm-1 at room temperature. Dendrite-free Zn plating/stripping with high reversibility can remain for over 2500 h. Subsequently, the fabricated solid-state zinc-ion battery with eliminated HER and suppressed Zn dendrites exhibited excellent cycling performance and could work normally in a range from -10 to 60 °C. This design inspired by eutectic solidification affords new insights into the multivalent solid electrochemistry suffering from slow ion migration.

2.
Acta Pharmacol Sin ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589686

RESUMO

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

3.
Environ Res ; 239(Pt 2): 117446, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37858695

RESUMO

This study investigated the feasibility of alleviating the negative influence of long-chain fatty acids (LCFAs) on anaerobic digestion by biochar, micron zero-valent iron, micron-magnetite (mFe3O4) and their combination. The results demonstrate that co-addition of biochar and 6 g/L mFe3O4 (BC+6 g/L mFe3O4) increased cumulative methane production by 50% as suffered from LCFAs inhibition exerted by 2 g/L glycerol trioleate. The BC+6 g/L mFe3O4 did best in accelerating total organic carbon degradation and volatile fatty acids conversion, through successively enriching Bacteroides, Corynebacterium, and DMER64 to dominant the bacterial community. The proportion of acetotrophic Methanothrix that could alternatively reduce CO2 to methane by accepting electrons via direct interspecies electron transfer (DIET) was 0.09% with BC+6 g/L mFe3O4, nine times more than the proportion in control. Prediction of functional genes revealed the enrichment of the bacterial secretion system, indicating that BC+6 g/L mFe3O4 promoted DIET by stimulating the secretion of extracellular polymeric substances. This study provided novel insights into combining biochar and iron-based conductive materials to enhance AD performance under LCFAs inhibition.


Assuntos
Ácidos Graxos Voláteis , Ferro , Anaerobiose , Metano , Reatores Biológicos , Esgotos
4.
Appl Opt ; 62(13): 3422-3430, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132843

RESUMO

For the modulation-based structured illumination microscopy system, how to obtain modulation distribution with an image has been a research hotspot. However, the existing frequency-domain single-frame algorithms (mainly including the Fourier transform method, wavelet method, etc.) suffer from different degrees of analytical error due to the loss of high-frequency information. Recently, a modulation-based spatial area phase-shifting method was proposed; it can obtain higher precision by retaining high-frequency information effectively. But for discontinuous (such as step) topography, it would be somewhat smooth. To solve the problem, we propose a high-order spatial phase shift algorithm that realizes robust modulation analysis of a discontinuous surface with a single-frame image. At the same time, this technique proposes a residual optimization strategy, so that it can be applied to the measurement of complex topography, especially discontinuous topography. Simulation and experimental results demonstrate that the proposed method can provide higher-precision measurement.

5.
Appl Opt ; 62(15): 3909-3916, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706700

RESUMO

Fourier single-pixel imaging (FSI) has attracted increased attention in recent years with the advantages of a wide spectrum range and low cost. FSI reconstructs a scene by directly measuring the Fourier coefficients with a single-pixel detector. However, the existing sampling method is difficult to balance the noise suppression and image details within a limited number of measurements. Here we propose a new sampling strategy for FSI to solve this problem. Both the generality of the spectral distribution of natural images in the Fourier domain and the uniqueness of the spectral distribution of the target images in the Fourier domain are considered in the proposed method. These two distributions are summed with certain weights to determine the importance of the Fourier coefficients. Then these coefficients are sampled in order of decreasing importance. Both the simulations and experiments demonstrate that the proposed method can capture more key Fourier coefficients and retain more details with lower noise. The proposed method provides an efficient way for Fourier coefficient acquisition.

6.
Mikrochim Acta ; 189(11): 406, 2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-36198886

RESUMO

A nanozyme-based competitive electrochemical immunosensor has been developed for the quantitative determination of E-selectin, a common adhesion molecule expressed by activated endothelial cells. A glassy carbon electrode modified with poly(azure A) and E-selectin antibody (GCE/PAA/Ab) was prepared. Au-CuO nanocomposite-labeled E-selectin, CD62E-Au-CuO, was synthetized, and it could be captured on GCE/PAA/Ab owing to the immunoreaction. The immobilized nanocomposites on GCE/PAA/Ab/CD62E-Au-CuO acted as nanozymes and were involved in the electrocatalytic process that caused the high cathodic peak current. The assembly of GCE/PAA/Ab/CD62E-Au-CuO was inhibited by E-selectin due to the competitive immunoreaction, which resulted in a decrease of the current signal. The cathodic peak current difference at - 0.35 V vs SCE was proportional to the concentration of E-selectin in the range 0.500-500 ng mL-1, and the limit of detection was estimated to be 226 pg mL-1. The cell morphology observation, the cell viability test, and the electrochemical measurement indicate that the injury of human umbilical vein endothelial cells was aggravated, and the release of E-selectin from the injured cells was gradually accelerated when the NaCl content in the growth medium increased.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Biossensoriais/métodos , Carbono/química , Cobre , Selectina E , Técnicas Eletroquímicas/métodos , Células Endoteliais , Ouro/química , Humanos , Imunoensaio/métodos , Cloreto de Sódio
7.
J Org Chem ; 86(2): 1964-1971, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33393302

RESUMO

Additive-free copper(I)-bromide-mediated radical cyclization reactions of α,α-dibromo ß-iminoesters were investigated, enabling the synthesis of a series of 5- or 6-brominated 2-aryl-1H-indole-3-carboxylates in moderate to good yields. The mechanistic study showed that (i) the bromine atom originated from the substrates and (ii) the bromination might be related to a 3-bromo-3H indole intermediate via an electrophilic bromine atom transfer. Furthermore, the practicality of this method was demonstrated by gram-scale synthesis and the potential for product derivatization toward other valuable multisubstituted indoles.

8.
Org Biomol Chem ; 19(24): 5377-5382, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34047749

RESUMO

Described here is a general and highly efficient method for the synthesis of 1H- and 3H-indoles. In the presence of CBr4 and a suitable base, the cyclization of N-aryl enamines proceeds with high efficiency. Unlike previous intramolecular cross dehydrogenative coupling (CDC) of the same substrates, this process does not require the use of either a transition metal or a stoichiometric amount of oxidant. This method also features operational simplicity, easy scalability and good substrate tolerability. Control experiments indicate the reactions may proceed in a tandem sequence of bromination and intramolecular Friedel-Crafts alkylation in a simple one-pot procedure.

9.
Scand J Clin Lab Invest ; 81(6): 488-493, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34369213

RESUMO

Although soluble urokinase plasminogen activator receptor (suPAR), T helper (Th)-1 and Th17 cells are separately reported to be dysregulated and correlate with disease severity in several infection-mediated diseases, fewer studies report their interaction and clinical value in sepsis management. Thus, this study aimed to investigate the correlation of blood suPAR with Th1 and Th17 cell proportion, as well as their diagnostic and prognostic value in elderly sepsis patients. Totally, 223 elderly sepsis patients were recruited. Serum suPAR was detected by enzyme-linked immunosorbent assay. Besides, Th1 and Th17 cell proportion from CD4+ T cells were determined by flow cytometry. For sepsis severity evaluation, Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Sequential Organ Failure Assessment (SOFA) score were used. Moreover, survival profile within 28 days was documented. The mean value of suPAR, Th1 cell proportion and Th17 cell proportion was 27.5 ± 15.1 ng/mL, 15.3 ± 4.3% and 4.0 ± 2.3%, respectively. Furthermore, suPAR was positively correlated with Th1 cell proportion, Th17 cell proportion, IFN-γ, IL-17 and TNF-α. Meanwhile, suPAR was positively correlated with APACHE II score and SOFA score, so did Th17 cell proportion. Regarding their prognostic value, suPAR and Th17 cell proportion were superior to differ survivors from deaths than Th1 cell proportion. SuPAR positively correlates with Th1, Th17 cell proportion; and they correlate with increased disease severity and mortality risk in elderly sepsis patients.


Assuntos
Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Sepse/sangue , Sepse/imunologia , Células Th1/imunologia , Células Th17/imunologia , Idoso , Biomarcadores/sangue , Citocinas/sangue , Feminino , Humanos , Masculino , Curva ROC , Fatores de Risco , Sepse/mortalidade , Sepse/patologia , Índice de Gravidade de Doença , Solubilidade , Sobreviventes
10.
Anal Chem ; 92(24): 15916-15926, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33263992

RESUMO

Endothelin-1 (ET-1) is a powerful endogenous vasoconstrictor and it is closely related to the pathogenesis of endothelial dysfunction that is commonly involved in the initiation of vascular inflammation and in the development of vascular diseases. A new method for the electrochemical immunoassay of ET-1 was put forward in this work. ET-1 antibodies (Ab), gold nanoparticles (GNPs), and copper ions were employed to synthesize nanoenzyme-labeled antibodies, Ab-GNPs-Cu(II) nanocomposites, and the latter was evaluated using transmission electron microscopy, dynamic light scattering, UV-vis absorption spectrophotometry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. These nanocomposites could be captured on a glassy carbon electrode (GCE) modified with poly(thionine) (PTH) and ET-1, GCE/PTH/ET-1. The immobilized nanoenzymes, GNPs-Cu(II) nanoparticles, played a peroxidase mimic role. Hydroxyl radicals, •OH, generated by a Fenton-type reaction, oxidized PTH and induced the considerable cathodic current on an assembled sandwich-type electrode. Owing to the competitive immunoreaction, ET-1 in the solution inhibited the capture of Ab-GNPs-Cu(II) nanocomposites. The deficiency of •OH caused the decline of the electrochemical response. The cathodic current change was in proportion to the ET-1 concentration from 0.5 to 500 ng mL-1. Cell morphology and viability investigations show that human umbilical vein endothelial cells, HUVECs, suffered from dysfunction when they were incubated in the presence of high-concentration glucose. Analyses on the growth medium using the developed method reveal that ET-1 was secreted by the injured cells and the release level of ET-1 was associated positively with the glucose concentration in the growth medium.


Assuntos
Cobre/química , Técnicas Eletroquímicas , Endotelina-1/análise , Imunoensaio , Nanoestruturas/química , Células Cultivadas , Humanos , Tamanho da Partícula , Propriedades de Superfície
11.
Environ Res ; 186: 109480, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32302869

RESUMO

Microwave assisted hydrothermal treatment (MHTC) was compared with torrefaction in terms of carbonization efficiency and physicochemical characteristics of char products. The utilization of produced char was optimized for composite solid biofuel production. The results show that MHTC significantly improved the binding capability of the microwave hydrochar (MHC) particles during co-densification with unprocessed biomass and coal. One possible contributor to the improved binding is the pseudo lignin formed during the MHTC, which led to a better interlocking of the feedstock particles and promoted the solid bridge formation. Composite pellet prepared with 80 wt% of torrefaction char (TC-120), 10 wt% of microwave hydrochar (MHC-30), and 10 wt% of Coal-04 showed a higher heating value of 24.54 MJ/kg and energy density of 26.43 GJ/m3, which is significantly higher than that of the raw cotton stalk pellet (16.77 MJ/kg and 18.76 GJ/m3, respectively), showing great promise as a solid biofuel. The moisture resistance and oxidation reactivity are also significantly improved. The results demonstrate that MHCs provides dual functionalities in acting as binder and fuel promoter in the production of composite biofuel. This study can provide new insight into the unique functions of MHC during fuel application, which demonstrates the great potential of applying MHTC in energy recovery from lignocellulosic biomass.


Assuntos
Carbono , Micro-Ondas , Biomassa , Físico-Química , Temperatura
12.
Appl Opt ; 56(8): 2301-2306, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-28375269

RESUMO

Broadband light interferometry, which is a well-developed method for surface profiling, has been applied with great success in the past years. Conventional multi-wavelength interferometric surface profilers mostly utilize the light irradiance to locate the zero fringe order, but the accuracy and stability can be negatively influenced by intensity fluctuations and external light disturbance, which is a serious problem. In this paper we discuss a hybrid technique combining light intensity and spectral modulation to determine zero optical path difference in which the light instability can be effectively suppressed. Additionally, the phase evaluation at each pixel will provide a high vertical resolution to obtain the characterization of the micro structure. The hybrid-interference method will not only improve the sensitivity of the measurement system but also level up the robustness and stability. Both simulation and experiment on a micro-dome structure have been presented to verify the effectiveness. Furthermore, the proposed method may be promising to replace the previously intensity-based method, especially in a complex application environment.

13.
Waste Manag Res ; 34(6): 578-83, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27067429

RESUMO

Pollution by heavy metals, such as copper and lead, has become a limiting factor for the land application of faecal manures, such as pig manure. This study was conducted to investigate the influence of composting process parameters, including aeration rate, moisture content and composting period, on the distribution of heavy metal species during composting, and to select an optimal parameter for copper and lead inactivation. Results showed that the distribution ratios of exchangeable fractions of copper and lead had a bigger decrease under conditions of aeration rate, 0.1 m(3) min(-1) m(-3), an initial moisture content of 65% and composting period of 50 days. Suboptimal composting process conditions could lead to increased availability of heavy metals. Statistical analysis indicated that the aeration rate was the main factor affecting copper and lead inactivation, while the effects of moisture content and composting period were not significant. The rates of reduction of copper-exchangeable fractions and lead-exchangeable fractions were positively correlated with increased pH. The optimal parameters for reducing heavy metal bioavailability during pig manure composting were aeration rate, 0.1 m(3) min(-1) m(-3), initial moisture content, 65%, and composting period, 20 days.


Assuntos
Cobre/análise , Chumbo/análise , Esterco , Eliminação de Resíduos de Serviços de Saúde/métodos , Solo/química , Ar , Animais , Cobre/farmacocinética , Fertilizantes , Concentração de Íons de Hidrogênio , Chumbo/farmacocinética , Esterco/análise , Eliminação de Resíduos de Serviços de Saúde/instrumentação , Poluentes do Solo/análise , Poluentes do Solo/farmacocinética , Sus scrofa , Temperatura
14.
Tumour Biol ; 36(3): 1595-601, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25596081

RESUMO

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas Supressoras de Tumor/genética , Adenoma/diagnóstico , Adenoma/genética , Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Carcinoma/genética , Humanos , Prognóstico , Regiões Promotoras Genéticas
15.
Appl Opt ; 53(29): 6663-9, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25322367

RESUMO

Based on grating shearing interferometry, a simple technique is introduced for focal length measurements of a microlens-array (MLA). The measurement system is composed of a He-Ne laser, condenser, collimator, the MLA under testing, a Ronchi grating, and CCD sensor. The plane wavefront from the collimator is transformed to a spherical wavefront by the MLA, while the curvature center is at the focus. Interference stripes appear at the overlap between the zero-order and first-order diffractive patterns of the grating and are detected by the CCD sensor. By analyzing the period change of stripes, the focal length is determined after the defocus of the grating is calculated. To validate the feasibility, an experiment is performed. The measurement uncertainty is discussed and measurement accuracy was determined to be 2%.

16.
Bioresour Technol ; 406: 131020, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909871

RESUMO

Hydrochar, a sustainable fertilizer rich in humic substances, is made from lignocellulose through hydrothermal conversion. However, hydrothermal humification (HTH) is challenged by low yields and limited selectivity in the resulting hydrochar. This study proved humic-like acids production can be enhanced under fast non-catalytic conditions (260 âˆ¼ 280 °C, 0 âˆ¼ 1 h). A higher yield (by 14.1 %) and selectivity (by 40.2 %) in hydrochar of humic-like acids than conventional HTH (<250 °C) were achieved. Meanwhile, decreased lignin derivatives, carbonyl and quinone groups, as well as increased sp2-C structures in the humic-like acids were observed. The synthesized humic-like acids exhibited a lower degree of aromatization and a higher molecular weight than commercial variants. Two pathways of humic-like acids formation of self-polymerization and the development of branched sidechains were hypothesized based on mass mitigation, carbon flow and aqueous phase compositions. This research contributes a novel approach to producing humic-like acids rich hydrochar for environmentally friendly fertilizer production.

17.
Bioresour Technol ; 395: 130375, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278456

RESUMO

Here, the mechanism of encapsulated anammox bacteria (AnAOB) driving efficient nitrogen removal in the mainstream partial nitritation/anammox process is revealed. The results show that a high nitrogen removal rate (1.21±0.02 kgN·(m3·d)-1) was achieved due to the abundant micropore structure inside the anammox immobilized filler, ensuring good connectivity, and a stable aggregation capacity, reducing dependence on extracellular polymeric substances. AnAOB were uniformly distributed throughout all regions of the immobilized filler, and their abundance was higher than that of the control anammox granular sludge (AnGS). Conversely, cracks appeared on the surface of the AnGS, and hollows formed inside. The metagenome analysis revealed that the immobilized filler supported the coexistence of multiple AnAOB, and the appropriate niche enhanced coordination between the AnAOB and dominant companion microorganisms. In contrast, AnGS exhibited stronger NH4+-N and NO2--N loops, potentially reducing the total nitrogen removal efficiency. This study promotes the mainstream application of anammox.


Assuntos
Compostos de Amônio , Oxidação Anaeróbia da Amônia , Reatores Biológicos/microbiologia , Compostos de Amônio/química , Oxirredução , Esgotos/microbiologia , Bactérias/genética , Nitrogênio/química , Desnitrificação
18.
Chin Med ; 19(1): 38, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429819

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera. PURPOSE: We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice. METHODS: We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin-eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells. RESULTS: SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

19.
Cell Res ; 34(2): 140-150, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38182887

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-born zoonotic bunyavirus that causes severe hemorrhagic fever and death in humans. CCHFV enters the cell via clathrin-mediated endocytosis which is dependent on its surface glycoproteins. However, the cellular receptors that are required for CCHFV entry are unknown. Here we show that the low density lipoprotein receptor (LDLR) is an entry receptor for CCHFV. Genetic knockout of LDLR impairs viral infection in various CCHFV-susceptible human, monkey and mouse cells, which is restored upon reconstitution with ectopically-expressed LDLR. Mutagenesis studies indicate that the ligand binding domain (LBD) of LDLR is necessary for CCHFV infection. LDLR binds directly to CCHFV glycoprotein Gc with high affinity, which supports virus attachment and internalization into host cells. Consistently, a soluble sLDLR-Fc fusion protein or anti-LDLR blocking antibodies impair CCHFV infection into various susceptible cells. Furthermore, genetic knockout of LDLR or administration of an LDLR blocking antibody significantly reduces viral loads, pathological effects and death following CCHFV infection in mice. Our findings suggest that LDLR is an entry receptor for CCHFV and pharmacological targeting of LDLR may provide a strategy to prevent and treat Crimean-Congo hemorrhagic fever.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Receptores de LDL , Animais , Humanos , Camundongos , Endocitose , Glicoproteínas/metabolismo , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo , Febre Hemorrágica da Crimeia/prevenção & controle , Receptores de LDL/metabolismo , Internalização do Vírus
20.
Cell Prolif ; 57(5): e13593, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38185757

RESUMO

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA-seq, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs-Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA-seq, bulk RNA-seq, and bioinformatic approaches, and found the highly expressed miR-27b-3p in CPPs-Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1-CREB1 axis via exosomal miR-27b-3p. Our study offers a novel insight into the role of CPPs-Exo in heart repair and highlights the potential of CPPs-Exo as a promising therapeutic strategy for MI.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Exossomos , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/metabolismo , Camundongos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Células-Tronco/metabolismo , Células-Tronco/citologia , Proliferação de Células , Diferenciação Celular , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/citologia
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