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1.
Immunity ; 54(6): 1200-1218.e9, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33951416

RESUMO

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/ß-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of ß-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, ß-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted ß-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This ß-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by ß-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Autorrenovação Celular/imunologia , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , SARS-CoV-2/imunologia , Biomarcadores , COVID-19/metabolismo , Citocinas/metabolismo , Suscetibilidade a Doenças/imunologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Transdução de Sinais
2.
World J Urol ; 42(1): 328, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753087

RESUMO

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.


Assuntos
Carcinoma de Células Renais , DNA Circular , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/diagnóstico , DNA Circular/sangue , DNA Circular/genética , Neoplasias Renais/sangue , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Feminino , Idoso
3.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612392

RESUMO

The glycocalyx is a proteoglycan-glycoprotein structure lining the luminal surface of the vascular endothelium and is susceptible to damage due to blast overpressure (BOP) exposure. The glycocalyx is essential in maintaining the structural and functional integrity of the vasculature and regulation of cerebral blood flow (CBF). Assessment of alterations in the density of the glycocalyx; its components (heparan sulphate proteoglycan (HSPG/syndecan-2), heparan sulphate (HS), and chondroitin sulphate (CS)); CBF; and the effect of hypercapnia on CBF was conducted at 2-3 h, 1, 3, 14, and 28 days after a high-intensity (18.9 PSI/131 kPa peak pressure, 10.95 ms duration, and 70.26 PSI·ms/484.42 kPa·ms impulse) BOP exposure in rats. A significant reduction in the density of the glycocalyx was observed 2-3 h, 1-, and 3 days after the blast exposure. The glycocalyx recovered by 28 days after exposure and was associated with an increase in HS (14 and 28 days) and in HSPG/syndecan-2 and CS (28 days) in the frontal cortex. In separate experiments, we observed significant decreases in CBF and a diminished response to hypercapnia at all time points with some recovery at 3 days. Given the role of the glycocalyx in regulating physiological function of the cerebral vasculature, damage to the glycocalyx after BOP exposure may result in the onset of pathogenesis and progression of cerebrovascular dysfunction leading to neuropathology.


Assuntos
Proteoglicanas de Heparan Sulfato , Sindecana-2 , Animais , Ratos , Glicocálix , Hipercapnia , Circulação Cerebrovascular , Heparitina Sulfato , Sulfatos de Condroitina
4.
Breast Cancer Res ; 25(1): 63, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37287069

RESUMO

BACKGROUND: Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown. METHODS: Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner. RESULTS: We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients. CONCLUSIONS: Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Células Mieloides , Macrófagos/metabolismo , Monócitos , Prognóstico , Microambiente Tumoral/genética
5.
Environ Microbiol ; 25(11): 2621-2635, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37543720

RESUMO

Following the discovery of Acanthamoeba polyphaga mimivirus, diverse giant viruses have been isolated. However, only a small fraction of these isolates have been completely sequenced, limiting our understanding of the genomic diversity of giant viruses. MinION is a portable and low-cost long-read sequencer that can be readily used in a laboratory. Although MinION provides highly error-prone reads that require correction through additional short-read sequencing, recent studies assembled high-quality microbial genomes only using MinION sequencing. Here, we evaluated the accuracy of MinION-only genome assemblies for giant viruses by re-sequencing a prototype marseillevirus. Assembled genomes presented over 99.98% identity to the reference genome with a few gaps, demonstrating a high accuracy of the MinION-only assembly. As a proof of concept, we de novo assembled five newly isolated viruses. Average nucleotide identities to their closest known relatives suggest that the isolates represent new species of marseillevirus, pithovirus and mimivirus. The assembly of subsampled reads demonstrated that their taxonomy and genomic composition could be analysed at the 50× sequencing coverage. We also identified a pithovirus gene whose homologues were detected only in metagenome-derived relatives. Collectively, we propose that MinION-only assembly is an effective approach to rapidly perform a genome-wide analysis of isolated giant viruses.


Assuntos
Vírus Gigantes , Vírus Gigantes/genética , Genômica , Análise de Sequência de DNA , Metagenoma , Sequenciamento de Nucleotídeos em Larga Escala
6.
Small ; : e2308192, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072794

RESUMO

The single-atom sites (SAs) have achieved enhanced performance toward oxygen reduction reaction (ORR) with the effective utilization of the active sites. However, the excess adsorption of the intermediates and the limited stability hinders performance improvement. Metal clusters with promising stability and weak adsorption can be used as potential substitutions, but the lack of active sites is considered undesirable for catalytic reactions. Herein, a framework of Fe nanoclusters combined with SAs on One dimensional (1D) carbon nanotubes (Fe3 C-NCNTs 90 min CC-1 ) is synthesized to confirm the synergistic atom-cluster interaction. The composite exhibits strong polarization and electron redistribution between nanocluster and SAs. The electron redistribution will significantly boost the electron transport and the desorption of the intermediates, which is confirmed by off-axis holography and DFT calculation. The electrocatalytic performance is significantly enhanced as the half-wave potential of ORR increased 75 mV and the potential of OER increased 133 mV compared with the sample without nanoclusters. Furthermore, such a bifunctional catalyst endows homemade Zn-air batteries (ZABs) with high power density and long-term stability. This work paves a facile route to design bifunctional ORR/OER electrocatalysts consisting of 0D composite structures.

7.
Arch Virol ; 168(3): 80, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740641

RESUMO

Acanthamoeba castellanii medusavirus J1 is a giant virus that was isolated from a hot spring in Japan in 2019. Recently, a close relative of this virus, named medusavirus stheno T3, was isolated in Japan. Here, we describe their morphological, genomic, and gene content similarities and also propose to create a new family, "Mamonoviridae", a new genus, "Medusavirus", and two species, "Medusavirus medusae" and "Medusavirus sthenus", to classify these two viruses within the phylum Nucleocytoviricota.


Assuntos
Vírus Gigantes , Vírus , Filogenia , Genoma Viral , Vírus/genética , Vírus Gigantes/genética , Genômica
8.
Genes Dev ; 29(23): 2420-34, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26584619

RESUMO

Telomerase inactivation causes loss of the male germline in worms, fish, and mice, indicating a conserved dependence on telomere maintenance in this cell lineage. Here, using telomerase reverse transcriptase (Tert) reporter mice, we found that very high telomerase expression is a hallmark of undifferentiated spermatogonia, the mitotic population where germline stem cells reside. We exploited these high telomerase levels as a basis for purifying undifferentiated spermatogonia using fluorescence-activated cell sorting. Telomerase levels in undifferentiated spermatogonia and embryonic stem cells are comparable and much greater than in somatic progenitor compartments. Within the germline, we uncovered an unanticipated gradient of telomerase activity that also enables isolation of more mature populations. Transcriptomic comparisons of Tert(High) undifferentiated spermatogonia and Tert(Low) differentiated spermatogonia by RNA sequencing reveals marked differences in cell cycle and key molecular features of each compartment. Transplantation studies show that germline stem cell activity is confined to the Tert(High) cKit(-) population. Telomere shortening in telomerase knockout strains causes depletion of undifferentiated spermatogonia and eventual loss of all germ cells after undifferentiated spermatogonia drop below a critical threshold. These data reveal that high telomerase expression is a fundamental characteristic of germline stem cells, thus explaining the broad dependence on telomerase for germline immortality in metazoans.


Assuntos
Células-Tronco Adultas/enzimologia , Regulação Enzimológica da Expressão Gênica , Espermatogônias/enzimologia , Telomerase/genética , Telomerase/metabolismo , Animais , Diferenciação Celular/genética , Células-Tronco Embrionárias/enzimologia , Citometria de Fluxo , Técnicas de Introdução de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética
9.
Molecules ; 28(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959871

RESUMO

In this study, a new 3D porous PVDF-foam-imprinted membrane (PPIM) for the selective separation of artemisinin (ART) was first prepared via the dopamine adhesion of pre-synthesized MIPs into the interior of the PPIM. In the PPIM, the pre-synthesized molecularly imprinted polymers (MIPs) with artesunate (ARU) as a dummy template were uniformly loaded on the interior of the membrane, avoiding the defects of recognition site encapsulation found in the conventional membrane. This membrane also exhibited excellent flux, which is beneficial in practical separation applications. The PPIM was systematically characterized via FT-IR, SEM, pore-size distribution analysis, water contact angle test, membrane flux, and mechanical performance analysis, respectively. In the static adsorption experiment, the pseudo-second-order kinetic model better fitted the rebinding data of ART. Under dynamic conditions, the ART adsorption capacity of the PPIM could be further remarkably improved by tailoring the flow rate to 3 mL min-1. In the selective separation experiment, with artemether (ARE) as the competition substrate, the selective separation ability (α) of the PPIM towards ART/artemether (ARE) reached its peak value (3.16) within only 10 min at this flow rate, which is higher than that of porous PVDF foam non-imprinted membranes (PPNM) (ca. 1.5), showing great separation efficiency in a short time. Moreover, the PPIM can be reused five times without a significant decrease in its adsorption capacities, showing good regeneration performance. This work highlights a simple strategy for constructing new MIMs with high flux and great mechanical strength to achieve the efficient selective separation of ART and ARE in practical applications.

10.
Proc Natl Acad Sci U S A ; 116(24): 11888-11893, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31138703

RESUMO

Neutrophils are vital for antimicrobial defense; however, their role during viral infection is less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. Here we report that BCL6 deficiency in myeloid cells exhibited drastically enhanced host resistance to severe influenza A virus (IAV) infection. In contrast to the notion that BCL6 functions to suppress innate inflammation, we find that myeloid BCL6 deficiency diminished lung inflammation without affecting viral loads. Using a series of Cre-transgenic, reporter, and knockout mouse lines, we demonstrate that BCL6 deficiency in neutrophils, but not in monocytes or lung macrophages, attenuated host inflammation and morbidity following IAV infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis in cells specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation or bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Partial neutrophil depletion led to diminished pulmonary inflammation and decreased host morbidity. Our results reveal a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection. Furthermore, our studies indicate that tissue-specific regulation of neutrophil survival modulates host inflammation and tissue immunopathology during acute respiratory viral infection.


Assuntos
Vírus da Influenza A/patogenicidade , Neutrófilos/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Pneumonia/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Animais , Apoptose/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Pulmão/metabolismo , Pulmão/virologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/fisiologia , Neutrófilos/virologia , Pneumonia/virologia , Infecções Respiratórias/metabolismo , Infecções Respiratórias/virologia
11.
Plant Dis ; 106(10): 2648-2655, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35394330

RESUMO

Rice false smut, caused by Ustilaginoidea virens, is one of the most destructive fungal diseases in rice-growing countries. Studies of the genetic diversity, evolution, and pathogenicity of U. virens can provide more information for disease control and cultivar breeding. Contrary to previous studies on the genetic diversity of different geographical populations of U. virens, this study analyzed the genetic variation of U. virens from different panicles of the same rice cultivar in a field in Yunnan Province using single nucleotide polymorphism molecular markers. A total of 183 polymorphic loci and five haplotypes, hap_1 to hap_5, were identified based on the 1,350-bp combined DNA fragment of 127 isolates, showing some genetic diversity. Hap_1 and hap_3 had the highest occurrence, indicating they were the dominant haplotypes in the field. Further analysis showed that most rice panicles could be coinfected by different haplotypes, and even a few spikelets could be coinfected by multiple haplotypes. The phylogeny indicated that all isolates were divided into five genetic groups. Groups I, II, and III clustered together and were distinguished from Groups IV and V. Significant genetic variations in five pairwise comparisons of panicle populations, accounting for 72.45% of the total variation, were found according to FST values. This variation might be caused by different field microenvironments and the uneven distribution of inoculum sources. An unweighted pair-group method with arithmetic means dendrogram and the population structure revealed that the genetic composition of the isolates collected from YN1, YN2, and YN4, which were dominated by the same genetic subgroup, was different from that collected from YN3. Finally, genetic recombination was found in 11 isolates; hap_2 and hap_5, probably as genetic recombination progenies produced by sexual hybridization between hap_1 and hap_3, acquired a greater virulence than their ancestors according to population structure and pathogenicity analyses. These results will help us understand the genetic diversity, evolution, and infection process of U. virens and aid in the development of more effective management strategies for rice false smut, including new cultivars with improved resistance.


Assuntos
Oryza , Ustilaginales , China , Hypocreales , Oryza/microbiologia , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único , Virulência/genética
12.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142116

RESUMO

CRISPR/Cas-based genome editing technologies, which allow the precise manipulation of plant genomes, have revolutionized plant science and enabled the creation of germplasms with beneficial traits. In order to apply these technologies, CRISPR/Cas reagents must be delivered into plant cells; however, this is limited by tissue culture challenges. Recently, viral vectors have been used to deliver CRISPR/Cas reagents into plant cells. Virus-induced genome editing (VIGE) has emerged as a powerful method with several advantages, including high editing efficiency and a simplified process for generating gene-edited DNA-free plants. Here, we briefly describe CRISPR/Cas-based genome editing. We then focus on VIGE systems and the types of viruses used currently for CRISPR/Cas9 cassette delivery and genome editing. We also highlight recent applications of and advances in VIGE in plants. Finally, we discuss the challenges and potential for VIGE in plants.


Assuntos
Edição de Genes , Vírus , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Genoma de Planta , Plantas/genética , Plantas Geneticamente Modificadas/genética , Vírus/genética
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(2): 143-147, 2022 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-35076908

RESUMO

OBJECTIVE: To identify the causative variants in 13 Chinese pedigrees affected with oculocutaneous albinism (OCA) so as to provide genetic counseling and prenatal diagnosis to them. METHODS: Thirteen unrelated pedigrees with clinically diagnosed OCA were collected and classified based on the manifestation of skin and eyes. With informed consent obtained from the participants, peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate variants were screened by targeted capture and next generation sequencing, and the results were validated by Sanger sequencing. Prenatal diagnosis was provided to the families upon their subsequent pregnancies. RESULTS: Causative variants were detected in all probands, including 10 with compound heterozygotes or homozygotes for TYR gene variants and 3 with compound heterozygotes for OCA2 gene variants. Among these, two variants [TYR: c.650G>C (p.Arg217Pro) and OCA2: c.516-2A>T] were unreported previously. The pathogenicity of the novel TYR: c.650G>C (p.Arg217Pro) variant was verified through bioinformatic analysis and prediction of three dimensional structure of the protein. Prenatal diagnosis was provided to 6 fetuses with a high risk for OCA. Four fetuses were found to be carriers, one did not carry the variants of the proband, and one was affected with OCA. CONCLUSION: Identification of the pathogenic variants in the 13 probands, including 2 novel ones, has expanded the mutational spectrum of OCA and enabled genetic counseling and prenatal diagnosis for the families.


Assuntos
Albinismo Oculocutâneo , Proteínas de Membrana Transportadoras , Albinismo Oculocutâneo/genética , China , Feminino , Testes Genéticos , Humanos , Proteínas de Membrana Transportadoras/genética , Monofenol Mono-Oxigenase/genética , Mutação , Linhagem , Gravidez , Diagnóstico Pré-Natal
14.
Small ; 17(46): e2103351, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651430

RESUMO

The advancement of electromagnetic (EM) protection technology promotes the urgent demand for the structural design of electromagnetic functional materials. Here, tadpole-like Fe@SiO2 @C-Ni (FSCN) composites with magnetic core-shell and nonspherical hollow architectures through multiple hydrolysis-polymerization reactions are reported. The Fe core and well-distributed Ni nanoparticles greatly promote the magnetic properties of FSCN and construct a multiscale magnetic coupling network. Meanwhile, the multishell composites consisting of carbon shell with Ni decorated possess an abundance of heterogeneous interfaces, generating effective interfacial polarization and relaxation. The hollow feature and the coordination of magnetic and dielectric capacities offer an optimized impedance balance, providing a fundament for the microwaves propagating into the absorber. Owing to the attractive effects resulted from the deliberate tadpole-like structure design, the FSCN composites ensure an effective EM energy conversion at the high-frequency region, which obtain the strongest reflection loss value of -45.2 dB and the extremely broad effective absorption bandwidth of 13.1 GHz. This work provides an important solution for magnetic-dielectric nanostructure design for microwave absorption and energy conversion materials.

15.
J Virol ; 93(9)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30787149

RESUMO

Alveolar macrophages (AM) play pivotal roles in modulating host defense, pulmonary inflammation, and tissue injury following respiratory viral infections. However, the transcriptional regulation of AM function during respiratory viral infections is still largely undefined. Here we have screened the expression of 84 transcription factors in AM in response to influenza A virus (IAV) infection. We found that the transcription factor PPAR-γ was downregulated following IAV infection in AM through type I interferon (IFN)-dependent signaling. PPAR-γ expression in AM was critical for the suppression of exaggerated antiviral and inflammatory responses of AM following IAV and respiratory syncytial virus (RSV) infections. Myeloid PPAR-γ deficiency resulted in enhanced host morbidity and increased pulmonary inflammation following both IAV and RSV infections, suggesting that macrophage PPAR-γ is vital for restricting severe host disease development. Using approaches to selectively deplete recruiting monocytes, we demonstrate that PPAR-γ expression in resident AM is likely important in regulating host disease development. Furthermore, we show that PPAR-γ was critical for the expression of wound healing genes in AM. As such, myeloid PPAR-γ deficiency resulted in impaired inflammation resolution and defective tissue repair following IAV infection. Our data suggest a critical role of PPAR-γ expression in lung macrophages in the modulation of pulmonary inflammation, the development of acute host diseases, and the proper restoration of tissue homeostasis following respiratory viral infections.IMPORTANCE Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.


Assuntos
Vírus da Influenza A/metabolismo , Macrófagos Alveolares/metabolismo , Infecções por Orthomyxoviridae/metabolismo , PPAR gama/biossíntese , Pneumonia Viral/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sinciciais Respiratórios/metabolismo , Animais , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/virologia , Macrófagos Alveolares/patologia , Macrófagos Alveolares/virologia , Camundongos , Camundongos Knockout , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/patologia , PPAR gama/genética , Pneumonia Viral/genética , Pneumonia Viral/patologia , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/patologia
16.
J Fish Dis ; 43(2): 215-225, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31770821

RESUMO

LuxR-type transcriptional factors are essential in many bacterial physiological processes. However, there have been no reports on their roles in Aeromonas hydrophila. In this study, six stable silent strains were constructed using shRNA. Significant decreases in the expression levels of luxR05 , luxR08 , luxR19 , luxR11 , luxR164 and luxR165 were shown in their respective strains by qRT-PCR. The luxR05 -RNAi and luxR164 -RNAi exhibit the most significant changes in sensitivity to kanamycin and gentamicin. The luxR05 -RNAi showed minimum biofilm formation and the least motility, while luxR164 -RNAi showed minimum biofilm formation, adhesion, growth and extracellular protease activity compared to the wild-type strain. In summary, the results of this paper suggest that all six luxR genes are involved in multiple physiological processes in A. hydrophila and that the roles of luxR05 and luxR164 are highly significant. The sensitivity of luxR05 -RNAi and luxR164 -RNAi to drugs may be closely related to biofilm formation. The luxR05 may play an important role in the pathogenicity of A. hydrophila by regulating the movement, adhesion and biofilm formation of bacteria, whereas luxR164 may be involved in similar functions by regulating bacterial adhesion, extracellular enzyme activity and growth. These results help further our understanding of the drug resistance and pathogenesis of A. hydrophila.


Assuntos
Aeromonas hydrophila/fisiologia , Aderência Bacteriana , Proteínas de Bactérias/genética , Biofilmes , Farmacorresistência Bacteriana , Proteínas Repressoras/genética , Transativadores/genética , Aeromonas hydrophila/efeitos dos fármacos , Aeromonas hydrophila/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , RNA Interferente Pequeno/genética , Proteínas Repressoras/metabolismo , Transativadores/metabolismo
17.
Sci Total Environ ; 912: 168834, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38036125

RESUMO

Atmosphere is an important component of the microplastics (MPs) cycle. However, studies on atmospheric MPs in peri-urban farmland ecosystems are limited. Herein, the occurrence, influencing factors and geographic sources of atmospheric MPs in peri-urban farmland ecosystems have been analyzed. The average deposition flux of atmospheric MPs was found to be 167.09 ± 92.03 item·m-2·d-1. Around 68 % MPs had particle size <1000 µm, while the main colors of MPs were black (40.71 %) and blue (20.64 %). Approximately 91 % MPs were fibers, while polyethylene terephthalate (49 %) and rayon (36.93 %) were observed as the major microplastic types. The main factors influencing the atmospheric deposition of MPs were gross domestic product (GDP), population density, air pressure, and wind direction. Deposition fluxes exhibited positive correlations with GDP, population density and air pressure, and negative correlations with wind direction. Combined with the backward trajectory model, MPs were mainly found to be originated from the southeast in September and from the northwest in October-February. The study of atmospheric MPs in farmland ecosystems in peri-urban areas is important for the protection of ecological environment, prevention of human diseases and control of MPs pollution.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Pequim , Plásticos , Ecossistema , Fazendas , China , Monitoramento Ambiental
18.
Front Pharmacol ; 15: 1257253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370471

RESUMO

PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) and needs to be inhibited when over-expressed. In order to study the PARP1 inhibitory effect of fused tetracyclic or pentacyclic dihydrodiazepinoindolone derivatives (FTPDDs) by quantitative structure-activity relationship technique, six models were established by four kinds of methods, heuristic method, gene expression programming, random forester, and support vector regression with single, double, and triple kernel function respectively. The single, double, and triple kernel functions were RBF kernel function, the integration of RBF and polynomial kernel functions, and the integration of RBF, polynomial, and linear kernel functions respectively. The problem of multi-parameter optimization introduced in the support vector regression model was solved by the particle swarm optimization algorithm. Among the models, the model established by support vector regression with triple kernel function, in which the optimal R 2 and RMSE of training set and test set were 0.9353, 0.9348 and 0.0157, 0.0288, and R2 cv of training set and test set were 0.9090 and 0.8971, shows the strongest prediction ability and robustness. The method of support vector regression with triple kernel function is a great promotion in the field of quantitative structure-activity relationship, which will contribute a lot to designing and screening new drug molecules. The information contained in the model can provide important factors that guide drug design. Based on these factors, six new FTPDDs have been designed. Using molecular docking experiments to determine the properties of new derivatives, the new drug was ultimately successfully designed.

19.
J Phys Chem Lett ; : 7118-7124, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959028

RESUMO

Mechanofluorochromic materials are a type of "smart" material because of their adjustable fluorescent properties under external mechanical force, making them significant members of the materials family. However, as the fluorescent characteristics of these materials highly depend on their microstructures, the still insufficiently in-depth research linking molecular structures to light emission motivates researchers to explore the fluorescent properties of these materials under external stimuli. In this work, based on synthetic [AgS4] microplates, we explore a fascinating mechanical-induced photoluminescent enhancement phenomenon. By applying mechanical force to solid-state [AgS4] to damage the surface morphology, a significant enhancement in photoluminescence is observed. Moreover, the emitted intensity increases with the extent of damage, which can be attributed to alterations in crystallinity. This work provides valuable insights into the relationship among photoluminescence, crystallinity, and mechanical force, offering new strategies for designing luminescent devices.

20.
Adv Mater ; 36(24): e2313411, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38469974

RESUMO

Precise manipulation of van der Waals forces within 2D atomic layers allows for exact control over electron-phonon coupling, leading to the exceptional quantum properties. However, applying this technique to diverse structures such as 3D materials is challenging. Therefore, investigating new hierarchical structures and different interlayer forces is crucial for overcoming these limitations and discovering novel physical properties. In this work, a multishelled ferromagnetic material with controllable shell numbers is developed. By strategically regulating the magnetic interactions between these shells, the magnetic properties of each shell are fine-tuned. This approach reveals distinctive magnetic characteristics including regulated magnetic domain configurations and enhanced effective fields. The nanoscale magnetic interactions between the shells are observed and analyzed, which shed light on the modified magnetic properties of each shell, enhancing the understanding and control of ferromagnetic materials. The distinctive magnetic interaction significantly boosts electromagnetic absorption at low-frequency frequencies used by fifth-generation wireless devices, outperforming ferromagnetic materials without multilayer structures by several folds. The application of magnetic interactions in materials science reveals thrilling prospects for technological and electronic innovation.

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