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1.
Artigo em Inglês | MEDLINE | ID: mdl-34473888

RESUMO

In this study, we successfully solve polymorphs A and B of zeolite EMM-17, which can only crystallize in sub-micrometer-sized crystals while containing complex stacking disorders, from the three-dimensional (3D) electron diffraction (ED) data. This is the first time that the atomic structure of this polymorph has been ab initio solved, and the result reveals a unique 10(12)×10(12)×11-ring channel system. Moreover, we acquire the first atomic-resolution images of EMM-17 using integrated differential phase-contrast scanning transmission electron microscopy. The images allow us to directly observe polymorphs B and C and discover a large number of local structural defects. Based on structural features unraveled from the reciprocal-space 3D ED data and real-space images, we propose a series of energetically feasible local structures in EMM-17. We also demonstrate that the unique porous structure of EMM-17 enables efficient kinetic separation of C6 alkane isomers.

2.
Sci Total Environ ; 791: 148283, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34412411

RESUMO

Canopy conductance, one of the key variables in simulating evapotranspiration, is strongly influenced by the physiological status of a plant and environmental factors, including photosynthetically active radiation, vapor pressure deficit, air temperature, soil moisture and so on. However, the restrictive functions used to represent these factors rarely consider the dynamics of physiological and environmental factors. This study proposed an improved canopy conductance model by regarding radiation and vapor pressure deficit as the two main influencing factors, quantifying the temporal variation in stomatal responses to radiation that notably adjust stomatal behavior, parameterizing maximum stomatal conductance with plant type-specific functions and proposing a new restrictive function for the VPD. The improved canopy conductance model was incorporated in a surface conductance model for estimating surface conductance and evapotranspiration at 8 flux stations at the Heihe River Basin and the Haihe River Basin. The estimated results were the most accurate when comparing to two other models. Furthermore, the model performance was acceptable when most of the parameters were assumed to be constant across the sites except the reference canopy conductance Gc, ref and the soil evaporation parameter αs, which suggests that the improved canopy conductance model could be used as a parsimony model for improving canopy conductance predictions and water use efficiency over typical climate zones and underlying surface types in North of China.


Assuntos
Transpiração Vegetal , Água , Clima , Rios , Temperatura
3.
Nat Commun ; 12(1): 4902, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385461

RESUMO

Efficient and precise base editors (BEs) for C-to-G transversion are highly desirable. However, the sequence context affecting editing outcome largely remains unclear. Here we report engineered C-to-G BEs of high efficiency and fidelity, with the sequence context predictable via machine-learning methods. By changing the species origin and relative position of uracil-DNA glycosylase and deaminase, together with codon optimization, we obtain optimized C-to-G BEs (OPTI-CGBEs) for efficient C-to-G transversion. The motif preference of OPTI-CGBEs for editing 100 endogenous sites is determined in HEK293T cells. Using a sgRNA library comprising 41,388 sequences, we develop a deep-learning model that accurately predicts the OPTI-CGBE editing outcome for targeted sites with specific sequence context. These OPTI-CGBEs are further shown to be capable of efficient base editing in mouse embryos for generating Tyr-edited offspring. Thus, these engineered CGBEs are useful for efficient and precise base editing, with outcome predictable based on sequence context of targeted sites.


Assuntos
Sistemas CRISPR-Cas , Citidina Desaminase/metabolismo , Edição de Genes/métodos , Aprendizado de Máquina , Uracila-DNA Glicosidase/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Caenorhabditis elegans/genética , Códon/genética , Citidina Desaminase/genética , Escherichia coli/genética , Feminino , Biblioteca Gênica , Células HEK293 , Humanos , Camundongos , Reprodutibilidade dos Testes , Uracila-DNA Glicosidase/genética
4.
Pharmacol Ther ; 226: 107867, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33895191

RESUMO

Farnesoid X receptor (FXR) influences bile acid homeostasis and the progression of various diseases. While the roles of hepatic and intestinal FXR in enterohepatic transport of bile acids and metabolic diseases were reviewed previously, the pathophysiological functions of FXR in non-gastrointestinal cells and tissues have received little attention. Thus, the roles of FXR in the liver, immune system, nervous system, cardiovascular system, kidney, and pancreas beyond the gastrointestinal system are reviewed herein. Gain of FXR function studies in non-gastrointestinal tissues reveal that FXR signaling improves various experimentally-induced metabolic and immune diseases, including non-alcoholic fatty liver disease, type 2 diabetes, primary biliary cholangitis, sepsis, autoimmune diseases, multiple sclerosis, and diabetic nephropathy, while loss of FXR promotes regulatory T cells production, protects the brain against ischemic injury, atherosclerosis, and inhibits pancreatic tumor progression. The downstream pathways regulated by FXR are diverse and tissue/cell-specific, and FXR has both ligand-dependent and ligand-independent activities, all of which may explain why activation and inhibition of FXR signaling could produce paradoxical or even opposite effects in some experimental disease models. FXR signaling is frequently compromised by diseases, especially during the progressive stage, and rescuing FXR expression may provide a promising strategy for boosting the therapeutic effect of FXR agonists. Tissue/cell-specific modulation of non-gastrointestinal FXR could influence the treatment of various diseases. This review provides a guide for drug discovery and clinical use of FXR modulators.

5.
Toxicol Sci ; 181(2): 273-284, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33662127

RESUMO

The idiosyncratic characteristics and severity of acetaminophen (APAP) overdose-induced hepatotoxicity render identifying the predisposing factors and mechanisms of APAP-induced liver toxicity necessary and urgent. Farnesoid X receptor (FXR) controls bile acid homeostasis and modulates the progression of various liver diseases. Although global FXR deficiency in mice enhances APAP intoxication, the mechanism remains elusive. In this study, an increased sensitivity to APAP-induced toxicity was found in global Fxr-null (Fxr-/-) mice, but was not observed in hepatocyte-specific or macrophage-specific Fxr-null mice, suggesting that global FXR deficiency enhances APAP hepatotoxicity via disruption of systematic bile acid homeostasis. Indeed, more bile acid accumulation was found in global Fxr-/- mice, while 2% cholestyramine diet feeding decreased serum bile acids and alleviated APAP hepatotoxicity in global Fxr-/- mice, suggesting that bile acid accumulation contributes to APAP toxicity. Bile acids were suspected to induce macrophage to release tumor necrosis factor-α (TNF-α), which is known to enhance the APAP hepatotoxicity. In vitro, deoxycholic acid (DCA), a secondary bile acid metabolite, significantly induced Tnfa mRNA and dose-dependently enhanced TNF-α release from macrophage, while the same dose of DCA did not directly potentiate APAP toxicity in cultured primary hepatocytes. In vivo, DCA enhanced TNF-α release and potentiated APAP toxicity, both of which were abolished by the specific TNF-α antagonist infliximab. These results reveal an FXR-DCA-TNF-α axis that potentiates APAP hepatotoxicity, which could guide the clinical safe use of APAP.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácido Desoxicólico , Hepatócitos , Fígado , Camundongos , Camundongos Endogâmicos C57BL
6.
Cell Death Dis ; 12(2): 174, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574236

RESUMO

Fulminant hepatitis (FH) is an incurable clinical syndrome where novel therapeutics are warranted. Withaferin A (WA), isolated from herb Withania Somnifera, is a hepatoprotective agent. Whether and how WA improves D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced FH is unknown. This study was to evaluate the hepatoprotective role and mechanism of WA in GalN/LPS-induced FH. To determine the preventive and therapeutic effects of WA, wild-type mice were dosed with WA 0.5 h before or 2 h after GalN treatment, followed by LPS 30 min later, and then killed 6 h after LPS treatment. To explore the mechanism of the protective effect, the macrophage scavenger clodronate, autophagy inhibitor 3-methyladenine, or gene knockout mouse lines NLR family pyrin domain containing 3 (Nlrp3)-null, nuclear factor-erythroid 2-related factor 2 (Nrf2)-null, liver-specific AMP-activated protein kinase (Ampk)a1 knockout (Ampka1ΔHep) and liver-specific inhibitor of KB kinase ß (Ikkb) knockout (IkkbΔHep) mice were subjected to GalN/LPS-induced FH. In wild-type mice, WA potently prevented GalN/LPS-induced FH and inhibited hepatic NLRP3 inflammasome activation, and upregulated NRF2 and autophagy signaling. Studies with Nrf2-null, Ampka1ΔHep, and IkkbΔHep mice demonstrated that the hepatoprotective effect was independent of NRF2, hepatic AMPKα1, and IκκB. Similarly, 3-methyladenine cotreatment failed to abolish the hepatoprotective effect of WA. The hepatoprotective effect of WA against GalN/LPS-induced FH was abolished after macrophage depletion, and partially reduced in Nlrp3-null mice. Consistently, WA alleviated LPS-induced inflammation partially dependent on the presence of NLRP3 in primary macrophage in vitro. Notably, WA potently and therapeutically attenuated GalN/LPS-induced hepatotoxicity. In conclusion, WA improves GalN/LPS-induced hepatotoxicity by targeting macrophage partially dependent on NLRP3 antagonism, while largely independent of NRF2 signaling, autophagy induction, and hepatic AMPKα1 and IκκB. These results support the concept of treating FH by pharmacologically targeting macrophage and suggest that WA has the potential to be repurposed for clinically treating FH as an immunoregulator.


Assuntos
Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Inflamassomos/antagonistas & inibidores , Fígado/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Necrose Hepática Massiva/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Vitanolídeos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Galactosamina , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamassomos/genética , Inflamassomos/metabolismo , Lipopolissacarídeos , Fígado/metabolismo , Fígado/patologia , Macrófagos Peritoneais/metabolismo , Necrose Hepática Massiva/induzido quimicamente , Necrose Hepática Massiva/metabolismo , Necrose Hepática Massiva/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos
7.
Arch Virol ; 166(2): 439-449, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389105

RESUMO

Chicken infectious anemia (CIA), caused by chicken anemia virus (CAV), is an important immunosuppressive disease that seriously threatens the global poultry industry. Here, we isolated and identified 30 new CAV strains from CAV-positive flocks. The VP1 genes of these strains were sequenced and analyzed at the nucleotide and amino acid levels and were found to have very similar nucleotide sequences (> 97% identity); however, they showed 93.9-100.0% sequence identity to the VP1 genes of 55 reference strains. Furthermore, alignment of the deduced amino acid sequences revealed some unique mutations. Phylogenetic analysis indicated the division of VP1 amino acid sequences into two groups (A and B) and four subgroups (A1, A2, A3 and A4). Interestingly, 22 of the newly isolated strains and some Asian reference strains belonged to the A1 group, whereas the remaining eight new isolates belonged to the A3 group. To evaluate the pathogenicity of the epidemic CAV strains from China, the representative strains CAV-JL16/8901 and CAV-HeN19/3001 and the reference strain Cux-1 were selected for animal experiments. Chickens infected with the isolates and reference strain all showed thymus atrophy and bone marrow yellowing. The mortality rates for CAV-JL16/8901, CAV-HeN19/3001, and the reference strain was 30%, 20%, and 0%, respectively, indicating that the epidemic strains pose a more serious threat to chickens. We not only analyzed the molecular evolution of the epidemic strains but also showed for the first time that the epidemic strains in China are more pathogenic than reference strain Cux-1. Effective measures should be established to prevent the spread of CIA in China.


Assuntos
Vírus da Anemia da Galinha/genética , Vírus da Anemia da Galinha/patogenicidade , Galinhas/virologia , Animais , China , Infecções por Circoviridae/virologia , DNA Viral/genética , Evolução Molecular , Genótipo , Epidemiologia Molecular/métodos , Filogenia , Doenças das Aves Domésticas/virologia , Análise de Sequência de DNA/métodos , Virulência/genética
8.
Small ; 16(33): e2000902, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32686318

RESUMO

Cu-exchanged LTA-type aluminosilicate catalyst has been considered as an efficient catalyst for the selective catalytic reduction of NOx with ammonia (NH3 -SCR). However, expensive organic structure-directing agents (OSDAs) and the corrosive fluoride medium are inevitably used to synthesize LTA-type molecular sieve (high-silica LTA-type aluminosilicate and its analogue LTA-type silicoaluminophosphate SAPO-42). Herein, a series of cheap and commercialized OSDAs, which are successfully applied for the targeted synthesis of SAPO-42 in the fluoride-free system, are identified by a novel RSS (refine, summarize, and search) approach. Furthermore, Cu-SAPO-42 catalysts are utilized for NH3 -SCR. Among these catalysts, Cu-SAPO-42 prepared with 2-(butylamino)ethanol (BAEA) as OSDA demonstrates the excellent activity even after hydrothermal aging at 800 °C for 16 h, which shows much better hydrothermal stability than the commercialized Cu-SAPO-34 catalyst with comparable Si and Cu contents. Electron paramagnetic resonance (EPR) spectroscopy and Rietveld refinement are performed to identify the locations of active Cu2+ ions. It turns out that the active Cu2+ ions are distributed near the center of single 6-rings of the lta cage.

9.
Adv Mater ; 32(26): e2000272, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32430991

RESUMO

High-silica zeolite Y is a desired catalytic material for oil refining and the petrochemical industry. However, its direct synthesis remains a symbolic challenge in the field of zeolite synthesis, with a limited improvement of the framework SiO2 /Al2 O3 ratio (SAR) from ≈5 to 9 over the past 60 years. Here, the synthesis of highly siliceous zeolite Y with tunable SAR up to 15.6 through a cooperative strategy is reported, which involves the use of FAU nuclei, a bulky organic structure-directing agent (OSDA), and a gel system with low alkalinity (named NOA-co strategy). A series of quaternary alkylammonium ions is discovered as effective OSDAs based on the NOA-co strategy, and the relevant crystallization mechanism is elucidated. Moreover, the high-silica products are demonstrated to have greatly improved (hydro)thermal stability, high concentration of strong acid sites, and uniform acid distribution, which lead to superior catalytic performance in the cracking of bulky hydrocarbons. It is anticipated that this synthetic strategy will benefit the synthesis and development of zeolitic catalysts in a wide range of reaction processes.

10.
Sci Total Environ ; 728: 138582, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353797

RESUMO

Agricultural water resource, mainly consumed through evapotranspiration, plays a critical role in agricultural production of arid and semiarid regions. Quantifying the changes of evapotranspiration in cropland (ETc), and its driving factors, may provide rich information for improving human land-use and water resource management. Here we first investigated the multi-year (2000-2015) changes in the ETc (mm yr-1) and associated driving factors of the Loess Plateau (LP), using a combination of the Vegetation Interfaces Processes model and a factorial analysis of variance. We found that the ETc of the LP showed a significant upward trend of 0.31 km3 yr-2 (3.33 mm yr-2) (p < .05) over the last 16 years, mainly driven by cropland changes (3.77% per year), which combined the contribution of cropland area changes and cropland leaf area index (LAIc) changes. We then examined the changes of the dominant driving factor: cropland, and results indicated that the cropland changes consisted of the decrease in cropland area (net decrease of 10.50 × 103 km2) and the increase in LAIc (increased by 10.72%), which suggest the actual contribution of the ETc uptrend was the increasing LAIc. Our further analysis on the causes of the increasing LAIc by correlating the LAIc with land-use management factors revealed that the cropland greening on the LP showed high positive correlations with the increasing inputs of total power of agriculture machinery and farm plastic film, followed by chemical fertilizer. The increase of LAIc was also promoted by the increased ratio of the garden fruits output to total crops output (increased by 67.12%) and multiple cropping (increased by 21.66%). These results suggest that the ETc uptrend can be related to the agricultural intensification. Our study highlights the need for a realistic representation of socio-economic development and human land-use practices in the sustainable optimal allocation of agricultural water resources on the LP.


Assuntos
Agricultura , Solo , China , Produtos Agrícolas , Fertilizantes
11.
Viruses ; 12(2)2020 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102240

RESUMO

Infectious bursal disease (IBD) is an immunosuppressive, highly contagious, and lethal disease of young chickens caused by IBD virus (IBDV). It results in huge economic loss to the poultry industry worldwide. Infection caused by very virulent IBDV (vvIBDV) strains results in high mortality in young chicken flocks. However, the replication characteristics of vvIBDV are not well studied. Publications have shown that virus protein 3 (VP3) binds to VP1 and viral double-stranded RNA, and together they form a ribonucleoprotein complex that plays a key role in virus replication. In this study, vvIBDV VP3 was used to identify host proteins potentially involved in modulating vvIBDV replication. Chicken eukaryotic translation elongation factor 1α (cheEF1α) was chosen to further investigate effects on vvIBDV replication. By small interfering RNA-mediated cheEF1α knockdown, we demonstrated the possibility of significantly reducing viral polymerase activity, with a subsequent reduction in virus yields. Conversely, over-expression of cheEF1α significantly increased viral polymerase activity and virus replication. Further study confirmed that cheEF1α interacted only with vvIBDV VP3 but not with attenuated IBDV (aIBDV) VP3. Furthermore, the amino acids at the N- and C-termini were important in the interaction between vvIBDV VP3 and cheEF1α. Domain III was essential for interactions between cheEF1α and vvIBDV VP3. In summary, cheEF1α enhances vvIBDV replication by promoting the activity of virus polymerase. Our study indicates cheEF1α is a potential target for limiting vvIBDV infection.


Assuntos
RNA Polimerases Dirigidas por DNA/metabolismo , Fatores de Iniciação em Eucariotos/genética , Vírus da Doença Infecciosa da Bursa/genética , Vírus da Doença Infecciosa da Bursa/patogenicidade , Replicação Viral/genética , Animais , Proteínas do Capsídeo/genética , Linhagem Celular , Galinhas/genética , Galinhas/virologia , RNA Polimerases Dirigidas por DNA/genética , Vírus da Doença Infecciosa da Bursa/enzimologia , Doenças das Aves Domésticas/virologia , Virulência
12.
Acta Pharm Sin B ; 10(1): 3-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993304

RESUMO

Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called "multiple organs-multiple hits" is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.

13.
Mol Ther Nucleic Acids ; 19: 775-789, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-31955009

RESUMO

CRISPR/Cas9-mediated homology-directed repair (HDR) can be leveraged to precisely engineer mammalian genomes. However, the inherently low efficiency of HDR often hampers to identify the desired modified cells. Here, we developed a novel universal surrogate reporter system that efficiently enriches for genetically modified cells arising from CRISPR/Cas9-induced HDR events (namely, the "HDR-USR" system). This episomally based reporter can be self-cleaved and self-repaired via HDR to create a functional puromycin selection cassette without compromising genome integrity. Co-transfection of the HDR-USR system into host cells and transient puromycin selection efficiently achieves enrichment of HDR-modified cells. We tested the system for precision point mutation at 16 loci in different human cell lines and one locus in two rodent cell lines. This system exhibited dramatic improvements in HDR efficiency at a single locus (up to 20.7-fold) and two loci at once (42% editing efficiency compared to zero in the control), as well as greatly improved knockin efficiency (8.9-fold) and biallelic deletion (35.9-fold) at test loci. Further increases were achieved by co-expression of yeast Rad52 and linear single-/double-stranded DNA donors. Taken together, our HDR-USR system provides a simple, robust and efficient surrogate reporter for the enrichment of CRISPR/Cas9-induced HDR-based precision genome editing across various targeting loci in different cell lines.

14.
J Virol ; 94(2)2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31666381

RESUMO

Infectious bursal disease virus (IBDV) is an important member of the Birnaviridae family, causing severe immunosuppressive disease in chickens. The major capsid protein VP2 is responsible for the binding of IBDV to the host cell and its cellular tropism. In order to find proteins that potentially interact with IBDV VP2, a liquid chromatography-mass spectrometry (LC-MS) assay was conducted, and the host chicken CD74 protein was identified. Here, we investigate the role of chicken CD74 in IBDV attachment. Coimmunoprecipitation assays indicated that the extracellular domain of CD74 interacted with the VP2 proteins of multiple IBDV strains. Knockdown and overexpression experiments showed that CD74 promotes viral infectivity. Confocal assays showed that CD74 overexpression allows the attachment of IBDV and subvirus-like particles (SVPs) to the cell surface of nonpermissive cells, and quantitative PCR (qPCR) analysis further confirmed the attachment function of CD74. Anti-CD74 antibody, soluble CD74, depletion of CD74 by small interfering RNA (siRNA), and CD74 knockdown in the IBDV-susceptible DT40 cell line significantly inhibited IBDV binding, suggesting a pivotal role of this protein in virus attachment. These findings demonstrate that CD74 is a novel important receptor for IBDV attachment to the chicken B lymphocyte cell line DT40.IMPORTANCE CD74 plays a pivotal role in the correct folding and functional stability of major histocompatibility complex class II (MHC-II) molecules and in the presentation of antigenic peptides, acting as a regulatory factor in the antigen presentation process. In our study, we demonstrate a novel role of CD74 during IBDV infection, showing that chicken CD74 plays a significant role in IBDV binding to target B cells by interacting with the viral VP2 protein. This is the first report demonstrating that CD74 is involved as a novel attachment receptor in the IBDV life cycle in target B cells, thus contributing new insight into host-pathogen interactions.


Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Proteínas Aviárias/imunologia , Linfócitos B/imunologia , Infecções por Birnaviridae/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Animais , Linfócitos B/patologia , Infecções por Birnaviridae/patologia , Embrião de Galinha , Galinhas , Células HeLa , Humanos , Doenças das Aves Domésticas/patologia
15.
Front Microbiol ; 10: 2225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632367

RESUMO

Infectious bursal disease (IBD) is one of the main threats to the poultry industry worldwide. In China, very virulent IBD virus (vvIBDV) is the main prevalent virus strain, causing inflammation, immunosuppression, and high mortality in young chickens. To determine whether this acute inflammation can trigger lesions or even death in chickens, it is important to study the mechanism of vvIBDV pathogenicity. Thus, in the current study, we investigated the inflammation response, bursal lesions, and mortality in chickens caused by vvIBDV at different time points postinfection. Results showed an upregulation of proinflammatory cytokines, including interleukin-1ß and interleukin-18, and macrophage infiltration in bursa in response to vvIBDV infection. High-throughput proteomic sequencing based on isobaric tags for relative and absolute quantitation showed that chicken macrophage migration inhibitory factor (chMIF) was upregulated uniquely in primary bursal cells infected with vvIBDV compared with infection by nonpathogenic attenuated IBDV. We confirmed that chMIF was upregulated by vvIBDV infection both in vivo and in vitro. Moreover, chMIF was extracellularly secreted by infected DT40 and primary bursal cells. Further experiments revealed that the secreted chMIF could induce migration of peripheral blood mononuclear cells and promote transcription of proinflammatory cytokines in chicken primary macrophages. Notably, these effects of chMIF could be reduced by using an MIF specific inhibitor. Thus, our study elucidates critical molecular determinants underlying vvIBDV-mediated initiation of acute inflammation, which might be pivotal to understand the mechanism of vvIBDV pathogenicity.

16.
Sci Total Environ ; 689: 534-545, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279200

RESUMO

The spatial distribution of water resources largely influences Earth ecosystems and human civilization. Being a major component of the global water cycle, evapotranspiration (ET) serves as an indicator of the availability of water resources. Understanding the actual ET (ETa) variation mechanism at different spatial and temporal scales can improve management of water use within the sustainable development limits. In this study, remote sensing derived ETa data were used to study water resource fluctuations in the Loess Plateau, China. This region covers diverse climate types from humid to arid and experienced large changes in vegetation cover during a revegetation project between 2000 and 2015. The relations between spatiotemporal variation of ETa, climate factors and vegetation change were explored using statistical methods. The results show that cropland, forestland and grassland take the largest percentage of total ETa. Total ETa exhibited a marginally increasing trend (p < 0.1) during 2000-2010 and no trend during 2011-2015. Windspeed and vegetation cover index highly influenced ETa, followed by atmospheric pressure, air humidity, precipitation, bright sunshine duration and temperature. Temperature has little effect on ETa throughout the Loess Plateau. The monitoring of water resources based upon water balance between precipitation, ETa and river flow changes shows that water consumption deficit is consistent with vegetation changes: it was large during 2000-2010 when vegetation increased rapidly and decreased after 2010. These results could help to develop different water saving strategies across the Loess Plateau and build a better monitoring system of water resources.


Assuntos
Mudança Climática , Conservação dos Recursos Naturais , Ecossistema , Transpiração Vegetal , China
17.
Front Aging Neurosci ; 11: 86, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057392

RESUMO

Background: Vascular dementia (VD) is a common type of disease in the elderly. Numerous clinical trials have suggested that hyperbaric oxygen is an effective and safe complementary therapy for aging-related disorders. However, there is no reliable systematic evidence regarding hyperbaric oxygen therapy (HBOT) for the treatment of VD. Therefore, we performed a meta-analysis to evaluate the clinical efficacy and safety of HBOT in treating VD. Methods: We methodically retrieved the clinical studies from eight databases (PubMed, Cochrane Library, Embase, Web of Science, Sino-Med, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WanFang) from their inception to November 2018. RevMan 5.3.5 was used for quality assessment and data analysis. Stata 15.1 was employed for publication bias detection and sensitivity analysis. Results: Twenty-five randomized clinical trials (RCTs) involving 1,954 patients met our inclusion criteria. These articles researched the HBOT + oxiracetam + conventional therapy (CT) vs. oxiracetam + CT (n = 13), HBOT + butylphthalide +CT vs. butylphthalide + CT (n = 5), HBOT + donepezil + CT vs. donepezil + CT (n = 4), HBOT + nicergoline + CT vs. nicergoline + CT (n = 2) and HBOT + CT vs. CT (n = 1). The results indicated that additional HBOT strikingly improved the Mini-Mental State Examination (MMSE) (MD = 4.00; 95% CI = 3.28-4.73; P < 0.00001), activities of daily living (ADL) (MD = -5.91; 95% CI = -6.45, -5.36; P < 0.00001) and ADL by Barthel index (BADL) (MD = 13.86; 95% CI = 5.63-22.10; P = 0.001) and increased the total efficacy rate (TEF) (OR = 4.84, 95% CI = 3.19-7.33, P < 0.00001). The adverse events rates were not statistically significant between the HBOT and CT groups (OR = 0.85, 95% CI = 0.26-2.78, P = 0.79). Conclusion: In view of the effectiveness and safety of HBOT, the present meta-analysis suggested that HBOT can be recommended as an effective and safe complementary therapy for the treatment of VD. Protocol Registration: PROSPERO (ID: CRD42019117178). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019117178.

18.
Front Genet ; 10: 347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057603

RESUMO

The SNP within intron 3 of the porcine IGF2 gene (G3072A) plays an important role for muscle growth and fat deposition in pigs. In this study, the StCas9 derived from Streptococcus thermophilus together with the Drosha-mediated sgRNA-shRNA structure were combined to boost the G to A base editing on the IGF2 SNP site, which we called "SNP editing." The codon-humanized StCas9 as we previously reported was firstly compared with the prevalently used SpCas9 derived from Streptococcus pyogenes using our idiomatic surrogate report assay, and the StCas9 demonstrated a comparable targeting activity. On the other hand, by combining shRNA with sgRNA, simultaneous gene silencing and genome targeting can be achieved. Thus, the novel IGF2.sgRNA-LIG4.shRNA-IGF2.sgRNA structure was constructed to enhance the sgRNA/Cas9-mediated HDR-based IGF2 SNP editing by silencing the LIG4 gene, which is a key molecule of the HDR's competitive NHEJ pathway. The sgRNA-shRNA/StCas9 all-in-one expression vector and the IGF2.sgRNA/StCas9 as control were separately used to transfect porcine PK15 cells together with an ssODNs donor for the IGF2 SNP editing. The editing events were detected by the RFLP assay, Sanger sequencing as well as Deep-sequencing, and the Deep-sequencing results finally demonstrated a significant higher HDR-based editing efficiency (16.38%) for our sgRNA-shRNA/StCas9 strategy. In short, we achieved effective IGF2 SNP editing by using the combined sgRNA-shRNA/StCas9 strategy, which will facilitate the further production of base-edited animals and perhaps extend for the gene therapy for the base correction of some genetic diseases.

19.
Int J Mol Med ; 43(6): 2376-2386, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942389

RESUMO

Macrophages can induce Fas ligand (FasL)­mediated apoptosis, and the deregulation of apoptosis is known to be associated with recurrent miscarriage (RM). The aim of the present study was to investigate the possible involvement of FasL in macrophage­mediated trophoblast apoptosis and its potential role in RM. Human decidual and placental villous tissues were collected from 81 women (21 for the RM group, 26 for the spontaneous abortion group and 34 for the control group) at 7­9 weeks of gestation. The distribution changes of macrophages and the expression of FasL on macrophages were evaluated by immunohistochemical, immunofluorescence and western blot analyses. A macrophage and trophoblast co­culture model was used to determine the effects of FasL on the apoptosis of trophoblasts. The results indicated that CD86+ macrophage populations in decidual tissues were significantly increased, accompanied by reduced CD163+ macrophages in the abortion and RM groups. Furthermore, the distribution of CD68+ macrophages was also significantly altered in specimens from the abortion and RM groups, and they were observed to have infiltrated into the trophoblast cells. In addition, elevated expression of FasL on CD68+ and CD86+ macrophages in the decidua was observed in the spontaneous abortion and RM groups of patients, and FasL was demonstrated to mediate the induction of trophoblast apoptosis by macrophages in co­culture. These results indicate that the aberration of macrophage­induced FasL­mediated apoptosis may represent one of the causes of RM.


Assuntos
Aborto Habitual/patologia , Apoptose , Decídua/patologia , Proteína Ligante Fas/análise , Macrófagos/patologia , Trofoblastos/patologia , Aborto Habitual/etiologia , Aborto Habitual/metabolismo , Adulto , Linhagem Celular , Decídua/citologia , Decídua/metabolismo , Proteína Ligante Fas/metabolismo , Feminino , Humanos , Macrófagos/metabolismo , Gravidez , Trofoblastos/citologia , Trofoblastos/metabolismo
20.
Mol Med Rep ; 19(4): 2620-2626, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720083

RESUMO

A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS­7) has been revealed to serve an important role in inflammation­associated diseases. However, the role of ADAMTS­7 in spontaneous abortion (SA) remains unclear. In the present study, human and mouse decidual tissues were used to detect the expression of ADAMTS­7 and cartilage oligomeric matrix protein (COMP) in mice with lipopolysaccharide (LPS)­induced abortion (10 mice/group), and in SA humans and the corresponding control group (21 participants in the SA group and 15 participants in the control group). The results revealed that ADAMTS­7 expression was upregulated and that COMP expression was downregulated in the mouse decidual tissue of the LPS­induced abortion group, when compared with that of the normal control group. The results were further confirmed by western blot analysis and reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis, which revealed increased ADAMTS­7 and decreased COMP expression at the protein and mRNA levels in mice treated with LPS. Additionally, the expression of ADAMTS­7 was negatively correlated with the expression of COMP in mice, with a correlation coefficient of ­0.936 (P<0.001). In addition, the expression of ADAMTS­7 and COMP exhibited was similar in the decidual tissue of SA patients when compared with the levels observed in the tissues of the normal control participants, as demonstrated by increased ADAMTS­7 expression and decreased COMP expression. Western blotting and RT­qPCR analysis revealed that ADAMTS­7 was increased and COMP was decreased in the decidual tissue of SA subjects. The correlation analysis of ADAMTS­7 and COMP in human decidual tissue also revealed a similar result, with a correlation coefficient of ­0.836 (P<0.001). The results of the present study demonstrated that ADAMTS­7 was upregulated and COMP was downregulated in the decidual tissues of humans and mice with SA, and a negative correlation was identified between the expression levels of ADAMTS­7 and COMP, thereby providing novel evidence for a better understanding of the pathogenesis of SA, which may lead to improvements in the clinical pregnancy outcomes of these individuals.


Assuntos
Aborto Espontâneo/etiologia , Proteína de Matriz Oligomérica de Cartilagem/genética , Regulação da Expressão Gênica , Proteína ADAMTS7/genética , Proteína ADAMTS7/metabolismo , Adulto , Animais , Biomarcadores , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Decídua/imunologia , Decídua/metabolismo , Decídua/patologia , Feminino , Humanos , Imuno-Histoquímica , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/imunologia , Camundongos , Gravidez
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