Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 177(7): 1714-1724.e12, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31080063

RESUMO

Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), cause severe and debilitating rheumatic diseases worldwide, resulting in severe morbidity and economic costs. Recently, MXRA8 was reported as an entry receptor. Here, we present the crystal structures of the mouse MXRA8, human MXRA8 in complex with the CHIKV E protein, and the cryo-electron microscopy structure of human MXRA8 and CHIKV virus-like particle. MXRA8 has two Ig-like domains with unique structural topologies. This receptor binds in the "canyon" between two protomers of the E spike on the surface of the virion. The atomic details at the interface between the two binding entities reveal that both the two domains and the hinge region of MXRA8 are involved in interaction with CHIKV E1-E2 residues from two protomers. Notably, the stalk region of MXRA8 is critical for CHIKV virus entry. This finding provides important information regarding the development of therapeutic countermeasures against those arthritogenic alphaviruses.


Assuntos
Vírus Chikungunya/química , Proteínas de Membrana/química , Proteínas do Envelope Viral/química , Internalização do Vírus , Animais , Vírus Chikungunya/metabolismo , Chlorocebus aethiops , Células HEK293 , Humanos , Proteínas de Membrana/metabolismo , Domínios Proteicos , Células Vero , Proteínas do Envelope Viral/metabolismo
2.
J Am Chem Soc ; 146(26): 17636-17645, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698551

RESUMO

Extensive machine-learning-assisted research has been dedicated to predicting band gaps for perovskites, driven by their immense potential in photovoltaics. Yet, the effectiveness is often hampered by the lack of high-quality band gap data sets, particularly for perovskites involving d orbitals. In this work, we consistently calculate a large data set of band gaps with a high level of accuracy, which is rigorously validated by experimental and state-of-the-art GW band gaps. Leveraging this achievement, our machine-learning-derived descriptor exhibits exceptional universality and robustness, proving effectiveness not only for single and double, halide and oxide perovskites regardless of the underlying atomic structures but also for hybrid organic-inorganic perovskites. With this approach, we comprehensively explore up to 15,659 materials, unveiling 14 unreported lead-free perovskites with suitable band gaps for photovoltaics. Notably, MASnBr3, FA2SnGeBr6, MA2AuAuBr6, FA2AuAuBr6, FA2InBiCl6, FA2InBiBr6, and Ba2InBiO6 stand out with direct band gaps, small effective masses, low exciton binding energies, and high stabilities.

3.
EMBO J ; 36(7): 919-933, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-28254839

RESUMO

Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and survival of the virus through its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains. Here, we present the crystal structures of ZIKV NS5 MTase in complex with an RNA cap analogue (m7GpppA) and the free NS5 RdRp. We have identified the conserved features of ZIKV NS5 MTase and RdRp structures that could lead to development of current antiviral inhibitors being used against flaviviruses, including dengue virus and West Nile virus, to treat ZIKV infection. These results should inform and accelerate the structure-based design of antiviral compounds against ZIKV.


Assuntos
Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Zika virus/química , Antivirais/metabolismo , Cristalografia por Raios X , Metiltransferases/química , Metiltransferases/metabolismo , Ligação Proteica , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/metabolismo
4.
EMBO J ; 35(20): 2170-2178, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27578809

RESUMO

The association of Zika virus (ZIKV) infections with microcephaly and neurological diseases has highlighted an emerging public health concern. Here, we report the crystal structure of the full-length ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis, and immune evasion. Of note, a long intertwined loop is observed in the wing domain of ZIKV NS1, and forms a hydrophobic "spike", which can contribute to cellular membrane association. For different flaviviruses, the amino acid sequences of the "spike" are variable but their common characteristic is either hydrophobic or positively charged, which is a beneficial feature for membrane binding. Comparative studies with West Nile and Dengue virus NS1 structures reveal conserved features, but diversified electrostatic characteristics on both inner and outer faces. Our results suggest different mechanisms of flavivirus pathogenesis and should be considered during the development of diagnostic tools.


Assuntos
Proteínas não Estruturais Virais/química , Zika virus , Cristalização , Conformação Proteica , Proteínas não Estruturais Virais/genética
5.
J Cell Biochem ; 120(3): 2994-3000, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30552706

RESUMO

OBJECTIVE: We aimed to investigate the association of macrophage inflammatory protein (MIP)-1α (CCL3) expression with the severity of acute pancreatitis (AP). METHODS: The patients with AP were selected and divided into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups according to the severity of AP. The pancreatic acinar cell line Ar42 j was treated with cerulein to induce in vitro cell AP model. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway in stimulated or transfected Ar42 j cells were detected. RESULTS: We detected that the upregulation of MIP-1α was associated with the severity of AP. Patients with SAP showed the highest MIP-1α contents, followed by MSAP, and, lastly, MAP. In cerulein-stimulated Ar42 j cells, the upregulation of MIP-1α, CCR5, TNF-α, and IL-6 was time dependent. In addition, in human recombinant MIP-1α treated Ar42 j cells, the upregulation of TNF-α and IL-6 was MIP-1α-dose-dependent. In contrast, we detected the inhibition of TNF-α and IL-6 in MIP-1α small interfering RNA (siRNA)-treated cells. Also, the activation of the JNK/p38 MAPK signaling pathway was induced and inhibited by human recombinant MIP-1α and MIP-1α siRNA, respectively. CONCLUSION: These results suggested that MIP-1α might be used as a biomarker for the prognosis of AP severity. The MIP-1α-induced inflammatory responses in AP were mediated by TNF-α and IL-6, which were associated with the activation of the JNK/p38 MAPK signaling pathway.


Assuntos
Quimiocina CCL3/metabolismo , Pancreatite/metabolismo , Receptores CCR1/metabolismo , Receptores CCR5/metabolismo , Regulação para Cima , Adulto , Idoso , Linhagem Celular , Ceruletídeo/efeitos adversos , Feminino , Humanos , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
6.
J Cell Biochem ; 120(1): 290-304, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30216510

RESUMO

Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.


Assuntos
Lesão Pulmonar Aguda/complicações , Lesão Pulmonar Aguda/metabolismo , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Pancreatite/complicações , Pancreatite/metabolismo , Quinases Ativadas por p21/metabolismo , Amilases/sangue , Animais , Modelos Animais de Doenças , Edema/metabolismo , Técnicas de Silenciamento de Genes , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Quinases Ativadas por p21/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Sensors (Basel) ; 19(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027186

RESUMO

Low-Power Wide-Area Network (LPWAN) is the technology that the Internet-of-Things (IoT) uses in long-distance, wide-coverage scenarios. As one of the ultra-narrowband (UNB) modulation techniques, M-ary position phase shift keying (MPPSK) modulation can provide high coverage and high reliability for LPWAN. This paper proposes a multipath separation method based on MPPSK modulation, which aims to eliminate the influence of multipath on the main path without increasing the spectrum overhead and system complexity. Specifically, the modulation parameter of the system is adjusted according to the delay value, so that the phase jump of the multipath signal falls outside the phase jump of the main path symbol to achieve separation of the multipath from the main path. Moreover, a normalized symbol joint decision method is proposed in order to reduce the introduced noise while using multipath information for decisions. The simulation results indicate that the multipath separation conditions given in this paper can meet the requirements of multipath separation of MPPSK signals. Compared with the existing mainstream decision scheme, the normalized symbol joint decision improves the demodulation performance of the system.

8.
J Cell Biochem ; 119(8): 6704-6714, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29693276

RESUMO

Severe acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP-ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP-ALI. This study aims to define the role of miR-339-3p in SAP-ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR-339-3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF-α, IL-6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT-qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP-ALI mice had decreased survival rate, increased levels of TNF-α, IL-6, AMS, MPO, and Schmidt scores. miR-339-3p was poorly expressed in lung tissue of SAP-ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR-339-3p. miR-339-3p inhibited the relative expression of the Akt/mTOR signaling pathway-related proteins, alleviated inflammation and edema of SAP-ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR-339-3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP-ALI mice.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Anexina A5/metabolismo , Apoptose , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Pancreatite/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Edema Pulmonar/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Doença Aguda , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Células Endoteliais/patologia , Regulação da Expressão Gênica , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/biossíntese , Camundongos , Pancreatite/complicações , Pancreatite/patologia , Edema Pulmonar/etiologia , Edema Pulmonar/patologia , Fator de Necrose Tumoral alfa/biossíntese
9.
Biochem Biophys Res Commun ; 498(1): 146-151, 2018 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-29462619

RESUMO

Intervention with dietary fibers is an important strategy to combat the global epidemic of obesity which is a consequence of energy imbalance. However, a possible role of the gut microbiota in effects of dietary fibers on energy homeostasis remains unclear. Here, we treated a high fat diet-induced obese (DIO) mouse model with soluble dietary fiber. Our results showed that soluble dietary fiber reduced body weight gain and the excessive accumulation of white fat tissue in DIO mice. Notably, soluble dietary fiber increased energy expenditure, but not change energy intake in DIO mice. In accordance, 16S rRNA sequencing revealed that the diversity of the gut microbiota was restored by soluble dietary fiber. Moreover, compared with controls, soluble dietary fiber resulted in a decreased ratio of Firmicutes/Bacteroidetes at the phylum level, and an increased relative abundance of the genera Roseburia at the genus level. Taken together, these findings indicate that soluble dietary fiber improves energy homeostasis and prevents obesity by increasing the diversity of the gut microbiota and the colonization of beneficial bacteria.


Assuntos
Fibras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Solubilidade , Aumento de Peso/efeitos dos fármacos
10.
Hum Brain Mapp ; 38(6): 3210-3225, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28345153

RESUMO

The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity - with DCM - revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval-based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp 38:3210-3225, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Matemática , Modelos Neurológicos , Vias Neurais/diagnóstico por imagem , Adulto , Encéfalo/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Vias Neurais/fisiologia , Oxigênio/sangue , Resolução de Problemas/fisiologia , Tempo de Reação/fisiologia , Adulto Jovem
11.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2809-2813, 2016 Aug.
Artigo em Zh | MEDLINE | ID: mdl-28914020

RESUMO

The hollow mesoporous silica nanoparticles (HMSNs) were prepared by hard template method, with a size of 300 nm and shell thickness of 25 nm. Borneol was loaded with solvent impregnation method in order to solve the stability problem of borneol in pharmaceutics, and the BET, TEM and FT-IR were used to characterize the HMSNs and the borneol-HMSNs drug delivery system. The optimal drug loading time, maximum drug loading capacity and the volatility of borneol were investigated. The results showed that HMSNs which were prepared at room temperature and neutral conditions had good sphericity, achieved high drug loading of borneol in a short time, and the drug loading was up to 74.04% within 6 hours; meanwhile, volatility of borneol in the system was greatly improved. This novel drug delivery system provides a new idea for wide application of borneol in the traditional Chinese medicine.


Assuntos
Canfanos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Medicina Tradicional Chinesa , Porosidade , Dióxido de Silício , Espectroscopia de Infravermelho com Transformada de Fourier , Volatilização
12.
Zhongguo Zhong Yao Za Zhi ; 40(18): 3579-84, 2015 Sep.
Artigo em Zh | MEDLINE | ID: mdl-26983203

RESUMO

1,3,5-Trimethylbenzene (1,3,5-TMB) was used as the pore-enlarging modifier to expand the pore size of MCM-41 (mobil company of matter) mesoporous silica nanoparticles. The solvent impregnation method was adopted to assemble non-water-soluble ß-carotene into the pore channel of MCM-41. The MCM-41 and drug assemblies were characterized by TEM, FT-IR, elemental analysis and N2 adsorption-desorption. The results showed that MCM-41 has good sphericity and regular pore structure. The research also investigated the optimal loading time, the drug loading and the vitro stability of the ß-carotene. As a drug carrier, the modified MCM-41 showing a shorter drug loading time, the drug loading as high as 85.58% and the stability of ß-carotene in drug assemblies has improved. The study of this new formulation provides a new way for ß-carotene application.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Dióxido de Silício/química , beta Caroteno/química , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , beta Caroteno/farmacologia
13.
J Affect Disord ; 354: 323-330, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494138

RESUMO

BACKGROUND: Arthritis is relatively common among middle-aged and older people and is a significant public health problem. However, research on the relationship between arthritis and mental health in older populations is currently limited. METHODS: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey. The 10-item Center for Epidemiologic Studies Depression Scale and 7-item Generalized Anxiety Disorder Scale were used to evaluate depressive and anxiety symptoms. Arthritis status was self-reported. Linear and logistic regression analyses were conducted to assess the impact of arthritis on depression, anxiety, and comorbid depression/anxiety symptoms. RESULTS: A total of 11,104 participants aged ≥65 years (mean age, 83.1 ± 11.1 years) were included in the analysis. We detected positive associations of arthritis with depression symptoms (adjusted odds ratio [OR]: 1.57, 95 % confidence interval [CI] 1.33 to 1.86), anxiety symptoms (adjusted OR: 1.48, 95 % CI: 1.15 to 1.90), and comorbid depression/anxiety symptoms (adjusted OR: 1.88, 95 % CI: 1.41 to 2.5) in the older adult population. Participants with arthritis had higher anxiety (adjusted linear regression coefficient: 0.43, 95 % CI: 0.24 to 0.63) and depression (adjusted linear regression coefficient: 0.87, 95 % CI: 0.57 to 1.14) scores compared with those without arthritis. In addition, there were no significant interaction effects between arthritis and participant characteristics on depression symptoms, anxiety symptoms, or comorbid depression/anxiety symptoms. CONCLUSIONS: Arthritis was positively associated with depression symptoms, anxiety symptoms, and comorbid depression/anxiety symptoms among older adults. Further cohort studies are needed to validate these associations.


Assuntos
Artrite , Depressão , Pessoa de Meia-Idade , Humanos , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/complicações , Estudos Transversais , Autorrelato , Ansiedade/epidemiologia , Ansiedade/complicações , Artrite/epidemiologia , China/epidemiologia
14.
Materials (Basel) ; 17(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38894013

RESUMO

Advanced oxidation processes (AOPs) represent one of the most promising strategies to generate highly reactive species to deal with organic dye-contaminated water. However, developing green and cost-effective catalysts is still a long-term goal for the wide practical application of AOPs. Herein, we demonstrated doping cobalt in porous carbon to efficiently catalyze the oxidation of the typically persistent organic pollutant rhodamine B, via multiple reactive species through the activation of peroxymonosulfate (PMS). The catalysts were prepared by facile pyrolysis of nanocomposites with a core of cobalt-loaded silica and a shell of phenolic resin (Co-C/SiO2). It showed that the produced 1O2 could effectively attack the electron-rich functional groups in rhodamine B, promoting its molecular chain breakage and accelerating its oxidative degradation reaction with reactive oxygen-containing radicals. The optimized Co-C/SiO2 catalyst exhibits impressive catalytic performance, with a degradation rate of rhodamine B up to 96.7% in 14 min and a reaction rate constant (k) as high as 0.2271 min-1, which suggested promising potential for its practical application.

15.
Biochem Cell Biol ; 91(6): 449-54, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24219287

RESUMO

The airway epithelial barrier function is important in maintaining the homeostasis in the body. A number of airway disorders are associated with the epithelial barrier dysfunction. The present study aims to elucidate a possible mechanism by which the proteolytic allergens compromise the epithelial barrier function. The airway epithelial cell line, RPMI 2650 cells (Rp cells) and kidney epithelial cell line, MDCK cells, were cultured to be monolayers and used as an in vitro epithelial barrier model. House dust mite antigen, Der P1 (Der) was used as an antigen that has the proteolytic property. The epithelial barrier permeability and transepithelial resistance (TER) were used as the indicators of epithelial barrier function. Both epithelial cell lines could endocytose Der in the culture. Some of the Der was transported across the epithelial barrier to the basal chambers of the Transwells without affecting the TER. The endocytic Der could suppress the expression of ubiquitin E3 lases A20 and further interfered with the fusion of endosome/lysosome in the epithelial cells. Mite antigen, Der, can interfere with the fusion of endosome/lysosome in epithelial cells to induce the epithelial barrier dysfunction.


Assuntos
Antígenos de Dermatophagoides/farmacologia , Proteínas de Artrópodes/farmacologia , Cisteína Endopeptidases/farmacologia , Endossomos/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Fusão de Membrana/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Animais , Transporte Biológico , Linhagem Celular , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Cães , Endocitose , Endossomos/metabolismo , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , Células Madin Darby de Rim Canino , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Permeabilidade , Proteólise , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa
16.
PLoS One ; 18(1): e0280136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36634101

RESUMO

High altitude pulmonary edema (HAPE) is a common respiratory disease in the high altitude area, which is rapid and harmful. We firstly conducted a case-control study to assess the potential association of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population. The study recruited 238 patients with HAPE and 230 healthy controls in Northwest China. Genomic DNA was extracted from blood samples, and gene polymorphisms were detected using the Agena MassARRAY platform. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P-value were used to evaluate the relationship between HAPE risk and CYP4F2 gene polymorphisms. Multi-factor dimension reduction (MDR) was used to assess the optimal interaction of CYP4F2 gene polymorphisms on HAPE risk. We found rs3093193 was shown to reduce the risk of HAPE (OR = 0.70, 95% CI = 0.52-0.93, P = 0.014), while rs12459936 was increased the susceptibility to HAPE (OR = 2.08, 95% CI = 1.33-3.26, P = 0.001). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk in people at age > 32 years old, and rs3093193 and rs3093110 were correlated with the HAPE risk in people at age ≤ 32 years old. Gender stratification analysis was found that rs3093193, rs12459936, and rs3093110 were all related to HAPE risk in males. A combination of rs12459936 and rs3093110 was the best multi-loci model with the highest testing accuracy. Our study is the first to provide the association between CYP4F2 gene polymorphisms and HAPE risk in the Chinese Han population.


Assuntos
Doença da Altitude , População do Leste Asiático , Masculino , Humanos , Adulto , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Doença da Altitude/genética , China/epidemiologia , Predisposição Genética para Doença , Família 4 do Citocromo P450/genética
17.
Front Mol Neurosci ; 16: 1205516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435575

RESUMO

Regulated secretion is conserved in all eukaryotes. In vertebrates granin family proteins function in all key steps of regulated secretion. Phase separation and amyloid-based storage of proteins and small molecules in secretory granules require ion homeostasis to maintain their steady states, and thus need ion conductances in granule membranes. But granular ion channels are still elusive. Here we show that granule exocytosis in neuroendocrine cells delivers to cell surface dominant anion channels, to which chromogranin B (CHGB) is critical. Biochemical fractionation shows that native CHGB distributes nearly equally in soluble and membrane-bound forms, and both reconstitute highly selective anion channels in membrane. Confocal imaging resolves granular membrane components including proton pumps and CHGB in puncta on the cell surface after stimulated exocytosis. High pressure freezing immuno-EM reveals a major fraction of CHGB at granule membranes in rat pancreatic ß-cells. A cryo-EM structure of bCHGB dimer of a nominal 3.5 Å resolution delineates a central pore with end openings, physically sufficient for membrane-spanning and large single channel conductance. Together our data support that CHGB-containing (CHGB+) channels are characteristic of regulated secretion, and function in granule ion homeostasis near the plasma membrane or possibly in other intracellular processes.

18.
Cytokine ; 59(1): 59-64, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22579114

RESUMO

BACKGROUND AND AIMS: Measles infection causes immune suppression that contributes to morbidity and mortality of the patients; the mechanism is poorly understood. Regulatory T cells (Treg) play a critical role in immune suppression. Integrin alphavbeta6 (avb6) is associated with Treg's function. This study aims to investigate into the mechanism by which measles C protein (MVP)-induced avb6 contributes the generation of Tregs in the lung. METHOD: MVP was introduced to mouse lung by nasal drops. The expression of avb6 by lung tissue was examined by reverse transcription polymerase chain reaction and Western blotting. The development of tolerogenic dendritic cells (DC) and Tregs in the lung and their functions was examined by flow cytometry. The suppressor function of MVP-induced Tregs was examined by cell culture models. RESULTS: The exposure to MVP markedly increased the expression of avb6 in the lung epithelial cells. Administration of MVP significantly suppressed the levels of IL-4 and IFNγ as well as increases in Tregs in lung tissue. DCs captured the MVP in the lung and differentiate into tolerogenic DCs; the latter has the ability to induce Treg development in the lung. Activation of MVP-induced Tregs powerfully suppressed polarized CD4(+) T cells. CONCLUSIONS: Exposure to MVP can induce Treg development in the lung that plays an important role in the suppression of CD4(+) T cell function.


Assuntos
Antígenos de Neoplasias/metabolismo , Tolerância Imunológica/imunologia , Integrinas/metabolismo , Pulmão/imunologia , Pulmão/virologia , Proteínas Virais/imunologia , Animais , Células Dendríticas/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologia , Proteínas Virais/administração & dosagem
19.
Front Plant Sci ; 13: 1010474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275564

RESUMO

In this paper, a method for predicting residual film content in the cotton field plough layer based on UAV imaging and deep learning was proposed to solve the issues of high labour intensity, low efficiency, and high cost of traditional methods for residual film content monitoring. Images of residual film on soil surface in the cotton field were collected by UAV, and residual film content in the plough layer was obtained by manual sampling. Based on the three deep learning frameworks of LinkNet, FCN, and DeepLabv3, a model for segmenting residual film from the cotton field image was built. After comparing the segmentation results, DeepLabv3 was determined to be the best model for segmenting residual film, and then the area of residual film was obtained. In addition, a linear regression prediction model between the residual film coverage area on the cotton field surface and the residual film content in the plough layer was built. The results showed that the correlation coefficient (R2), root mean square error, and average relative error of the prediction of residual film content in the plough layer were 0.83, 0.48, and 11.06%, respectively. It indicates that a quick and accurate prediction of residual film content in the cotton field plough layer can be realized based on UAV imaging and deep learning. This study provides certain technical support for monitoring and evaluating residual film pollution in the cotton field plough layer.

20.
Front Plant Sci ; 13: 991191, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160956

RESUMO

To accurately evaluate residual plastic film pollution in pre-sowing cotton fields, a method based on modified U-Net model was proposed in this research. Images of pre-sowing cotton fields were collected using UAV imaging from different heights under different weather conditions. Residual films were manually labelled, and the degree of residual film pollution was defined based on the residual film coverage rate. The modified U-Net model for evaluating residual film pollution was built by simplifying the U-Net model framework and introducing the inception module, and the evaluation results were compared to those of the U-Net, SegNet, and FCN models. The segmentation results showed that the modified U-Net model had the best performance, with a mean intersection over union (MIOU) of 87.53%. The segmentation results on images of cloudy days were better than those on images of sunny days, with accuracy gradually decreasing with increasing image-acquiring height. The evaluation results of residual film pollution showed that the modified U-Net model outperformed the other models. The coefficient of determination(R2), root mean square error (RMSE), mean relative error (MRE) and average evaluation time per image of the modified U-Net model on the CPU were 0.9849, 0.0563, 5.33% and 4.85 s, respectively. The results indicate that UAV imaging combined with the modified U-Net model can accurately evaluate residual film pollution. This study provides technical support for the rapid and accurate evaluation of residual plastic film pollution in pre-sowing cotton fields.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA