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1.
J Cancer ; 15(1): 68-78, 2024.
Article in English | MEDLINE | ID: mdl-38164269

ABSTRACT

Background: The presence of microvascular invasion (MVI) significantly worsens the surgical outcome of hepatocellular carcinoma (HCC). The purpose of this research was to investigate the survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with MVI after hepatectomy. Methods: A retrospective analysis was conducted on 1372 HCC patients who underwent curative liver resection in four medical institutions. In order to minimize confounding factors and selection bias between groups, Propensity Score Matching (PSM) (1:1) was performed to ensure balanced clinical characteristics. Results: A total of 1056 patients were enrolled after PSM, including 672 patients with MVI and 384 patients without MVI. Adjuvant TACE improves DFS (Median, 36 months vs 14 months, p < 0.001) and OS (Median, NA vs 32 months, p < 0.001) in patients harboring MVI, but not in those (all p > 0.05) lacking MVI. In different different CNLC stages, adjuvant TACE improved DFS (CNLC stage I, Median, 37 vs 15 months; CNLC stage II, Median, 25 vs 11 months, p < 0.001) and OS (CNLC stage I, Median, NA vs 32 months, p < 0.001; CNLC stage II, Median, NA vs 26 months, p = 0.002) in patients who carried MVI, but not in those (CNLC stage I-II, all p > 0.05) who lacked MVI. Conclusions: Adjuvant TACE may be a potentially effective treatment option for improving survival outcomes in early-HCC patients harboring MVI, but not in those lacking MVI.

2.
Int J Nurs Stud ; 147: 104582, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37672971

ABSTRACT

BACKGROUND: The elderly patients admitted to cardiac intensive care unit (CICU) are at relatively high risk for developing delirium. A simple and reliable predictive model can benefit them from early recognition of delirium followed by timely and appropriate preventive strategies. OBJECTIVE: To explore the role of frailty in delirium prediction and develop and validate a delirium predictive model including frailty for elderly patients in CICU. DESIGN: A prospective, observational cohort study. SETTINGS: CICU at China-Japan Friendship Hospital from March 1, 2022 to August 25, 2022 (derivation cohort); CICU at Beijing Anzhen Hospital affiliated to Capital Medical University from March 14, 2023 to May 8, 2023 (external validation cohort). PARTICIPANTS: A total of 236 and 90 participants were enrolled in the derivation and external validation cohorts, respectively. Participants in the derivation cohort were assigned into either the delirium (n = 70) or non-delirium group (n = 166) based on the occurrence of delirium. METHODS: The simplified Chinese version of the Confusion Assessment Method for the Diagnosis of Delirium in the Intensive Care Unit was used to assess delirium twice a day at 8:00-10:00 and 18:00-20:00 until the onset of delirium or discharge from the CICU. Frailty was assessed using the FRAIL scale during the first 24 h in the CICU. Other possible risk factors were collected prospectively through patient interviews and medical records review. After processing missing data via multiple imputations, univariate analysis and bootstrapped forward stepwise logistic regression were performed to select optimal predictors and develop the models. The models were internally validated using bootstrapping and evaluated comprehensively via discrimination, calibration, and clinical utility in both the derivation and external validation cohorts. RESULTS: The study developed D-FRAIL predictive model using FRAIL score, hearing impairment, Acute Physiology and Chronic Health Evaluation-II score, and fibrinogen. The area under the receiver operating characteristic curve (AUC) was 0.937 (95% confidence interval [CI]: 0.907-0.967) and 0.889 (95%CI: 0.840-0.938) even after bootstrapping in the derivation cohort. Inclusion of frailty was demonstrated to improve the model performance greatly with the AUC increased from 0.851 to 0.937 (p < 0.001). In the external validation cohort, the AUC of D-FRAIL model was 0.866 (95%CI: 0.782-0.907). Calibration plots and decision curve analysis suggested good calibration and clinical utility of the D-FRAIL model in both the derivation and external validation cohorts. CONCLUSIONS: For elderly patients in the CICU, FRAIL score is an independent delirium predictor and the D-FRAIL model demonstrates superior performance in predicting delirium.


Subject(s)
Delirium , Frailty , Humans , Aged , Frailty/diagnosis , Frail Elderly , Prospective Studies , Delirium/diagnosis , Delirium/prevention & control , Intensive Care Units , Risk Factors
3.
Mol Clin Oncol ; 18(6): 46, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37206430

ABSTRACT

Angiomatous meningioma (AM) is a relatively rare subtype of WHO grade I meningioma. A relatively rare case of AM was recently encountered in a 45-year-old woman. The present case not only observed the typical AM histological pattern but also a large number of cells with bizarre, large, deeply staining and unevenly distributed nuclei. These cells with bizarre nuclei showed a similar pattern of immunoreactivity as meningeal epithelial cells. Although the presence of a large number of cells with bizarre nuclei in this case increased tumour cell atypia, the cells did not differ with regard to proliferative activity and mitotic imaging. Therefore, the patient was ultimately diagnosed as having AM with bizarre nuclei, WHO grade I. This manifestation of nuclear atypia and pleomorphism may be due to 'degenerative changes' in pre-existing, long-established vascular lesions, similar to those seen in degenerative schwannomas and symplastic haemangioma, rather than being considered an indicator of malignancy.

4.
Angew Chem Int Ed Engl ; 62(22): e202302232, 2023 May 22.
Article in English | MEDLINE | ID: mdl-36991542

ABSTRACT

Perylene diimide tethered pillar[5]arene derivatives form aggregates in non-polar organic solvents, and the complexation of cationic amino acid ethyl ester (cAA-OEt) with the aggregates induce a central-to-planar-to-helical chirality transfer, leading to intensive circular dichroism (CD) signals having dissymmetric factors (gabs ) of up to 3.67×10-2 . The hierarchical chiral induction exhibited an intriguing threshold dose effect, namely, the chiral induction does not occur in the low concentration range of cAA-OEt but is triggered when cAA-OEt exceeds a threshold concentration. The inhibited interconversion between the Rp and Sp conformers of pillar[5]arene, which is further restricted in the aggregation, plays a crucial role in the threshold effect. When adding enantiopure cAA-OEt first to the threshold concentration and then adding an equal amount of the antipodal cAA-OEt to give cAA-OEt in racemic form, CD spectra having the same sign as the CD induced by first adding pure cAA-OEt were induced, thus showing an unprecedented "first come, first served" effect.

5.
Dis Markers ; 2023: 4397829, 2023.
Article in English | MEDLINE | ID: mdl-36845016

ABSTRACT

Background: This study investigated the mechanism of microRNA (miRNA, miR) in microvesicles (MVs) secreted by endothelial progenitor cells (EPCs) involved in renal function in vivo and in vitro injury repair of rat primary kidney cells (PRKs). Methods: Gene Expression Omnibus analysis of potential target miRNAs in nephrotic rats. Real-time quantitative polymerase chain reaction verified the correlation of these miRNAs and screened the effective target miRNAs and their downstream putative target mRNAs. Western blot analyzes the protein levels of DEAD-box helicase 5 (DDX5) and the activation of the proapoptotic factor caspase-3/9 (cleaved). Dil-Ac-LDL staining, immunofluorescence, and a transmission electron microscope (TEM) were used to identify the successful isolation of EPCs and PRKs and the morphology of MVs. Cell Counting Kit-8 was used to detect the effect of miRNA-mRNA on the proliferation of PRKs. Standard biochemical kits were used to detect biochemical indicators in rat blood and urine. Dual-luciferase analysis of miRNA binding to mRNA was conducted. The effect of miRNA-mRNA interaction on the apoptosis level of PRKs was analyzed by flow cytometry. Results: A total of 13 rat-derived miRNAs were potential therapeutic targets, and miR-205 and miR-206 were screened as the targets of this study. We found that the EPC-MVs alleviated the increase of blood urea nitrogen and urinary albumin excretion and the decrease in creatinine clearance caused by hypertensive nephropathy in vivo. The effect of MVs in improving renal function indicators was promoted by miR-205 and miR-206 and inhibited by knockdown of expressed miR-205 and miR-206. In vitro, angiotensin II (Ang II) promoted growth inhibition and apoptosis of PRKs, and similarly, dysregulated miR-205 and miR-206 affected the induction of Ang II. We then observed that miR-205 and miR-206 cotargeted the downstream target DDX5 and regulated its transcriptional activity and translational levels, while also reducing the activation of proapoptotic factors caspase-3/9. Overexpressed DDX5 reversed the effects of miR-205 and miR-206. Conclusion: By upregulating the expression of miR-205 and miR-206 in MVs secreted by EPC, the transcriptional activity of DDX5 and the activation of caspase-3/9 can be inhibited, thereby promoting the growth of PRKs and protecting the injury caused by hypertensive nephropathy.


Subject(s)
Endothelial Progenitor Cells , MicroRNAs , Rats , Animals , Endothelial Progenitor Cells/metabolism , Caspase 3 , MicroRNAs/genetics , MicroRNAs/metabolism , Kidney/metabolism , Apoptosis/genetics , RNA, Messenger , DEAD-box RNA Helicases/genetics
6.
Chem Commun (Camb) ; 58(98): 13584-13587, 2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36416482

ABSTRACT

The complexation of prism[5]arenes with amino acid derivatives showed association constants of up to 107 M-1, significant CD with gabs of up to 0.8 × 10-2 and CPL with glum of 2 × 10-3. The absolute configuration-CD signal correlation was established. The CD spectra varied significantly with the substituents on the prism[5]arenes.

7.
Angew Chem Int Ed Engl ; 61(48): e202210755, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36205517

ABSTRACT

Although the synthesis of α-tertiary amino acids (ATAAs) has been extensively studied, the development of an inexpensive and facile methodology to incorporate multifunctionality on ATAAs remains challenging. In this article, we present a single-step radical approach for the modular synthesis of functionally diverse ATAAs. This synthesis takes place under mild conditions with an absence of metals, photocatalysts, and all other additives. We demonstrate the broad applications of this approach on a variety of aliphatic and aromatic carboxylic acids, alkenes, 1,3-enynes, and oxazolones. The results prove that our method provides excellent functional group tolerance and late-stage applicability, as well as gram-scale synthesis via flow chemistry. Additionally, we include mechanistic studies which reveal that the excited state of oxazolone enolate upon light excitation is a key intermediate that acts as a radical precursor and an efficient reductant.


Subject(s)
Alkenes , Amino Acids , Alkenes/chemistry , Carboxylic Acids , Metals
8.
Environ Sci Technol ; 56(16): 11473-11481, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35914180

ABSTRACT

Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal mortality and adverse birth outcomes. Fine particulate matter (PM2.5) has been linked to HDP risk; however, limited studies have explored the relationships between specific chemical constituents of PM2.5 and HDP risk. Based on maternal data from the China Labor and Delivery Survey (CLDS), this study included a total of 67,659 participants from 95 participant hospitals in 25 provinces of China between March 1, 2015, and December 31, 2016. Maternal exposure to total PM2.5 mass and six main components during pregestation and pregnancy were estimated using the Combined Geoscience-Statistical Method. Multilevel logistic regression models were applied to quantify the associations, controlling for sociodemographic characteristics. We found that an interquartile range (IQR) increase in PM2.5 exposure during the second trimester was associated with a 14% increase in HDP risk (95% CI: 2%, 29%). We observed that black carbon (BC) and SO42- had larger or comparable estimates of the effect than total PM2.5 mass. The association estimates were greater in the gestational hypertension group than in the group of pre-eclampsia and eclampsia. Our findings suggest that PM2.5 exposure and specific chemical components (particularly BC and SO42-) were associated with an increased HDP risk in China.


Subject(s)
Air Pollutants , Air Pollution , Hypertension, Pregnancy-Induced , Prenatal Exposure Delayed Effects , Air Pollutants/analysis , Air Pollution/analysis , China/epidemiology , Cohort Studies , Female , Humans , Hypertension, Pregnancy-Induced/epidemiology , Maternal Exposure , Particulate Matter/analysis , Pregnancy
9.
Virulence ; 13(1): 781-793, 2022 12.
Article in English | MEDLINE | ID: mdl-35481413

ABSTRACT

Streptococcus suis can cause severe infections in pigs and humans. The tonsils of pigs are major niches for S. suis, and different serotypes of S. suis can be found in the same tonsil. Pig tonsil colonization by S. suis is believed to be an important source of infection for humans and pigs. However, how S. suis competes for a stable tonsil niche is unknown. Here, we found that S. suis strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage in vivo. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of S. suis. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets S. suis, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of S. suis in the tonsil niche, which might have important implications for S. suis epidemiology, potentially influencing strain prevalence and disease progression.


Subject(s)
Bacteriocins , Streptococcus suis , Animals , Anti-Bacterial Agents/pharmacology , Bacteriocins/genetics , Bacteriocins/pharmacology , Palatine Tonsil/microbiology , RNA, Ribosomal, 16S , Swine
10.
Res Vet Sci ; 143: 41-49, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34973538

ABSTRACT

Streptococcal infections are very common in humans and animals, and they are usually treated with antibiotics. Multidrug-resistant Streptococcus strains have continuously emerged in recent years, prompting the search for alternatives to antibiotics. The use of endolysins encoded by phages has presented a promising alternative approach to treatment. In this study, a novel prophage endolysin, Ply0643, was identified from the prophage S. a 04. At an optimal concentration (30 µg/mL), rPly0643 exhibited broad and strong lysosomal enzyme activity against 66 Streptococcus strains from different sources while also maintaining high lytic activity over a wide pH range (pH 6-10) and a broad range of temperatures (28 °C-45 °C). Two in vivo treatments of rPly0643 (total 0.8 mg/mouse) significantly protected mice (80%) from lethal bacteriaemia with Streptococcus suis, and single treatments of rPly0643 (0.1 mg/gland) significantly reduced Streptococcus agalactiae concentrations and inflammation in murine mammary glands. These findings collectively demonstrate that Ply0643 exhibits good bactericidal activity both in vitro and in vivo, and therefore represents a useful antibacterial agent for combatting streptococcal infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Endopeptidases/therapeutic use , Mastitis , Streptococcal Infections , Animals , Female , Mastitis/drug therapy , Mice , Streptococcal Infections/drug therapy , Streptococcus agalactiae , Streptococcus suis
11.
Environ Pollut ; 289: 117823, 2021 Nov 15.
Article in English | MEDLINE | ID: mdl-34325093

ABSTRACT

Effective reducing exposure to fine particulate matter (PM2.5) during commuting can help lower the risk of adverse health effects therefrom; however, few studies have examined the influence of different background levels of air pollution-particularly in China where PM2.5 concentrations are high globally. In this study, personal sampling was conducted to measure individual exposure during five different modes of commuting (bus, metro, car, bicycle and walking) in Shanghai, China. A total of 125 measurements were conducted for five days under haze and non-haze conditions, following which the corresponding doses of PM2.5 inhaled were estimated. The mean concentrations (±standard deviation, SD, 1-min averaging) of background PM2.5 were 155.9 (±98.7) µg/m3 during haze and 36.3 (±17.6) µg/m3 under the non-haze conditions. Under both conditions, active commuters were exposed to higher PM2.5 concentrations than those using motorized commuting modes (Wilcoxon test, p < 0.01). Moreover, driving with closed windows and air conditioning effectively reduces the PM2.5 concentrations in cars by 35 %-57 %. Cyclists inhaled the highest doses (539.8 ± 313.2 and 134.8 ± 71.3 µg/h under haze and non-haze conditions, respectively), whereas car drivers inhaled the lowest doses (28.8 ± 21.2 and 3.7 ± 2.6 µg/h under haze and non-haze conditions, respectively). Individual exposure to PM2.5 during commuting varied with the modes; the discrepancy between the latter depended largely on the ambient concentration. Our findings provided evidence that traffic-related air pollution contributed to daily pollutant exposure and highlighted the importance of taking personal protective measures while commuting, particularly during haze.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , China , Environmental Exposure/analysis , Environmental Monitoring , Particulate Matter/analysis , Transportation , Vehicle Emissions/analysis
12.
Chemosphere ; 283: 131179, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34146873

ABSTRACT

It remains unclear whether carbon content in airway macrophages (AM) can predict personal short-term exposure to fine particulate matter (PM2.5) air pollution and its respiratory health effects. We aimed to evaluate the pathway from personal PM2.5 exposure to adverse respiratory outcomes through AM carbon content. We designed a longitudinal panel study with 3 scheduled follow-ups among 113 non-smoking patients of chronic obstructive pulmonary disease in Shanghai, China, from April 2017 to January 2019. We quantified AM carbon content from induced sputum by image analysis, tested lung function and measured sputum levels of 4 pro-inflammatory cytokines and 2 anti-inflammatory cytokines. We applied the "meet in the middle" approach incorporating linear mixed-effect models to evaluate the associations from external PM2.5 exposure to respiratory outcomes through AM carbon content. Our results indicated that personal exposure to PM2.5 within 24 h was significantly associated with decreased forced expiratory volume in 1s and anti-inflammatory cytokines, as well as increased macrophages and pro-inflammatory cytokines. These changes were accompanied by increased areas of AM carbon and higher percentage of AM area occupied by carbon, both of which were associated with increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory cytokines. Exposure to ambient black carbon and organic carbon in PM2.5 within 2 days was significantly associated with increased AM carbon area and percentage of AM area occupied by carbon. Our findings reinforced the causality in respiratory health effects of PM2.5 in which increased AM carbon content might serve as a valid exposure biomarker.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/analysis , Biomarkers , Carbon , China , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Humans , Macrophages/chemistry , Particulate Matter/analysis , Particulate Matter/toxicity
13.
Vet Microbiol ; 259: 109149, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34147764

ABSTRACT

Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans and pigs. The S. suis cps31 strains (SS31) were frequently isolated from healthy or diseased pigs and one human infection case caused by SS31 was reported in Thailand in 2015. However, except for a few epidemiologic studies, little information is available for SS31. To characterize SS31, a total of 75 SS31 strains were analyzed, including 52 strains that were isolated from healthy or diseased pigs and 23 strains whose information was accessed from NCBI. The MLST analysis showed that SS31 exhibited high heterogeneity. The phylogenetic analysis and minimum core-genome (MCG) classification revealed that 75 strains were clustered into 3 lineages. Strains from NCBI mainly at Lineage 2 belong to MCG7-3, and most of strains from China at Lineage 3 belong to MCG7-2. This finding indicated that their evolutionary path was different. All SS31 strains were resistant to more than three classes of antimicrobial agents, and major antimicrobial resistance genes for strains from Lineage 3 were carried by prophages. This observation is different from the previous observation that integrative conjugative elements and integrative and mobilizable elements are major vehicles of antimicrobial resistance genes for S. suis. In addition to strains isolated from diseased pigs, seven of 47 strains isolated from clinically healthy pigs were also pathogenic in a zebrafish infection model. These findings reveal unique characteristics of SS31 and contribute to establishing public health surveillance for SS31 and clarifying the diversity of S. suis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Phylogeny , Streptococcal Infections/veterinary , Streptococcus suis/drug effects , Streptococcus suis/pathogenicity , Animals , Drug Resistance, Multiple, Bacterial , Evolution, Molecular , Genotype , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Multilocus Sequence Typing , Streptococcal Infections/microbiology , Streptococcus suis/classification , Streptococcus suis/genetics , Swine , Swine Diseases/microbiology , Virulence/genetics , Zebrafish
14.
Mikrochim Acta ; 188(2): 40, 2021 01 13.
Article in English | MEDLINE | ID: mdl-33442843

ABSTRACT

A new strategy has been developed for the determination of trace lead ions (Pb2+) based on hexagonal boron nitride (h-BN) laden with point defect. The defect-laden boron nitride (D-BN) was synthesized by a thermal polymerization route, in which melamine borate was used as a precursor. The defect microstructure was confirmed by photoluminescence (PL) and x-ray diffraction (XRD) techniques. As compared with h-BN, the D-BN-modified glassy carbon electrode (GCE) showed an enhanced electrochemical response towards Pb2+ peaking at - 0.551 V (vs. SCE), which was evidenced by linear sweep anodic stripping voltammetry (LSASV) results. The point defect plays a pivotal role in the electrocatalytic reaction process, which can mediate the electronic structure and surface properties of h-BN. Accordingly, the sensor presented a low detection limit of 0.15 µg/L towards Pb2+ and a wide linear response concentration range from 0.5 to 400 µg/L (correlation coefficient = 0.995). In view of its superior selectivity, stability, and reproducibility, the proposed method was applied for Pb2+ determination in real samples and exhibited satisfactory results. This work provides insight for the construction of electrochemical sensor with high-performance by engineering defects of modifying materials. Defect-loaden h-BN exhibited enhanced electrocatalytic redox reaction towards lead ions and thus a novel Pb2+ sensor with high performances was constructed.


Subject(s)
Boron Compounds/chemistry , Electrochemical Techniques/methods , Lead/analysis , Drinking Water/analysis , Electrochemical Techniques/instrumentation , Electrodes , Lakes/analysis , Limit of Detection , Reproducibility of Results , Water Pollutants, Chemical/analysis
15.
Chem Sci ; 12(46): 15399-15406, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34976361

ABSTRACT

The oxindole scaffold represents an important structural feature in many natural products and pharmaceutically relevant molecules. Herein, we report a visible-light-induced modular methodology for the synthesis of complex 3,3'-disubstituted oxindole derivatives. A library of valuable fluoroalkyl-containing highly sterically congested oxindole derivatives can be synthesized by a catalytic three-component radical coupling reaction under mild conditions (metal & photocatalyst free, >80 examples). This strategy shows high functional group tolerance and broad substrate compatibility (including a wide variety of terminal or non-terminal alkenes, conjugated dienes and enynes, and a broad array of polyfluoroalkyl iodide and oxindoles), which enables modular modification of complex drug-like compounds in one chemical step. The success of solar-driven transformation, large-scale synthesis, and the late-stage functionalization of bioactive molecules, as well as promising tumor-suppressing biological activities, highlights the potential for practical applications of this strategy. Mechanistic investigations, including a series of control experiments, UV-vis spectroscopy and DFT calculations, suggest that the reaction underwent a sequential two-step radical-coupling process and the photosensitive perfluoroalkyl benzyl iodides are key intermediates in the transformation.

16.
Org Lett ; 22(23): 9184-9189, 2020 12 04.
Article in English | MEDLINE | ID: mdl-33185451

ABSTRACT

An environmentally friendly electrochemical approach for iodoamination of various indole derivatives with a series of unactivated amines, amino acid derivatives, and benzotriazoles (more than 80 examples) has been developed. This strategy was further applied in late-stage functionalization of natural products and pharmaceuticals and gram-scale synthesis and radiosynthesis of 131I-labeled compounds. Fundamental insights into the mechanism of the reaction based on control experiments, density functional theory calculation, and cyclic voltammetry are provided.

17.
Neuropsychiatr Dis Treat ; 16: 789-800, 2020.
Article in English | MEDLINE | ID: mdl-32280223

ABSTRACT

PURPOSE: Excitatory amino acid transporters (EAATs) have an indispensable function in the reuptake of extracellular glutamate. To investigate the relationship and the expression of neuronal and astrocytic markers after brain ischemia, the temporal profile of glial EAATs in both peripheral and core regions of the cortex was examined. METHODS: Transient common carotid artery occlusion was used to induce unilateral transient forebrain ischemia of Mongolian gerbils, and post-ischemic brains (6 h to 2 w) were collected and prepared for immunohistochemical and Western blotting analysis of glutamine synthetase (GS), GLT-1, GLAST, S100ß, and NeuN, and for Alizarin red staining of calcium deposits. RESULTS: The expression of GLAST and GLT-1 were significantly escalated at 6 h both in the core and periphery regions, while reduced from 12 h to 2 w in the core region post-ischemia. GS-positive cells increased at 6 h both in the core and periphery regions, while the density of Alizarin red-positive cells increased and peaked at 12 h in the ischemic cortex. The density of S100ß-positive cells decreased in the ischemic core and increased in the periphery region. Immunofluorescence staining showed that S100ß and TUNEL double-positive cells increased at 12 h in the core region. CONCLUSION: The results of GLT-1 and GLAST expression in the cortex indicate that their up-regulation was time-dependent and occurred in the acute post-ischemia period, whereas their down-regulation was region-dependent and it is involved in the pathological progress of nerve cell and glial cell death, and has a series of cascade reactions.

18.
Neuropsychiatr Dis Treat ; 15: 3143-3153, 2019.
Article in English | MEDLINE | ID: mdl-31806980

ABSTRACT

PURPOSE: Epidemiology research has demonstrated that magnesium (Mg) deficiency is associated with a high incidence of Parkinson's disease (PD). It is known that the systemic administration of MgSO4 is not able to elevate the Mg concentration in cerebrospinal fluid (CSF). This study aims to verify the protective effect of magnesium-L-threonate (MgT) in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model. METHODS: C57BL/6J mice were orally administered MgT or MgSO4 for 4 weeks, and received MPTP in the third week. After analysis of open-field and rotarod tests on the last day, tyrosine hydroxylase (TH) immunopositive cells and protein levels were quantified in the substantia nigra pars compacta (SNpc) and striatum. The expression of inducible nitric oxide synthase (iNOS) level was evaluated. Mg concentration in serum and CSF was measured after oral administration of MgSO4 or MgT in normal mice. Mg concentration in the CSF was increased in the mice treated with MgT but not MgSO4. RESULTS: The total distance and mean speed in open-field tests, and the time spent on rotarod in the MgT group were increased, compared with MPTP group. The MgT treatment but not MgSO4 dose-dependently attenuated the loss of TH-positive neurons, and the reduction of the TH expression in the SNpc. The MgT treatment also inhibited the expression of iNOS as measured by immunohistochemistry and Western blots. Double-immunofluorescence staining of TH and iNOS showed iNOS-positive cells were collocalized for TH-positive cells. CONCLUSION: The treatment with MgT is associated with an increase of Mg in the CSF. MgT, rather than MgSO4, can significantly attenuate MPTP-induced motor deficits and dopamine (DA) neuron loss.

19.
Mikrochim Acta ; 186(12): 819, 2019 11 20.
Article in English | MEDLINE | ID: mdl-31748881

ABSTRACT

An electrochemical sensor is described for the simultaneous determination of hydroquinone (HQ) and catechol (CC) based on a nanocomposite consisting of gold nanoparticles and graphitic carbon nitride (g-C3N4). The nanocomposite was synthesized via one-step thermal polymerization route and characterized by X-ray diffraction, transmission electron microscopy, and Fourier transform infrared techniques. The results confirmed the close contact between gold nanoparticles and g-C3N4. The nanocomposites exhibited the enhanced electrocatalytic redox towards HQ and CC. A glassy carbon electrode was modified with the nanocomposite to obtain a sensor that exhibited favorable analytical properties in the simultaneous detection of HQ and CC, with voltammetric peaks typically near -0.14 and - 0.02 V (vs. saturated calomel electrode). Linear responses are found between 1.0 and 320 µM for HQ (with a 0.3 µM detection limit; at S/N = 3), and between 0.1 and 320 µM for CC (with a 0.04 µM detection limit; at S/N = 3). The sensor was applied for the simultaneous determination of HQ and CC in spiked water samples, and acceptable recoveries were achieved. The superior sensing properties of the electrode are attributed to the synergy between the microstructure (heterojunction and porosity) and the π interactions between phenolic isomers and g-C3N4. Graphical abstractA novel electrochemical sensor is demonstrated for the simultaneous determination of hydroquinone and catechol based on a nanocomposite consisting of gold nanoparticles (AuNPs) and graphitic carbon nitride (g-C3N4).

20.
Org Lett ; 21(19): 7702-7707, 2019 10 04.
Article in English | MEDLINE | ID: mdl-31553193

ABSTRACT

Reported herein is an effective strategy for oxidative cross-coupling of indoles with various aldehydes. The strategy is based on a two-step transformation via a well-known Mannich-type reaction and a C-N bond cleavage for carbonyl introduction. The key step-the C-N bond cleavage of the Mannich product-was enabled by electrochemistry. This strategy (with over 40 examples) ensures excellent functional-group tolerance as well as late-stage functionalization of pharmaceutical molecules.

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