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1.
Small ; 20(11): e2308440, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37888806

RESUMO

Under the high current density, the excessive strong adsorption of H* intermediates and H2 accumulation the catalysts are the major obstacle to the industrial application of hydrogen evolation reaction (HER) catalysts. Herein, through experimental exploration, it is found that the superaerophobic Nitrogen (N)-doped carbon material can promote the rapid release of H2 and provide H* desorption site for the hydrogen spillover process, which makes it have great potential as the catalysts support for hydrogen spillover. Based on this discovery, this work develops the hydrogen spillover catalyst with electron-rich Pt sites loaded on N-doped carbon nanocage (N-CNC) with adjustable work function. Through a series of comprehensive electrochemical tests, the existence of hydrogen spillover effort has been proved. Moreover, the in situ tests showed that pyrrolic-N can activate adjacent carbon sites as the desorption sites for hydrogen spillover. The Pt@N-1-CNC with the minimum work function difference (ΔΦ) between Pt NPs and support shows superior hydrogen evolution performance, only needs overpotential of 12.2 mV to reach current density of 10 mA cm-2 , outstanding turnover frequency (TOF) (44.7 s-1 @100 mV) and superior durability under the 360 h durability tests at current density of 50 mA cm-2 .

2.
J Transl Med ; 22(1): 478, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769534

RESUMO

BACKGROUND: Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo implantation but disturbs fetomaternal immune-tolerance, has been widely regarded as a major cause of miscarriage; however, the underlying mechanisms resulting in decidual impairment are largely unknown. METHODS: With informed consent, decidual tissue from patients with spontaneous abortion or normal pregnant women was collected to detect the expression profile of UCHL1. Human endometrial stromal cells (HESCs) were used to explore the roles of UCHL1 in decidualization and dNK modulation, as well as the mechanisms involved. C57/BL6 female mice (7-10 weeks old) were used to construct pregnancy model or artificially induced decidualization model to evaluate the effect of UCHL1 on mice decidualization and pregnancy outcome. RESULTS: The Ubiquitin C-terminal hydrolase L1 (UCHL1), as a deubiquitinating enzyme, was significantly downregulated in decidua from patients with miscarriage, along with impaired decidualization and decreased dNKs. Blockage of UCHL1 led to insufficient decidualization and resultant decreased expression of cytokines CXCL12, IL-15, TGF-ß which were critical for generation of decidual NK cells (dNKs), whereas UCHL1 overexpression enhanced decidualization accompanied by increase in dNKs. Mechanistically, the promotion of UCHL1 on decidualization was dependent on its deubiquitinating activity, and intervention of UCHL1 inhibited the activation of JAK2/STAT3 signaling pathway, resulting in aberrant decidualization and decreased production of cytokines associated with dNKs modulation. Furthermore, we found that inhibition of UCHL1 also disrupted the decidualization in mice and eventually caused adverse pregnancy outcome. CONCLUSIONS: UCHL1 plays significant roles in decidualization and dNKs modulation during pregnancy in both humans and mice. Its deficiency indicates a poor pregnancy outcome due to defective decidualization, making UCHL1 a potential target for the diagnosis and treatment of miscarriage.


Assuntos
Aborto Espontâneo , Decídua , Células Matadoras Naturais , Camundongos Endogâmicos C57BL , Ubiquitina Tiolesterase , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/deficiência , Feminino , Decídua/metabolismo , Animais , Gravidez , Aborto Espontâneo/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/imunologia , Adulto , Camundongos , Células Estromais/metabolismo , Transdução de Sinais
3.
BMC Infect Dis ; 24(1): 514, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778273

RESUMO

BACKGROUND: As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China's National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. METHODS: A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. RESULTS: Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P < 0.05). Impressively, significantly more PWH had the higher level of baseline, peak and recent CD4 cell counts in the living group compared to those in the dead group. Due to multicollinearity effect, after excluding confounders, the following factors were found to be significantly associated with mortality by multivariate Cox regression analysis: (1) male sex (hazard ratio (HR) = 1.268 [1.032, 1.559]; P = 0.024); (2) time from HIV confirmation to ART initiation ≥ 6 months (HR = 1.962 [1.631, 2.360]; P < 0.001); (3) peak CD4 cell count: Peak CD4 < 100cells/µL group (HR = 16.093 [12.041, 21.508]; P < 0.001), 100cells/µL ≤ x < 200cells/µL group (HR = 7.904 [6.148, 10.160]; P < 0.001), 200cells/µL ≤ x < 350cells/µL group (HR = 3.166 [2.519, 3.980]; P < 0.001), 350cells/µL ≤ x < 500cells/µL group (HR = 1.668 [1.291, 2.155]; P < 0.001). CONCLUSION: Interestingly, patients in male, time from HIV confirmation to ART initiation ≥ 6 months, or peak CD4 count < 500 cells/µl had inferior clinical outcomes, in other word, a lower peak CD4 cell count significantly increased the risk of death, and peak CD4 cell was independent in predicting the overall survival of PWH. It is important to promote "early diagnosis and treatment of HIV" and regularly monitor CD4 levels in HIV/AIDS to evaluate the efficacy of ART and immune reconstitution, and optimize the ART regimen in time to further reduce the mortality of PWH.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Estudos Retrospectivos , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/imunologia , Infecções por HIV/virologia , Feminino , Adulto , Contagem de Linfócito CD4 , Pessoa de Meia-Idade , China/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Terapia Antirretroviral de Alta Atividade
4.
Inorg Chem ; 62(31): 12337-12344, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37490736

RESUMO

Aerogels, as three-dimensional porous materials, have attracted much attention in almost every field owing to their unique structural properties. Designing high-entropy alloy aerogels (HEAAs) to quinary and above remains an enormous challenge due to the different reduction potentials and nucleation/growth kinetics of different constituent metals. Herein, a novel and universal chelating co-reduction strategy to prepare HEAAs at room temperature in the water phase is proposed. The addition of chelators (ethylenediaminetetraacetic acid tetrasodium salt, sodium citrate, salicylic acid, and 4,4'-bipyridine) with a certain strong coordination capacity can adjust the reduction potential of different metal components, which is the key to synthesize single-phase solid solution alloys successfully. The optimized AgRuPdAuPt HEAA can be an excellent electrocatalyst for hydrogen evolution reaction (HER) with an ultrasmall overpotential of 22 mV at 10 mA cm-2 and excellent stability for 24 h in an alkaline solution. In situ Raman spectroscopy unveils the enhanced hydrogen evolution reaction mechanism of HEAAs. Overall, this work provides a novel chelating co-reduction strategy for the facile and versatile synthesis and design of advanced HEAAs and broadens the development and utilization of multi-elemental alloy electrocatalysts.

5.
Nat Mater ; 20(11): 1539-1544, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34426660

RESUMO

High-efficiency blue phosphorescence emission is essential for organic optoelectronic applications. However, synthesizing heavy-atom-free organic systems having high triplet energy levels and suppressed non-radiative transitions-key requirements for efficient blue phosphorescence-has proved difficult. Here we demonstrate a simple chemical strategy for achieving high-performance blue phosphors, based on confining isolated chromophores in ionic crystals. Formation of high-density ionic bonds between the cations of ionic crystals and the carboxylic acid groups of the chromophores leads to a segregated molecular arrangement with negligible inter-chromophore interactions. We show that tunable phosphorescence from blue to deep blue with a maximum phosphorescence efficiency of 96.5% can be achieved by varying the charged chromophores and their counterions. Moreover, these phosphorescent materials enable rapid, high-throughput data encryption, fingerprint identification and afterglow display. This work will facilitate the design of high-efficiency blue organic phosphors and extend the domain of organic phosphorescence to new applications.


Assuntos
Conformação Molecular
6.
J Environ Sci (China) ; 115: 265-276, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34969454

RESUMO

Luoyang is a typical heavy industrial city in China, with a coal-dominated energy structure and serious air pollution. Following the implementation of the clean air actions, the physicochemical characteristics and sources of PM2.5 have changed. A comprehensive study of PM2.5 was conducted from October 16, 2019 to January 23, 2020 to evaluate the effectiveness of previous control measures and further to provide theory basis for more effective policies in the future. Results showed that the aerosol pollution in Luoyang in autumn and winter is still serious with the average concentration of 91.1 µg/m3, although a large reduction (46.9%) since 2014. With the contribution of nitrate increased from 12.5% to 25.1% and sulfate decreased from 16.7% to 11.2%, aerosol pollution has changed from sulfate-dominate to nitrate-dominate. High NO3-/SO42- ratio and the increasing of NO3-/SO42- ratio with the aggravation of pollution indicating vehicle exhaust playing an increasingly important role in PM2.5 pollution in Luoyang, especially in the haze processes. Secondary inorganic ions contributed significantly to the enhancement of PM2.5 during the pollution period. The high value of Cl-/Na+ and EC concentration indicate coal combustion in Luoyang is still serious. The top three contributor sources were secondary inorganic aerosols (33.3%), coal combustion (13.6%), and industrial emissions (13.4%). Close-range transport from the western and northeastern directions were more important factors in air pollution in Luoyang during the sampling period. It is necessary to strengthen the control of coal combustion and reduce vehicle emissions in future policies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Nitratos , Material Particulado/análise , Estações do Ano , Emissões de Veículos/análise
7.
J Sci Food Agric ; 101(14): 6043-6052, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33857333

RESUMO

BACKGROUND: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography. RESULTS: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H2 O2 -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures. CONCLUSION: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Codonopsis/química , Pectinas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Linhagem Celular , Humanos , Fator de Transcrição NF-E2/genética , Fator de Transcrição NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pectinas/farmacologia , Raízes de Plantas/química
8.
J Sci Food Agric ; 101(6): 2491-2499, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33063324

RESUMO

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Codonopsis/química , Medicamentos de Ervas Chinesas/química , Frutanos/química , Inulina/química , Prebióticos/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Codonopsis/classificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Frutanos/isolamento & purificação , Frutanos/farmacologia , Humanos , Inulina/isolamento & purificação , Inulina/farmacologia , Lactobacillus/efeitos dos fármacos , Lactobacillus/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Polimerização
9.
Adv Exp Med Biol ; 1207: 391-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671761

RESUMO

Autophagy is an essential biological process for cells to maintain their homeostasis. It is a complex regulatory system that integrates innate and adaptive immunity. The role of autophagy in immune diseases has been paid more and more attention with the deepening of the mutual regulation and mechanism of autophagy and immunity. It is found that the aberrant autophagy is closely related to inflammatory diseases, including infections, adaptive immune-associated inflammation and inflammatory bowel disease. Autophagy plays critical roles in the activation of NLRP3 inflammasome, the clearance of bacterial and viral infections and what is more, the function of adaptive immune cells.


Assuntos
Autofagia/imunologia , Inflamação/imunologia , Inflamação/patologia , Imunidade Adaptativa , Humanos , Imunidade Inata , Infecções/imunologia , Infecções/microbiologia , Infecções/virologia , Inflamassomos , Doenças Inflamatórias Intestinais
10.
Adv Exp Med Biol ; 1207: 401-403, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671762

RESUMO

As a result of its multifunction both in innate and adaptive immune systems, autophagy has been demonstrated to take part in the pathogenesis of several immune-related diseases. The study on the pathological mechanism of autophagy in these diseases may provide an experimental and theoretical basis for targeted intervention of autophagy in the prevention and treatment of immune diseases. To date, it has been reported that autophagy can eliminate impaired mitochondrial to inhibit the activation of NLRP3 inflammasome which promotes the progression of atherosclerosis. Moreover, enhanced autophagy can effectively prevent the occurrence of GVHD. It also plays a key role in the development of viral hepatitis. Therefore, autophagy might be a promising regulatory target for the treatment of immune-related diseases.


Assuntos
Autofagia , Doenças do Sistema Imunitário , Humanos , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/patologia , Inflamassomos , Mitocôndrias/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR
11.
Adv Exp Med Biol ; 1207: 405-408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671763

RESUMO

Alterations of autophagy contribute to the progression of various autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and systemic sclerosis (SSc). In patients with SLE, autophagy defects result in poor clearance of phagocytic fragments and excessive secretion of inflammatory factors. The disorder of autophagy in IBD patients is closely related to the regulation of inflammatory factors and the clearance of pathogenic pathogens of enteropathy. The increase of autophagy in synovioblasts of RA patients will promote RA-associated synovitis. The autophagy of fibroblasts in SSc patients is dysfunctional, leading to overactive wound healing. Understanding the role of autophagy in the pathogenesis may give us hints on the therapy of autoimmune diseases.


Assuntos
Doenças Autoimunes , Autofagia , Artrite Reumatoide , Humanos , Doenças Inflamatórias Intestinais , Lúpus Eritematoso Sistêmico , Escleroderma Sistêmico
12.
J Cell Mol Med ; 23(2): 1470-1485, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30556290

RESUMO

Focal inflammation and remyelination failure are major hallmarks of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we found that leonurine, a bioactive alkaloid, alleviated EAE disease severity along with reduced central nervous system inflammation and myelin damage. During the pathogenesis of EAE, leonurine dramatically suppressed the recruitment of encephalitogenic T cells into the central nervous system, whereas did not impair periphery immune responses and microglia activation. Mechanistically, leonurine protected mice against demyelination along with enhanced remyelination through promoting the maturation of oligodendrocytes in both EAE and cuprizone-induced demyelination mouse models. Moreover, we identified that the expression of demethylase jumonji domain-containing protein D3 was significantly enhanced upon treatment of leonurine, which suppressed the trimethylation of histone H3 lysine-27 and enhanced oligodendrocyte maturation accordingly. Collectively, our study identified the therapeutic effect of leonurine on EAE model, which potentially represents a promising therapeutic strategy for multiple sclerosis, even other demyelination disorders.


Assuntos
Ácido Gálico/análogos & derivados , Inflamação/tratamento farmacológico , Histona Desmetilases com o Domínio Jumonji/genética , Esclerose Múltipla/tratamento farmacológico , Animais , Diferenciação Celular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Cuprizona/toxicidade , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental , Ácido Gálico/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/patologia , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Bainha de Mielina/genética , Neurogênese/efeitos dos fármacos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Remielinização/efeitos dos fármacos
13.
PLoS Pathog ; 13(1): e1006198, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28141833

RESUMO

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons.


Assuntos
Vírus Hantaan/fisiologia , Febre Hemorrágica com Síndrome Renal/epidemiologia , Interações Hospedeiro-Patógeno , Zoonoses/epidemiologia , Animais , Teorema de Bayes , China/epidemiologia , Ecologia , Meio Ambiente , Feminino , Geografia , Febre Hemorrágica com Síndrome Renal/transmissão , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Filogenia , Gravidez , Chuva , Risco , Roedores , Estações do Ano , Zoonoses/virologia
14.
Mol Phylogenet Evol ; 131: 219-227, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30316948

RESUMO

As species serve as basic units of study in many fields of biology, assessments of species limits are fundamental for such studies. Here, we used a multilocus dataset and different coalescent-based methods to analyze species delimitation and phylogenetic relationships in the Brownish-flanked Bush Warbler Horornis fortipes complex, which is widespread in the Sino-Himalayan region. We also examined the vocal and morphometric divergence within this complex. Our genetic results suggested that Horornis fortipes is composed of at least three independently evolving lineages, which diverged 1.1-1.8 million years ago. However, these lineages have hardly diverged in song or morphometrics and only very slightly in plumage. Our result indicate that there are three incipient species in Horonis fortipes complex diverged in central Himalayas and Hengduan Mountains, but not between the continent and Taiwan island.


Assuntos
Ecossistema , Ilhas , Filogenia , Aves Canoras/classificação , Animais , Teorema de Bayes , Variação Genética , Geografia , Aves Canoras/anatomia & histologia , Aves Canoras/genética , Especificidade da Espécie , Taiwan , Fatores de Tempo , Vocalização Animal/fisiologia
15.
Blood ; 129(20): 2737-2748, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-28246193

RESUMO

Modulating T-cell alloreactivity has been a main strategy to reduce graft-versus-host disease (GVHD), a life-threatening complication after allogeneic hematopoietic stem-cell transplantation (HSCT). Genetic deletion of T-cell Ezh2, which catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3), inhibits GVHD. Therefore, reducing Ezh2-mediated H3K27me3 is thought to be essential for inhibiting GVHD. We tested this hypothesis in mouse GVHD models. Unexpectedly, administration of the Ezh2 inhibitor GSK126, which specifically decreases H3K27me3 without affecting Ezh2 protein, failed to prevent the disease. In contrast, destabilizing T-cell Ezh2 protein by inhibiting Hsp90 using its specific inhibitor AUY922 reduced GVHD in mice undergoing allogeneic HSCT. In vivo administration of AUY922 selectively induced apoptosis of activated T cells and decreased the production of effector cells producing interferon γ and tumor necrosis factor α, similar to genetic deletion of Ezh2. Introduction of Ezh2 into alloreactive T cells restored their expansion and production of effector cytokines upon AUY922 treatment, suggesting that impaired T-cell alloreactivity by inhibiting Hsp90 is achieved mainly through depleting Ezh2. Mechanistic analysis revealed that the enzymatic SET domain of Ezh2 directly interacted with Hsp90 to prevent Ezh2 from rapid degradation in activated T cells. Importantly, pharmacological inhibition of Hsp90 preserved antileukemia activity of donor T cells, leading to improved overall survival of recipient mice after allogeneic HSCT. Our findings identify the Ezh2-Hsp90 interaction as a previously unrecognized mechanism essential for T-cell responses and an effective target for controlling GVHD.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Linfócitos T/imunologia , Animais , Proteína Potenciadora do Homólogo 2 de Zeste/química , Proteínas de Choque Térmico HSP90/metabolismo , Hematopoese/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Histonas/metabolismo , Indóis/farmacologia , Isoxazóis/farmacologia , Lisina/metabolismo , Metilação/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor/metabolismo , Domínios Proteicos , Estabilidade Proteica/efeitos dos fármacos , Piridonas/farmacologia , Resorcinóis/farmacologia , Linfócitos T/efeitos dos fármacos , Transplante Homólogo
16.
Molecules ; 24(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600890

RESUMO

In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-ß-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of ß-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that ß-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.


Assuntos
Codonopsis/química , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Hidrólise , Imunidade nas Mucosas/efeitos dos fármacos , Fatores Imunológicos/química , Camundongos , Estrutura Molecular , Monossacarídeos/química , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Análise Espectral
17.
Angew Chem Int Ed Engl ; 58(40): 14140-14145, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31359548

RESUMO

Provided here is evidence showing that the stacking between triplet chromophores plays a critical role in ultralong organic phosphorescence (UOP) generation within a crystal. By varying the structure of a functional unit, and different on-off UOP behavior was observed for each structure. Remarkably, 24CPhCz, having the strongest intermolecular interaction between carbazole units exhibited the most impressive UOP with a long lifetime of 1.06 s and a phosphorescence quantum yield of 2.5 %. 34CPhCz showed dual-emission UOP and thermally activated delayed fluorescence (TADF) with a moderately decreased phosphorescence lifetime of 770 ms, while 35CPhCz only displayed TADF owing to the absence of strong electronic coupling between triplet chromophores. This study provides an explanation for UOP generation in crystal and new guidelines for obtaining UOP materials.

18.
Angew Chem Int Ed Engl ; 58(52): 18776-18782, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31646717

RESUMO

Amorphous purely organic phosphorescence materials with long-lived and color-tunable emission are rare. Herein, we report a concise chemical ionization strategy to endow conventional poly(4-vinylpyridine) (PVP) derivatives with ultralong organic phosphorescence (UOP) under ambient conditions. After the ionization of 1,4-butanesultone, the resulting PVP-S phosphor showed a UOP lifetime of 578.36 ms, which is 525 times longer than that of PVP polymer itself. Remarkably, multicolor UOP emission ranging from blue to red was observed with variation of the excitation wavelength, which has rarely been reported for organic luminescent materials. This finding not only provides a guideline for developing amorphous polymers with UOP properties, but also extends the scope of room-temperature phosphorescence (RTP) materials for practical applications in photoelectric fields.

19.
Blood ; 127(25): 3270-80, 2016 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-27143255

RESUMO

Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naïve T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy.


Assuntos
Técnicas de Reprogramação Celular/métodos , Reprogramação Celular , Células Dendríticas/metabolismo , Doença Enxerto-Hospedeiro/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Linfócitos T/imunologia , Animais , Células Dendríticas/fisiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/imunologia , Leucemia/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doadores de Tecidos , Transplante Homólogo
20.
Malar J ; 17(1): 234, 2018 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-29914492

RESUMO

BACKGROUND: Malaria parasites and related haemosporidian parasites are widespread and may cause severe diseases in birds. These pathogens should be considered in projects aiming breeding of birds for purposes of sustained ex situ conservation. Cranes are the 'flagship species' for health assessment of wetland ecosystems, and the majority of species are endangered. Malaria parasites and other haemosporidians have been reported in cranes, but the host-parasite relationships remain insufficiently understood. Morbidity of cranes due to malaria has been reported in Beijing Zoo. This study report prevalence, diversity and distribution of malaria parasites and related haemosporidians in cranes in Beijing Zoo and suggest simple measures to protect vulnerable individuals. METHODS: In all, 123 cranes (62 adults and 61 juveniles) belonging to 10 species were examined using PCR-based testing and microscopic examination of blood samples collected in 2007-2014. All birds were maintained in open-air aviaries, except for 19 chicks that were raised in a greenhouse with the aim to protect them from bites of blood-sucking insects. Bayesian phylogenetic analysis was used to identify the closely related avian haemosporidian parasites. RESULTS: Species of Plasmodium (5 lineages), Haemoproteus (1) and Leucocytozoon (2) were reported. Malaria parasites predominated (83% of all reported infections). The overall prevalence of haemosporidians in juveniles was approximately seven-fold higher than in adults, indicating high susceptibility of chicks and local transmission. Juvenile and adult birds hosted different lineages of Plasmodium, indicating that chicks got infection from non-parent birds. Plasmodium relictum (pSGS1) was the most prevalent malaria parasite. Mortality was not reported in adults, but 53% of infected chicks died, with reports of co-infection with Plasmodium and Leucocytozoon species. All chicks maintained in the greenhouse were non-infected and survived. Species of Leucocytozoon were undetectable by commonly used PCR protocol, but readily visible in blood films. CONCLUSION: Crane chicks often die due to malaria and Leucocytozoon infections, which they likely gain from wild free-living birds in Beijing Zoo. Molecular diagnostics of crane Leucocytozoon parasites needs improvement. Because the reported infections are mainly chick diseases, the authors recommend maintaining of juvenile birds in vector-free facilities until the age of approximately 6 months before they are placed in open-air aviaries.


Assuntos
Animais de Zoológico , Aves , Haemosporida/isolamento & purificação , Infecções por Protozoários/mortalidade , Animais , Pequim/epidemiologia , Biodiversidade , Malária Aviária/epidemiologia , Malária Aviária/mortalidade , Malária Aviária/parasitologia , Plasmodium/isolamento & purificação , Prevalência , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/parasitologia , Especificidade da Espécie
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