17 research outputs found

    Hepatotoxicity-Related Oxidative Modifications of Thioredoxin 1/Peroxiredoxin 1 Induced by Different Cadmium-Based Quantum Dots

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    The hepatotoxicity of cadmium-based quantum dots (Cd-QDs) has become the focus with their extensive applications in biomedicine. Previous reports have demonstrated that high oxidative stress and consequent redox imbalance play critical roles in their toxicity mechanisms. Intracellular antioxidant proteins, such as thioredoxin 1 (Trx1) and peroxiredoxin 1 (Prx1), could regulate redox homeostasis through thiol-disulfide exchange. Herein, we hypothesized that the excessive reactive oxygen species (ROS) induced by Cd-QD exposure affects the functions of Trx1 or Prx1, which further causes abnormal apoptosis of liver cells and hepatotoxicity. Thereby, three types of Cd-QDs, CdS, CdSe, and CdTe QDs, were selected for conducting an intensive study. Under the same conditions, the H2O2 level in the CdTe QD group was much higher than that of CdS or CdSe QDs, and it also corresponded to the higher hepatotoxicity. Mass spectrometry (MS) results show that excessive H2O2 leads to sulfonation modification (−SO3H) at the active sites of Trx1 (Cys32 and Cys35) and Prx1 (Cys52 and Cys173). The irreversible oxidative modifications broke their cross-linking with the apoptosis signal-regulating kinase 1 (ASK1), resulting in the release and activation of ASK1, and activation of the downstream JNK/p38 signaling finally promoted liver cell apoptosis. These results highlight the key effect of the high oxidative stress, which caused irreversible oxidative modifications of Trx1 and Prx1 in the mechanisms involved in Cd-QD-induced hepatotoxicity. This work provides a new perspective on the hepatotoxicity mechanisms of Cd-QDs and helps design safe and reliable Cd-containing nanoplatforms

    Table_1_A Prospective Study on the Association Between Grip Strength and Cognitive Function Among Middle-Aged and Elderly Chinese Participants.docx

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    ObjectiveTo study the efficacy of grip strength (GS) as a predictor of cognitive function in a large, nationwide sample of Chinese participants aged 45 years and above.MethodsWe used data from three waves (W1, W2, and W3) fielded by the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was tested biennially and calculated using two categories: episodic memory and mental intactness. Demographics, health behaviors, and medical conditions were considered potential confounders. Using multivariate linear regression models (MLRMs), we examined the association between baseline GS (measure in W1) and cognitive function in W3. Using a generalized estimating equation (GEE), we examined baseline GS as a predictor of cognitive function change.ResultsTotal 9,333 individuals (53.2% women), with a mean baseline episodic memory score of 6.5, mean baseline mental intactness score of 7.2, and aged over 45 years (mean age = 58.6), were selected. The mean follow-up time was 4.0 years (range: 3.3–5.0 years). Using MLRMs and comparing the lowest GS score with the highest baseline GS score, we observed a significant correlation with a higher global cognitive function in both women (β = 1.061, p ConclusionHigher baseline level of GS was significantly related to better cognitive function and slowed the rate of its decline. Thus, it is an independent predictor of better cognitive status in middle-aged and elderly Chinese.</p

    Table_1_Living Preference Modifies the Associations of Living Arrangements With Loneliness Among Community-Dwelling Older Adults.docx

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    ObjectivesLiving arrangement has been reported to have a significant influence on feelings of loneliness in older adults, but their living preferences may confound the association. This study aimed to investigate whether the associations of living arrangements with loneliness differ in community-dwelling older adults according to different living preferences.MethodsIn the 2008/2009 (baseline) and 2011/2012 (follow-up) waves of the Chinese Longitudinal Healthy Longevity Survey, living arrangements [living with children mainly (LWC), living with spouse only (LWS), and living alone (LA)], living preferences [preferring living with children (PreLWC) and preferring living alone/only with spouse (PreLA)], and feelings of loneliness were assessed. The effect modifications of living preferences in the associations of living arrangements with loneliness were estimated using logistic regression models, and corresponding odds ratios (ORs) were calculated.ResultsLiving preferences significantly modified the associations of living arrangements with loneliness at baseline (p for interaction = 0.009 for LWS and = 0.015 for LA). Compared with LWC, LWS was protective for loneliness only in the PreLA older adults at baseline (OR = 0.53, 95% CI = 0.45–0.64, p ConclusionLiving preference modifies the associations of living arrangements with loneliness, and those who prefer living with children but live alone are more likely to feel lonely. It is recommended that living preferences should be considered when managing loneliness in community-dwelling older adults.</p

    Comparison of Different Neural Network Architectures for Plasmonic Inverse Design

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    The merge between nanophotonics and a deep neural network has shown unprecedented capability of efficient forward modeling and accurate inverse design if an appropriate network architecture and training method are selected. Commonly, an iterative neural network and a tandem neural network can both be used in the inverse design process, where the latter is well known for tackling the nonuniqueness problem at the expense of more complex architecture. However, we are curious to compare these two networks’ performance when they are both applicable. Here, we successfully trained both networks to inverse design the far-field spectrum of plasmonic nanoantenna, and the results provide some guidelines for choosing an appropriate, sufficiently accurate, and efficient neural network architecture

    <i>In Vitro</i>, <i>In Vivo</i>, and <i>In Silico</i> Activities of Ginkgolic Acid C15:1 against Streptococcus agalactiae Clinical Isolates

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    Streptococcus agalactiae is the major cause of invasive neonatal infections and is a recognized pathogen associated with various diseases in nonpregnant adults. The emergence and spread of antibiotic-resistant S. agalactiae necessitate the development of a novel antibacterial agent. Here, the potential antibacterial activities and mechanisms of ginkgolic acid C15:1 (GA (15:1)) from Ginkgo biloba against clinical S. agalactiae are characterized. The MIC50 and MIC90 values for GA (15:1) against 72 clinical S. agalactiae isolates were 6.25 and 12.5 μM, respectively. GA (15:1) showed a strong bactericidal effect against both planktonic bacteria and bacteria embedded in biofilms as well as significant effectiveness in suppressing the growth of S. agalactiae biofilms. Moreover, GA (15:1) possesses intracellular antibacterial activity and could significantly decrease the bacterial burden in the intraperitoneal infection model of S. agalactiae. Mechanistic studies showed that GA (15:1) triggers membrane damage of S. agalactiae through a unique dual-targeting mechanism of action (MoA). First, GA (15:1) targets phospholipids in the bacterial cytoplasmic membrane. Second, by using mass-spectrometry-based drug affinity responsive target stability (DARTS) and molecular docking, lipoprotein signaling peptidase II (lspA) was identified as a target protein of GA (15:1), whose role is crucial for maintaining bacterial membrane depolarization and permeabilization. Our findings suggest a potential therapeutic strategy for developing GA (15:1) to combat S. agalactiae infections

    Relative Quantification of N‑Glycopeptide Sialic Acid Linkage Isomers by Ion Mobility Mass Spectrometry

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    Sialic acids decorate the surface of glycoproteins and play important roles in a variety of pathological processes. Although the mass spectrometry (MS) based linkage-specific analysis of sialylated N-glycopeptide is developing rapidly, quantitative analysis of these isomers still remains a challenge. Herein, we reported a novel quantitative strategy that can unambiguously identify and relatively quantify linkage-specific N-glycopeptides using ion mobility mass spectrometry (IM-MS). Without the assistance of derivatization, this method can relatively quantify sialic acid isomers of intact glycopeptides by using their characteristic fragment ions in IM-MS. Moreover, good linearity (R2 > 0.99) of relative quantification within a dynamic range of 2 orders of magnitude and high reproducibility (coefficient of variation (CV) n = 3) were demonstrated. Finally, our results illustrated the aberrant sialylation of haptoglobin (Hp) in hepatocellular carcinoma (HCC), where the ratios of α2,3 to α2,6 sialylation of seven N-glycopeptides were found to be significantly altered (p < 0.01) in HCC individuals (n = 27) compared with healthy controls (n = 27)

    The moderating role of COMT and BDNF polymorphisms on transfer effects following multi- and single-domain cognitive training among community-dwelling Shanghainese older adults

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    Given the increase in research suggesting benefit following cognitive training in older adults, researchers have started to investigate the potential moderating role of genetic polymorphisms on transfer effects. The objective of this study was to evaluate the moderating effect of catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) polymorphisms on transfer effects following a single-domain or multi-domain training intervention in healthy community-dwelling older adults. A total of 104 men and women living in Shanghai were randomized to a multi-domain or a single-domain cognitive training (SDCT) group. COMT rs4818 SNP and the BDNF rs6265 SNP were analyzed from blood. At pre-intervention, post-intervention and at 6-month follow-up, participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Color-Word Stroop Test (CWST), the Trails Making Test (TMT) and the Visual Reasoning Test (VRT). COMT was found to moderate immediate memory transfer effects following single-domain training only, with G/- carriers displaying greater benefits than C/C carriers. BDNF was found to moderate attention and inhibition independent of the training, with Met/- carriers displaying better performance than Val/Val carriers. Overall, individualizing training methods with full consideration of genetic polymorphisms may promote the maximization of cognitive training benefits.  </p
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