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1.
J Neuroinflammation ; 21(1): 254, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39385200

RESUMO

In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1+/UCHL1+ EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer's disease (AD), and Parkinson's disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1+/UCHL1+ EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1+/UCHL1+, NMDAR2A+, and NFL+ EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1+/UCHL1+ EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A+ and NFL+ EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration.


Assuntos
Biomarcadores , Receptor 1 de Quimiocina CX3C , Vesículas Extracelulares , Microglia , Esclerose Múltipla , Humanos , Biomarcadores/sangue , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Microglia/metabolismo , Receptor 1 de Quimiocina CX3C/metabolismo , Receptor 1 de Quimiocina CX3C/genética , Feminino , Masculino , Pessoa de Meia-Idade , Ubiquitina Tiolesterase/metabolismo , Adulto , Idoso , Estudos de Coortes
2.
Food Res Int ; 190: 114600, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945570

RESUMO

Browning commonly appeared in apple processing, which varied in different apple varieties. Present work investigated the metabolomics of four varieties apple of Yataka, Gala, Sansa, and Fuji, which possessed different browning characteristics and related enzymes. Sansa as browning insensitive apple variety, exhibited the least chroma change with the lowest PPO activity and the highest SOD activity among the four apple varieties. Browning inhibition pretreatment increased the activity of SOD and PAL and decreased PPO and POD activity. In addition, metabolomic variances among the four apple varieties (FC), their browning pulp (BR) and browning inhibition pulp (CM) were compared. And the key metabolites were in-depth analyzed to match the relevant KEGG pathways and speculated metabolic networks. There were 487, 644, and 494 significant differential metabolites detected in FC, BR and CM, which were consisted of lipids, benzenoids, phenylpropanoids, organheterocyclic compounds, organic acids, nucleosides, accounting for 23 %, 11 %, 15 %, 16 %, 11 % of the total metabolites. The differential metabolites were matched with 39, 49, and 36 KEGG pathways in FC, BR, and CM, respectively, in which other secondary metabolites biosynthesis metabolism was the most significant in FC, lipid metabolism was the most significant in BR and CM, and energy metabolism was markedly annotated in CM. Notably, Sansa displayed the highest number of differential metabolites in both its BR (484) and CM (342). The BR of Sansa was characterized by flavonoid biosynthesis, while the other three apple varieties were associated with α-linolenic acid metabolism. Furthermore, in browning sensitive apple varieties, the flavonoid and phenylpropanoid biosynthesis pathway was significantly activated by browning inhibition pretreatment. Phenolic compounds, lipids, sugars, organic acids, nucleotides, and adenosine were regulated differently in the four apple varieties, potentially serving as key regulatory sites. Overall, this work provides novel insight for browning prevention in different apple varieties.


Assuntos
Frutas , Malus , Metabolômica , Malus/metabolismo , Malus/classificação , Frutas/metabolismo , Frutas/química , Manipulação de Alimentos/métodos , Reação de Maillard
3.
Food Chem X ; 22: 101337, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38601949

RESUMO

Hot air drying (HD), vacuum freeze drying (FD), and pilot-scale freeze drying (PSFD) are extensively used to prepare peach slices. However, the aroma of hot air drying and vacuum freeze-drying is yet to be addressed. In this study, HS-SPME-GC-MS was used to characterize and quantify the volatile compounds in peach slices. First, 33, 36, and 46 volatile compounds were identified and quantified in the HD, FD, and PSFD groups, respectively. PSFD is preferable to HD and FD in terms of the volatile compound types, content, and aroma profiles. PSFD was selected for subsequent permeation and dehydration experiments. The key aroma compounds with an OAV ≥ 1 were found in the PSFD30 group. GC-O analysis was conducted on the PSFD30 group, leading to the preliminary identification of 2-methylbutanal, pentanal, hexanal, 2-hexenal, phenylacetaldehyde, ethyl acetate, 2-methylbutyl acetate, ethyl lactate, linalool, methyl heptenone, and γ-octalactone as distinctive aromas in dried peach slices.

4.
J Neurol ; 271(2): 918-928, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37848650

RESUMO

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).


Assuntos
Disfunção Cognitiva , Doença de Machado-Joseph , Humanos , Cerebelo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Estudos Transversais , Doença de Machado-Joseph/complicações , Doença de Machado-Joseph/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estudos Prospectivos
5.
JAMA Neurol ; 80(10): 1105-1112, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37669037

RESUMO

Importance: Immunoglobulin G autoantibodies for aquaporin 4 (AQP4-IgG) serve as diagnostic biomarkers for neuromyelitis optica spectrum disorder (NMOSD), and the most sensitive and specific laboratory tests for their detection are cell-based assays (CBAs). Nevertheless, the limited availability of special instruments limits the widespread use of CBAs in routine laboratories. Objective: To validate an enzyme immunodot assay for simple and rapid detection of AQP4-IgG. Design, Setting, and Participants: This multicenter case-control study, conducted from May 2020 to February 2023, involved 4 medical centers (3 in China and 1 in Korea). The study included patients with AQP4-IgG-positive NMOSD, patients with other immune-related diseases, and healthy control individuals. Participants were excluded if they did not agree to participate or if their serum sample had turbidity. Exposures: Serum AQP4 antibodies measured with immunodot assay. Main Outcomes and Measures: The main outcome was performance of the immunodot assay compared with the gold standard CBA for detecting AQP4-IgG. To examine generalizability, cross-validation in Korea and at a second site in China, validation of patients with other immune-related diseases, and follow-up validation of the original cohort were performed. Results: A total of 836 serum samples were collected; 400 were included in the diagnostic study and 436 in the validation sets. In a head-to-head diagnostic study involving 200 patients with NMOSD with AQP4-IgG (mean [SD] age, 43.1 [13.5] years; 188 [94%] female) and 200 healthy controls, use of an immunodot assay demonstrated antibody detection performance comparable to that of the gold standard (κ = 98.0%). The validation sets included 47 patients with NMOSD and 26 patients with other autoimmune diseases from Korea, 31 patients with NMOSD at a second site in China, 275 patients with other diseases, and 57 patients with NMOSD at follow-up. In the validation study, of 436 cases, 2 (<1%) were false positive and none were false negative. The CBA identified 332 AQP4-IgG-positive samples and 504 negative samples (200 [40%] in controls and 304 [60%] in patients with other diseases); 2 of the positive cases (<1%) were false negative and 4 of the negative cases (<1%) were false positive. The overall sensitivity of the immunodot assay was 99.4% (95% CI, 97.8%-99.9%), and the specificity was 99.2% (95% CI, 98.0%-99.8%). Conclusions and Relevance: This case-control study found that the immunodot assay was comparable to CBA for detecting AQP4-IgG. With its time- and cost-efficient characteristics, the immunodot assay may be a practical option for AQP4-IgG detection.


Assuntos
Neuromielite Óptica , Humanos , Feminino , Adulto , Masculino , Estudos de Casos e Controles , Aquaporina 4 , Autoanticorpos , Imunoglobulina G
6.
Int J Pediatr Otorhinolaryngol ; 170: 111599, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37196371

RESUMO

OBJECTIVE: The aim of this study was to summarize the clinical features of congenital preauricular fistula (CPF) in pediatric patients to improve the levels of diagnosis and treatment, reduce the rates of missed diagnosis and recurrence, and shorten the total diagnosis and treatment time. METHODS: A total of 353 patients with CPF who were admitted to the Department of Otolaryngology in The Children's Hospital, Zhejiang University School of Medicine between January 2019 and December 2021 was enrolled in this retrospective observational study. Follow ups for 12-42 months were performed to investigate the classification, surgical methods, and postoperative conditions of CPF and to compare the recurrence rate, complication rate, and total diagnosis and treatment time between the active infection CPF group (AICPFG) and infection-controlled/non-infected CPF group (IC/NICPFG). RESULTS: In 316 cases (89.5%) out of the 353 patients, the natural fistula orifice was located in front of the crus helicis; in 33 cases (9.4%), the natura fistula orifice was located at the crus helicis; and in 4 cases (1.1%), the natura fistula orifice was located in the external acoustic meatus. The AICPFG had 52 cases (14.7%), including 1 case (0.28%) of recurrence and 2 cases (0.56%) of infection at the incision site. The IC/NICPFG had 301 cases (85.3%), including 4 cases (1.13%) of recurrence, 6 cases (1.7%) of infection at the incision site, and 1 case (0.28%) of scar formation at the incision site. There were no significant differences in the recurrence rates and postoperative complications between the AICPFG and IC/NICPFG (p > 0.05). There was a statistically significant difference in the total diagnosis and treatment time between the AICPFG and IC/NICPFG (p < 0.05). CONCLUSION: A reasonable classification of CPF, use of appropriate surgical methods, and belonging to the AICPFG do not increase the recurrence and complication rates of children but shorten the total treatment course, relieve patients' suffering, reduce treatment costs, and achieve a better clinical prognosis.


Assuntos
Orelha , Fístula , Humanos , Criança , Fístula/diagnóstico , Fístula/etiologia , Fístula/cirurgia , Meato Acústico Externo , Resultado do Tratamento , Cartilagem da Orelha , Estudos Retrospectivos , Recidiva
7.
Chem Pharm Bull (Tokyo) ; 71(5): 349-353, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36858603

RESUMO

The direct modification of structurally complex natural product dehydroepiandrosterone (DHEA) through iron-catalyzed direct hydroamination of DHEA with various nitro(hetero)arenes was carried out to afford 5α-arylamino-DHEAs (1-25) in good yields (53-72%). Though as a radical reaction, it features high stereoselectivity, and only the 5α-substituted derivatives were produced. The in vitro antiproliferative activity of these synthesized compounds against the human breast cancer MCF-7 cell was evaluated, showing that most of DHEA analogues possessed the moderate cytotoxic activity. The preliminary structure-activity relationship analysis revealed that the electron-withdrawing groups installed at the para-position of arylamine ring had a great contribution to the improvement of the DHEA's cytotoxic potency. Among them, (4-trifluoromethylaniline)-DHEA (4) displayed the most potent cytotoxicity, with an IC50 value of 19.3 µM, which was 2.3-fold more active than DHEA.


Assuntos
Antineoplásicos , Desidroepiandrosterona , Humanos , Desidroepiandrosterona/farmacologia , Sulfato de Desidroepiandrosterona , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Catálise
8.
BMC Bioinformatics ; 23(1): 562, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575396

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. METHODS: The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan-Meier (K-M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. RESULTS: A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K-M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p < 0.05) and Tgds (p < 0.01) was higher in the high-risk group than in the low-risk group. Spearman's correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. CONCLUSION: In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Glicosilação , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Fatores de Risco , Algoritmos , Manosiltransferases
9.
Am J Transl Res ; 14(8): 5622-5629, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105007

RESUMO

OBJECTIVE: To explore the significance of liraglutide combined with dapagliflozin or empagliflozin in the prevention of early diabetic nephropathy (DN) and its effects on renal function indices. METHODS: Three hundred patients with type 2 diabetes mellitus (T2DM) treated in our hospital from April 2019 to April 2020 were retrospectively included and divided into two groups according to different treatment regimens. Among them, 150 patients who received liraglutide alone were included in the single-drug group, and 150 patients treated with liraglutide combined with dapagliflozin or empagliflozin were included in the combination group. The baseline data and the improvement of inflammatory indices, blood glucose indices and renal function-related indices were compared between the two groups of patients. RESULTS: The baseline data such as age, body mass index, retinopathy, and course of disease had no significant difference between the two groups (P > 0.05). After treatment, the waist-to-hip ratio, total body fat percentage, total body fat mass, total body lean mass, and A/G ratio were significantly decreased in both groups (P < 0.05) compared with before treatment, and were significantly lower in the combination group than in the single-drug group (P < 0.05). The combination group had significantly lower urinary transferrin (Tf), neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor (TNF)-α, insulin-like growth factor 1 (IGF-1), retinol-binding protein (RBP), homocysteine (Hcy), brain natriuretic peptide (BNP), 24 h urinary albumin excretion ratio (UAER), urine albumin to creatinine ratio (UACR) and urinary liver-type fatty acid binding protein (L-FABP) levels, and higher secretory frizzled-related protein 5 levels than the single-drug group after treatment (P < 0.05). CONCLUSION: Liraglutide combined with dapagliflozin or empagliflozin treatment can effectively reduce the levels of Tf, NGAL and TNF-α in patients with T2DM, and improve the renal function in terms of IGF-1, RBP, Hcy, BNP, UAER, UACR, L-FABP, showing high treatment safety.

10.
BMJ Open ; 12(1): e054011, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017251

RESUMO

INTRODUCTION: Hereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic-clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment. METHODS AND ANALYSIS: In this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests. ETHICS AND DISSEMINATION: The study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public. TRIAL REGISTRATION NUMBER: NCT04006418.


Assuntos
Paraplegia Espástica Hereditária , Adulto , Estudos de Casos e Controles , China , Estudos de Coortes , Hospitais , Humanos , Estudos Longitudinais , Mutação , Estudos Prospectivos , Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/patologia
11.
Rev Sci Instrum ; 92(4): 043001, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243418

RESUMO

Cavity-stabilized ultra-stable optical oscillators are one of the core ingredients in the ground-based or spaceborne precision measurements such as optical frequency metrology, test of special relativity, and gravitational wave observation. We report in detail the development of two ultra-stable systems based on 1064-nm neodymium-doped yttrium aluminum garnet lasers and 20-cm optical cavities. The optical cavities adopt ultra-low-loss silica mirrors with compensating rings. An electro-optic crystal with a wedged angle is used to reduce the residual amplitude modulation. Using two-stage thermal control, long-term stabilities of 100 µK are achieved for the outer wall of the vacuum chamber housing the optical cavity. Two additional thermal shields increased the time constant of the optical cavities to 70 h. By operating the optical cavity at the temperature of zero coefficient of thermal expansion, the frequency stability reaches 2.5 × 10-16 at 10 s averaging time and remains below 5 × 10-16 with an extended time of 1000 s after removing the first- and second-order drifts. The dependence of the laser linewidth on the measurement time is tested against a simplified theoretical model.

13.
Org Lett ; 21(14): 5575-5580, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31246482

RESUMO

A CuH-catalyzed atropoenantioselective reduction of Bringmann's lactones via dynamic kinetic resolution has been disclosed. This protocol features a broad substrate scope and good functional group tolerance and allows the rapid assembly of various valuable axially chiral biaryls in good to high yields (up to 92% yield) with high to excellent enantioselectivities (up to 96% ee). Moreover, this report represents a rare example that a carbonyl group of esters is reduced under homogeneous asymmetric CuH catalysis.

14.
Appl Opt ; 58(3): 690-694, 2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30694256

RESUMO

Residual amplitude modulation is one of the major stability-degrading factors in many precision measurements. Using an electro-optic (EO) crystal with wedged input and output surfaces is an effective way to suppress residual amplitude modulation. Here the mechanism of residual amplitude modulation in this approach is investigated. The residual amplitude modulations measured in standard and wedged EO crystals bear similarities in their temperature and polarization dependences, implying that a mixture of the two orthogonal polarizations in the extraordinary light is responsible for the residual amplitude modulation in the wedged EO crystal. Similar to a standard EO crystal, a non-uniform spatial distribution of residual amplitude modulation is also observed in the extraordinary light emerging from the wedged EO crystal. The optical isolator after the EO crystal is replaced by a Faraday rotator, and an improvement in the long-term stability is observed. With the wedged-crystal approach, residual amplitude modulation as low as 2×10-7 is observed, contributing a frequency instability of 8×10-18 (500 s) in Pound-Drever-Hall frequency stabilization with a discrimination slope of 1×10-4 V/Hz.

15.
J Am Chem Soc ; 140(26): 8064-8068, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29920089

RESUMO

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SNAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H2.

16.
J Microbiol Biotechnol ; 28(6): 849-859, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29847864

RESUMO

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule Retro-2cycl has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of Retro-2cycl, could inhibit HSV-2 infection, with 50% inhibitory concentrations of 5.58 µM and 6.35 µM in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of 116.5 µM. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.


Assuntos
Antivirais/farmacologia , Benzamidas/farmacologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/crescimento & desenvolvimento , Tiofenos/farmacologia , Animais , Chlorocebus aethiops , Efeito Citopatogênico Viral , Concentração Inibidora 50 , Células Vero , Ensaio de Placa Viral
17.
Dalton Trans ; 47(22): 7395-7398, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29770394

RESUMO

An approximately equatorial three-coordinated dysprosium(iii) complex DyL2[N(SiMe3)2] (L = bis(2-(2,5-dimethyl-1H-pyrrol-1-yl)ethyl)amine) with an additional neutral auxiliary pyrrole ligand was synthesised and structurally characterized. The magnetic property measurement shows that it is an equatorial charge distributed field-induced single-molecule magnet. Ab initio calculations reveal that the neutral pyrrole ligand plays an important role in stabilizing the ground doublet and thus enhancing the magnetic anisotropy.


Assuntos
Disprósio/química , Imãs/química , Compostos Organometálicos/química , Compostos de Silício/química , Anisotropia , Cristalografia por Raios X , Ligantes , Estrutura Molecular , Compostos Organometálicos/síntese química , Pirróis/química , Compostos de Silício/síntese química
18.
Rev Sci Instrum ; 89(12): 125120, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30599616

RESUMO

Many precision measurements using rotating optical cavities have tight requirement on the level of a rotating platform on which the cavities are installed. We develop a single-stage tilt control system as one part of the experimental setup for testing Lorentz invariance using two optical cavities that are perpendicular to each other. Home built voice-coil actuators, together with a tilt sensor and control electronics, are adopted to simultaneously suppress the tilt of the rotating platform in two orthogonal directions. The large cross coupling between two orthogonal axes is observed, and its mechanism is examined. By adding a compensating weight, the loop instability resulting from the cross coupling is effectively removed. With the active control, the variation of the tilt around each of the two axes is reduced from the free-running value of ±30 µrad to within ±0.2 µrad, independently measured by using a second tilt sensor. This residual tilt has a component at the rotational frequency with an amplitude of 0.1 µrad, which contributes a systematical offset of 1.8 × 10-17 to the Lorentz violating parameter κ e- ZZ, estimated by assuming that the tilt sensitivity of the optical cavity is 1 × 10-16/µrad. Further improvement is still possible by using piezo-electric actuators that exhibit higher resonant frequencies, a different approach that will suppress the residual variation of the tilt to within ±0.01 µrad and allow a reduced systematical offset of 1.8 × 10-18 for κ e- ZZ.

19.
J Food Sci Technol ; 54(12): 3818-3826, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29085124

RESUMO

The purpose of this study was to gain insights into the variations in quality characteristics of white-flesh peach fruits. Eighteen cultivars of north of China were investigated. The quality evaluation indicators, including color, physico-chemical and nutritional attributes were measured. Analysis of variance revealed that all the indicators showed significant differences among the cultivars, except edible rate. Principal Component Analysis (PCA) conducted to distinguish the indicators among cultivars, suggested that the most important factors affecting the peach quality could be reduced into nine principal components. Crude fiber content, glucose content, peel-b*, TA, moisture content, pulp-firmness, quinic content, shikimic content and edible rate could be regarded as the characteristic indicators for PC1, PC2, PC3,PC4, PC5, PC6, PC7, PC8 and PC9, respectively. Cluster analysis classified the different cultivars into five main groups on the basis of the measured quality evaluation indicators, and the results were in good accordance with PCA results.

20.
Oncotarget ; 8(33): 54993-55002, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903397

RESUMO

Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers. Further, 5-FU-medied inhibition of in-situ HCC growth was dramatically sensitized with DlgR2 silence. DlgR2 siRNA injection indeed downregulated DlgR2 in ex-vivo cultured tumor-derived DCs (tDCs). More importantly, tDCs activity was boosted following DlgR2 siRNA. These cells presented with upregulated CD80, CD86 and MHC-II. Production of interleukin-12 and tumor necrosis factor-α was also increased in the DlgR2-silenced tDCs. We propose that DlgR2 knockdown likely boosts the activity of tumor-associated DCs, and inhibits growth of in-situ HCC xenografts.

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