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1.
Artigo em Inglês | MEDLINE | ID: mdl-38568198

RESUMO

Two Gram-negative, non-spore-forming, non-motile, non-flagellated bacteria, designated strains D6T and DH64T, were isolated from surface water of the Pacific Ocean. For strain D6T, growth occurred at 10-40 °C, pH 5.5-9.0 and in the presence of 0-8.0 % NaCl (w/v). For strain DH64T, growth occurred at 10-40 °C, pH 5.5-8.5 and in the presence of 0.5-8.0 % NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains D6T and DH64T both belonged to the genera Flagellimonas, with the highest sequence identities to Flagellimonas taeanensis JCM 17757T (98.2 %) and Flagellimonas marinaquae JCM 11811T (98.6 %), respectively. The 16S rRNA gene sequence identity between strains D6T and DH64T was 95.9 %. The average amino acid identity and digital DNA-DNA hybridization values between the two strains and the nearest phylogenetic neighbours were 66.7-93.3 % and 16.1-38.5 %, respectively. The major respiratory quinone of both strains was menaquinone-6. The major polar lipid was phosphatidylethanolamine. The major fatty acids were identified similarly as iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. The genomic G+C contents of strains D6T and DH64T were determined to be 45.5 and 42.6 mol%, respectively. The combined genotypic and phenotypic data show that the strains represent two novel species within genera Flagellimonas, for which the names Flagellimonas baculiformis sp. nov. and Flagellimonas crocea sp. nov. are proposed, with type strains D6T (=MCCC M28982T=KCTC 92604T) and DH64T (=MCCC M28986T=KCTC 92975T).


Assuntos
Ácidos Graxos , Cloreto de Sódio , Oceano Pacífico , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Água do Mar
2.
Ther Drug Monit ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38648661

RESUMO

BACKGROUND: This study comprehensively examined the demographic and clinical characteristics of patients undergoing valproic acid therapy and explored their potential impact on plasma valproic acid concentrations. All enrolled patients were administered the extended-release formulation. An in-depth investigation of factors, including dose, age, sex, body mass index, co-administered medications, and laboratory test findings, was conducted to evaluate their potential influence on study outcomes. METHODS: In total, 164 patients met the inclusion criteria and were included in the analysis. The patient age ranged from 13 to 60 years, with a median age of 25.71 years. Most patients (89%) received a daily dose of 1 g valproic acid. Co-administered psychiatric medications included aripiprazole, quetiapine, and lorazepam. Laboratory test results, such as hemoglobin and transaminase levels, were also collected as part of the study. RESULTS: The average plasma valproic acid plasma concentration was 79.8 mg/L. The dose significantly affected valproic acid concentrations, as a higher percentage of measurements exceeded the therapeutic range at a daily dose of 1 g. Furthermore, females exhibited significantly higher valproic acid concentrations compared with males at the same dose (P < 0.05). However, different age groups showed no statistically significant differences in valproic acid concentrations (P > 0.05). The co-administered antipsychotic and antidepressant medications significantly affected valproate concentrations, as reflected in the multiple regression model (P < 0.01). CONCLUSIONS: This study offers valuable insights into the demographic and clinical characteristics of patients undergoing valproic acid therapy. It highlights the influence of dose, sex, and concomitant medications on plasma valproic acid concentrations. Overall, these findings can help guide dose adjustments and implement personalized treatment strategies in valproic acid therapy.

3.
PLoS Genet ; 17(4): e1009505, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33886546

RESUMO

The development of male and female gametophytes is a pre-requisite for successful reproduction of angiosperms. Factors mediating vesicular trafficking are among the key regulators controlling gametophytic development. Fusion between vesicles and target membranes requires the assembly of a fusogenic soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) complex, whose disassembly in turn ensures the recycle of individual SNARE components. The disassembly of post-fusion SNARE complexes is controlled by the AAA+ ATPase N-ethylmaleimide-sensitive factor (Sec18/NSF) and soluble NSF attachment protein (Sec17/α-SNAP) in yeast and metazoans. Although non-canonical α-SNAPs have been functionally characterized in soybeans, the biological function of canonical α-SNAPs has yet to be demonstrated in plants. We report here that the canonical α-SNAP in Arabidopsis is essential for male and female gametophytic development. Functional loss of the canonical α-SNAP in Arabidopsis results in gametophytic lethality by arresting the first mitosis during gametogenesis. We further show that Arabidopsis α-SNAP encodes two isoforms due to alternative splicing. Both isoforms interact with the Arabidopsis homolog of NSF whereas have distinct subcellular localizations. The presence of similar alternative splicing of human α-SNAP indicates that functional distinction of two α-SNAP isoforms is evolutionarily conserved.


Assuntos
Arabidopsis/genética , Gametogênese/genética , Desenvolvimento Vegetal/genética , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/genética , ATPases Associadas a Diversas Atividades Celulares/genética , Processamento Alternativo/genética , Arabidopsis/crescimento & desenvolvimento , Células Germinativas Vegetais/crescimento & desenvolvimento , Mitose/genética , Proteínas Sensíveis a N-Etilmaleimida/genética , Isoformas de Proteínas/genética
4.
Small ; : e2307252, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38054813

RESUMO

Efficient bifunctional hydrogen electrocatalysis, encompassing both hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR), is of paramount significance in advancing hydrogen-based societies. While non-precious-metal-based catalysts, particularly those based on nickel (Ni), are essential for alkaline HER/HOR, their intrinsic catalytic activity often falls short of expectations. Herein, an internal electric field (IEF) strategy is introduced for the engineering of heterogeneous nickel-vanadium oxide nanosheet arrays grown on porous nickel foam (Ni-V2 O3 /PNF) as bifunctional electrocatalysts for hydrogen electrocatalysis. Strikingly, the Ni-V2 O3 /PNF delivers 10 mA cm-2 at an overpotential of 54 mV for HER and a mass-specific kinetic current of 19.3 A g-1 at an overpotential of 50 mV for HOR, placing it on par with the benchmark 20% Pt/C, while exhibiting enhanced stability in alkaline electrolytes. Density functional theory calculations, in conjunction with experimental characterizations, unveil that the interface IEF effect fosters asymmetrical charge distributions, which results in more thermoneutral hydrogen adsorption Gibbs free energy on the electron-deficient Ni side, thus elevating the overall efficiency of both HER and HOR. The discoveries reported herein guidance are provided for further understanding and designing efficient non-precious-metal-based electrocatalysts through the IEF strategy.

5.
EMBO Rep ; 22(8): e51978, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34232545

RESUMO

Zika virus (ZIKV) infection during pregnancy is linked to various developmental brain disorders. Infants who are asymptomatic at birth might have postnatal neurocognitive complications. However, animal models recapitulating these neurocognitive phenotypes are lacking, and the circuit mechanism underlying behavioral abnormalities is unknown. Here, we show that ZIKV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic-like behaviors including repetitive self-grooming and impaired social memory in offspring. In the medial prefrontal cortex (mPFC), ZIKV-affected offspring mice exhibit excitation and inhibition imbalance and increased cortical activity. This could be explained by dysregulation of inhibitory neurons and synapses, and elevated neural activity input from mPFC-projecting ventral hippocampus (vHIP) neurons. We find structure alterations in the synaptic connections and pattern of vHIP innervation of mPFC neurons, leading to hyperconnectivity of the vHIP-mPFC pathway. Decreasing the activity of mPFC-projecting vHIP neurons with a chemogenetic strategy rescues social memory deficits in ZIKV offspring mice. Our studies reveal a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Feminino , Hipocampo , Inflamação , Camundongos , Córtex Pré-Frontal , Gravidez
6.
Artigo em Inglês | MEDLINE | ID: mdl-37000637

RESUMO

A Gram-stain-negative, non-motile, rod-shaped bacterial strain, designated C281T, was isolated from seawater sampled at the Marshallese seamount chain. Results of 16S rRNA gene analysis revealed that strain C281T was most closely related to Membranihabitans marinus CZ-AZ5T with 92.7 % sequence similarity. Phylogenetic analysis indicated that the new isolate represented a novel species by forming a distinctive lineage within the family Saprospiraceae. The DNA G+C content of strain C281T was 38.4 mol%. The genome sizes of strain C281T and the reference strain M. marinus CZ-AZ5T were 5 962 917 and 5 395 999 bp, respectively. The average nucleotide identity and in silico DNA-DNA hybridization values between strains C281T and M. marinus CZ-AZ5T were found to be low (69.3 and 17.6 %, respectively). Different functional genes were found in the genome of strain C281T, such as CZC CBA, polysaccharide utilization loci and linear azol(in)e-containing peptide cluster coding genes. The NaCl range for growth was 0.5-15.0 %. Positive results were obtained for hydrolysis of Tween 60 and urease. MK-7 was the sole respiratory quinone. The major fatty acids were C16 : 1 ω6c and/or C16 : 1 ω7c, iso-C15 : 0 and iso-C15 : 1 F. The major polar lipids of strain C281T were phosphatidylethanolamine, phosphatidylglycerol, two unidentified lipids and five unidentified glycolipids. On the basis of its taxonomic characteristics, the isolate represents a novel species of the genus Membranihabitans, for which the name Membranihabitans maritimus sp. nov. (type strain C281T=KCTC 92171T=MCCC M27001T) is proposed.


Assuntos
Ácidos Graxos , Fosfolipídeos , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , Água do Mar/microbiologia
7.
Biol Cell ; 114(10): 276-292, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35713972

RESUMO

BACKGROUND: HIV-1 Nef regulates several cellular functions in an infected cell which results in viral persistence and AIDS pathogenesis. The currently understood molecular mechanism(s) underlying Nef-dependent cellular function(s) are unable to explain how events are coordinately regulated in the host cell. Intracellular membranous trafficking maintains cellular homeostasis and is regulated by Rab GTPases - a member of the Ras superfamily. RESULTS: In the current study, we tried to decipher the role of Nef on the Rab GTPases-dependent complex and vesicular trafficking. Expression profiling of Rabs in Nef-expressing cells showed that Nef differentially regulates the expression of individual Rabs in a cell-specific manner. Further analysis of Rabs in HIV-1NL4-3 or ΔNef infected cells demonstrated that the Nef protein is responsible for variation in Rabs expression. Using a panel of competitive peptide inhibitors against Nef, we identified the critical domain of HIV-1 Nef involved in modulation of Rabs expression. The molecular function of Nef-mediated upregulation of Rab5 and Rab7 and downregulation of Rab11 increased the transport of SERINC5 from the cell surface to the lysosomal compartment. Moreover, the Nef-dependent increase in Rab27 expression assists exosome release. Reversal of Rabs expression using competitive inhibitors against Nef and manipulation of Rabs expression reduced viral release and infectivity of progeny virions. CONCLUSION: This study demonstrates that Nef differentially regulates the expression of Rab proteins in HIV-1 infected cells to hijack the host intracellular trafficking, which augments viral replication and HIV-1 pathogenesis. SIGNIFICANCE: Our study emphasized the indispensable role of HIV-1 protein Nef on various aspects of the intracellular trafficking regulated by Rabs GTPases, which explained how HIV-1 Nef may hijack membrane trafficking pathways in infected cells.


Assuntos
HIV-1 , HIV-1/fisiologia , Proteínas de Membrana/metabolismo , Vírion/química , Vírion/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/análise , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
8.
Phys Chem Chem Phys ; 25(8): 6362-6368, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36779323

RESUMO

Batteries have become a ubiquitous daily necessity, which are popularly applied to mobile phones and electric vehicles according to their size. Improving the battery cycle life and storage is important, but unexpected discharge products still restrict the upper limit of batter performance such as Li2O2, LiO2, and Li2S. In this study, we calculated electrons and phonons presenting the basic energy states in crystal using the first-principles calculations. The Li2O2 and Li2S are almost insulating due to the wide bandgap from their electronic structure, and doped-active p-orbital may be one of the pathways to improve crystal conduction due to the tendency of the density of states. The LiO2 is metallic, and the electronic structure and phonons show that the discharge products have an ionic feature. In addition, the ionic crystal can produce a larger DC permittivity because it possesses macroscopic polarisation. For Li2O2 and Li2S, the Raman peak of the O-O bonding is strong, while the Raman peak of the S-ion is very weak. The enhanced Raman peak of the S-ion presents a possibility to prevent the shuttle effect in Li-S batteries.

9.
Angew Chem Int Ed Engl ; 62(21): e202301126, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36961328

RESUMO

N-heterocyclic carbene (NHC)-catalyzed enantioselective Mannich-type reactions of the biomass-derived platform compound 5-(chloromethyl)furfural (CMF) with imines were developed. A series of high-value-added chiral amines were afforded in good to high yields with excellent regio- and enantioselectivities. The bifunctional NHC derived from ʟ-pyroglutamic acid efficiently steered the remote addition of the trienolate intermediate to the imine in a highly stereocontrolled manner. This represents the first enantioselective reaction proceeding via an NHC-bound trienolate intermediate.

10.
Plant J ; 106(3): 801-816, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33595139

RESUMO

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis (litchi). Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth and increased levels of hexoses, particularly galactose, as well as pectin abundance in the cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter and electrophoretic mobility shift assays all demonstrated that a UDP-glucose-4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in the expression of the A. thaliana homolog AtUGE2-4 in response to LcERF2 overexpression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism, and thus pedicel growth, in part by repressing the expression of LcUGE.


Assuntos
Parede Celular/metabolismo , Frutas/metabolismo , Litchi/metabolismo , Proteínas de Plantas/metabolismo , UDPglucose 4-Epimerase/metabolismo , Arabidopsis , Ensaio de Desvio de Mobilidade Eletroforética , Frutas/enzimologia , Frutas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Genes de Plantas/genética , Litchi/enzimologia , Litchi/crescimento & desenvolvimento , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , UDPglucose 4-Epimerase/genética
11.
BMC Pregnancy Childbirth ; 22(1): 906, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471261

RESUMO

BACKGROUND: Embryonic chromosomal abnormality is one of the significant causative factors of pregnancy loss. Our goal was to investigate the differences of chromosomal abnormality between different conception modes in miscarried products of conception (POCs). METHODS: A retrospective study included 262 miscarried POCs from 167 women undergoing assisted reproductive treatment (ART) and 95 spontaneous pregnant (SP) women during March 2019 to March 2022 in Renmin Hospital of Wuhan University. Subgroups were divided according to age, fertilization method, types and stages of embryo transfer. The profiles of cytogenetic abnormalities in the miscarried POCs were measured via next-generation sequencing. RESULTS: The rate of chromosomal abnormality in the fresh embryo transfer group and the cleavage embryo transfer group was significantly higher than that in the frozen embryo transfer group (79.2% vs. 36%, P = 0.0001) and the blastocyst transfer group (66.7% vs. 32.1%, P = 0.0001) respectively. There was no significant difference in the rate of chromosomal abnormalities when compared by maternal age (49.2% vs. 62%, P = 0.066), types of conception (49.7% vs. 57.9%, P = 0.202), fertilization method (49.6% vs. 48.7%, P = 0.927) and frequency of abortion (56% vs. 47.6%, P = 0.183). However, the women aged ≥ 35 years had more frequent numerical abnormality (P = 0.002); patients using assisted reproductive technology had more rate of chromosomal structural abnormalities (26.5% vs. 7.3%, P = 0.005); the ICSI fertilization group has more frequency of deletion/microdeletion than the IVF fertilization group (80% vs. 31.3%, P = 0.019). CONCLUSION: Blastocyst transfer might help to reduce the incidence of miscarriage. In addition, "freezing all" should be considered if encountered hyper ovarian stimulation, to avoid the negative effect of high estrogen environment on embryo development. The higher incidence of structural abnormalities in miscarried POCs from assisted reproductive patients reminds us to pay attention to the safety of the technology for offspring.


Assuntos
Aborto Espontâneo , Transtornos Cromossômicos , Gravidez , Humanos , Feminino , Fertilização in vitro , Estudos Retrospectivos , Transferência Embrionária/métodos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/genética , Aberrações Cromossômicas
12.
Phys Rev Lett ; 126(1): 011601, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33480754

RESUMO

We derive the generalized partial wave expansion for N→M scattering amplitude in terms of spinor helicity variables. The basis amplitudes of the expansion with definite angular momentum j consist of the Poincaré Clebsch-Gordan coefficients. Moreover, we obtain a series of selection rules that restrict the anomalous dimension matrix of effective operators and how effective operators contribute to some 2→N amplitudes at the loop level.

13.
Appl Opt ; 60(7): 2100-2108, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690304

RESUMO

Intelligent photonic circuits (IPCs) tuned with an appropriate phase-shift vector could enable a photonic intelligent matrix possibly implemented in multiple neural layers for a task-oriented topologies. A photonic Mach-Zehnder Interferometer (MZI) is a fundamental photonic component in IPCs, whose matrix representation could be broadcasted into an arbitrary matrix that is equipped with an optimized phase-shift vector. The initialized MZIs' phases are tentatively probed between analytical elements and a digital weight matrix that is learned from samples with efficient compatible learning for complex-valued neural networks. Nonlinear least squares is utilized to formulate a phase determination system to refine the optimal phase-shift solutions. The robustness of phase determination system for photonic neural networks is discussed in detail. For a preliminary implementation, a basic 4×4 intelligent photonic neural network is utilized to verify the proof of concept on phase-shift determination in IPC through numerical experiments.

14.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466443

RESUMO

Fruit cracking is a disorder of fruit development in response to internal or external cues, which causes a loss in the economic value of fruit. Therefore, exploring the mechanism underlying fruit cracking is of great significance to increase the economic yield of fruit trees. However, the molecular mechanism underlying fruit cracking is still poorly understood. Litchi, as an important tropical and subtropical fruit crop, contributes significantly to the gross agricultural product in Southeast Asia. One important agricultural concern in the litchi industry is that some famous varieties with high economic value such as 'Nuomici' are susceptible to fruit cracking. Here, the cracking-susceptible cultivar 'Nuomici' and cracking-resistant cultivar 'Huaizhi' were selected, and the samples including pericarp and aril during fruit development and cracking were collected for RNA-Seq analysis. Based on weighted gene co-expression network analysis (WGCNA) and the "ball-skin versus bladder effect" theory (fruit cracking occurs upon the aril expanding pressure exceeds the pericarp strength), it was found that seven co-expression modules genes (1733 candidate genes) were closely associated with fruit cracking in 'Nuomici'. Importantly, we propose that the low expression level of genes related to plant hormones (Auxin, Gibberellins, Ethylene), transcription factors, calcium transport and signaling, and lipid synthesis might decrease the mechanical strength of pericarp in 'Nuomici', while high expression level of genes associated with plant hormones (Auxin and abscisic acid), transcription factors, starch/sucrose metabolism, and sugar/water transport might increase the aril expanding pressure, thereby resulting in fruit cracking in 'Nuomici'. In conclusion, our results provide comprehensive molecular events involved in the "ball-skin versus bladder effect" on fruit cracking in litchi.


Assuntos
Frutas/genética , Litchi/genética , Doenças das Plantas/genética , Metabolismo dos Carboidratos/genética , Regulação da Expressão Gênica de Plantas/genética , Reguladores de Crescimento de Plantas/genética , Proteínas de Plantas/genética , RNA-Seq/métodos , Transdução de Sinais/genética , Fatores de Transcrição/genética
15.
BMC Pregnancy Childbirth ; 20(1): 394, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641013

RESUMO

BACKGROUND: Compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), Corona Virus Disease 2019(COVID-19) spread more rapidly and widely. The population was generally susceptible. However, reports on pregnant women infected with SARS-CoV-2 were very limited. By sharing the clinical characteristics, treatments and outcomes of 18 patients with COVID-19 during late pregnancy, we hope to provide some references for obstetric treatment and management. METHODS: A total of 18 patients with COVID-19 treated at Renmin Hospital of Wuhan University were collected. The epidemiological characteristics, clinical manifestations, laboratory tests, chest CT and pregnancy outcomes were performed for analysis. RESULTS: 1. 18 cases of late pregnancy infected with SARS-CoV-2 pneumonia were delivered at 35 + 5 weeks to 41 weeks. According to the clinical classification of COVID-19, 1 case was mild type, 16 cases were ordinary type, and 1 case was severe type. 2. According to imaging examinations: 15 (83%) cases showed unilateral or bilateral pneumonia, 2 (11%) cases had pulmonary infection with pleural effusion, and 1 (6%) case had no abnormal imaging changes. 8 (44%) cases were positive and 10 (56%) cases were negative for nasopharyngeal-swab tests of SARS-CoV-2. 3. Among the 18 newborns, there were 3 (17%) premature infants, 1 (6%) case of mild asphyxia, 5 (28%) cases of bacterial pneumonia, 1 (6%) case of gastrointestinal bleeding, 1 (6%) case of necrotizing enteritis, 2 (11%) cases of hyperbilirubinemia and 1 (6%) case of diarrhea. All the newborns were negative for the first throat swab test of SARS-CoV-2 after birth. 4. Follow-up to Mar 7, 2020, no maternal and neonatal deaths occurred. CONCLUSIONS: The majority of patients in late term pregnancy with COVID-19 were of ordinary type, and they were less likely to develop into critical pneumonia after early isolation and antiviral treatment. Vertical transmission of SARS-CoV-2 was not detected, but the proportion of neonatal bacterial pneumonia was higher than other neonatal diseases in newborns.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/virologia , Adulto , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Recém-Nascido , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , SARS-CoV-2
16.
J Neurosci ; 38(23): 5367-5383, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29760177

RESUMO

The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B, which were also accompanied by increased global DNA methylation. Bisulfite-converted genomic DNA sequencing in the HIV-1 Tat-exposed mouse primary microglial cells further confirmed increased DNA methylation of the primary miR-124-1 and primary miR-124-2 promoters. Bioinformatic analyses identified MECP2 as a novel 3'-UTR target of miR-124. This was further validated in mouse primary microglial cells wherein HIV-1 Tat-mediated downregulation of miR-124 resulted in increased expression of MECP2, leading in turn to further repression of miR-124 via the feedback loop. In addition to MECP2, miR-124 also modulated the levels of STAT3 through its binding to the 3'-UTR, leading to microglial activation. Luciferase assays and Ago2 immunoprecipitation determined the direct binding between miR-124 and 3'-UTR of both MECP2 and STAT3. Gene silencing of MECP2 and DNMT1 and overexpression of miR-124 blocked HIV-1 Tat-mediated downregulation of miR-124 and microglial activation. In vitro findings were also confirmed in the basal ganglia of SIV-infected rhesus macaques (both sexes). In summary, our findings demonstrate a novel mechanism of HIV-1 Tat-mediated activation of microglia via downregulation of miR-124, leading ultimately to increased MECP2 and STAT3 signaling.SIGNIFICANCE STATEMENT Despite the effectiveness of combination antiretroviral therapy in controlling viremia, the CNS continues to harbor viral reservoirs. The persistence of low-level virus replication leads to the accumulation of early viral proteins, including HIV-1 Tat protein. Understanding the epigenetic/molecular mechanism(s) by which viral proteins, such as HIV-1 Tat, can activate microglia is thus of paramount importance. This study demonstrated that HIV-1 Tat-mediated DNA methylation of the miR-124 promoter leads to its downregulation with a concomitant upregulation of the MECP2-STAT3-IL6, resulting in microglial activation. These findings reveal an unexplored epigenetic/molecular mechanism(s) underlying HIV-1 Tat-mediated microglial activation, thereby providing a potential target for the development of therapeutics aimed at ameliorating microglial activation and neuroinflammation in the context of HIV-1 infection.


Assuntos
Infecções por HIV/metabolismo , Proteína 2 de Ligação a Metil-CpG/metabolismo , MicroRNAs/metabolismo , Microglia/virologia , Fator de Transcrição STAT3/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Animais , Metilação de DNA/fisiologia , Epigênese Genética/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , HIV-1 , Macaca mulatta , Masculino , Camundongos , MicroRNAs/genética , Microglia/metabolismo , Regiões Promotoras Genéticas/genética , Transdução de Sinais/fisiologia , Síndrome de Imunodeficiência Adquirida dos Símios/metabolismo
17.
J Cell Biochem ; 120(10): 16516-16523, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31131477

RESUMO

The functions of miR-182-5p in the pathogenesis of diabetic nephropathy (DN) remain largely unclear. Here, we studied the roles and relationship between miR-182-5p and CD2AP in the development of DN. We used real-time polymerase chain reaction (PCR) to compare miR-182-5p expression between DN and control groups, while computational analysis and luciferase assays were used to confirm CD2AP as a miR-182-5p target. Western blot and real-time PCR were then used to measure the messenger RNA (mRNA) and protein expression of CD2AP in the presence of miR-182-5p. The results showed that miR-182-5p was highly expressed in cells isolated from people with DN. In addition, the luciferase activity of cells transfected with wild-type/mutant CD2AP confirmed CD2AP as a direct target of miR-182-5p. The expression levels of CD2AP mRNA and protein were much lower in the DN group compared with that in the normal group. In addition, the expression levels of CD2AP mRNA and protein were evidently increased by a miR-182-5p inhibitor, but notably downregulated by miR-182-5p mimics or CD2AP small interfering RNA (siRNA). Furthermore, miR-182-5p and CD2Ap siRNA significantly reduced the survival rate and viability of transfected cells, while the miR-182-5p inhibitor exhibited an opposite effect. These findings indicated the presence of a negative regulatory relationship between miR-182-5p and CD2AP in podocytes cells and suggested that the overexpression of miR-182-5p contributes to the pathogenesis of DN.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Proteínas do Citoesqueleto/metabolismo , Nefropatias Diabéticas/metabolismo , Regulação da Expressão Gênica , MicroRNAs/biossíntese , Podócitos/metabolismo , Idoso , Linhagem Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Podócitos/patologia , Fatores de Risco
18.
Phys Chem Chem Phys ; 21(29): 16213-16222, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31298246

RESUMO

The electronic structure and magnetic properties of ten formamidinium transition metal iodides in the ground state and under strain have been studied. These formamidinium transition metal iodides have a stable cubic perovskite structure. In the ground state, FAVI3 is a spin gapless semiconductor, and FAScI3, FATiI3, FACrI3, FAFeI3, FACoI3 and FANiI3 are ferromagnetic half-metals. They all have 100% spin polarization and integer total magnetic moment. Under the action of strain, the high spin polarization of some formamidinium transition metal iodides can still be well maintained, and several novel spin gapless semiconductors such as FATiI3, FAFeI3 and FACoI3 have been discovered. Magnetic studies show that these formamidinium transition metal iodides with half-metal, semiconductor and spin-gapless semiconductor properties have integral total magnetic moments under strain ranging from -10.0% to 10.0%. These newly discovered half-metallic ferromagnetic materials and spin gapless semiconductors have broad application prospects in the field of spintronics due to their high spin polarization.

19.
Eur Arch Otorhinolaryngol ; 276(9): 2565-2576, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240455

RESUMO

PURPOSE: Nasopharyngeal carcinoma (NPC) is one of the most malignant head and neck carcinomas with unique epidemiological features. In this study, we aimed to identify the novel NPC-related genes and biological pathways, shedding light on the potential molecular mechanisms of NPC. METHODS: Based on Gene Expression Omnibus (GEO) database, an integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in NPC compared to normal control. The genes which were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction (PPI) network construction were used to uncover biological functions of DEGs. RESULTS: Two DNA methylation and five gene expression datasets were incorporated. A total of 1074 genes were up-regulated and 939 genes were down-regulated in NPC were identified. A total of 719 differential methylation CpG sites (DMCs) including 1 hypermethylated sites and 718 hypomethylated sites were identified. Among which, 11 genes were both DEGs and DMGs in NPC. Pathways in cancer, p53 signaling pathway and Epstein-Barr virus infection were three pathways significantly enriched pathways in DEmRNAs of NPC. The PPI network of top 50 DEGs were consisted of 191 nodes and 191 edges. CONCLUSIONS: Our study was helpful to elucidate the underlying mechanism of NPC and provide clues for therapeutic methods.


Assuntos
Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo , Infecções por Vírus Epstein-Barr/genética , Redes Reguladoras de Genes/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Mapas de Interação de Proteínas , Transdução de Sinais
20.
Hepatobiliary Pancreat Dis Int ; 18(6): 557-561, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31474445

RESUMO

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is one of the minimally invasive options for choledocholithiasis. Primary closure of the common bile duct (CBD) upon completion of laparoscopic choledochotomy is safe in selected patients. The present study aimed to evaluate the feasibility and safety of primary closure of CBD after LCBDE in patients aged 70 years or older. METHODS: A total of 116 patients (51 males and 65 females) who suffered from choledocholithiasis and underwent primary closure of the CBD (without T-tube drainage) after LCBDE from January 2003 to December 2017 were recruited. They were classified into two groups according to age: group A (≥70 years, n = 56), and group B (<70 years, n = 60). The preoperative characteristics, intraoperative details, and postoperative outcomes of the two groups were evaluated. RESULTS: The mean operative time was 172.02 min for group A and 169.92 min for group B (P = 0.853). The mean hospital stay was 7.40 days for group A and 5.38 days for group B (P < 0.001). Bile leakage occurred in two patients in group A and one in group B (3.57% vs 1.67%, P = 0.952). There were no significant differences in the rates of postoperative complications and mortality between the two groups. At median follow-up time of 60 months, stone recurrence was detected in one patient in group A and two in group B (1.79% vs 3.33%, P = 1.000). Stenosis of CBD was not observed in group A and slight stenosis in one patient in group B (0 vs 1.67%, P = 1.000). CONCLUSION: Primary closure of the CBD upon completion of laparoscopic choledochotomy is safe and feasible in elderly patients ≥70 years old.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/mortalidade , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/mortalidade , Ducto Colédoco/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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