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1.
Nano Lett ; 23(17): 7934-7940, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37624088

RESUMO

Garnet-based solid-state electrolytes are considered crucial candidates for solid-state Li batteries due to their high Li+ conductivity and nonflammability; however, poor interfacial contact with the Li anode and growth of Li dendrites limit their application. Herein, a high-activity titanium-oxygen cluster is used as a brazing filler to braze the Li6.5La3Zr1.5Ta0.5O12 (LLZTO) with an Li anode into the whole unit. The brazing layer leads to a significantly lower interfacial impedance of 8.32 Ω cm2. Furthermore, the brazing layer is an isotropic amorphous ion-electron hybrid conductive layer, which significantly promotes Li+ transport and regulates the distribution of the electric field, therefore inhibiting the growth of Li dendrites. The cell exhibits an ultrahigh critical current density of 2.3 mA cm-2 and stable cycling of over 4000 h at 0.5 mA cm-2 (25 °C).

2.
Angew Chem Int Ed Engl ; 63(21): e202402004, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38531783

RESUMO

Water molecules, which act as both solvent and reactant, play critical roles in photocatalytic reactions for methanol conversion. However, the influence of water on the adsorption of methanol and desorption of liquid products, which are two essential steps that control the performance in photocatalysis, has been well under-explored. Herein, we reveal the role of water in heterogeneous photocatalytic processes of methanol conversion on the platinized carbon nitride (Pt/C3N4) model photocatalyst. In situ spectroscopy techniques, isotope effects, and computational calculations demonstrate that water shows adverse effects on the adsorption of methanol molecules and desorption processes of methanol oxidation products on the surface of Pt/C3N4, significantly altering the reaction pathways in photocatalytic methanol conversion process. Guided by these discoveries, a photothermal-assisted photocatalytic system is designed to achieve a high solar-to-hydrogen (STH) conversion efficiency of 2.3 %, which is among the highest values reported. This work highlights the important roles of solvents in controlling the adsorption/desorption behaviours of liquid-phase heterogeneous catalysis.

3.
J Med Virol ; 95(1): e28150, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36112136

RESUMO

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.


Assuntos
COVID-19 , Ácido Glutâmico , Humanos , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Metabolômica , Biomarcadores
4.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34704923

RESUMO

The highly pathogenic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a severe respiratory virus. Recent reports indicate additional central nervous system (CNS) involvement. In this study, human DPP4 transgenic mice were infected with MERS-CoV, and viral antigens were first detected in the midbrain-hindbrain 4 days post-infection, suggesting the virus may enter the brainstem via peripheral nerves. Neurons and astrocytes throughout the brain were infected, followed by damage of the blood brain barrier (BBB), as well as microglial activation and inflammatory cell infiltration, which may be caused by complement activation based on the observation of deposition of complement activation product C3 and high expression of C3a receptor (C3aR) and C5a receptor (C5aR1) in neurons and glial cells. It may be concluded that these effects were mediated by complement activation in the brain, because of their reduction resulted from the treatment with mouse C5aR1-specific mAb. Such mAb significantly reduced nucleoprotein expression, suppressed microglial activation and decreased activation of caspase-3 in neurons and p38 phosphorylation in the brain. Collectively, these results suggest that MERS-CoV infection of CNS triggers complement activation, leading to inflammation-mediated damage of brain tissue, and regulating of complement activation could be a promising intervention and adjunctive treatment for CNS injury by MERS-CoV and other coronaviruses.


Assuntos
Encéfalo/patologia , Proteínas do Sistema Complemento/imunologia , Infecções por Coronavirus/patologia , Dipeptidil Peptidase 4/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologia , Encéfalo/irrigação sanguínea , Encéfalo/imunologia , Encéfalo/virologia , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Humanos , Inflamação , Camundongos , Camundongos Transgênicos , Microglia/imunologia , Microglia/patologia
5.
Eur J Nucl Med Mol Imaging ; 48(2): 570-579, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32814979

RESUMO

PURPOSE: To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). METHODS: One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. RESULTS: Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P = 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P < 0.05). In multivariate analysis, TLR (P < 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P < 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. CONCLUSION: Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Neoplasias Renais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Organização Mundial da Saúde
6.
BMC Infect Dis ; 21(1): 1183, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819019

RESUMO

BACKGROUND: We investigate the long-term effects of SARS-CoV on patients' lung and immune systems 15 years post-infection. SARS-CoV-2 pandemic is ongoing however, another genetically related beta-coronavirus SARS-CoV caused an epidemic in 2003-2004. METHODS: We enrolled 58 healthcare workers from Peking University People's Hospital who were infected with SARS-CoV in 2003. We evaluated lung damage by mMRC score, pulmonary function tests, and chest CT. Immune function was assessed by their serum levels of globin, complete components, and peripheral T cell subsets. ELISA was used to detect SARS-CoV-specific IgG antibodies in sera. RESULTS: After 15 years of disease onset, 19 (36.5%), 8 (34.6%), and 19 (36.5%) subjects had impaired DL (CO), RV, and FEF25-75, respectively. 17 (30.4%) subjects had an mMRC score ≥ 2. Fourteen (25.5%) cases had residual CT abnormalities. T regulatory cells were a bit higher in the SARS survivors. IgG antibodies against SARS S-RBD protein and N protein were detected in 11 (18.97%) and 12 (20.69%) subjects, respectively. Subgroup analysis revealed that small airway dysfunction and CT abnormalities were more common in the severe group than in the non-severe group (57.1% vs 22.6%, 54.5% vs 6.1%, respectively, p < 0.05). CONCLUSIONS: SARS-CoV could cause permanent damage to the lung, which requires early pulmonary rehabilitation. The long-lived immune memory response against coronavirus requires further studies to assess the potential benefit. Trial registration ClinicalTrials.gov, NCT03443102. Registered prospectively on 25 January 2018.


Assuntos
Anticorpos Antivirais , COVID-19 , Humanos , Pulmão , Pandemias , SARS-CoV-2
7.
Sensors (Basel) ; 21(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064829

RESUMO

Insects constitute a very important part of the global ecosystem and include pollinators, disease vectors, and agricultural pests, all with pivotal influence on society. Monitoring and control of such insects has high priority, and automatic systems are highly desirable. While capture and analysis by biologists constitute the gold standard in insect identification, optical and laser techniques have the potential for high-speed detection and automatic identification based on shape, spectroscopic properties such as reflectance and fluorescence, as well as wing-beat frequency analysis. The present paper discusses these approaches, and in particular presents a novel method for automatic identification of mosquitos based on image analysis, as the insects enter a trap based on a combination of chemical and suction attraction. Details of the analysis procedure are presented, and selectivity is discussed. An accuracy of 93% is achieved by our proposed method from a data set containing 122 insect images (mosquitoes and bees). As a powerful and cost-effective method, we finally propose the combination of imaging and wing-beat frequency analysis in an integrated instrument.


Assuntos
Culicidae , Animais , Abelhas , Ecossistema , Insetos , Mosquitos Vetores , Asas de Animais
8.
J Virol ; 93(17)2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31189716

RESUMO

Zika virus (ZIKV) infection in pregnant women can lead to fetal deaths and malformations. We have previously reported that ZIKV envelope protein domain III (EDIII) is a subunit vaccine candidate with cross-neutralization activity; however, like many other subunit vaccines, its efficacy is limited. To improve the efficacy of this subunit vaccine, we identified a nonneutralizing epitope on ZIKV EDIII surrounding residue 375, which is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We then shielded this epitope with an engineered glycan probe. Compared to the wild-type EDIII, the mutant EDIII induced significantly stronger neutralizing antibodies in three mouse strains and also demonstrated significantly improved efficacy by fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, the mutant EDIII immune sera significantly enhanced the passive protective efficacy by fully protecting mice against lethal ZIKV challenge; this passive protection was positively associated with neutralizing antibody titers. We further showed that the enhanced efficacy of the mutant EDIII was due to the shielding of the immunodominant nonneutralizing epitope surrounding residue 375, which led to immune refocusing on the neutralizing epitopes. Taken together, the results of this study reveal that an intrinsic limitation of subunit vaccines is their artificially exposed immunodominant nonneutralizing epitopes, which can be overcome through glycan shielding. Additionally, the mutant ZIKV protein generated in this study is a promising subunit vaccine candidate with high efficacy in preventing ZIKV infections in mice.IMPORTANCE Viral subunit vaccines generally show low efficacy. In this study, we revealed an intrinsic limitation of subunit vaccine designs: artificially exposed surfaces of subunit vaccines contain epitopes unfavorable for vaccine efficacy. More specifically, we identified an epitope on Zika virus (ZIKV) envelope protein domain III (EDIII) that is buried in the full-length envelope protein but becomes exposed in recombinant EDIII. We further shielded this epitope with a glycan, and the resulting mutant EDIII vaccine demonstrated significantly enhanced efficacy over the wild-type EDIII vaccine in protecting animal models from ZIKV infections. Therefore, the intrinsic limitation of subunit vaccines can be overcome through shielding these artificially exposed unfavorable epitopes. The engineered EDIII vaccine generated in this study is a promising vaccine candidate that can be further developed to battle ZIKV infections.


Assuntos
Anticorpos Neutralizantes/metabolismo , Epitopos/imunologia , Proteínas do Envelope Viral/química , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Antivirais/metabolismo , Modelos Animais de Doenças , Epitopos/química , Epitopos/genética , Feminino , Humanos , Camundongos , Testes de Neutralização , Gravidez , Domínios Proteicos , Vacinas de Subunidades Antigênicas/imunologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/imunologia
9.
Appl Opt ; 59(10): C1-C7, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32400560

RESUMO

Laser-induced fluorescence is a powerful measurement method for determining the concentration of organic pollutants as well as the amount of algae in water. It can be applied in remote sensing of natural waters and has the advantages of high speed and sensitivity. In this paper, we present a compact handheld fluorosensor system for water quality assessment. The power of the technique is demonstrated in measurements at a river system in South China.


Assuntos
Corantes Fluorescentes/química , Tecnologia de Sensoriamento Remoto/métodos , Poluentes Químicos da Água/análise , Qualidade da Água , China , Monitoramento Ambiental/métodos , Rios/química , Espectrometria de Fluorescência
10.
J Virol ; 92(18)2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29950421

RESUMO

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). We further tested their receptor-binding affinity, recognizing epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV receptor. The binding site of the Nbs on the RBD was mapped to be around residue Asp539, which is part of a conserved conformational epitope at the receptor-binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing activity against divergent MERS-CoV strains isolated from humans and camels. Particularly, NbMS10-Fc had significantly extended half-life in vivo; a single-dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy by completely protecting humanized mice from lethal MERS-CoV challenge. Overall, this study proves the feasibility of producing cost-effective, potent, and broad-spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti-MERS-CoV therapeutics.IMPORTANCE Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/prevenção & controle , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Anticorpos de Domínio Único/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/química , Sítios de Ligação/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Epitopos/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Ligação Proteica , Anticorpos de Domínio Único/economia , Anticorpos de Domínio Único/isolamento & purificação , Anticorpos de Domínio Único/metabolismo , Glicoproteína da Espícula de Coronavírus/genética
11.
Bioorg Med Chem Lett ; 29(16): 2415-2427, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31230974

RESUMO

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.


Assuntos
Antivirais/farmacologia , Carbamatos/farmacologia , Descoberta de Drogas , Hepacivirus/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Antivirais/síntese química , Antivirais/química , Carbamatos/síntese química , Carbamatos/química , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Genótipo , Hepacivirus/genética , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Compostos Macrocíclicos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Sofosbuvir/química , Relação Estrutura-Atividade , Sulfonamidas/química , Comprimidos/química , Comprimidos/farmacologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
12.
BMC Ophthalmol ; 19(1): 77, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871533

RESUMO

BACKGROUND: This study aimed to investigate the completion rate, visual performance, and adverse outcomes of femtosecond laser-assisted cataract surgery (FLACS) in Chinese patients. METHODS: This is a prospective, single-arm, multicenter registry study of 19 cataract surgery clinics in China. Chinese patients with cataract who underwent FLACS using the Alcon LenSx® laser system in single eye (n = 1140) or both eyes (n = 201) were enrolled and data were collected between March 2015 and August 2016. Clinical characteristics were recorded before surgery, and on postoperative days 1, 7, and 30. For surgery on both eyes, the second eye was included in the analysis only if it was operated within 30 days after the first eye surgery. The primary outcome was the completion rate of circular anterior capsulotomy. Secondary outcomes for lens fragmentation, corneal incision, and intraocular lens (IOL) implantation included best corrected distance visual acuity (BCDVA) and completion rates. Adverse events (AEs) were recorded. RESULTS: The completion rates of circular anterior capsulotomy, lens fragmentation, corneal incision, and IOL implantation were 98.6% (95% CI: 97.8-99.1%), 99.5% (95% CI: 99.1-99.8%), 97.6% (95% CI: 96.7-98.3%), and 100% (95% CI: 99.8-100%), respectively. BCDVA preoperatively and at postoperative day 30 were 1.134 ± 0.831 logMAR and 0.158 ± 0.291 logMAR, respectively. The proportion of eyes with BCDVA of 20/20 or better was 1.6% at baseline and 41.3% at postoperative day 30. AE incidence was 0.32%, with posterior capsule rupture present in 0.19% of eyes. CONCLUSION: FLACS using the LenSx® laser system can achieve satisfactory results in a real-world setting.


Assuntos
Extração de Catarata/métodos , Terapia a Laser/métodos , Adulto , Idoso , Capsulorrexe/estatística & dados numéricos , China , Feminino , Humanos , Complicações Intraoperatórias , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Acuidade Visual
13.
Small ; 14(48): e1803344, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30345625

RESUMO

As a popular strategy, interlayer expansion significantly improves the Li-ion diffusion kinetics in the MoS2 host, while the large interlayer spacing weakens the van der Waals force between MoS2 monolayers, thus harming its structural stability. Here, an oxygen-incorporated MoS2 (O-MoS2 )/graphene composite as a self-supported intercalation host of Li-ion is prepared. The composite delivers a specific capacity of 80 mAh g-1 in only 36 s at a mass loading of 1 mg cm-2 , and it can be cycled 3000 times (over 91% capacity retention) with a 5 mg cm-2 loading at 2 A g-1 . The O-MoS2 exhibits a dominant 1T phase with an expanded layer spacing of 10.15 Å, leading to better Li-ion intercalation kinetics compared with pristine MoS2 . Furthermore, ex situ X-ray diffraction tests indicate that O-MoS2 sustains a stable structure in cycling compared with the gradual collapse of pristine MoS2 , which suffers from excessive lattice breathing. Density functional theory calculations suggest that the MoOx (OH)y pillars in O-MoS2 interlayers not only expand the layer spacing, but also tense the MoS2 layers to avoid exfoliation in cycling. Therefore, the O-MoS2 shows a pseudolayered structure, leading to remarkable durability besides the outstanding rate capability as a Li-ion intercalation host.

14.
Crit Care Med ; 46(5): e419-e425, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29293144

RESUMO

OBJECTIVES: Complement activation product C5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning. This study is to explore the efficiency of anti-C5a-based intervention on systemic inflammatory responses induced by paraquat poisoning. DESIGN: Study of cynomolgus macaque model and plasma from paraquat-poisoning patients. SETTING: Laboratory investigation. SUBJECTS: Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16). INTERVENTIONS: The neutralizing antihuman C5a antibody (IFX-1) was administered to investigate the new treatment strategy for paraquat-induced systemic inflammatory responses in cynomolgus macaque model. In addition, C5a activation in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade role of anti-C5a antibody in activation of inflammatory cells. MEASUREMENTS AND MAIN RESULTS: Dysregulated complement activation and the subsequent cytokine storm were found in patients with acute lung injury and in a primate model of paraquat poisoning. Targeted inhibition of C5a by IFX-1 led to marked alleviation of systemic inflammatory responses and multiple organ damage in the primate model. In addition, blockade of C5a activity in plasma from patients completely inhibited activation of CD11b on blood granulocytes from normal donors, suggesting that IFX-1 may alleviate the excessive activation of inflammatory responses and have clinical utility for patients with acute lung injury. CONCLUSIONS: Anti-C5a antibodies such as IFX-1 may be used as effective therapeutics for treatment of those suffering from systemic inflammatory responses induced by chemical poisoning like paraquat.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Anticorpos Neutralizantes/uso terapêutico , Complemento C5a/antagonistas & inibidores , Herbicidas/toxicidade , Paraquat/toxicidade , Edema Pulmonar/terapia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/terapia , Animais , Ativação do Complemento/imunologia , Complemento C5a/imunologia , Macaca fascicularis
15.
J Virol ; 91(1)2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27795425

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. IMPORTANCE: MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Infecções por Coronavirus/prevenção & controle , Dipeptidil Peptidase 4/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/administração & dosagem , Animais , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Sítios de Ligação , Camelus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/genética , Feminino , Expressão Gênica , Humanos , Evasão da Resposta Imune , Camundongos , Camundongos Endogâmicos BALB C , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Modelos Moleculares , Mutação , Testes de Neutralização , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Receptores Virais/química , Receptores Virais/genética , Receptores Virais/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Vacinas Virais/biossíntese
16.
Appl Opt ; 57(35): 10164-10171, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30645222

RESUMO

A dual-band continuous-wave (CW) light detection and ranging (lidar) system has been developed for particle classification. In this lidar system, the range-resolved atmospheric backscattering signal is recorded by an optical imaging system satisfying the Scheimpflug principle instead of the conventional time-of-flight approach. It is thus possible to employ low-cost and compact CW diode lasers, facilitating the development of a robust multiple-wavelength atmospheric lidar system that can attain high accuracy of the retrieved parameters of atmospheric particles. The present work demonstrates a dual-band Scheimpflug lidar system employing two diode lasers at 405 nm (0.5 W) and 808 nm (3.2 W). Exposures are milliseconds apart and interpolated. Measurements of various types of particles and smoke have been performed to verify the feasibility of using the present system for improved particle classification and sizing, for the situation when plumes were dilute and no significant opacity was detected.

17.
Appl Opt ; 57(19): 5258, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30117813

RESUMO

This publisher's note corrects the author listing and a figure caption in Appl. Opt.57, 3481 (2018)APOPAI0003-693510.1364/AO.57.003481.

18.
Appl Opt ; 57(13): 3481-3487, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726517

RESUMO

Chinese hybrid rice of different varieties, growing in paddies in the Pingqiao district, north of Xinyang city, Henan province, China, was studied in detailed spectroscopic characteristics using laser-induced fluorescence. The base for the studies was the new South China Normal University mobile lidar laboratory, which was dispatched on site, providing facilities both for laboratory studies using a 405 nm excitation source as well as remote sensing measurements at ranges from around 40 m-120 m, mostly employing the 532 nm output from a Nd:YAG laser. We, in particular, studied the spectral influence of the species varieties as well as the level of nitrogen fertilization supplied. Specially developed contrast functions as well as multivariate techniques with principal components and Fisher's discriminate analyses were applied, and useful characterization of the rice could be achieved. The chlorophyll content mapping of the 30 zones was obtained with the remote sensing measurements.


Assuntos
Clorofila/análise , Fluorescência , Lasers de Estado Sólido , Nitrogênio/análise , Oryza/química , Tecnologia de Sensoriamento Remoto/métodos , Espectrometria de Fluorescência , China , Oryza/genética
19.
Ophthalmologica ; 239(2-3): 128-132, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29190623

RESUMO

PURPOSE: The aim of this study was to assess the axial length/corneal radius of curvature ratio changes after posterior scleral reinforcement (PSR) for pathologic myopia. PROCEDURES: This study enrolled 32 pathologically myopic eyes treated with PSR and 35 untreated pathologically myopic eyes. Axial length, refractive error, best corrected visual acuity, corneal radius of curvature, and the axial length/corneal radius of curvature ratio were evaluated during the 1-year follow-up. RESULTS: There were no statistical differences in each parameter between the 2 groups at baseline. Significant differences were found between the 2 groups in both axial elongation and best corrected visual acuity improvement. The average axial length/horizontal corneal radius of curvature ratio significantly decreased in the PSR group. CONCLUSION: The PSR surgery can effectively delay the axial elongation in pathological myopia. Axial length/horizontal corneal radius of curvature ratio significantly decreased, which may indicate less myopic progression after surgery.


Assuntos
Comprimento Axial do Olho/patologia , Córnea/diagnóstico por imagem , Miopia Degenerativa/diagnóstico , Esclera/cirurgia , Acuidade Visual , Comprimento Axial do Olho/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Miopia Degenerativa/fisiopatologia , Miopia Degenerativa/cirurgia , Estudos Retrospectivos , Fatores de Tempo
20.
Sensors (Basel) ; 18(3)2018 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-29562684

RESUMO

To achieve strength augmentation, endurance enhancement, and human assistance in a functional autonomous exoskeleton, control precision, back drivability, low output impedance, and mechanical compactness are desired. In our previous work, two elastic modules were designed for human-robot interaction sensing and compliant control, respectively. According to the intrinsic sensing properties of the elastic module, in this paper, only one compact elastic module is applied to realize both purposes. Thus, the corresponding control strategy is required and evolving internal model control is proposed to address this issue. Moreover, the input signal to the controller is derived from the deflection of the compact elastic module. The human-robot interaction is considered as the disturbance which is approximated by the output error between the exoskeleton control plant and evolving forward learning model. Finally, to verify our proposed control scheme, several experiments are conducted with our robotic exoskeleton system. The experiment shows a satisfying result and promising application feasibility.


Assuntos
Extremidade Inferior , Elasticidade , Exoesqueleto Energizado , Humanos
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