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1.
Small ; 20(21): e2309353, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38098371

RESUMO

Defect engineering is recognized as an attractive method for modulating the electronic structure and physicochemical characteristics of carbon materials. Exploiting heteroatom-doped porous carbon with copious active sites has attracted great attention for capacitive deionization (CDI). However, traditional methods often rely on the utilization of additional heteroatom sources and strong corrosive activators, suffering from low doping efficiency, insufficient doping level, and potential biotoxicity. Herein, hydrogen-bonded organic frameworks (HOFs) are employed as precursors to synthesize N, O co-doped porous carbon via a simple and green reverse defect engineering strategy, achieving controllable heavy doping of heteroatoms. The N, O co-doping triggers significant pseudocapacitive contribution and the surface pore structure supports the formation of the electric double layer. Therefore, when HOF-derived N, O co-doped carbon is used as CDI electrodes, a superior salt adsorption capacity of 32.29 ± 1.42 mg g-1 and an outstanding maximum salt adsorption rate of 10.58 ± 0.46 mg g-1 min-1 at 1.6 V in 500 mg L-1 NaCl solution are achieved, which are comparable to those of state-of-the-art carbonaceous electrodes. This work exemplifies the effectiveness of the reverse nitrogen-heavy doping strategy on improving the carbon structure, shedding light on the further development of rational designed electrode materials for CDI.

2.
Microb Pathog ; 189: 106606, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437994

RESUMO

Fungal keratitis (FK) is a highly blinding infectious corneal disease caused by pathogenic fungi. Candida albicans (C. albicans) is one of the main pathogens of fungal keratitis. Extracellular vesicles (EVs), lipid bilayer compartments released by almost all living cells, including fungi, have garnered attention for their role in pathogenic microbial infection and host immune responses in recent years. Studies have reported that pretreating the host with fungal EVs can reduce the inflammatory response of the host when attacked by fungi and reduce the lethality of fungal infection. However, there are no studies that have evaluated whether C. albicans EVs can modulate the inflammatory response associated with C. albicans keratitis. Our study revealed that C. albicans EVs could activate the polymorphonuclear cells (PMNs) and promote their secretion of proinflammatory cytokines and nitric oxide (NO), enhance their phagocytic and fungicidal abilities against C. albicans. C. albicans EVs also induced a proinflammatory response in RAW264.7 cells, which was characterized by increased production of inflammatory cytokines and elevated expression of the chemokine CCL2. Similarly, stimulation of C. albicans EVs to RAW264.7 cells also enhanced the phagocytosis and killing ability of cells against C. albicans. Besides, in our in vivo experiments, after receiving subconjunctival injection of C. albicans EVs, C57BL/6 mice were infected with C. albicans. The results demonstrated that pre-exposure to C. albicans EVs could effectively diminish the severity of keratitis, reduce fungal load and improve prognosis. Overall, we conclude that C. albicans EVs can modulate the function of immune cells and play a protective role in C. albicans keratitis.


Assuntos
Vesículas Extracelulares , Ceratite , Animais , Camundongos , Candida albicans/fisiologia , Camundongos Endogâmicos C57BL , Ceratite/microbiologia , Citocinas
3.
Mol Psychiatry ; 28(2): 919-930, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36280756

RESUMO

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Etanol/farmacologia , Depressão/psicologia , Inflamassomos/metabolismo , Hipocampo/metabolismo
4.
Environ Sci Technol ; 56(15): 10710-10720, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35546088

RESUMO

Efficient degradation of organic pollutants by oxidative radicals is challenging in the complex soil environment because of the invalid consumption of radicals by nontarget background substances and the generation of secondary halogenated organic pollutants. Nonradical-based oxidation is a promising pollutant removal method due to its high selectivity and environmental adaptability. Herein, a biochar-supported sheetlike CuO (e-CuO@BC) was developed, which exhibited efficient activation of peroxydisulfate (PDS) via nonradical pathways. The activation mechanisms were identified as (i) formation of surface-bonding active complexes via an outer-sphere interaction between e-CuO@BC and PDS and (ii) the continuous generation of 1O2 by the cycling of the Cu(I)/Cu(II) redox couple. In addition, the activation of PDS primarily occurred at the crystal facet (001) of e-CuO occupied by Cu atoms and was well facilitated by the Cu-O-C bond, which induced electron-rich centers around CuO. Two oxidative species from PDS activation, including surface-bonding active complexes and 1O2, showed a highly selective degradation toward electron-rich pollutants. Moreover, a highly efficient mineralization of organic pollutants and an effective inhibition on the generation of toxic byproducts (i.e., halogenated organics) was indicated by the intermediate and final degradation products. This study provides a comprehensive understanding of the heterogeneous activation process of PS by the e-CuO@BC catalyst for electron-rich organic pollutant removal.


Assuntos
Poluentes Ambientais , Oxigênio Singlete , Carvão Vegetal , Cobre , Elétrons
5.
Int J Mol Sci ; 23(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35409046

RESUMO

The strategies of genetic dereplication and manipulation of epigenetic regulators to activate the cryptic gene clusters are effective to discover natural products with novel structure in filamentous fungi. In this study, a combination of genetic dereplication (deletion of pesthetic acid biosynthetic gene, PfptaA) and manipulation of epigenetic regulators (deletion of histone methyltransferase gene PfcclA and histone deacetylase gene PfhdaA) was developed in plant endophytic fungus Pestalotiopsis fici. The deletion of PfptaA with PfcclA and/or PfhdaA led to isolation of 1 novel compound, pestaloficiol X (1), as well as another 11 known compounds with obvious yield changes. The proposed biosynthesis pathway of pestaloficiol X was speculated using comparative analysis of homologous biosynthetic gene clusters. Moreover, phenotypic effects on the conidial development and response to oxidative stressors in the mutants were explored. Our results revealed that the new strain with deletion of PfcclA or PfhdaA in ΔPfptaA background host can neutralise the hyperformation of conidia in the PfptaA mutant, and that the ΔPfptaA ΔPfhdaA mutant was generally not sensitive to oxidative stressors as much as the ΔPfptaA ΔcclA mutant in comparison with the single mutant ΔPfptaA or the parental strains. This combinatorial approach can be applied to discover new natural products in filamentous fungi.


Assuntos
Produtos Biológicos , Fungos , Produtos Biológicos/metabolismo , Epigênese Genética , Epigenômica , Fungos/metabolismo , Plantas/metabolismo
6.
Environ Sci Technol ; 55(13): 8613-8621, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34165282

RESUMO

The addition of Fe2O3 into furnaces is a promising method for arsenic pollution control. Nevertheless, Fe2O3 particles undergo serious sintering under actual furnace temperatures. To improve its sintering resistance, Fe2O3 hollow microspheres were synthesized by the template method and were tested in flue gas containing SO2 and NO in the range of 1000-1300 °C. The results demonstrated that the amount of arsenic captured could be steadily maintained above 5 mg/g throughout the operating temperature range, and Fe2O3 microspheres could maintain the originally developed pore structure and hollow morphology well even at 1200 °C. Based on product analysis and density functional theory calculations, the fixation pathway of arsenic was proposed. In no oxygen conditions, As2O3 was first bound to the Fe2O3 surface by forming an -O-As-O-Fe stable structure and then was oxidized by lattice oxygen. The introduction of O2 could regenerate the consumed lattice oxygen and therefore promote arsenic capture. Finally, the oxidized arsenic was fixed in products in the form of FeAsO4. Additionally, the impact of acid gases was also investigated. SO2 showed a notable inhibiting effect on arsenic capture, while the impact of NO was less noticeable.


Assuntos
Arsênio , Ácidos , Gases , Microesferas , Oxirredução
7.
Environ Sci Technol ; 54(15): 9672-9680, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32635724

RESUMO

The lack of fundamental understanding of the chemistry governing elemental mercury (Hg0) immobilization over metal chalcogenides (MChals) is the key challenge impeding the interpretations of Hg0 behaviors in global cycles. This work therefore made the first endeavor toward the establishment of a roadmap capable of describing and depicting Hg0 sequestrations by various MChals. The results suggest that the binding energy between the metal cations and chalcogen anions is a proper descriptor that could predict the immobilization behaviors of Hg0 over zinc chalcogenides (ZnS and ZnSe) that exhibit an identical molecular structure, i.e., the lower the binding energy was, the higher the Hg0 sequestration performance that was obtained. The validity of this descriptor was further demonstrated over a series of MChals sharing structural similarities. A scaling relationship was thus established, which further proved the Hg0 immobilization performance of MChals was generally in reverse proportion to the above-mentioned binding energy. Although there is still a long way toward the proposal of a full roadmap that can predict and depict the Hg0 immobilization behaviors over all MChals, this work marks the first step on this road and provides guides for further studies by understanding the fundamentals governing Hg0 sequestration over MChals with structural similarities.


Assuntos
Mercúrio , Metais
8.
Sensors (Basel) ; 20(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397323

RESUMO

Web-core sandwich panels have gained the popularity in various fields, especially aviation and shipbuilding, etc. Penetration welding was considered as an effective process to manufacture such a structure through a T-joint. To ensure the formation quality and mechanical properties of weld, the welding torch needs to be aligned with the T-joint position. However, it is difficult to locate the T-joint position (i.e., the position of core panel) because of the shielding of the face panels. This paper investigated the detection of T-joint position from the face panel side in web-core sandwich panels based on eddy current technology. First, we designed an experimental system for the weld position detection of T-joints from the face panel side. The relationships are investigated between the characteristics of the eddy current detection signal and the primary parameters of the detection system (including excitation frequency, coil outer diameter, and lift off distance) and the T-joint (including thickness of the core panel, gap distance, and thickness of the cover panel). Corresponding experiments were carried out with variable primary parameters, and the influence mechanism of the primary parameters on the detection results in terms of sensitivity and dynamic performance was elaborated to set up the theoretical basis for the detection. Finally, weld position detection experiments were carried out on TC4 titanium alloy T-joint specimens with 3 mm-thick face panel and 5 mm-thick core panel. Results showed that the maximum detection error was 0.482 mm, and the average error was 0.234 mm. This paper provided a possible technical solution to the automatic tracking problem for the welding of T-joints in the web-core sandwich panels.

9.
J Microencapsul ; 35(3): 249-258, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29624456

RESUMO

γ-Cyclodextrin metal-organic frameworks (γ-CD-MOFs) are highly porous and bio-friendly novel materials formed by γ-CD as an organic ligand and potassium ion as an inorganic metal centre. The aim of this study was to enhance the stability of vitamin A palmitate (VAP) using γ-CD-MOFs as the carrier. Herein, γ-CD-MOFs displayed VAP microencapsulating capacity of 9.77 ± 0.24% with molar ratio as nMOFs:nVAP = 3.2:1.0. It was important to find that the improved stability of VAP microencapsulated by γ-CD-MOFs without addition of any antioxidant(s) was better than that of the best available reference product in the market, with 1.6-fold elongated half-life. The protecting mechanism of γ-CD-MOFs for VAP contributed that VAP molecules preferentially curled inside the cavities of dual γ-CD pairs in γ-CD-MOFs. It was proved that γ-CD-MOFs were an efficient new carrier to deliver and protect VAP for food and pharmaceutical applications.


Assuntos
Antioxidantes/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Estruturas Metalorgânicas/química , Vitamina A/análogos & derivados , gama-Ciclodextrinas/química , Antioxidantes/administração & dosagem , Cristalização , Diterpenos , Estabilidade de Medicamentos , Modelos Moleculares , Tamanho da Partícula , Ésteres de Retinil , Vitamina A/administração & dosagem , Vitamina A/química
10.
J Infect Dis ; 215(1): 56-63, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28077584

RESUMO

BACKGROUND: This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine. METHOD: In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years. RESULTS: Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P < .0001), and the vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P < .0001). Geometric mean titers of neutralizing antibody in participants remained high during the 2-year follow-up period, and no vaccine-related serious adverse events were recorded. CONCLUSIONS: Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children. CLINICAL TRIALS REGISTRATION: NCT01508247.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Pré-Escolar , China , Método Duplo-Cego , Infecções por Enterovirus/virologia , Seguimentos , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Humanos , Esquemas de Imunização , Imunogenicidade da Vacina , Lactente , Fatores de Tempo , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
11.
Lancet ; 385(9984): 2272-9, 2015 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-25817373

RESUMO

BACKGROUND: Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. METHODS: We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. FINDINGS: Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (p<0·0001). We recorded no statistical differences in other adverse reactions and laboratory tests across groups. Glycoprotein-specific antibody titres were significantly increased in participants in the low-dose and high-dose vaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; p<0·0001) and day 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2], respectively; p<0·0001). T-cell responses peaked at day 14 at a median of 465·0 spot-forming cells (IQR 180·0-1202·5) in participants in the low-dose group and 765·0 cells (400·0-1460·0) in those in the high-dose group. 21 (18%) participants had mild fever (n=9 in the placebo group, n=6 in the low-dose group, and n=6 in the high-dose group). No serious adverse events were recorded. INTERPRETATION: Our findings show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days. FUNDING: China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.


Assuntos
Vacinas contra Ebola , Adolescente , Adulto , Ensaios Clínicos Fase I como Assunto , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Feminino , Glicoproteínas/imunologia , Humanos , Fenômenos Imunogenéticos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(12): 1047-51, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26887297

RESUMO

OBJECTIVE: To analyze the dynamic pattern and the distributive characteristics of neutralizing antibody against enterovirus 71 (EV-A71 ) in children aged 6-35 months in Jiangsu province from 2012 to 2014. METHODS: From March, 2012 to March, 2014, a total of 1 276 children aged between 6 and 35 months were regularly followed up on day 0, year 1 and year 2 for EV-A71 neutralizing antibody test based on the enterovirus surveillance system, with the method of reporting by their guardian or being visited in Ganyu Sheyang Taixing Donghai Pizhou and Baoying in Jiangsu province. At the same time, samples were taken from the suspected persons infected by enterovirus. The χ(2) test or variance analysis was used to compare the difference of the positive rates and the geometric mean titer(GMT) of EV-A71 neutralizing antibody in different subjects. RESULTS: In 2 years follow-up, the positive rates of EV-A71 antibody increased as the growth of the age,and the positive rates on day 0, year 1 and year 2 were 22.57% (288/1 276), 37.72%(444/1 177) and 42.84%(422/985), respectively (χ(2) values were 39.33, 56.41, 32.25; P< 0.001).The GMTs were 9.95, 15.37 and 24.05, respectively (F values were 22.90,46.36,41.58;P<0.001). In 2 years, the annually new infection rates were 13.47%(158/1 173) and 20.73%(192/926),respectively, and the annually decay rates of EV-A71 antibody were 2.81%(33/1 173) and 8.10%(75/926). CONCLUSIONS: In 2012 to 2014, the positive rates and the GMTs of EV-A71 antibody of children increased as the growth of the age in Jiangsu. The higher annually new infection rate was in children aged 3 to 4 years. The EV-A71 neutralizing antibody level could maintain at least two years after natural infection.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Estudos Soroepidemiológicos
13.
Lancet ; 381(9871): 1037-45, 2013 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-23352749

RESUMO

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/efeitos adversos , Anticorpos Antivirais/sangue , Formação de Anticorpos/efeitos dos fármacos , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Lactente , Masculino , Resultado do Tratamento , Vacinas Virais/imunologia
14.
Lancet ; 381(9882): 2024-32, 2013 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-23726161

RESUMO

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/efeitos adversos , Compostos de Alúmen , Anticorpos Antivirais/sangue , Pré-Escolar , Método Duplo-Cego , Infecções por Enterovirus/imunologia , Feminino , Humanos , Imunidade Ativa/fisiologia , Lactente , Estimativa de Kaplan-Meier , Masculino , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/efeitos adversos
15.
ACS Infect Dis ; 10(2): 500-512, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38175918

RESUMO

Fungal keratitis (FK) is a refractory global disease characterized by a high incidence of blindness and a lack of effective therapeutic options, and Aspergillus fumigatus (A. fumigatus, AF) is one of the most common causative fungi. This study aimed to investigate the role of extracellular vesicles (EVs) from A. fumigatus in the immune cell function and their protective role in A. fumigatus keratitis in order to explore their therapeutic potential. First, we isolated and characterized the EVs (AF-derived EVs). In vitro, we stimulated RAW264.7 cells and polymorphonuclear cells with AF-derived EVs. The expression levels of inflammatory factors increased in both immune cells along with an M1 polarization variation of RAW264.7 cells. After being incubated with AF-derived EVs, both immune cells exhibited an increased conidia-phagocytic index and a decreased conidia survival rate. In vivo, we injected EVs subconjunctivally on mice resulting in a heightened production of secretory immunoglobulin A (sIgA) in tear fluid. By the injection of EVs on mice in advance, a significant reduction in severity of A. fumigatus FK was witnessed by lower clinical scores, inflammatory appearances, and mitigated fungal load. Collectively, these results positioned AF-derived EVs as a promising and innovative immune therapy for combating FK, while also providing a platform for further investigation into developing an optimal formulation for modulating inflammation in the context of FK.


Assuntos
Aspergilose , Vesículas Extracelulares , Infecções Oculares Fúngicas , Ceratite , Animais , Camundongos , Aspergillus fumigatus/fisiologia , Aspergilose/tratamento farmacológico , Aspergilose/metabolismo , Ceratite/microbiologia , Inflamação , Infecções Oculares Fúngicas/tratamento farmacológico
16.
Nat Commun ; 15(1): 1292, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346957

RESUMO

Highly efficient decontamination of elemental mercury (Hg0) remains an enormous challenge for public health and ecosystem protection. The artificial conversion of Hg0 into mercury chalcogenides could achieve Hg0 detoxification and close the global mercury cycle. Herein, taking inspiration from the bio-detoxification of mercury, in which selenium preferentially converts mercury from sulfoproteins to HgSe, we propose a biomimetic approach to enhance the conversion of Hg0 into mercury chalcogenides. In this proof-of-concept design, we use sulfur-rich polyphenylene sulfide (PPS) as the Hg0 transporter. The relatively stable, sulfur-linked aromatic rings result in weak adsorption of Hg0 on the PPS rather than the formation of metastable HgS. The weakly adsorbed mercury subsequently migrates to the adjacent selenium sites for permanent immobilization. The sulfur-selenium pair affords an unprecedented Hg0 adsorption capacity and uptake rate of 1621.9 mg g-1 and 1005.6 µg g-1 min-1, respectively, which are the highest recorded values among various benchmark materials. This work presents an intriguing concept for preparing Hg0 adsorbents and could pave the way for the biomimetic remediation of diverse pollutants.

17.
J Control Release ; 368: 483-497, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458571

RESUMO

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis.


Assuntos
Aspergilose , Infecções Oculares Fúngicas , Ceratite , Óxido de Zinco , Animais , Camundongos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Óxido de Zinco/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Natamicina/uso terapêutico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Sistemas de Liberação de Medicamentos , Camundongos Endogâmicos C57BL
18.
Chemosphere ; 337: 139441, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37422218

RESUMO

In present work, a novel catalyst of cobalt supported on silica-composited biochar (Co@ACFA-BC) derived from fly ash and agricultural waste was synthesized. A series of characterizations confirmed that Co3O4 and Al/Si-O compounds were successfully embedded on the surface of biochar, which triggered superior catalytic activity for PMS activation towards phenol degradation. Particularly, the Co@ACFA-BC/PMS system could completely degrade phenol in the wide pH range, and was almost unaffected by environmental factors including humic acid (HA), H2PO4-, HCO3-, Cl-, and NO3-. Further quenching experiment and EPR analysis proved that both radical (SO4·-, ·OH, O2·-) and non-radical (1O2) pathways were involved in the catalytic reaction system, and the excellent PMS activation was attributed to the electron pair cycling of Co2+/Co3+ and the active sites provided by Si-O-O and Si/Al-O bonds on the catalyst surface. Meanwhile, the carbon shell effectively inhibited the leaching of metal ions, enabling the Co@ACFA-BC catalyst to maintain excellent catalytic activity after four cycles. Finally, biological acute toxicity assay demonstrated that the toxicity of phenol could be significantly reduced after being treated by Co@ACFA-BC/PMS. Overall, this work provides a promising strategy for solid waste valorization and a feasible methodology for green and efficient treatment of refractory organic pollutants in water environment.


Assuntos
Poluentes Ambientais , Peróxidos , Peróxidos/química , Dióxido de Silício , Fenóis , Oxirredução
19.
Medicine (Baltimore) ; 102(24): e34011, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37327300

RESUMO

The objective of this study was to evaluate the effect of maturing fetal lung on clinical efficacy of acetaminophen in the treatment of premature infants with patent ductus arteriosus (PDA). A total of 441 premature infants admitted to our hospital from May 2020 to May 2021 were recruited, including 152 premature infants receiving fetal lung maturation (13 cases of PDA closure with drug use and 2 cases failed) and 289 cases without maturing fetal lung (17 cases of PDA closure and 8 cases failed). Finally, a total of 30 cases were enrolled in this clinical trial. All infants were divided into groups A and B according to whether fetal lung maturation was adopted before delivery. In group A, 13 infants received fetal lung maturation, and 17 in group B did not undergo fetal lung maturation. Infants in both groups were orally given with acetaminophen. After 3-day treatment, the second course of treatment was given immediately if PDA was not closed. The PDA closure rate and patency rate of PDA at the end of 2 treatment courses were statistically compared between 2 groups. The feeding intolerance, upper gastrointestinal bleeding, renal failure, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular-intraventricular hemorrhage, the age at total enteral nutrition and the length of hospital stay were also compared between 2 groups. After the 1st and 2nd treatment courses, the PDA closure rate in group A was 84.61%, significantly higher than 52.94% in group B (P < .05), whereas there was no significant difference in the PDA patency rate between 2 groups (P > .05). No significant differences were observed regarding the feeding intolerance, renal failure, necrotizing enterocolitis, periventricular-intraventricular hemorrhage, bronchopulmonary dysplasia, the length of hospital stay and the age at total enteral nutrition between 2 groups (all P > .05). In addition, the incidence of upper gastrointestinal bleeding in group A was 7.69%, slightly lower than 5.88% in group B (P > .05). Compared with premature infants untreated with fetal lung maturation interventions before delivery, premature infants who receive fetal lung maturation interventions combined with acetaminophen for PDA are likely to obtain a higher PDA closure rate and a lower incidence rate of the upper gastrointestinal bleeding.


Assuntos
Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Enterocolite Necrosante , Humanos , Recém-Nascido , Acetaminofen/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Permeabilidade do Canal Arterial/tratamento farmacológico , Enterocolite Necrosante/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Recém-Nascido Prematuro , Pulmão
20.
World Neurosurg ; 175: e55-e63, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36907270

RESUMO

BACKGROUND: Diabetes insipidus (DI) is a common complication after endoscopic transsphenoidal surgery (TSS) for pituitary adenoma (PA), which affects the quality of life in patients. Therefore, there is a need to develop prediction models of postoperative DI specifically for patients who undergo endoscopic TSS. This study establishes and validates prediction models of DI after endoscopic TSS for patients with PA using machine learning algorithms. METHODS: We retrospectively collected information about patients with PA who underwent endoscopic TSS in otorhinolaryngology and neurosurgery departments between January 2018 and December 2020. The patients were randomly split into a training set (70%) and a test set (30%). The 4 machine learning algorithms (logistic regression, random forest, support vector machine, and decision tree) were used to establish the prediction models. Area under the receiver operating characteristic curves were calculated to compare the performance of the models. RESULTS: A total of 232 patients were included, and 78 patients (33.6%) developed transient DI after surgery. Data were randomly divided into a training set (n = 162) and a test set (n = 70) for development and validation of the model, respectively. The area under the receiver operating characteristic curve was highest in the random forest model (0.815) and lowest in the logistic regression model (0.601). Invasion of pituitary stalk was the most important feature for model performance, closely followed by macroadenomas, size classification of PA, tumor texture, and Hardy-Wilson suprasellar grade. CONCLUSIONS: Machine learning algorithms identify preoperative features of importance and reliably predict DI after endoscopic TSS for patients with PA. Such a prediction model may enable clinicians to develop individualized treatment strategy and follow-up management.


Assuntos
Adenoma , Diabetes Insípido , Diabetes Mellitus , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Qualidade de Vida , Adenoma/cirurgia , Adenoma/complicações , Diabetes Insípido/diagnóstico , Diabetes Insípido/etiologia , Aprendizado de Máquina , Complicações Pós-Operatórias/etiologia
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