Highly Electroactive Co2+-Based Metal-Organic Frameworks as an Efficient Coreaction Accelerator for Amplifying Near-Infrared Electrochemiluminescence of Gold Nanoclusters in Biomarkers Immunoassay.

Metal nanoclusters (NCs) as a new kind of luminophore have acquired sufficient interest, but their widespread application is restricted on account of their relatively low electrochemiluminescence (ECL) efficiency. Then, aqueous metal NCs with high ECL efficiency were strongly anticipated, especially for the ultrasensitive analysis of biomarkers. Herein, a near-infrared (NIR) ECL biosensing strategy for the test of neuron-specific enolase (NSE) was proposed by utilizing N-acetyl-l-cysteine (NAC)- and cysteamine (Cys)-stabilized gold NCs (NAC/Cys-AuNCs) as ECL emitters with the NIR ECL emission around 860 nm and a metal-organic framework/palladium nanocubes (ZIF-67/PdNCs) hybrid as the coreaction accelerator through their admirable electrocatalytic activity. The NIR emission would reduce photochemical injury to the samples and even realize nondestructive analysis with highly strong susceptibility and suitability. Furthermore, the utilization of ZIF-67/PdNCs could improve the ECL response of NAC/Cys-AuNCs by facilitating the oxidation of the coreactant triethylamine (TEA), leading to the production of a larger quantity of reducing intermediate radical TEA•+. Consequently, NAC/Cys-AuNCs with ZIF-67/PdNCs displayed 2.7 fold enhanced ECL emission compared with the single NAC/Cys-AuNCs using TEA as the coreactant. In addition, HWRGWVC (HWR), a heptapeptide, was introduced to immobilize antibodies for the specially binding Fc fragment of the antibodies, which improved the binding efficiency and sensitivity. As a result, a "signal-on" immunosensor for NSE analysis was obtained with an extensive linear range of 0.1 to 5 ng/mL and a low limit of detection (0.033 fg/mL) (S/N = 3). This study provides a wonderful method for the development of an efficient nondestructive immunoassay.

The regulatory roles of socio-economic status, social and intellectual activity in the relationship between alcohol consumption and cognitive decline trajectory in middle-aged and elderly Chinese: A prospective cohort study.

OBJECTIVES: To determine the relationship between alcohol consumption and cognitive decline, and to further explore the potential regulatory role of education, socio-economic status (SES), and social or intellectual activity in this relationship. METHODS: 6197 participants aged 45-75 years with four repeated measures data from 2011 to 2018 were included. A mixed-effect model was used to explore the relationship between alcohol consumption and the rate of change in cognitive decline, a latent class growth mixed model (LCGMM) was applied to determine the potential trajectory of cognitive decline, and finally, the mediating and moderating analyses were used to determine the regulatory effect of all four variables on the relationship between alcohol consumption and potential trajectory. RESULTS: Compared to never-drinkers, moderate alcohol consumption was a protective factor for overall cognitive function (ß = 0.13, 95% CI: 0.04-0.20, p < 0.001), but there was no statistical correlation with the decline rate of cognitive function. And this protective effect was no longer significant after additional adjustments for education, SES, social and intellectual activity. The LCGMM model divided participants into two trajectories, a high-level-to-decline group including 79.75% of participants (quadratic: ß [SE]: -0.90 [0.07], p < 0.001), and a low-level-to-decline group including 20.25% participants (linear: ß [SE]: -3.05 [0.49], p < 0.001). With the latter as the reference, SES played a reverse regulation role in the harmful effect of heavy drinking on cognitive trajectories (odd ratio [OR] = 0.46, 95% CI: 0.23-0.93, p < 0.05). Social and intellectual activities played a negative mediating role in the harmful effect of alcohol consumption on cognitive trajectories (light: OR = 0.96, p < 0.001; moderate: OR = 0.96, p < 0.001; heavy: OR = 0.97, p < 0.01). CONCLUSIONS: Alcohol itself has no protective effect on the decline of longitudinal cognitive trajectory. But the regulatory effect of SES, social and intellectual activities slows down the harm of alcohol consumption on the decline of cognitive function. CLINICAL TRIAL REGISTRATION: The data used in this study are from publicly available databases. They are retrospective cohort studies without any intervention. Therefore, no clinical trial registration has been conducted.

Comparing the efficacy of thyroglobulin and thyroglobulin/ thyroid-stimulating hormone ratio models in predicting a successful response to radioactive iodine therapy.

BACKGROUND: The thyroglobulin (Tg)/ thyroid-stimulating hormone (TSH) ratio has manifested to be a reliable marker for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to compare the efficacy of Tg and Tg/TSH ratio models in predicting a successful response to radioactive iodine therapy. METHODS: One thousand six hundred forty-two DTC patients receiving 131I radiotherapy were finally enrolled in this retrospective study. The patients were divided into a training set (n = 973) and a validation set (n = 669) by the patient consultation time (July 2019). A receiver-operating characteristic curve was constructed for Tg and the Tg/TSH ratio to establish their cutoffs. Then, the variables were screened by univariate logistic regression and incorporated into logistic prediction models by stepwise regression, where Tg/TSH was excluded from model 1 and Tg was excluded from model 2. RESULTS: In 1642 enrolled DTC patients, the first 131I radiotherapy had an excellent response in 855 patients. The cut-offs for Tg level and Tg/TSH ratio were 3.40 ng/ mL [area under the curve (AUC): 0.789] and 36.03 ng/mIU (AUC: 0.788), respectively. In addition, the AUC of the model including Tg was higher than that of the model including Tg/TSH in both the training set (0.837 vs 0.833) and the testing set (0.854 vs 0.836). CONCLUSIONS: Both Tg and Tg/TSH ratios could be considered predictors of the effects of the first 131I ablative therapy. However, the prediction model including Tg performed better than the model including Tg/TSH.

Cysteine Modification of Glutathione-Stabilized Au Nanoclusters to Red-Shift and Enhance the Electrochemiluminescence for Sensitive Bioanalysis.

Screening new electrochemiluminescence (ECL) emitters for the design of sensitive detection strategies with even long emission wavelength is intensively anticipated in ECL evolution. Herein, a promising modification strategy for improving the ECL performance of Au nanoclusters (AuNCs) as a water-soluble luminophore was proposed. Upon the introduction of l-cysteine (l-Cys) onto the surface of glutathione (GSH)-stabilized AuNCs (GSH-AuNCs), the dual-thiol bond between l-Cys and GSH was formed to limit the intramolecular motion and nonradiative relaxation of the excited state from the capping agents, which resulted in the enhancement of monochromatic ECL emission of GSH-AuNCs with a red-shifted wavelength. By utilizing triethylamine as a coreactant, the ECL of l-Cys/GSH-AuNCs was about 1.5-fold stronger than that of GSH-AuNCs, and the emission wavelength red-shifted from 660 to 780 nm at a relatively low potential, which could decrease the interference in bioassay and the photochemical damage in nondestructive detection. As a proof of application, a sandwich-type immunosensing method for CYFRA 21-1 was proposed with l-Cys/GSH-AuNCs as the signal tag, which displayed a wide linear ranging from 0.2 fg/mL to 2 ng/mL and a limit of detection down to 0.067 fg/mL at 3S/N. This work provides a wonderful strategy for promoting the performance of ECL emitters.

Hollow Double-Shell CuCo2O4@Cu2O Heterostructures as a Highly Efficient Coreaction Accelerator for Amplifying NIR Electrochemiluminescence of Gold Nanoclusters in Immunoassay.

The evolution of electrochemiluminescence (ECL) emission amplified by coreaction accelerator in near-infrared (NIR) area has been overwhelmingly anticipated for ultrasensitive detection of disease biomarkers. Herein, the hollow double-shell CuCo2O4@Cu2O (HDS-CuCo2O4@Cu2O) heterostructures were conveniently prepared and utilized as an attractive coreaction accelerator to improve the NIR ECL performance of gold nanoclusters (AuNCs) for the first time. Benefiting from perfect-matched lattice spacing, unique Cu2O nanoparticles (NPs) were formed in situ on the layered-hollow CuCo2O4 nanospheres (NSs) to obtain HDS-CuCo2O4@Cu2O heterostructures. The formed heterojunctions supplied shorter charge transfer distance and better interfacial charge transfer efficiency as well as more effective separation performance. Consequently, HDS-CuCo2O4@Cu2O heterostructures as an admirable electroactive substrate could significantly promote the formation of sufficient coreactant intermediate radicals to react with AuNCs cationic radicals, realizing about 3-folds stronger NIR ECL response than that of individual AuNCs. In addition, the AuNCs templated by l-methionine (l-Met) exhibited NIR ECL emission around 830 nm, which could decrease the photochemical damage to even realize a nondestructive detection with improved susceptibility and circumambient adaptability. Subsequently, a well site-oriented fixation strategy utilizing HWRGWVC heptapeptide as the specific antibody immobilizer was introduced to further preserve the bioactivity of antibody on the HDS-CuCo2O4@Cu2O and AuNCs surface along with enhancing the incubation performance markedly. In view of the progressive sensing mechanism, a NIR immunosensor was obtained for the ultrasensitive analysis of CYFRA21-1, which achieved a broad linear ranging from 2 fg/mL to 50 ng/mL and a low limit of detection (LOD) of 0.67 fg/mL (S/N = 3).

Dumbbell Plate-Shaped AIEgen-Based Luminescent MOF with High Quantum Yield as Self-Enhanced ECL Tags: Mechanism Insights and Biosensing Application.

It is widely known that high-performance electrochemiluminescence (ECL) emitters play a crucial part in improving the detection sensitivity of the ECL strategy. Through the combination of aggregation-induced emission luminogens (AIEgens), 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene (H4 TCBPE) with Zr(IV) cations, a dumbbell plate-shaped metal-organic framework (MOF) with high luminous efficiency is synthesized as ECL tags. The resultant MOF exhibits stronger ECL activity than those of H4 TCBPE monomers and aggregates. Herein, this phenomenon is defined as the coordination-triggered electrochemiluminescence (CT-ECL) enhancement effect. Furthermore, the nearly matched ECL and photoluminescence (PL) spectra imply the bandgap emission mechanism. Remarkably, polyethyleneimine (PEI) as the coreactant is covalently connected with MOF to form the uniquely self-enhanced ECL complex of Zr-TCBPE-PEI, where the robust ECL signal is captured owing to the intramolecular-like coreaction acceleration. Based on the resonance energy transfer (RET) behavior, the AuPd@SiO2 composite is designed as the high-efficiency quencher. In this manner, an innovative and ultrasensitive ECL sensor is constructed for neuron-specific enolase (NSE) detection through sandwich-type immunoreaction, with the detection limit down to 52 fg ml-1 . The present study has gone some way toward designing MOF-based self-luminescent ECL materials, thus paving a new avenue to expand the late-model ECL emitters for immunoassay.

TRIM7 suppresses cell invasion and migration through inhibiting HIF-1α accumulation in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic malignancy characterized by deregulated hypoxia-inducible factor signaling, genetic and epigenetic alterations. Metastasis is the leading cause of mortality from ccRCC, and understanding the underlying mechanism of this event will provide better strategies for its management. Here, we identify tripartite motif containing 7 (TRIM7) as a tumor suppressor in ccRCC cells, which negatively regulates hypoxia-inducible factor 1α (HIF-1α) signaling through targeting the proto-oncogene Src. We observed the downregulated expression of TRIM7 in clinical ccRCC tissues and its correlation with the poor prognosis. In Caki-1 cells, depletion of TRIM7 increased cell migration and invasion under normoxic and hypoxic conditions. TRIM7 markedly reduced the abundance of Src protein via the ubiquitin-proteasome pathway. Further study showed that TRIM7 affected HIF-1α accumulation through targeting either the Src-triggered PI3K/AKT/mTOR signaling pathway or reactive oxygen species production. Overall, our findings highlight a novel mechanism for negative regulation of HIF-1 signaling pathway by TRIM7 and define a promising therapeutic strategy for ccRCC by modulating TRIM7.

Mothers caring experiences of children with congenital hand or foot abnormalities: A phenomenological study.

PURPOSE: To explore the mothers' caring experiences of children with congenital hand or foot abnormalities, and to inform the development of tailored intervention strategies to improve the mothers' well-being. DESIGN AND METHODS: A qualitative study design was used. A purposive sample of 23 women whose children had congenital abnormalities of the hand or foot were enrolled. Semi-structured, in-depth interviews were conducted from December 2019 to May 2020. The Colaizzi's phenomenological approach was used for data analysis. RESULTS: Data analysis revealed four main themes: (a) dynamic negative affect; (b) low health literacy; (c) mothers' need for support; and (d) the shift in social activity and family role. Eleven subthemes were involved in these themes. CONCLUSIONS: Women whose children have abnormal hands or feet have complicated care experiences and are under tremendous psychological pressure. Some mothers also encounter financial difficulties. PRACTICE IMPLICATIONS: This study assessed the psychological impact on mothers of children with congenital hand or foot abnormalities. Our findings illustrate the needs of mothers, and call attention to this specific group. The findings may help inform healthcare and social interventions to facilitate the recovery of the affected children and cater to the needs of these families. Healthcare providers should provide adequate instructions to the parents regarding the provision of home management care following discharge from the hospital.

Nurses' ethical challenges caring for people with COVID-19: A qualitative study.

BACKGROUND: Ethical challenges are common in clinical nursing practice, and an infectious environment could put nurses under ethical challenges more easily, which may cause nurses to submit to negative emotions and psychological pressure, damaging their mental health. PURPOSE: To examine the ethical challenges encountered by nurses caring for patients with the novel coronavirus pneumonia (COVID-19) and to provide nurses with suggestions and support regarding promotion of their mental health. RESEARCH DESIGN AND METHOD: A qualitative study was carried out using a qualitative content analysis. The participants were 18 nurses who agreed to attend an interview and describe their own experiences of providing care to COVID-19 patients in China. They were purposively sampled, and structured, in-depth interviews were performed. Data were iteratively collected and analyzed from February to March 2020. ETHICAL CONSIDERATIONS: The proposal was approved by the Research Ethics Committee of the Second Hospital of Shandong University, China. FINDINGS: The findings revealed three main themes and 10 categories. The themes were the following: (1) ethical challenges (people with COVID-19, inequality, professional ethics, and job competency); (2) coping styles (active control and planning, seeking support as well as catharsis, and staying focused); and (3) impacts on career (specialized nursing skills, scientific research ability, and management skills). CONCLUSION: Nurses faced ethical challenges on multiple fronts in caring for COVID-19 patients. The results may help nurses with more safety, ethics, and humanistic care in nursing practice.

Prognosis of pregnancy-associated breast cancer: a meta-analysis.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Definitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation. RESULTS: A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P < 0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR = 1.59, 95% CI 1.30-1.82), and the mortality was not significantly different at 70 months after the last delivery (HR = 1.14, 95% CI 0.99-1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum (70 months after the last delivery) to capture the increased risk. CONCLUSION: This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately 6 years postpartum.

The alternative strategy for designing covalent drugs through kinetic effects of pi-stacking on the self-assembled nanoparticles: a model study with antibiotics.

It is still a huge challenge to find a new strategy for rationally designing covalent drugs because most of them are discovered by serendipity. Considering that the effect of covalent drugs is closely associated with the kinetics of the reaction between drug molecule and its target protein, here we first demonstrate an example of the kinetic effect of pi-stacking of drug molecules on covalent antimicrobial drug design. When PEGylated 7-aminocephalosporanic acid (PEG-ACA) is used as a substrate drug, pi-stacking of  the ACA group via the self-assembly of PEG-ACA on the surface of gold nanoparticles (i.e. Au@ACA) exhibits antibacterial activity against E. coli fourfold higher than a PEG-ACA monomer does. The reason can be reasonably attributed to the kinetic rate enhancement for the covalent reaction between Au@ACA and penicillin binding proteins. We believe that the self-assembly of functional groups onto the surface of gold nanoparticles represents a new strategy for covalent drug design.

Characterization and complete genome sequence analysis of Staphylococcus aureus bacteriophage JS01.

Staphylococcus aureus is a primary pathogen that causes bovine mastitis resulting in serious economic losses and herd management problems in dairy cows. A novel bacteriophage, JS01, specifically infecting bovine S. aureus, was isolated from milk of mastitis-affected cattle. TEM observation showed that it belonged to the family Siphovirus. The JS01 strain demonstrated a broad host range. The prediction result of PHACTS suggested that the JS01 strain was temperate phage. The JS01 genome is 43,458 bp long, with a GC content of 33.32% and no tRNAs. Annotation and functional analysis of the predicted ORFs revealed six functional groups: structure and morphology, DNA replication and regulation, packaging, lysogeny, lysis, and pathogenicity. Comparative analysis between JS01, S. aureus MSSA476, and S. aureus prophage PVL was also performed. The characterization and genomic analysis of JS01 provide a better understanding of S. aureus-targeting bacteriophages and useful information for the development of phage-based biocontrol agents against S. aureus.

A novel quantitative body shape score for detecting association between obesity and hypertension in China.

BACKGROUND: Obesity is a major independent risk factor for chronic diseases such as hypertension and coronary diseases, it might not be only related to the amount of body fat but its distribution. The single body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) or waist to stature ratio (WSR) provides limited information on fat distribution, and the debate about which one is the best remained. On the other hand, the current classification of body shape is qualitative rather than quantitative, and only crudely measure fat distribution. Therefore, a synthetical index is highly desirable to quantify body shape. METHODS: Based on the China Health and Nutrition Survey (CHNS) data, using Lohmäller PLSPM algorithm, six Partial Least Squares Path Models (PLSPMs) between the different obesity measurements and hypertension as well as two synthetical body shape scores (BSS1 by BMI/WC/Hip circumference, BSS2 by BMI/WC/WHR/WSR) were created. Simulation and real data analysis were conducted to assess their performance. RESULTS: Statistical simulation showed the proposed model was stable and powerful. Totally 15,172 (6,939 male and 8,233 female) participants aged from 18 to 87 years old were included. It indicated that age, height, weight, WC, WHR, WSR, SBP, DBP, the prevalence of hypertension and obesity were significantly sex-different. BMI, WC, WHR, WSR, Hip, BSS1 and BSS2 between hypertension and normotensive group are significantly different (p < 0.05). PLSPM method illustrated the biggest path coefficients (95% confidence interval, CI) were 0.220(0.196, 0.244) for male and 0.205(0.182, 0.228) for female in model of BSS1. The area under receiver-operating characteristic curve (AUC(95% CI)) of BSS1(0.839(0.831,0.847)) was significantly larger than that of BSS2(0.834(0.825,0.842)) as well as the four single indices for female, and similar trend can be found for male. CONCLUSIONS: BSS1 was an excellent measurement for quantifying body shape and detecting the association between body shape and hypertension.

A routine biomarker-based risk prediction model for metabolic syndrome in urban Han Chinese population.

BACKGROUND: Many MetS related biomarkers had been discovered, which provided the possibility for building the MetS prediction model. In this paper we aimed to develop a novel routine biomarker-based risk prediction model for MetS in urban Han Chinese population. METHODS: Exploring Factor analysis (EFA) was firstly conducted in MetS positive 13,345 males and 3,212 females respectively for extracting synthetic latent predictors (SLPs) from 11 routine biomarkers. Then, depending on the cohort with 5 years follow-up in 1,565 subjects (male 1,020 and female 545), a Cox model for predicting 5 years MetS was built by using SLPs as predictor; Area under the ROC curves (AUC) with 10 fold cross validation was used to evaluate its power. Absolute risk (AR) and relative absolute risk (RAR) were calculated to develop a risk matrix for visualization of risk assessment. RESULTS: Six SLPs were extracted by EFA from 11 routine health check-up biomarkers. Each of them reflected the specific pathogenesis of MetS, with inflammatory factor (IF) contributed by WBC & LC & NGC, erythrocyte parameter factor (EPF) by Hb & HCT, blood pressure factor (BPF) by SBP & DBP, lipid metabolism factor (LMF) by TG & HDL-C, obesity condition factor (OCF) by BMI, and glucose metabolism factor (GMF) by FBG with the total contribution of 81.55% and 79.65% for males and females respectively. The proposed metabolic syndrome synthetic predictor (MSP) based predict model demonstrated good performance for predicting 5 years MetS with the AUC of 0.802 (95% CI 0.776-0.826) in males and 0.902 (95% CI 0.874-0.925) in females respectively, even after 10 fold cross validation, AUC was still enough high with 0.796 (95% CI 0.770-0.821) in males and 0.897 (95% CI 0.868-0.921) in females. More importantly, the MSP based risk matrix with a series of risk warning index provided a feasible and practical tool for visualization of risk assessment in the prediction of MetS. CONCLUSIONS: MetS could be explained by six SLPs in Chinese urban Han population. The proposed MSP based predict model demonstrated good performance for predicting 5 years MetS, and the MetS-based matrix provided a feasible and practical tool.

The protective effects of Trolox-loaded chitosan nanoparticles against hypoxia-mediated cell apoptosis.

Antioxidants have potentials to treat hypoxia-mediated oxidative stress related diseases. However, their therapeutic efficacy is restricted due to its poor cellular uptake efficiency and poor cell membrane permeability. To resolve these issues, we prepare the hydroxyethylated chitosan nanoparticles as drug carriers for the delivery of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (Trolox), which was considered as a model compound. The experiment on cellular uptake and subcellular localization of Trolox-loaded chitosan nanoparticles (Trolox-CSNPs) indicate that Trolox-CSNPs enter the cells via the caveolae-mediated endocytosis pathway and traffic with endosomes. Furthermore, compared with Trolox, Trolox-CSNPs exert a higher protective effect against the hypoxia-mediated oxidative stress. Molecular basis of apoptosis study reveals that Trolox-CSNPs can directly block the mitochondria dependent apoptotic pathway through up-regulation of Bcl-2 expression and inhibiting the activation of Bax, Caspase-3 expression. In conclusion, the hydroxyethylated chitosan is a promising drug nanocarrier to deliver antioxidants for the treatment of hypoxia-mediated disease. From the clinical editor: Antioxidants are potentially beneficial in oxidative stress-related diseases, although cellular uptake of most antioxidants is suboptimal. In this study, hydroxyethylated chitosan nanoparticles are demonstrated as promising drug carriers in a Trolox-model system.

Construction of an alternative NADPH regeneration pathway improves ethanol production in Saccharomyces cerevisiae with xylose metabolic pathway.

Full conversion of glucose and xylose from lignocellulosic hydrolysates is required for obtaining a high ethanol yield. However, glucose and xylose share flux in the pentose phosphate pathway (PPP) and glycolysis pathway (EMP), with glucose having a competitive advantage in the shared metabolic pathways. In this work, we knocked down ZWF1 to preclude glucose from entering the PPP. This reduced the [NADPH] level and disturbed growth on both glucose or xylose, confirming that the oxidative PPP, which begins with Zwf1p and ultimately leads to CO2 production, is the primary source of NADPH in both glucose and xylose. Upon glucose depletion, gluconeogenesis is necessary to generate glucose-6-phosphate, the substrate of Zwf1p. We re-established the NADPH regeneration pathway by replacing the endogenous NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene TDH3 with heterogenous NADP + -GAPDH genes GDH, gapB, and GDP1. Among the resulting strains, the strain BZP1 (zwf1Δ, tdh3::GDP1) exhibited a similar xylose consumption rate before glucose depletion, but a 1.6-fold increased xylose consumption rate following glucose depletion compared to the original strain BSGX001, and the ethanol yield for total consumed sugars of BZP1 was 13.5% higher than BSGX001. This suggested that using the EMP instead of PPP to generate NADPH reduces the wasteful metabolic cycle and excess CO2 release from oxidative PPP. Furthermore, we used a copper-repressing promoter to modulate the expression of ZWF1 and optimize the timing of turning off the ZWF1, therefore, to determine the competitive equilibrium between glucose-xylose co-metabolism. This strategy allowed fast growth in the early stage of fermentation and low waste in the following stages of fermentation.

Mechanism and cellular kinetic studies of the enhancement of antioxidant activity by using surface-functionalized gold nanoparticles.

The enhanced antioxidant activity of surface-functionalized gold nanoparticles (AuNPs) synthesized by self-assembly has attracted great attention, but little is known about the mechanism behind the enhanced activity. To address this challenge, the antioxidant activity of Au@PEG3SA (i.e., surface-functionalization of spherical AuNPs with the antioxidant salvianic acid A) was used as an example to illustrate the mechanism of the enhanced activity. Evaluation of the antioxidant activity was performed in a radical-scavenging reaction between Au@PEG3SA and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. As expected, the rate constant for the reaction of Au@PEG3SA with DPPH was about nine times greater than that for the salvianic acid A monomer. A comparative analysis of the spectral characteristics of Au@PEG3SA and the salvianic acid A monomer further imply that the enhancement of the antioxidative reaction kinetics may be ascribed to the variation in the transition state for the DPPH-radical scavenging reaction through π-π stacking interactions between and among adjacent groups on the surface of Au@PEG3SA. On the other hand, the kinetic enhancement of Au@PEG3SA on reactive-oxygen-species (ROS) scavenging can be observed in living cells and in vivo, which possibly provides new insight for the bioapplication of self-assembly of surface-functionalized AuNPs.

Sex-specific association of exposure to a mixture of phenols, parabens, and phthalates with thyroid hormone and antibody levels in US adolescents and adults.

Individuals are exposed to multiple phenols, parabens, and phthalates simultaneously since they are important endocrine-disrupting compounds (EDCs) and share common exposure pathways. It is necessary to assess the effects of the co-exposure of these EDCs on thyroid hormones (THs). In this study, data included 704 adolescents and 2911 adults from the 2007-2012 National Health and Nutrition Examination Survey (NHANES). Serum THs measured total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). And 16 EDCs (3 phenols, 2 parabens, and 11 phthalates) were measured from urine. The relationship between single EDCs and single THs was analyzed using generalized linear regression. And results showed that several EDCs were positively associated with serum T3 and FT3 levels in boys but negatively associated with serum T4 and FT4 levels in girls. And in adults, five EDCs were negatively associated with T3, T4, or FT4. The effects of co-exposure to 16 EDCs on THs were calculated using Bayesian kernel machine regression and quantile-based g-computational modeling, confirmed that co-exposure was related to the increase of T3 in adolescents and the decrease of T4 in both adolescents and adults. Besides, nonlinear and linear relationships were identified between co-exposure and the risk of positive TPOAb and TgAb in girls and adult females, respectively. In conclusion, phenols, parabens, and phthalates as a mixture might interfere the concentrations of THs and thyroid autoantibodies, and the interfering effect varies significantly by sex as well as by age. Further prospective research is warranted to investigate the causal effects and underlying mechanisms of co-exposure on thyroid dysfunction.

Europium-based metal-organic framework with acid-base buffer structure as electrochemiluminescence luminophore for hyperstatic trenbolone trace monitoring under wide pH range.

The wide and even whole pH range electrochemiluminescence (ECL) is attractive for steroid estrogens detection under harsh conditions (such as strong acid and alkali). Herein, we presented an efficient europium-based metal-organic framework (Eu-MOF) as ECL luminophore, which has been synthesized via the specific 2, 4-bis(3, 5-dicarboxyphenylamino)-6-oltriazine (H4BDPO) ligand with acid-base buffering effect. The functional groups with weak acid and base endowed the H4BDPO with eight ionogenic group states, thereout different total charges of H4BDPO were derived, thus high and steady ECL signals of Eu-MOF were acquired under different environments with pH = 1.0-14.0. Most notably, combined with the means of UV-vis, fluorescence spectra, cyclic voltammetry (CV) and density functional theory (DFT) calculations, the Eu-MOF has been explored different luminescence mechanisms with variational total charges. The constructed ECL biosensor based on the Eu-MOF realized sensitive detection of trenbolone under wide pH range (In order to maintain the biological activity of antigen and antibody, the studied pH value is 5-8.5), in which the limits of detection were 3.95 fg/mL (pH = 5.0), 2.36 fg/mL (pH = 7.4) and 5.48 fg/mL (pH = 8.5) respectively. This work provides a considerable method to realize efficient trace detection of steroid estrogens under the wide or even whole pH conditions.

Protecting effect of phosphorylation on oxidative damage of D1 protein by down-regulating the production of superoxide anion in photosystem II membranes under high light.

The physiological significance of photosystem II (PSII) core protein phosphorylation has been suggested to facilitate the migration of oxidative damaged D1 and D2 proteins, but meanwhile the phosphorylation seems to be associated with the suppression of reactive oxygen species (ROS) production, and it also relates to the degradation of PSII reaction center proteins. To more clearly elucidate the possible protecting effect of the phosphorylation on oxidative damage of D1 protein, the degradation of oxidized D1 protein and the production of superoxide anion in the non-phosphorylated and phosphorylated PSII membranes were comparatively detected using the Western blotting and electron spin resonance spin-trapping technique, respectively. Obviously, all of three ROS components, including superoxide anion, hydrogen peroxide and hydroxyl radical are responsible for the degradation of oxidized D1 protein, and the protection of the D1 protein degradation by phosphorylation is accompanied by the inhibition of superoxide anion production. Furthermore, the inhibiting effect of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a competitor to Q(B), on superoxide anion production and its protecting effect on D1 protein degradation are even more obvious than those of phosphorylation. Both DCMU effects are independent of whether PSII membranes are phosphorylated or not, which reasonably implies that the herbicide DCMU and D1 protein phosphorylation probably share the same target site in D1 protein of PSII. So, altogether it can be concluded that the phosphorylation of D1 protein reduces the oxidative damage of D1 protein by decreasing the production of superoxide anion in PSII membranes under high light.