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1.
Genes Dev ; 37(15-16): 743-759, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37669874

RESUMO

Protein tyrosine phosphatases (PTPs) are critical regulators of signal transduction but have yet to be exploited fully for drug development. Receptor protein tyrosine phosphatase δ (RPTPδ/PTPRD) has been shown to elicit tumor-promoting functions, including elevating SRC activity and promoting metastasis in certain cell contexts. Dimerization has been implicated in the inhibition of receptor protein tyrosine phosphatases (RPTPs). We have generated antibodies targeting PTPRD ectodomains with the goal of manipulating their dimerization status ectopically, thereby regulating intracellular signaling. We have validated antibody binding to endogenous PTPRD in a metastatic breast cancer cell line, CAL51, and demonstrated that a monoclonal antibody, RD-43, inhibited phosphatase activity and induced the degradation of PTPRD. Similar effects were observed following chemically induced dimerization of its phosphatase domain. Mechanistically, RD-43 triggered the formation of PTPRD dimers in which the phosphatase activity was impaired. Subsequently, the mAb-PTPRD dimer complex was degraded through lysosomal and proteasomal pathways, independently of secretase cleavage. Consequently, treatment with RD-43 inhibited SRC signaling and suppressed PTPRD-dependent cell invasion. Together, these findings demonstrate that manipulating RPTP function via antibodies to the extracellular segments has therapeutic potential.


Assuntos
Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Transdução de Sinais , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Dimerização , Linhagem Celular , Monoéster Fosfórico Hidrolases
2.
Small ; 20(3): e2304945, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37675818

RESUMO

Reversible three-electron redox of Cr3+ /Cr6+ in layered cathode materials for rechargeable batteries is very attractive in layered cathode materials, which leads to high capacity and energy density for rechargeable batteries. However, the poor reversibility and Cr-ion migration make it very challenging. In this work, by introducing V ions into tetrahedral sites of layer-structured NaCrO2 , reversible three-electron redox of Cr3+ /Cr6+ is realized successfully in NaCr0.92 V0.05 O2 (NCV05) cathode for potassium-ion batteries with a cut-off voltage of 4.0 V. V ions can weaken the attraction of Cr to electrons, leading to enhanced valence change of Cr ions. On the other hand, V in tetrahedral sites can facilitate the reversible migration of Cr between octahedral and tetrahedral sites via coulombic repulsion to realize the reversible redox between Cr3+ and Cr6+ during charge and discharge processes. In addition, V ions can inhibit the phase transition from O3 phase to O'3 phase during the charge process by adjusting the crystal lattices. As a result, the NaCr0.92 V0.05 O2 cathode exhibits a high reversible capacity of 130 mAh g-1 with promising cycle stability and rate capability. The strategy opens new opportunity for developing high-capacity cathode materials for potassium-ion batteries.

3.
BMC Public Health ; 24(1): 440, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347483

RESUMO

BACKGROUND: Due to the chronic nature of HIV, mental health has become a critical concern in people living with HIV (PLWHIV). However, little knowledge exists about the association between fear of progression (FoP) and medical coping modes (MCMs) in PLWHIV in China. METHODS: A cohort of 303 PLWHIV were consecutively enrolled and their demographic, clinical and psychological information was collected. The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Social Support Rating Scale (SSRS), Internalized HIV Stigma Scale (IHSS) and MCMs Questionnaire were utilized. RESULTS: Of the participants, 215 PLWHIV were classified into the low-level FoP group, and 88 were grouped into the high-level FoP group based on their FoP-Q-SF scores, according to the criteria for the classification of dysfunctional FoP in cancer patients. The high-level group had a higher proportion of acquired immunodeficiency syndrome (AIDS) stage (P = 0.005), lower education levels (P = 0.027) and lower income levels (P = 0.031). Additionally, the high-level group had lower scores in social support (P < 0.001) and its three dimensions, with total SSRS scores showing a negative correlation with two dimensions of FoP-Q-SF, namely physical health (r2 = 0.0409, P < 0.001) and social family (r2 = 0.0422, P < 0.001). Further, the high-level group had higher scores in four dimensions of internalized HIV stigma, and a positive relationship was found to exist between IHSS scores and FoP-Q-SF scores for physical health (r2 = 0.0960, P < 0.001) and social family (r2 = 0.0719, P < 0.001). Social support (OR = 0.929, P = 0.001), being at the AIDS stage (OR = 3.795, P = 0.001), and internalized HIV stigma (OR = 1.028, P < 0.001) were independent factors for FoP. Furthermore, intended MCMs were evaluated. FoP were positively correlated with avoidance scores (r2 = 0.0886, P < 0.001) and was validated as the only factor for the mode of confrontation (OR = 0.944, P = 0.001) and avoidance (OR = 1.059, P = 0.001) in multivariate analysis. CONCLUSION: The incidence of dysfunctional FoP in our study population was relatively high. High-level FoP was associated with poor social support, high-level internalized HIV stigma and a negative MCM among PLWHIV.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Estudos Transversais , Capacidades de Enfrentamento , HIV , Progressão da Doença , Medo/psicologia , Infecções por HIV/epidemiologia , Inquéritos e Questionários
4.
Nature ; 550(7676): 380-383, 2017 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-28992630

RESUMO

Graphene oxide membranes-partially oxidized, stacked sheets of graphene-can provide ultrathin, high-flux and energy-efficient membranes for precise ionic and molecular sieving in aqueous solution. These materials have shown potential in a variety of applications, including water desalination and purification, gas and ion separation, biosensors, proton conductors, lithium-based batteries and super-capacitors. Unlike the pores of carbon nanotube membranes, which have fixed sizes, the pores of graphene oxide membranes-that is, the interlayer spacing between graphene oxide sheets (a sheet is a single flake inside the membrane)-are of variable size. Furthermore, it is difficult to reduce the interlayer spacing sufficiently to exclude small ions and to maintain this spacing against the tendency of graphene oxide membranes to swell when immersed in aqueous solution. These challenges hinder the potential ion filtration applications of graphene oxide membranes. Here we demonstrate cationic control of the interlayer spacing of graphene oxide membranes with ångström precision using K+, Na+, Ca2+, Li+ or Mg2+ ions. Moreover, membrane spacings controlled by one type of cation can efficiently and selectively exclude other cations that have larger hydrated volumes. First-principles calculations and ultraviolet absorption spectroscopy reveal that the location of the most stable cation adsorption is where oxide groups and aromatic rings coexist. Previous density functional theory computations show that other cations (Fe2+, Co2+, Cu2+, Cd2+, Cr2+ and Pb2+) should have a much stronger cation-π interaction with the graphene sheet than Na+ has, suggesting that other ions could be used to produce a wider range of interlayer spacings.

5.
Clin Exp Hypertens ; 44(5): 451-458, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35531646

RESUMO

BACKGROUND: To investigate the association between hypertension and clinical outcomes, including in-hospital mortality, intensive care unit (ICU) admission, and invasive ventilation in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We implemented a systematic search of PubMed for articles that assessed clinical outcomes of hypertensive patients infected with SARS-CoV-2. The primary outcomes evaluated included: in-hospital mortality, ICU admission, and the use of invasive ventilation. RESULTS: A total of 18 studies were included, involving 13,293 patients and covering from January 25, 2020, to April 20, 2020. The relationship between hypertension and prognosis in COVID-19 patients was evaluated. Results showed that hypertension was a risk factor for in-hospital mortality in COVID-19 patients (RR: 2.20, 95% CI, 1.83-2.65, P < .001). Moreover, patients with hypertension were more likely to be admitted to ICU (RR: 1.86, 95% CI, 1.13-3.07, P = .001) and to use invasive ventilation (RR: 2.99, 95% CI, 1.73-5.17, P < .001). CONCLUSIONS: Among COVID-19 patients, those combined with hypertension had a significantly higher risk of in-hospital deaths, admission to ICU, and need for invasive ventilation.


Assuntos
COVID-19 , Hipertensão , COVID-19/complicações , Humanos , Hipertensão/complicações , Unidades de Terapia Intensiva , Prognóstico , SARS-CoV-2
6.
Environ Sci Technol ; 55(9): 5689-5700, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33797233

RESUMO

Residential solid fuel combustion (RSFC) is a key cause of air pollution in China. In these serial studies, field measurements of RSFC from 166 rural households in eastern China were conducted to update the database of emission factors (EFs) and chemical profiles of gaseous and particulate organic pollutants, and the present study focuses on the intermediate volatile organic compounds (IVOCs), which are precursors of secondary organic aerosol (SOA). The results show that the averaged EFs of IVOCs (EFIVOC) for crop straw, fuelwood, and coal are 550.7 ± 397.9, 416.1 ± 249.5, and 361.9 ± 308.0 mg/kg, respectively, which are among the EFIVOC of gasoline vehicle, diesel vehicle, non-road machinery, and heavy fuel oil vessel, and are significantly affected by fuel, stove, and combustion efficiency. The percentages of normal alkanes (n-alkanes), branched alkanes (b-alkanes), polycyclic aromatic hydrocarbons (PAHs), and unresolved complex mixture from RSFC are 3.5 ± 1.6, 8.0 ± 3.7, 17.6 ± 6.7, and 70.9 ± 8.1%, respectively, and the compositions are featured by lower b-alkanes and higher PAHs than those of vehicle sources. The proportions of some individual n-alkanes and PAHs (such as n-C12-n-C15, naphthalene, and its alkyl substituents) can be used as indicators to differentiate RSFC from vehicle sources, while methoxyphenols can be used to distinguish biomass burning from coal combustion. Based on China's energy statistics, the total IVOC emissions from RSFC in 2014 were 175.9 Gg. These data will help to update the IVOC emission inventory and improve the estimates of SOA production in China.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
7.
Environ Sci Technol ; 55(8): 4483-4493, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33715364

RESUMO

The residential sector is a major source of air pollutant emission inventory uncertainties. A nationwide field emission measurement campaign was conducted in rural China to evaluate the variabilities of realistic emission factors (EFs) from indoor solid fuel combustion. For a total of 1313 burning events, the overall average EFs (±standard deviation) of PM2.5 were 8.93 ± 6.95 and 7.33 ± 9.01 g/kg for biomass and coals, respectively, and 89.3 ± 51.2 and 114 ± 87 g/kg for CO. Higher EFs were found from burning of uncompressed straws, while lower EFs were found from processed biomass pellets, coal briquettes, and relatively clean anthracite coals. Modified combustion efficiency was found to be the most significant factor associated with variations in CO EFs, whereas for PM2.5, fuel and stove differences determined its variations. Weak correlations between PM2.5 and CO indicated high uncertainties in using CO as a surrogate for PM2.5. EFs accurately fit log-normal distributions, and obvious spatial heterogeneity was observed attributed to different fuel-stove combinations across the country. Emission estimation variabilities, which are determined by the interquartile ranges divided by the median values, were notably reduced when spatially resolved EFs were adopted in the inventory.


Assuntos
Poluentes Atmosféricos , Utensílios Domésticos , Poluentes Atmosféricos/análise , Biomassa , China , Carvão Mineral/análise , Material Particulado/análise
8.
Ecotoxicol Environ Saf ; 196: 110542, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32276160

RESUMO

Historical residual of persistent organic pollutants (POPs) in flood sediment from a karst cave were investigated. Fifteen vertical sediment samples were collected from a 6 m-deep flood sediment profile in the Longwang Cave, and the concentrations of organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs) and particle size distribution in the sediments were analysed. The concentrations of OCPs and PAHs varied from 0.85 ng g-1 to 63.1 ng g-1 (mean 8.11 ng g-1) and 5.05 ng g-1 to 82.6 ng g-1 (mean 13.9 ng g-1), respectively; major PAHs in the profile were 2- and 3-ringed PAHs and a few were 5- or 6- ringed PAHs, which indicated less influence from industry but a high impact from the local combustion of coal and biomass; HCHs and DDTs in the profile were historically residual in this region, and HCHs mainly originated from the application of Lindane, while DDTs originated from the application of dicofol and technical DDTs; no significant correlation between the concentrations of OCPs and PAHs and the sedimental particle size in the sediments was found.


Assuntos
Hidrocarbonetos Clorados/história , Resíduos de Praguicidas/história , Hidrocarbonetos Policíclicos Aromáticos/história , Poluentes Químicos da Água/história , Cavernas , China , Inundações , Sedimentos Geológicos/química , História do Século XX , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise
9.
J Environ Sci (China) ; 91: 262-270, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32172975

RESUMO

Ship auxiliary engines contribute large amounts of air pollutants when at berth. Biodiesel, including that from waste cooking oil (WCO), can favor a reduction in the emission of primary pollutant when used with internal combustion engines. This study investigated the emissions of gaseous intermediate-volatile organic compounds (IVOCs) between WCO biodiesel and marine gas oil (MGO) to further understand the differences in secondary organic aerosol (SOA) production of exhausts. Results revealed that WCO exhaust exhibited similar IVOC composition and volatility distribution to MGO exhaust, despite the differences between fuel contents. While WCO biodiesel could reduce IVOC emissions by 50% as compared to MGO, and thus reduced the SOA production from IVOCs. The compositions and volatility distributions of exhaust IVOCs varied to those of their fuels, implying that fuel-component-based SOA predicting model should be used with more cautions when assessing SOA production of WCO and MGO exhausts. WCO biodiesel is a cleaner fuel comparing to conventional MGO on ship auxiliary engines with regard to the reductions in gaseous IVOC emissions and corresponding SOA productions. Although the tests were conducted on test bench, the results could be considered as representative due to the widely applications of the test engine and MGO fuel on real-world ships.


Assuntos
Poluentes Atmosféricos/análise , Biocombustíveis/análise , Culinária , Gasolina/análise , Navios , Emissões de Veículos/análise , Volatilização
10.
Biochem Biophys Res Commun ; 512(3): 479-485, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905413

RESUMO

Lung cancer is one of the leading causes of cancer-related death in developed countries. Despite decades of intensive efforts to comate this malignant disease, the prognosis of lung cancer remains unfavorable and is especially poor in advanced non-small cell lung cancer (NSCLC). However, whether and how the m6A demethylase FTO functions in lung cancer cells remain unknown. Here in the present study, we show that FTO plays an oncogenic role in human NSCLC. FTO mRNA and protein levels were overexpressed in human NSCLC tissues and cell lines, which was associated with the reduced m6A content. We next knocked down FTO expression in human lung cancer cell lines with lentivirus-mediated shRNAs and the cellular proliferation assay demonstrated that FTO loss-of-function reduced the proliferation rate of cancer cells. FTO knockdown also inhibited the colony formation ability of lung cancer cells. Importantly, our xenograft experiment showed that FTO knockdown reduced lung cancer cells growth in vivo. Mechanism analysis demonstrated that FTO decreased the m6A level and increased mRNA stability of ubiquitin-specific protease (USP7), which was relied on the demethylase activity of FTO. USP7 mRNA level was overexpressed in human lung cancer tissues and USP7 expression was positively correlated with FTO mRNA level. Genetic knockdown or pharmacological inhibition (P5091 or P22027) of USP7 reduced the proliferation rate of lung cancer cells and decreased the capacity of colony formation of lung cancer cells in vitro, whereas lung cancer cells growth inhibition by FTO knockdown is restored by overexertion of USP7. Collectively, our findings demonstrate that the m6A demethylase FTO promotes the growth of NSCLC cells by increasing the expression of USP7.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Peptidase 7 Específica de Ubiquitina/genética , Adenosina/análogos & derivados , Adenosina/genética , Linhagem Celular Tumoral , Humanos , RNA Mensageiro/genética
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(3): 271-274, 2019 Mar 10.
Artigo em Zh | MEDLINE | ID: mdl-30835363

RESUMO

OBJECTIVE: To assess the association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy. METHODS: Peripheral blood samples were taken from 186 epileptic patients for whom 66 cases standard regime of carbamazepine treatment was effective. Genotypes of rs3812718 and rs1813502 loci of the SCN1A gene were determined by Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Correlation between genotypes of patients and efficacy of carbamazepine treatment was analyzed. RESULTS: Three genotypes (GG, GA and AA) were detected at both rs3812718 and rs1813502 loci of the SCN1A gene. A significant difference was found in allelic distribution (chi-square=17.810, P=0.000) and genotypic distribution (chi-square=17.873, P=0.000) of the rs3812718 locus between the effective group and ineffective group. No such difference was found with the rs1813502 locus (chi-square=1.606, P=0.206; chi-square=1.546, P=0.462, respectively). Compared with the GG+GA genotype, the AA genotype at rs3812718 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR=3.776, 95%CI: 2.007-7.105). Among the 66 patients who were responsive to carbamazepine treatment, those with the AA genotype for rs3812718 or rs1813502 shown no significant difference in their blood concentration of carbamazepine compared with those with the GG+GA genotype (t=1.562, P=0.125; t=0.843, P=0.562, respectively). rs3812718 and rs1813502 were not in strong linkage disequilibrium. CONCLUSION: Polymorphisms of rs3812718 of the SCN1A gene is associated with carbamazepine resistance among ethnic Zhuang Chinese epilepsy patients from Baise region.


Assuntos
Epilepsia , Polimorfismo de Nucleotídeo Único , Anticonvulsivantes , Carbamazepina , Genótipo , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1
12.
Respir Res ; 19(1): 262, 2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30594196

RESUMO

BACKGROUND: This study investigated the function of SMAD3 (SMAD family member 3) in regulating PAX6 (paired box 6) in non-small cell lung cancer. METHODS: First, qRT-PCR was employed to detect SMAD3 expression in cancer tissues along with normal tissues and four cell lines, including BEAS-2B, H125, HCC827 and A549 cells. SMAD3 was knocked down by small interference RNA (siRNA), and then its expression was determined via qRT-PCR and Western blot analysis. The correlation between SMAD3 and PAX6 was determined by double luciferase reporter experiments and chromatin immunoprecipitation (ChIP) assay. Cell viability was evaluated by CCK-8 and colony forming assays, while cell migration and invasion were detected by Transwell analysis. RESULTS: SMAD3 and PAX6 were upregulated in lung cancer tissues and cancer cells. Knocking down SMAD3 and PAX6 by transfection with siRNAs specifically suppressed the expression of SMAD3 and PAX6 mRNA and protein levels. SMAD3 could promote PAX6 transcriptional activity by binding to its promoter. Reduced expression of SMAD3 led to the downregulation of PAX6 mRNA and protein levels along with decreased cell migration, invasion, proliferation and viability in A549 and HCC827 cells. PAX6 overexpression altered the si-SMAD3-induced inhibition of cell migration, invasion, proliferation and viability in A549 and HCC827 cells. Additionally, PAX6 knockdown alone also repressed the cell migration, invasion, proliferation and viability of the cell lines. CONCLUSIONS: SMAD3 promotes the progression of non-small cell lung cancer by upregulating PAX6 expression.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Fator de Transcrição PAX6/biossíntese , Proteína Smad3/biossíntese , Transcrição Gênica/fisiologia , Células A549 , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fator de Transcrição PAX6/genética , Proteína Smad3/genética
13.
Sensors (Basel) ; 18(6)2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29843461

RESUMO

Sitting posture is the position in which one holds his/her body upright against gravity while sitting. Poor sitting posture is regarded as an aggravating factor for various diseases. In this paper, we present an inverse piezoresistive nanocomposite sensor, and related deciphering neural network, as a new tool to identify human sitting postures accurately. As a low power consumption device, the proposed tool has simple structure, and is easy to use. The strain gauge is attached to the back of the user to acquire sitting data. A three-layer BP neural network is employed to distinguish normal sitting posture, slight hunchback and severe hunchback according to the acquired data. Experimental results show that our method is both realizable and effective, achieving 98.75% posture identification accuracy. This successful application of inverse piezoresistive nanocomposite sensors reveals that the method could potentially be used for monitoring of diverse physiological parameters in the future.


Assuntos
Técnicas Biossensoriais/métodos , Monitorização Fisiológica/métodos , Movimento/fisiologia , Postura/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanocompostos/química , Redes Neurais de Computação , Adulto Jovem
14.
Fish Shellfish Immunol ; 52: 278-88, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27033469

RESUMO

LvTAK1, a member of transforming growth factor ß-activated kinase 1 (TAK1) families, has been identified from Litopenaeus vannamei in this study. The full length of LvTAK1 is 2670 bp, including a 2277 bp open reading frame (ORF) that encoded a putative protein of 758 amino acids with a calculated molecular weight of ∼83.4 kDa LvTAK1 expression was most abundant in muscles and was up-regulated in gills after LPS, Vibrio parahaemolyticus, Staphylococcus aureus, Poly (I:C) and WSSV challenge. Both in vivo and in vitro experiments indicated that LvTAK1 could activate the expression of several antimicrobial peptide genes (AMPs). In addition, the dsRNA-mediated knockdown of LvTAK1 enhanced the susceptibility of shrimps to Vibrio parahaemolyticus, a kind of Gram-negative bacteria. These results suggested LvTAK1 played important roles in anti-bacterial infection. CoIP and subcellular localization assay demonstrated that LvTAK1 could interact with its binding protein LvTAB2, a key component of IMD pathway. Moreover, over-expression of LvTAK1 in Drosophila S2 cell could strongly induce the promoter activity of Diptericin (Dpt), a typical AMP which is used to read out of the activation of IMD pathway. These findings suggested that LvTAK1 could function as a component of IMD pathway. Interestingly, with the over-expression of LvTAK1 in S2 cell, the promoter activity of Metchnikowin (Mtk), a main target gene of Toll/Dif pathway, was up-regulated over 30 times, suggesting that LvTAK1 may also take part in signal transduction of the Toll pathway. In conclusion, we provided some evidences that the involvement of LvTAK1 in the regulation of both Toll and IMD pathways, as well as innate immune against bacterial infection in shrimp.


Assuntos
Doenças dos Peixes/enzimologia , Doenças dos Peixes/imunologia , MAP Quinase Quinase Quinases/genética , Penaeidae/enzimologia , Penaeidae/imunologia , Vibrioses/veterinária , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Doenças dos Peixes/genética , MAP Quinase Quinase Quinases/química , MAP Quinase Quinase Quinases/imunologia , Penaeidae/genética , Penaeidae/microbiologia , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Vibrio/fisiologia , Vibrioses/genética , Vibrioses/imunologia , Vibrioses/metabolismo
15.
Fish Shellfish Immunol ; 48: 285-94, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26707780

RESUMO

Mitogen-activated protein kinase kinase 7 (MKK7) is a key signal transduction regulator in c-Jun N-terminal kinase (JNK) signaling pathway, which is involved in a wide range of physiological and pathological processes. In this study, we described the molecular cloning of a new member of MKK7 group from Litopenaeus vannamei named as LvMKK7. The full-length cDNA of LvMKK7 was 3093 bp in length, with an open reading frame (ORF) of 1440bp encoding a putative protein of 479 amino acids. LvMKK7 contained a conserved kinase domain of 261 amino acids in which there was a characteristic S-K-A-K-T motif as a potential target site of phosphorylation by MKKK. Moreover, subcellular localization showed LvMKK7 was located in both the cytoplasm and the nucleus of Drosophila S2 cells. Real-time PCR indicated that LvMKK7 was universally expressed in all tested tissues and its expression in hepatopancreas was responsive to the challenge of LPS, Poly (I:C), Vibrio parahaemolyticus, Staphhylococcus aureus and white spot syndrome virus (WSSV). In addition, co-immunoprecipitation assay demonstrated that LvJNK was phosphorylated and activated by LvMKK7, which suggested LvMKK7 was the upper regulator of LvJNK. Furthermore, RNAi-mediated knockdown of LvMKK7 enhanced the sensitivity of shrimps to V. parahaemolyticus infection. Overall, our results suggested that LvMKK7 may play important roles in the shrimp innate immunity.


Assuntos
Proteínas de Peixes , Proteínas Quinases JNK Ativadas por Mitógeno , MAP Quinase Quinase 7 , Penaeidae , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Infecções por Vírus de DNA/genética , Infecções por Vírus de DNA/veterinária , DNA Complementar/genética , Drosophila , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Hepatopâncreas/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos , MAP Quinase Quinase 7/genética , MAP Quinase Quinase 7/metabolismo , Dados de Sequência Molecular , Penaeidae/genética , Penaeidae/metabolismo , Poli I-C , RNA Mensageiro/metabolismo , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/veterinária , Staphylococcus aureus , Vibrio , Vibrioses/genética , Vibrioses/veterinária , Vírus da Síndrome da Mancha Branca 1
16.
Fish Shellfish Immunol ; 46(2): 206-16, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26102459

RESUMO

In Drosophila, TAB2, an important intermediate in the IMD signaling pathway, plays critical roles in the innate immune response in response to bacterial and viral infection. However, the role of TAB-related proteins in the immune response of shrimp has not yet been established. Here, we reported the identification of a TAB2-like gene in Litopenaeus vannamei designated as LvTAB2. The full-length cDNA of LvTAB2 was 2160 bp with an open reading frame of 1827 bp, which encoded a putative protein of 608 amino acids including a ubiquitin binding domain (CUE) at the N-terminal and a Zinc Finger domain (ZnF) at the C-terminus. Real-time RT-PCR analysis showed that LvTAB2 was expressed in all tested tissues and the expression levels of LvTAB2 in gills and hemocytes were positively induced in response to LPS, Vibrio parahemolyticus and White Spot Syndrome Virus (WSSV) challenges. Dual luciferase reporter assays demonstrated that LvTAB2 was able to induce the expression of antimicrobial peptide (AMP) genes, including Drosophila Attacin A and shrimp Penaeidins. Interestingly, over-expression of LvTAB2 could up-regulate the promoter activities of L. vannamei Vago1, Vago3 and Vago4 genes in S2 cells. To our knowledge, it was the first report that TAB2 participated in innate immune signaling to regulate the expression of Vago genes in invertebrates. Moreover, RNAi-mediated knockdown of LvTAB2 enhanced sensitivity of L. vannamei to Vibrio parahaemolyticus infection and caused elevated virus loads after WSSV infection. We suggested that the LvTAB2 may play important roles in the shrimp innate immunity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Artrópodes/genética , Regulação da Expressão Gênica , Penaeidae/genética , Penaeidae/imunologia , Vibrio/fisiologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Dados de Sequência Molecular , Especificidade de Órgãos , Penaeidae/microbiologia , Penaeidae/virologia , Filogenia
17.
Artigo em Inglês | MEDLINE | ID: mdl-38574755

RESUMO

BACKGROUND AND OBJECTIVE: Stereo-electroencephalography (SEEG) electrodes are implanted using a variety of stereotactic technologies to treat refractory epilepsy. The value of SINO-robot for SEEG electrode implantation is rarely reported. The aim of the current study was to assess the value of SINO-robot in conjunction with Angio Render technology, in SEEG electrode implantation. We also assess its efficacy by examining factors such as localization error, operation time, and complications. METHODS: Between June 2018 and October 2020, we retrospectively reviewed 58 patients who underwent SEEG implantation to resect or ablate their epileptogenic zone (EZ) while minimizing the risk of hemorrhage. SINO-robot combined with Angio Render technology-assisted SEEG electrode implantation was used to visualize each patient' blood vessel in a 3D plane. The 3D view functionality was used to increase the safety and accuracy of the implantation, and reducing the risk of hemorrhage by avoiding said blood vessel. RESULTS: In this study, 634 SEEG electrodes were implanted in 58 patients. The mean 10.92(range 5- 18) leads per patient. The mean entry point localization error (EPLE) was 0.94 ± 0.23 mm (range: 0.39- 1.63 mm), and the mean target point localization error (TPLE) was 1.49 ± 0.37 mm (range: 0.80-2.78 mm). The mean operating time per lead (MOTPL) was 6. 18 ± 1.80 min (range: 3.02- 14.61 min). And the mean depth of electrodes was 56.96± 3.62 mm (range:27.23-124.85 mm). At a follow-up of at least one year, totally 81.57% (47/58) of patients achieved an Engel class I of seizure freedom. There were 2 patients with asymptomatic brain hematomas following SEEG placement, and no late complications or mortality in this cohort. CONCLUSIONS: SINO-robot in conjunction with Angio Render technology assist, in SEEG electrode implantation is safe and accurate in mitigating the risk of intracranial hemorrhage in patients suffering from drug-resistant epilepsy.

18.
Diabetes Metab Syndr Obes ; 17: 1999-2010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765471

RESUMO

Purpose: This study aims to investigate the relationship between estimated pulse wave velocity (ePWV) and metabolic syndrome (MetS) in people living with HIV (PLWH), proposing a novel and convenient predictor for early detection of MetS in PLWH. Patients and Methods: A total of 485 PLWH were enrolled. These participants were categorized into two groups based on the estimated pulse wave velocity (ePWV) level. Demographic and clinical data were collected to investigate the correlation between ePWV and MetS. Results: The cohort of 485 PLWH was categorized into high-ePWV and low-ePWV groups based on ePWV cutoff value of 10 m/s. We observed significant differences in components of MetS including triglycerides (TG, P < 0.05), HDL cholesterol (HDL-C, P < 0.01), systolic blood pressure (SBP, P < 0.001), diastolic blood pressure (DBP, P < 0.05), and fasting plasma glucose (FPG, P < 0.001) between the two groups. Furthermore, we employed receiver operating characteristic (ROC) curves to demonstrate the effectiveness of ePWV as a predictive indicator for MetS in PLWH (AUC = 0.739, P < 0.001). According to the ROC curve, the optimal cut-off value of ePWV was 7.4 m/s, and its sensitivity and specificity in diagnosing MetS in PLWH were 79.03% and 64.07%, respectively. Although the 7.4 m/s cutoff increased the false positive rate compared to the traditional cutoff, it significantly reduced the rate of missed diagnoses, effectively identifying 79.03% of PLWH with MetS. Conclusion: ePWV is a non-invasive and convenient novel biomarker with predictive capabilities for MetS in PLWH.

19.
Seizure ; 117: 275-283, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579502

RESUMO

OBJECTIVE: Accurate detection of focal cortical dysplasia (FCD) through magnetic resonance imaging (MRI) plays a pivotal role in the preoperative assessment of epilepsy. The integration of multimodal imaging has demonstrated substantial value in both diagnosing FCD and devising effective surgical strategies. This study aimed to enhance MRI post-processing by incorporating positron emission tomography (PET) analysis. We sought to compare the diagnostic efficacy of diverse image post-processing methodologies in patients presenting MRI-negative FCD. METHODS: In this retrospective investigation, we assembled a cohort of patients with negative preoperative MRI results. T1-weighted volumetric sequences were subjected to morphometric analysis program (MAP) and composite parametric map (CPM) post-processing techniques. We independently co-registered images derived from various methods with PET scans. The alignment was subsequently evaluated, and its correlation was correlated with postoperative seizure outcomes. RESULTS: A total of 41 patients were enrolled in the study. In the PET-MAP(p = 0.0189) and PET-CPM(p = 0.00041) groups, compared with the non-overlap group, the overlap group significantly associated with better postoperative outcomes. In PET(p = 0.234), CPM(p = 0.686) and MAP(p = 0.672), there is no statistical significance between overlap and seizure-free outcomes. The sensitivity of using the CPM alone outperformed the MAP (0.65 vs 0.46). The use of PET-CPM demonstrated superior sensitivity (0.96), positive predictive value (0.83), and negative predictive value (0.91), whereas the MAP displayed superior specificity (0.71). CONCLUSIONS: Our findings suggested a superiority in sensitivity of CPM in detecting potential FCD lesions compared to MAP, especially when it is used in combination with PET for diagnosis of MRI-negative epilepsy patients. Moreover, we confirmed the superiority of synergizing metabolic imaging (PET) with quantitative maps derived from structural imaging (MAP or CPM) to enhance the identification of subtle epileptogenic zones (EZs). This study serves to illuminate the potential of integrated multimodal techniques in advancing our capability to pinpoint elusive pathological features in epilepsy cases.


Assuntos
Epilepsia , Displasia Cortical Focal , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Epilepsia/diagnóstico por imagem , Displasia Cortical Focal/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/normas , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Estudos Retrospectivos
20.
Infect Dis Ther ; 12(2): 637-647, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633817

RESUMO

INTRODUCTION: Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among HBeAg-seropositive patients with alanine aminotransferase (ALT) < 2 upper limits of normal (ULN). This study aimed to evaluate the efficacy of antiviral therapy for these patients. METHODS: In total, 102 treatment-naive patients who were HBeAg seropositive with ALT < 2 ULN and had received nucleotide analogs were included, and their clinical data were retrospectively analyzed. RESULTS: After 96-week treatment, 84.3% (n = 86), 26.5% (n = 27) and 20.6% (n = 21) patients achieved virological response, HBeAg seroclearance and HBeAg seroconversion, respectively. Logistic regression analysis revealed that baseline AST (odds ratio [OR] = 1.069, 95% confidence interval [CI] 1.014-1.127, p = 0.014), serum HBV DNA (OR = 0.540, 95% CI 0.309-0.946, p = 0.031) and quantitative HBsAg levels (OR = 0.147, 95% CI 0.036-0.597, p = 0.007) were independent factors for virological response. At baseline, HBsAg < 4.63 log10 IU/ml was identified as a strong predictor for the 96-week virological response, with a concordance rate of 0.902. Moreover, the levels of liver stiffness values (8.30 ± 3.86 vs. 6.17 ± 1.91, p < 0.001) at week 96 had significantly declined compared to baseline. CONCLUSION: Nucleotide analog treatment effectively suppressed HBV DNA in patients with HBeAg-seropositive chronic hepatitis B with ALT < 2 × ULN and greatly improved liver fibrosis. The study also found that HBsAg < 4.63 log10 IU/ml was a strong predictor of the virological response.

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