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1.
IUBMB Life ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012196

RESUMO

Osteoporosis (OP) is a systemic metabolic bone disease resulting in reduced bone strength and increased susceptibility to fractures, making it a significant public health and economic problem worldwide. The clinical use of anti-osteoporosis agents is limited because of their serious side effects or the high cost of long-term use. The Xianlinggubao (XLGB) formula is an effective traditional Chinese herbal medicine commonly used in orthopedics to treat osteoporosis; however, its mechanism of action remains unclear. In this study, we screened 40 small RNAs derived from XLGB capsules and found that XLGB28-sRNA targeting TNFSF11 exerted a significant anti-osteoporosis effect in vitro and in vivo by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis. Oral administration of bencaosome [16:0 Lyso PA+XLGB28-sRNA] effectively improved bone mineral density and reduced the damage to the bone microstructure in mice. These results suggest that XLGB28-sRNA may be a novel oligonucleotide drug that promotes osteogenesis and inhibits osteoclastogenesis in mice.

2.
IUBMB Life ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935610

RESUMO

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

3.
IUBMB Life ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38923653

RESUMO

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

4.
Phys Rev Lett ; 132(25): 256503, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996236

RESUMO

The recently discovered superconductivity with critical temperature T_{c} up to 80 K in the double-layer Nickelate La_{3}Ni_{2}O_{7-δ} under pressure has drawn great attention. Here, we report the positive muon spin relaxation (µ^{+}SR) study of polycrystalline La_{3}Ni_{2}O_{6.92} under ambient pressure. Zero-field µ^{+}SR experiments reveal the existence of magnetic order in La_{3}Ni_{2}O_{6.92} with T_{N}=154 K. The weak transverse field µ^{+}SR measurements reveal the bulk nature of magnetism. In addition, a small quantity of oxygen deficiencies can greatly broaden the internal magnetic field distribution sensed by muons.

5.
Respir Res ; 24(1): 306, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057804

RESUMO

BACKGROUND: Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. RESULTS: Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. CONCLUSIONS: Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Humana , Lesão Pulmonar , Humanos , Animais , Camundongos , Lesão Pulmonar/induzido quimicamente , Lisossomos , Óxido de Alumínio , Dióxido de Silício
6.
Cell ; 133(2): 235-49, 2008 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-18423196

RESUMO

Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.


Assuntos
Estresse Oxidativo , Síndrome do Desconforto Respiratório/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Humanos , Influenza Humana/metabolismo , Interleucina-6/metabolismo , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Infecções por Orthomyxoviridae/metabolismo , Fosfolipídeos/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Transdução de Sinais
7.
Entropy (Basel) ; 25(9)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37761652

RESUMO

Recent research has shown that visual-text pretrained models perform well in traditional vision tasks. CLIP, as the most influential work, has garnered significant attention from researchers. Thanks to its excellent visual representation capabilities, many recent studies have used CLIP for pixel-level tasks. We explore the potential abilities of CLIP in the field of few-shot segmentation. The current mainstream approach is to utilize support and query features to generate class prototypes and then use the prototype features to match image features. We propose a new method that utilizes CLIP to extract text features for a specific class. These text features are then used as training samples to participate in the model's training process. The addition of text features enables model to extract features that contain richer semantic information, thus making it easier to capture potential class information. To better match the query image features, we also propose a new prototype generation method that incorporates multi-modal fusion features of text and images in the prototype generation process. Adaptive query prototypes were generated by combining foreground and background information from the images with the multi-modal support prototype, thereby allowing for a better matching of image features and improved segmentation accuracy. We provide a new perspective to the task of few-shot segmentation in multi-modal scenarios. Experiments demonstrate that our proposed method achieves excellent results on two common datasets, PASCAL-5i and COCO-20i.

8.
Angew Chem Int Ed Engl ; 62(50): e202315136, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37902429

RESUMO

The helical twisting tendency of liquid crystals (LCs) is generally governed by the inherent configuration of the chiral emitter. Here, we introduce the multistage inversion of supramolecular chirality as well as circularly polarized luminescence (CPL) by manipulating the ratio of single enantiomeric emitters (R-PCP) to LC monomers (5CB). Increasing the content of R-PCP from 1 wt % to 3 wt % inverted the helix of LCs from left-handed to right-handed, accompanying a CPL sign changed from positive to negative. The biaxiality of chiral emitters, as well as the steric effect of chiral-chiral and chiral-achiral interaction, were identified as the reasons for helical sense inversion. Due to the strong helical twisting power, 4 wt % R-PCP drove the photonic band gap (PBG) of chiral LCs to match up with their emission range, leading to an inversion of the CPL again with a high dissymmetry factor (≈1.2). Directly adjusting the PBG using chiral emitters is seldom achieved in cholesteric LCs. On this basis, an achiral sensitizer PtTPBP was assembled into the helical superstructure. The generation of triplet-triplet annihilation-induced upconverted CPL from R-PCP and the downshifting CPL from PtTPBP with opposite rotation was achieved in a single chiral LC system by tuning the position of the PBG.

9.
PLoS Pathog ; 16(3): e1008341, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176725

RESUMO

Infection with avian influenza A H5N1 virus results in acute lung injury (ALI) and has a high mortality rate (52.79%) because there are limited therapies available for treatment. Drug repositioning is an economical approach to drug discovery. We developed a method for drug repositioning based on high-throughput RNA sequencing and identified several drugs as potential treatments for avian influenza A H5N1 virus. Using high-throughput RNA sequencing, we identified a total of 1,233 genes differentially expressed in A549 cells upon H5N1 virus infection. Among these candidate genes, 79 drug targets (corresponding to 59 approved drugs) overlapped with the DrugBank target database. Twenty-two of the 41 commercially available small-molecule drugs reduced H5N1-mediated cell death in cultured A549 cells, and fifteen drugs that protected A549 cells when administered both pre- and post-infection were tested in an H5N1-infection mouse model. The results showed significant alleviation of acute lung injury by amitriptyline HCl (an antidepressant drug), flavin adenine dinucleotide (FAD; an ophthalmic agent for vitamin B2 deficiency), azacitidine (an anti-neoplastic drug) and calcitriol (an active form of vitamin D). All four agents significantly reduced the infiltrating cell count and decreased the lung injury score in H5N1 virus-infected mice based on lung histopathology, significantly improved mouse lung edema by reducing the wet-to-dry weight ratio of lung tissue and significantly improved the survival of H5N1 virus-infected mice. This study not only identifies novel potential therapies for influenza H5N1 virus-induced lung injury but also provides a highly effective and economical screening method for repurposing drugs that may be generalizable for the prevention and therapy of other diseases.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Amitriptilina/administração & dosagem , Azacitidina/administração & dosagem , Calcitriol/administração & dosagem , Influenza Humana/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Animais , Modelos Animais de Doenças , Reposicionamento de Medicamentos , Feminino , Flavina-Adenina Dinucleotídeo/administração & dosagem , Humanos , Virus da Influenza A Subtipo H5N1/fisiologia , Influenza Humana/virologia , Pulmão/imunologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
10.
IUBMB Life ; 74(6): 532-542, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35383402

RESUMO

Coronavirus disease 2019, a newly emerging serious infectious disease, has spread worldwide. To date, effective drugs against the disease are limited. Traditional Chinese medicine was commonly used in treating COVID-19 patients in China. Here we tried to identify herbal effective lipid compounds from the lipid library of 92 heat-clearing and detoxication Chinese herbs. Through virtual screening, enzymatic activity and inhibition assays, and surface plasmon resonance tests, we identified lipid compounds targeting the main protease (Mpro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and verified their functions. Here, we found that natural lipid compounds LPC (14:0/0:0) and LPC (16:0/0:0) could target SARS-CoV-2 Mpro , recover cell death induced by SARS-CoV-2, and ameliorate acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by bacterial lipopolysaccharides and virus poly (I:C) mimics in vivo and in vitro. Our results suggest that LPC (14:0/0:0) and LPC (16:0/0:0) might be potential pan remedy against ARDS.


Assuntos
Lesão Pulmonar Aguda , Tratamento Farmacológico da COVID-19 , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Lipídeos , Camundongos , Simulação de Acoplamento Molecular , SARS-CoV-2
11.
J Autoimmun ; 130: 102840, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35598407

RESUMO

Cell death is important in the elimination of damaged cells such as virus-infected cells and also is closely involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). The retinoic acid-inducible gene-I (RIG-I), one cytosolic RNA innate sensor, can trigger antiviral innate response by inducing production of type I interferons (IFN-I). However, the function of RIG-I, once translocated from cytoplasm to nucleus at the late stage of viral infection when IFN-I production is almost terminated, remains poorly understood. Here, we reported that RIG-I is accumulated in the nucleus of macrophages and fibroblasts after virus infection, and nuclear RIG-I is present in peripheral blood mononuclear cells (PBMCs) from SLE patients. We found that nuclear RIG-I interacts with the first 20 amino acids of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and attenuates the anti-apoptotic properties of APEX1, therefore promoting apoptosis of virus-infected cells to suppress viral infection through an IFN-I-independent way at the late stage of viral infection. Together, our findings reveal a non-canonical role of nuclear RIG-I in the induction of cellular apoptosis, besides its activation of IFN-I expression as the cytosolic innate sensor. This study provides new insight to the regulation of infection, IFN-I and autoimmune diseases by nuclear RIG-I-APEX1 interaction.


Assuntos
Doenças Autoimunes , Leucócitos Mononucleares , Apoptose , Proteína DEAD-box 58/genética , Humanos , Receptores Imunológicos
12.
Respir Res ; 23(1): 38, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35189885

RESUMO

BACKGROUND: Studies on the associations between ambient temperature and asthma hospitalizations are limited, and the results are controversial. We aimed to assess the short-term effects of ambient temperature on the risk of asthma hospitalizations and quantify the hospitalization burdens of asthma attributable to non-optimal temperature in adults in Beijing, China. METHODS: We collected daily asthma hospitalizations, meteorological factors and air quality data in Beijing from 2012 to 2015. We applied a time-stratified case-crossover design and fitted a distributed lag non-linear model with a conditional quasi-Poisson regression to explore the association between ambient temperature and adult asthma hospitalizations. The effect modifications of these associations by gender and age were assessed by stratified analyses. We also computed the attributable fractions and numbers with 95% empirical confidence intervals (eCI) of asthma hospitalizations due to extreme and moderate temperatures. RESULTS: From 2012 to 2015, we identified a total of 18,500 hospitalizations for asthma among adult residents in Beijing, China. Compared with the optimal temperature (22 °C), the cumulative relative risk (CRR) over lag 0-30 days was 2.32 with a 95% confidence interval (CI) of 1.57-3.42 for extreme cold corresponding to the 2.5th percentile (- 6.5 °C) of temperature distribution and 2.04 (95% CI 1.52-2.74) for extreme heat corresponding to the 97.5th percentile (29 °C) of temperature distribution. 29.1% (95% eCI 17.5-38.0%) of adult asthma hospitalizations was attributable to non-optimum temperatures. Moderate cold temperatures yielded most of the burdens, with an attributable fraction of 20.3% (95% eCI 9.1-28.7%). The temperature-related risks of asthma hospitalizations were more prominent in females and younger people (19-64 years old). CONCLUSIONS: There was a U-shaped association between ambient temperature and the risk of adult asthma hospitalizations in Beijing, China. Females and younger patients were more vulnerable to the effects of non-optimum temperatures. Most of the burden was attributable to moderate cold. Our findings may uncover the potential impact of climate changes on asthma exacerbations.


Assuntos
Asma/terapia , Hospitalização/estatística & dados numéricos , Medição de Risco/métodos , Temperatura , Adulto , Asma/epidemiologia , Pequim/epidemiologia , Estudos Cross-Over , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Biochem Biophys Res Commun ; 579: 168-174, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34607170

RESUMO

Rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), displays a robust hypoglycemic action in patients with type 2 diabetes mellitus (T2DM) and elicits serious adverse reactions, especially hepatotoxicity and cardiotoxicity. Here, we aims to find a new natural PPAR-γ agonist with less adverse reactions than rosiglitazone in db/db mice. The method of virtual screening was used to identify a PPAR-γ agonist 18:0 Lyso PC from an in-house natural product library. We verified its pharmacological effects and adverse reactions comparing with rosiglitazone in vivo and in vitro. 18:0 Lyso PC exhibited pharmacological effects similar to those of rosiglitazone in db/db mice. Moreover, 18:0 Lyso PC showed a lower extent of liver injury and cardiotoxicity in db/db mice. The mechanism, by which this natural compound alleviates metabolic syndrome, involves a reduction in fatty acid synthesis mediated by activation of the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase-alpha (AMPKα) and acetyl-CoA carboxylase (ACC) and an increase expression of uncoupled protein 1 (UCP1) and PPAR-γ coactivator-1 alpha (PGC1-α). 18:0 Lyso PC, a natural compound, can show a similar hypoglycemic effect to rosiglitazone by activating PPAR-γ, while eliciting markedly fewer adverse reactions than rosiglitazone.


Assuntos
Produtos Biológicos/química , Coração/efeitos dos fármacos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , Lisofosfolipídeos/química , PPAR gama/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP , Acetil-CoA Carboxilase/metabolismo , Animais , Cardiotoxicidade , Química Farmacêutica/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos/metabolismo , Lipídeos/química , Masculino , Medicina Tradicional Chinesa , Camundongos , Simulação de Acoplamento Molecular , Rosiglitazona
14.
J Allergy Clin Immunol ; 146(1): 119-127.e4, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32360286

RESUMO

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.


Assuntos
Biomarcadores/sangue , Quimiocina CCL7/sangue , Quimiocina CXCL10/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Idoso , Betacoronavirus , COVID-19 , Estado Terminal , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Adulto Jovem
15.
Appl Microbiol Biotechnol ; 104(10): 4321-4332, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32232531

RESUMO

Separation and enrichment of phenolics from peony flowers were performed to improve the anti-biofilm and antibacterial activities for the first time. Through several times of separation, the purity of phenolics components increased significantly, and the anti-biofilm and antibacterial activities of phenolics components against E. coli and S. aureus were also significantly improved. Finally, the phenolics of peony flowers in the eluent of silica gel column chromatography (PPF-ESGCC) were found to exhibit the highest anti-biofilm and antibacterial activities. The inhibition rates of PPF-ESGCC on biofilms of E. coli and S. aureus were 77.93%, and 87.03% respectively, at a very low concentration (1/2 MIC, 0.235 mg/mL). It was found that the biofilm inhibition was achieved by inhibiting their swimming, swarming, twitching motilities, exopolysaccharide (EPS) production, and quorum sensing (QS). Moreover, there was a positive dose-dependent relationship (r = 0.75 to 1) between the inhibition rates and concentrations of PPF-ESGCC during the critical biofilm-formation stage (1-3 days). Chemical composition analysis showed the PPF-ESGCC comprised of gallic acid, kaempferol-7-O-glucoside, and apigenin-7-O-glucoside. In conclusion, PPF-ESGCC exhibited strong inhibitory effect on biofilm formation and gallic acid, kaempferol-7-O-glucoside, and apigenin-7-O-glucoside might play a crucial role in inhibiting biofilm formation. Meanwhile, this study indicated that PPF-ESGCC, a new natural QS inhibitor and biofilm inhibitor, could be used as a novel intervention strategy to enhance the safety and quality of food.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Paeonia/química , Fenóis/farmacologia , Flores/química , Testes de Sensibilidade Microbiana , Fenóis/isolamento & purificação , Percepção de Quorum/efeitos dos fármacos
16.
Sensors (Basel) ; 20(22)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233710

RESUMO

Hot film sensors detect the flow shear stress based on the forced convection heat transfer to the fluid. Current hot film sensors have been significantly hindered by the relatively low sensitivity due to the massive heat conduction to the substrate. This paper describes the design, fabrication, simulation, and testing of a novel flow sensor with dual-layer hot film structures. More specifically, the heat conduction was insulated from the sensing heater to the substrate by controlling both sensing and guarding heaters working at the same temperature, resulting in a higher sensitivity. The experiment and simulation results showed that the sensitivity of the dual-layer hot film sensor was significantly improved in comparison to the single-layer sensor. Additionally, the dual-layer sensor was designed and fabricated in an integrated, flexible, and miniaturized manner. Its small size makes it an excellent candidate for flow detection.

17.
Clin Infect Dis ; 68(7): 1100-1109, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30124826

RESUMO

BACKGROUND: H5N6 avian influenza virus (AIV) has caused sporadic, recurring outbreaks in China and Southeast Asia since 2013, with 19 human infections and 13 deaths. Seventeen of these infections occurred since December 2015, indicating a recent rise in the frequency of H5N6 cases. METHODS: To assess the relative threat of H5N6 virus to humans, we summarized and compared clinical data from patients infected with H5N6 (n = 19) against data from 2 subtypes of major public health concern, H5N1 (n = 53) and H7N9 (n = 160). To assess immune responses indicative of prognosis, we compared concentrations of serum cytokines/chemokines in patients infected with H5N6, H5N1, H7N9, and 2009 pandemic H1N1 and characterized specific immune responses from 1 surviving and 2 nonsurviving H5N6 patients. RESULTS: H5N6 patients were found to have higher incidences of lymphopenia and elevated alanine aminotransferase and lactate dehydrogenase levels compared with H5N1 and H7N9 patients. Hypercytokinemia was detected at substantially higher frequencies from H5N6 patients compared to those infected with other AIV subtypes. Evaluation of adaptive immunity showed that both humoral and cellular responses could be detected in the H5N6-infected survivor, but cellular responses were absent in the nonsurvivors. In addition, the surviving patient had lower concentrations of both pro- and anti-inflammatory cytokines/chemokines compared to the nonsurvivors. CONCLUSIONS: Our results support that H5N6 virus could potentially be a major public health threat, and suggest it is possible that the earlier acquisition of cellular immunity and lower concentrations of cytokines/chemokines contributed to survival in our patient. Analysis of more patient samples will be needed to draw concrete conclusions.


Assuntos
Citocinas/sangue , Imunidade Celular , Imunidade Humoral , Vírus da Influenza A/imunologia , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A/classificação , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Connect Tissue Res ; 59(3): 274-286, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28910556

RESUMO

Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. By replicating the native interactions between collagen and the SIBLING proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. In this work, bone sialoprotein, osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C), and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation. It was shown that DSP and DPP slowed down fibrillogenesis, while other SIBLINGs had limited impact. In addition, the denaturation time was faster in the presence of DSP and OPN, indicating a negative impact. The role of calcium ions in these processes was also investigated. The presence of calcium ions sped up fibrillogenesis in all scenarios tested, but it had a negative impact by reducing the extent. Calcium also sped up the denaturation in most cases, with the exception of DMP1-C and DSP where the opposite was seen. Calcium had a similar effect on the proteoglycan variants in the fibrillogenesis process, but had no impact on the denaturation process in the presence of these two. It is believed that incorporating DMP1-C or DSP on the surface of a bone implant may improve the collagen interactions with the implant, thereby facilitating improved osteointegration.


Assuntos
Osso e Ossos/metabolismo , Colágeno Tipo I/metabolismo , Sialoproteína de Ligação à Integrina/metabolismo , Precursores de Proteínas/metabolismo , Animais , Colágeno/metabolismo , Dentina/metabolismo , Proteoglicanas/metabolismo , Ratos , Sialoglicoproteínas/metabolismo
19.
J Immunol ; 197(3): 824-33, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27354218

RESUMO

The H5N1 avian influenza virus causes severe disease and high mortality, making it a major public health concern worldwide. The virus uses the host cellular machinery for several steps of its life cycle. In this report, we observed overexpression of the ubiquitin-like protein FAT10 following live H5N1 virus infection in BALB/c mice and in the human respiratory epithelial cell lines A549 and BEAS-2B. Further experiments demonstrated that FAT10 increased H5N1 virus replication and decreased the viability of infected cells. Total RNA extracted from H5N1 virus-infected cells, but not other H5N1 viral components, upregulated FAT10, and this process was mediated by the retinoic acid-induced protein I-NF-κB signaling pathway. FAT10 knockdown in A549 cells upregulated type I IFN mRNA expression and enhanced STAT1 phosphorylation during live H5N1 virus infection. Taken together, our data suggest that FAT10 was upregulated via retinoic acid-induced protein I and NF-κB during H5N1 avian influenza virus infection. And the upregulated FAT10 promoted H5N1 viral replication by inhibiting type I IFN.


Assuntos
Interferon Tipo I/biossíntese , Infecções por Orthomyxoviridae/metabolismo , Ubiquitinas/metabolismo , Replicação Viral/fisiologia , Animais , Western Blotting , Linhagem Celular , Técnicas de Silenciamento de Genes , Humanos , Virus da Influenza A Subtipo H5N1 , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Orthomyxoviridae/imunologia , Reação em Cadeia da Polimerase , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Regulação para Cima
20.
Langmuir ; 33(16): 3949-3953, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28394611

RESUMO

Re-entrant microstructures exhibit excellent wetting stability under different pressure levels, but the underlying mechanism determined by wetting transition behavior at the microscale level remains unclear. We propose the "wetting chip" method for in situ assessment of the dynamic behavior of wetting transition in re-entrant microstructures. High sag and transverse depinning were observed in re-entrant microstructures. Analysis indicated that high sag and transverse depinning mainly influenced the stability of the structures. The threshold pressure and longevity of wetting transition were predicted and experimentally verified. The design criteria of wetting stability, including small geometry design, hydrophobic material selection, and sidewall condition, were also presented. The proposed method and model can be applied to different shapes and geometry microstructures to elucidate wetting stability.

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