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Background: Central pancreatectomy is a surgical procedure for benign and low-grade malignant tumors which located in the neck and proximal body of the pancreas that facilitates the preservation of pancreatic endocrine and exocrine functions but has a high morbidity rate, especially postoperative pancreatic fistula (POPF). The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness between minimally invasive central pancreatectomy (MICP) and open central pancreatectomy (OCP) basing on perioperative outcomes. Methods: An extensive literature search to compare MICP and OCP was conducted from October 2003 to October 2023 on PubMed, Medline, Embase, Web of Science, and the Cochrane Library. Fixed-effect models or random effects were selected based on heterogeneity, and pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: A total of 10 studies with a total of 510 patients were included. There was no significant difference in POPF between MICP and OCP (OR = 0.95; 95% CI [0.64, 1.43]; P = 0.82), whereas intraoperative blood loss (MD = − 125.13; 95% CI [− 194.77, -55.49]; P < 0.001) and length of hospital stay (MD = − 2.86; 95% CI [− 5.00, − 0.72]; P = 0.009) were in favor of MICP compared to OCP, and there was a strong trend toward a lower intraoperative transfusion rate in MICP than in OCP (MD = 0.34; 95% CI [0.11, 1.00]; P = 0.05). There was no significant difference in other outcomes between the two groups. Conclusion: MICP was as safe and effective as OCP and had less intraoperative blood loss and a shorter length of hospital stay. However, further studies are needed to confirm the results. [ABSTRACT FROM AUTHOR]

To investigate current status of quality of life and the association between depression and symptom burden in a sample of Chinese maintenance hemodialysis (MHD) patients. Methods: A self-designed patient general information questionnaire, disease-related information questionnaire, dialysis patient symptom burden scale, depression scale, and quality of survival scale were used to investigate 380 maintenance haemodialysis patients in haemodialysis centres. A regression model of the factors affecting the quality of survival was established using structural equation modelling. Results: The regression model data had a high goodness of fit: c2/df = 4.736, RMSEA = 0.099, GFI = 0.918, CFI = 0.972, TLI = 0.962, SRMR = 0.0469. Structural equation model analysis showed that depression had a positive predictive effect on symptom burden, β = 0.398, P < 0.001; Symptom burden had a negative predictive effect on the quality of life, β =− 0.851, P < 0.001; and Depression had a negative predictive effect on the quality of life, β =− 0.151, P < 0.001. Depression indirectly affects the quality of life through symptom burdens. Conclusion: Depression and symptom burden directly or indirectly affect the quality of life in patients with maintenance hemodialysis. Symptom burden moderates the relationship between depression and quality of life as a mediating variable. [ABSTRACT FROM AUTHOR]

Enzyme-linked electrochemical immunosensors have attracted considerable attention for the sensitive and selective detection of various targets in clinical diagnosis, food quality control, and environmental analysis. In order to improve the performances of conventional immunoassays, significant efforts have been made to couple enzyme-linked or nanozyme-based catalysis and redox cycling for signal amplification. The current review summarizes the recent advances in the development of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling for signal amplification. The special features of redox cycling reactions and their synergistic functions in signal amplification are discussed. Additionally, the current challenges and future directions of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling are addressed. [ABSTRACT FROM AUTHOR]

Purpose: Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA). Methods: This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg. Results: There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS <13.5% had a significant elevated risk with elevated office BP (OR,1.49[95%CI 1.05-2.10], P=0.025), compared to the highest quartile (percent SWS >39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group. Conclusion: In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP. This is the first study to investigate the association between decreased SWS and incident elevated office BP in non-hypertensive OSA patients. Our results found that in non-hypertensive OSA patients, decreased SWS is associated with elevated office BP. The relationship between decreased SWS and elevated office BP in OSA patients was evident especially in men and in those <60 years old. [ABSTRACT FROM AUTHOR]

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune‐responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP+-induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD. [ABSTRACT FROM AUTHOR]

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune‐responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP+-induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD. [ABSTRACT FROM AUTHOR]

Alcohol consumption is a leading risk factor and increases the risk of liver diseases, cancers, tuberculosis, and injuries. The relationship between alcohol use and cardiovascular risk is complex. While it is well established that heavy alcohol use and binge drinking harm cardiovascular health, the effect of light-to-moderate alcohol consumption remains controversial. Observational studies have repeatedly confirmed the U- or J-shaped relationship between alcohol consumption and cardiovascular disease risk, with the lowest risk observed in the light-to-moderate drinking group. However, the protective effect of low-level alcohol has been challenged by recent genetic epidemiological studies with Mendelian randomization. Such studies have their own limitations, and the application of this methodology in studying alcohol has been questioned. Results from the latest Global Burden of Diseases, Injuries, and Risk Factors Study suggest that the impact of alcohol consumption on health depends on the age structure and the distribution of disease burden and underlying causes in a given population. For young adults, even small amounts of alcohol cause heath loss. For older adults facing a high burden of cardiovascular diseases, light-to-moderate alcohol consumption may improve cardiovascular health outcomes. Mechanistically, all types of alcoholic beverages, including wine, spirits, and beer, have been shown to increase the levels of high-density lipoprotein cholesterol and adiponectin, and reduce the level of fibrinogen. Nonalcoholic components of wine, especially polyphenolic compounds like resveratrol, may additionally enhance endothelial nitric oxide production, and provide antioxidant and anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Background: Femoral neck fractures are serious consequence of osteoporosis (OP), numbers of people are working on the micro—mechanisms of femoral neck fractures. This study aims to investigate the role and weight of microscopic properties on femoral neck maximum load (Lmax), funding the indicator which effects Lmax most. Methods: A total of 115 patients were recruited from January 2018 to December 2020. Femoral neck samples were collected during the total hip replacement surgery. Femoral neck Lmax, micro—structure, micro—mechanical properties, micro—chemical composition were all measured and analyzed. Multiple linear regression analyses were performed to identify significant factors that affected the femoral neck Lmax. Results: The Lmax, cortical bone mineral density (cBMD), cortical bone thickness (Ct. Th), elastic modulus, hardness and collagen cross—linking ratio were all significantly decreased, whereas other parameters were significantly increased during the progression of OP (P < 0.05). In micro—mechanical properties, elastic modulus has the strongest correlation with Lmax (P < 0.05). The cBMD has the strongest association with Lmax in micro—structure (P < 0.05). In micro—chemical composition, crystal size has the strongest correlation with Lmax (P < 0.05). Multiple linear regression analysis showed that elastic modulus was most strongly related to Lmax (β = 0.920, P = 0.000). Conclusions: Compared with other parameters, elastic modulus has the greatest influence on Lmax. Evaluation of microscopic parameters on femoral neck cortical bone can clarify the effects of microscopic properties on Lmax, providing a theoretical basis for the femoral neck OP and fragility fractures. [ABSTRACT FROM AUTHOR]

The influence of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on plasma adiponectin remains not comprehensively evaluated. We performed a meta-analysis to systematically evaluate the effect of SGLT2 inhibitors on plasma level of adiponectin in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials comparing SGLT-2 inhibitors with non-active controls on plasma adiponectin in T2DM patients were retrieved by search of the Medline (PubMed), Embase, and CENTER (Cochrane Library) databases from inception to April 5, 2022. Study characteristics and outcome data were independently extracted by two authors. A random-effect model by incorporating the potential between-study heterogeneity was used to combine the results. Fourteen studies with 2142 patients contributed to the meta-analysis. Compared to placebo, SGLT-2 inhibitors significantly increased plasma adiponectin [standard mean difference (SMD): 0.35, 95% CI: 0.24 to 0.46, p<0.001] with mild heterogeneity (I2=19%). Predefined subgroup analyses suggested that tofogliflozin (SMD: 0.37, p<0.001), luseogliflozin (SMD: 0.51, p<0.001), and ipragliflozin (SMD: 0.34, p<0.001) were associated with increased adiponectin, but not for dapagliflozin (SMD: 0.14, p 0.26). In addition, SGLT-2 inhibitors were associated with increased adiponectin in studies from Asia (SMD: 0.42, p<0.001), but not in studies from the western countries (SMD: 0.16, p 0.17). Moreover, the increment of adiponectin was more significant in patients with body mass index (BMI)<30 kg/m2 (SMD: 0.46, p<0.001) than that in patients with BMI≤30 kg/m2 (SMD: 0.19, p 0.02, p for subgroup difference 0.01). In conclusion, SGLT-2 inhibitors could significantly increase plasma adiponectin as compared with placebo in T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Femoral neck fractures are the worst consequence of osteoporosis (OP), and its early prevention and treatment have become a public health problem. This study aims to investigate the relationship of bone-related biomarkers, femoral neck bone mineral density (BMD) and maximum load (Lmax), selecting the indicator which can reflect femoral neck bone loss and reduced bone strength.Methods: A total of 108 patients were recruited from January 2017 to December 2019. Venous blood samples were collected from patients before total hip replacement, and femoral neck samples were collected during the surgery. Femoral neck BMD, femoral neck Lmax, bone-related markers (serum levels of bone turnover markers, protein expression of type I collagen (COL-I) and osteopontin (OPN) in femoral neck) were all measured and analyzed.Results: The expression of COL-I in femoral neck were significantly decreased, whereas other markers were all significantly increased with the decreasing of femoral neck BMD and Lmax (P < 0.05). Among them, serum C-terminal telopeptide of type I collagen (CTX) levels and OPN expression of femoral neck were increased in osteopenia. In multiple linear regression analysis, CTX and OPN were both negatively correlated with femoral neck BMD and Lmax, and they were independent factors of femoral neck BMD and Lmax, whereas COL-I was independent factor affecting Lmax (P < 0.05). Besides, CTX was negatively correlated with COL-I (β = -0.275, P = 0.012) and positively correlated with OPN (β = 0.295, P = 0.003).Conclusions: Compared with other indicators, serum CTX was more sensitive to differences in bone mass and bone strength of femoral neck, and could be considered as surrogate marker for OPN and COL-I.Early measurement of CTX could facilitate the diagnosis of osteopenia and provide a theoretical basis for delaying the occurrence of femoral neck OP and fragility fractures. [ABSTRACT FROM AUTHOR]

Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings. • Isobavachin exhibits dose-dependent hepatocellular toxicity • Isobavachin induces autophagy in AML12 cells by regulating AMPK and PI3K/Akt/mTOR signaling pathways. • Autophagy can be used as one of the mechanisms to study the hepatocyte toxicity of isobavachin. [ABSTRACT FROM AUTHOR]

Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1 , LOC729197 , ATP8A2 , NDST4 , and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT 2 A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil. [Display omitted] • The antidepressant mechanism of action of Rosa damascena essential oil may involve the modulation of the serotonergic synapse signaling pathway, which regulates the expression relevant proteins in the ERK-CREB-BDNF pathway. • Joint transcriptomics and metabolomics analyses validated that Rosa damascena essential oil regulates the tryptophan metabolic pathway. • Rosa damascena essential oil ameliorates hippocampal neuronal damage induced by CUMS and modulates neurotransmitter levels. • The key active components in Rosa damascena essential oil responsible for its antidepressant effects may include citronellol, geraniol and (E,E)-farnesol. [ABSTRACT FROM AUTHOR]

Simultaneous detection of active and inactive proteases is clinically meaningful for improving diagnostic specificity. In this work, we reported an electrochemical method for simultaneous immunoassays of active and total proteases. Magnetic beads (MBs) were used as the solid supports for immobilization of capture antibodies and enrichment of targets. For the detection of active protease, the proteolytic-reaction-based analysis was carried out by the generation of Cu2+-binding peptide, in which a label-free peptide was used as the proteolytic substrate. The redox potential of the resulting peptide-Cu2+ complex was intrinsically distinguished from that of free Cu2+, thus allowing the "signal-on" detection of active protease. For the immunoassay of total protease in a sandwich-like format, electroactive metal-organic frameworks (Cu-MOFs) were used as the signal tags. The captured Cu-MOFs could directly produce a well-defined electrochemical signal from the reduction of Cu2+ ions. The analytical performances of the immunoplatform were evaluated by determining the model analytes of free and total prostate-specific antigen (fPSA and tPSA) in buffer and serum. The detection limits were found to be 0.3 pM for fPSA and 2 pM for tPSA. This work proposed a new strategy for simultaneous detection of active and total proteases, which should be evaluable for clinical diagnosis and treatment of protease-relative diseases. [Display omitted] • Electrochemical biosensors were designed for simultaneous detection of active and inactive proteases. • Proteolytic-reaction-based analysis was performed for the detection of active protease. • The activity analysis was based on the difference in the redox potential of peptide-Cu2+ complex and free Cu2+. • Total proteases were determined in a sandwich-like format with metal-organic framework as signal tag. [ABSTRACT FROM AUTHOR]

β-Ga 2 O 3 is an ultrawide bandgap (UWBG) semiconductor with excellent ensemble of attributes. To optimize the machining technologies and improve the mechanical performances, the plastic deformation mechanism of β-Ga 2 O 3 is necessary to thoroughly understand. In this work, nanoindentation experiments were conducted on (100) and (010) oriented β-Ga 2 O 3 to study the incipient plasticity with small indentation depths. It is indicated that the yield strength, elastic modulus and hardness for the (100) plane are higher than those of the (010) plane. Observations in the deformation morphology confirms that the deformed zone of the (100) plane is constrained in a hemispherical volume below the indentation with a radius about ten times larger than the indentation depth. However, for the (010) plane, a "one dimensional" plastic zone is formed in front of the tip with near one hundred times deeper than the penetration depth of the indenter. The deformation behavior is dominated by stacking faults, twins and dislocations for the (100) plane, while only dislocations are responsible for the plastic deformation of the (010) plane. ● The yield strength, elastic modulus and hardness for (100) plane of β-Ga 2 O 3 single crystals are higher than that of (010) plane. ● The deformed zone of the (100) plane was constrained in a hemispherical volume below the indentation, however, a "one dimensional" plastic zone was created for the (010) plane. ● The (100) plane is more brittle than (010) plane under the indentation test. [ABSTRACT FROM AUTHOR]

Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2. • High-fat diet triggers endothelial dysfunction in the ophthalmic artery. • ROS generation is increased in ophthalmic arteries from mice exposed to high-fat diet. • RAGE and NOX2 expression are elevated in ophthalmic arteries from mice subjected to high-fat diet. [ABSTRACT FROM AUTHOR]

In this study, we reported a facile and economical strategy for producing a functional protein-based composite film that was based on soybean protein isolate (SPI), eggshell membrane (ESM) and eugenol (Eu). The composite films were also characterized by mechanical, water vapor permeability (WVP), UV barrier, water resistance, hydrophobicity, antioxidant and antimicrobial activity. The results suggested the appropriate content of ESM could significantly enhance the mechanical, barrier, water resistance and hydrophobicity performances of the film. The addition of Eu into the SPI/ESM film could improve not only these properties, but also antimicrobial and antioxidant properties. The intermolecular interaction between SPI, ESM and Eu was mainly hydrogen bond confirmed by the Fourier-transform infrared spectroscopy (FTIR). The scanning electron microscopy (SEM) and X-ray diffraction (XRD) indicated a good compatibility existed between SPI and ESM, and the Eu could be well emulsified and dispersed into the SPI/ESM film matrices network. Such edible films carried potentially developed in active packaging applications. [ABSTRACT FROM AUTHOR]

Polyphenols are secondary metabolites of plants that have been widely studied for their health benefits as antioxidants. In the last decade, several clinical trials and epidemiological studies have shown that long-term consumption of polyphenol-rich diet protects against chronic diseases such as cancers and cardiovascular diseases. Current cardiovascular studies have also suggested an important role of gut microbiota and circadian rhythm in the pathogenesis metabolic and cardiovascular diseases. It is known that polyphenols can modulate the composition of core gut microbiota and interact with circadian clocks. In this article, we summarize recent findings, review the molecular mechanisms and the potential of polyphenols as dietary supplements for regulating gut microbiota and circadian rhythms, and discuss future research directions. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc. [ABSTRACT FROM AUTHOR]

Biotinylated peptide-Cu2+ nanoparticles (Cu-P NPs) were synthesized via "one-pot" self-assembly. The peptide P conststs of a hydrophobic dipeptide (FF), a tripeptide (KGH), and a biotin moiety attached to the terminal amino group of the Lys residue. The Cu-P NPs contain abundant catalytically active Cu2+ ions which are liberated by acid-induced dissolution. The released Cu2+ ions catalyze the oxidization of 3,3′,5,5′-tetramethylbenzidine (TMB) by H2O2 because of their intrinsic peroxidase activity, and this results in the formation of a blue-green coloration. Based on the streptavidin–biotin interaction, the Cu-P NPs were employed to establish an enzyme-free colorimetric method for determination of prostate-specific antigen (PSA) as a model biomarker. Under optimal conditions, the linear response range is 0.001–1 ng mL−1, with a limit of detection as low as 1 pg mL−1. [ABSTRACT FROM AUTHOR]

• Protease can be used as the signal label of electrochemical biosensors. • Protease catalyzed the generation of a Cu(II)-binding peptide. • The peptide-Cu(II) complex exhibits an electrocatalytic ability for water oxidation. • The signal was amplified by enzyme label and redox cycling of peptide-Cu(II) and H 2 O. • The detection limit of this method for prostate-specific antigen is down to 10 pg/mL. This work reported that protease can be used as the signal label to amplify the signal of electrochemical immunosensors. Carbon nanotube (CNT) was used as the carrier of recognition antibody and signal label. The nanolabel was captured by sensor electrode via a sandwich-type immunoreaction. Protease on the surface of nanolabel can catalyze the hydrolysis of peptide substrate to liberate an amino terminal Cu(II)- and Ni(II)-binding (ATCUN) peptide. The released ATCUN peptide can bind with Cu(II) to generate an electrocatalyst which exhibits high electrocatalytic ability for water oxidation. Thus, the signal was amplified again by the redox cycling between ATCUN-Cu(II) and H 2 O. The immunosensor exhibits low background current because of the poor redox activity of peptide substrate and the high oxidation overpotential of H 2 O molecule. Based on the signal amplification of protease and redox cycling, the target concentration as low as 10 pg/mL can be readily measured with prostate-specific antigen (PSA) as the model analyte. The proposed immunosensor was applied to determine PSA in human serum samples with satisfactory results. [ABSTRACT FROM AUTHOR]

Chemical compounds in soybean (Glycine max (L.) Merr.) seed have great effects on the flavour and taste of soymilk. The 1-octen-3-ol content in soybean seed could produce sensory off-flavours (mushrooms, lavender, rose and hay flavour) during the processing of soymilk. The most effective way to reduce off-flavours of soymilk is the screening and utilisation of soybean cultivars with reduced 1-octen-3-ol content. However, genomic study of 1-octen-3-ol in soybean has not previously been reported. In the present work, a natural population of 90 diverse soybean accessions was used to dissect the genetic basis of 1-octen-3-ol content in soybean seed through genome-wide association analysis by using 26 822 single nucleotide polymorphisms (SNPs). Twenty-one novel quantitative trait nucleotides (QTNs) were thus identified to be associated with 1-octen-3-ol content in soybean seed. Among them, 13 QTNs overlapped with, or were located in, the linked regions of known QTNs for protein, oil and/or fatty acid content in soybean seed. The functional genes located in the 200-kb genomic region of each peak SNP were considered possible candidates related to 1-octen-3-ol, such as genes involved in amino acid metabolism, protein content, and hormone metabolism. The identified loci with beneficial alleles and the candidate genes may be valuable for improving the off-flavours of soymilk. Twenty-one novel QTNs were identified to be associated with 1-octen-3-ol content in soybean seed through 90 diverse soybean accessions and 26822 SNPs. Among them, 13 QTNs overlapped with, or were located in, the linked regions of known QTNs for soybean seed compositions. The candidate genes located in the 200-kb genomic region of each peak SNP were also identified. These QTNs and their candidate information were valuable for future marker-assisted breeding. [ABSTRACT FROM AUTHOR]

Thermal expansion tensor represents a key parameter for the numerical modeling of the crystal growth process. However, the modeling of β-Ga2O3 commonly utilizes one single thermal expansion constant that misses its anisotropic nature and temperature-dependent characteristics. Herein, we addressed this limitation by calibrating an anisotropic, temperature-dependent thermal expansion tensor using the experimental lattice parameters of β-Ga2O3 up to 1200 K. We found that COMSOL Multiphysics simulations employing the calibrated tensor yield stress distribution remarkably distinct from those relying on the commonly assumed constants. Specifically, our simulations predict a von Mises stress concentration near the crystal bottom, which explains the experimentally observed crack formation at corresponding locations. This contrasts with the simulations using the single-value thermal expansion constant, which fails to predict such stress concentration. The physical origin of crystal cracking is found to be rooted in the compressive force exerted by the iridium crucible during the cooling process. Our findings suggest that the physical anisotropy of β-Ga2O3 should be carefully considered in modeling and simulation. With the calibrated thermal expansion tensor, we provide a validated set of thermomechanical parameters for reliable β-Ga2O3 crystal growth simulations. [ABSTRACT FROM AUTHOR]

Significance: Social and demographic changes have led to an increased prevalence of loneliness and social isolation in modern society. Recent Advances: Population-based studies have demonstrated that both objective social isolation and the perception of social isolation (loneliness) are correlated with a higher risk of mortality and that both are clearly risk factors for cardiovascular disease (CVD). Lonely individuals have increased peripheral vascular resistance and elevated blood pressure. Socially isolated animals develop more atherosclerosis than those housed in groups. Critical Issues: Molecular mechanisms responsible for the increased cardiovascular risk are poorly understood. In recent reports, loneliness and social stress were associated with activation of the hypothalamic-pituitary-adrenocortical axis and the sympathetic nervous system. Repeated and chronic social stress leads to glucocorticoid resistance, enhanced myelopoiesis, upregulated proinflammatory gene expression, and oxidative stress. However, the causal role of these mechanisms in the development of loneliness-associated CVD remains unclear. Future Directions: Elucidation of the molecular mechanisms of how CVD is induced by loneliness and social isolation requires additional studies. Understanding of the pathomechanisms is essential for the development of therapeutic strategies to prevent the detrimental effects of social stress on health. Antioxid. Redox Signal. 28, 837-851. [ABSTRACT FROM AUTHOR]

The authors report on an amperometric method for the determination of glycoprotein by using an aptamer as the bioreceptor. The detection scheme is making use of aggregated citrate-capped silver nanoparticles (AgNPs) on a gold electrode. Aggregation is accomplished by addition of 4-mercaptophenylboronic acid (MPBA) which acts as a cross-linker due to the formation of Ag-S bonds and of boronate esters. A thiolated DNA aptamer was then attached to the electrode in order to capture glycoprotein. Once captured, the glycoprotein reacts with MPBA through the formation of boronate esters. The electrochemical signal is thus amplified by the formation of a network of AgNPs which act as redox reporters. To demonstrate the feasibility of the method, prostate specific antigen (PSA) was chosen as a model analyte. The detection limit for PSA is as low as 0.2 pg mL. In our preception, this method provides a powerful tool for studying the glycan function in biological and physiological processes. [ABSTRACT FROM AUTHOR]

Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, NO and leptin. This anticontractile effect of PVAT is lost under conditions of obesity. The central mechanism underlying this PVAT dysfunction in obesity is likely to be an 'obesity triad' (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to the impairment of PVAT-derived vasoregulators. The production of hydrogen sulfide, NO and adiponectin by PVAT is reduced in obesity, whereas the vasodilator response to leptin is impaired (vascular leptin resistance). Strikingly, the vasodilator response to acetylcholine is reduced only in PVAT-containing, but not in PVAT-free thoracic aorta isolated from diet-induced obese mice, indicating a unique role for PVAT in obesity-induced vascular dysfunction. Furthermore, PVAT dysfunction has also been observed in small arteries isolated from the gluteal/visceral fat biopsy samples of obese individuals. Therefore, PVAT may represent a new therapeutic target for vascular complications in obesity. A number of approaches are currently being tested under experimental conditions. Potential therapeutic strategies improving PVAT function include body weight reduction, enhancing PVAT hydrogen sulfide release (e.g. rosiglitazone, atorvastatin and cannabinoid CB1 receptor agonists) and NO production (e.g. arginase inhibitors), inhibition of the renin-angiotensin-aldosterone system, inhibition of inflammation with melatonin or cytokine antagonists, activators of AMP-activated kinase (e.g. metformin, resveratrol and diosgenin) and adiponectin releasers or expression enhancers.Linked Articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. [ABSTRACT FROM AUTHOR]

Background and Purpose: We have recently shown that a reduced function of endothelial nitric oxide synthase (eNOS) in the perivascular adipose tissue (PVAT) contributes crucially to obesity-induced vascular dysfunction in mice. The current study was conducted to test the hypothesis that vascular dysfunction in obesity can be reversed by in vivo improvement of PVAT eNOS activity.Experimental Approach: Male C57BL/6J mice were fed a high-fat diet (HFD) for 22 weeks to induce obesity. During the last 4 weeks of HFD feeding, the obese mice were treated p.o. with the standardized Crataegus extract WS® 1442, which has been shown previously to improve eNOS activity.Key Results: Diet-induced obesity in mice markedly reduced the vasodilator response of thoracic aorta to acetylcholine in wire myograph experiments. Strikingly, this vascular dysfunction was only evident in PVAT-containing aorta but not in PVAT-free aorta. In vivo treatment of obese mice with WS® 1442 had no effect on body weight or epididymal fat mass, but completely restored the vascular function of PVAT-containing aorta. Feeding a HFD led to a reduced phosphorylation and an enhanced acetylation of PVAT eNOS, both effects were reversed by WS® 1442 treatment.Conclusion and Implications: PVAT plays a key role in vascular dysfunction in diet-induced obese mice. Not obesity itself, but a PVAT dysfunction is responsible for obesity-induced vascular disorders. Improving PVAT function by pharmacological means (e.g. with WS® 1442) can ameliorate vascular function even without reducing body weight or fat mass.Linked Articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. [ABSTRACT FROM AUTHOR]

Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). Experiments using gene-disrupted mice have demonstrated that eNOS has antihypertensive, antithrombotic, and antiatherosclerotic effects. Recent studies show that eNOS is expressed not only in the endothelium but also in the perivascular adipose tissue (PVAT). Resveratrol prevents eNOS uncoupling and upregulates eNOS expression and activity. These effects of resveratrol are well established for the eNOS enzyme in the endothelium. Interestingly, resveratrol also improves PVAT function. However, a causal role for eNOS in the effects of resveratrol on PVAT function has not yet been verified and needs to be studied in the future. [ABSTRACT FROM AUTHOR]

The antioxidant effects of resveratrol (3,5,4'-trihydroxy-trans-stilbene) contribute substantially to the health benefits of this compound. Resveratrol has been shown to be a scavenger of a number of free radicals. However, the direct scavenging activities of resveratrol are relatively poor. The antioxidant properties of resveratrol in vivo are more likely to be attributable to its effect as a gene regulator. Resveratrol inhibits NADPH oxidase-mediated production of ROS by down-regulating the expression and activity of the oxidase. This polyphenolic compound reduces mitochondrial superoxide generation by stimulating mitochondria biogenesis. Resveratrol prevents superoxide production from uncoupled endothelial nitric oxide synthase by up-regulating the tetrahydrobiopterin-synthesizing enzyme GTP cyclohydrolase I. In addition, resveratrol increases the expression of various antioxidant enzymes. Some of the gene-regulating effects of resveratrol are mediated by the histone/protein deacetylase sirtuin 1 or by the nuclear factor-E2-related factor-2. In this review article, we have also summarized the cardiovascular effects of resveratrol observed in clinical trials.Linked Articles: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. [ABSTRACT FROM AUTHOR]

Soluble alpha-synuclein (α-syn) oligomer is believed to be a reliable molecular biomarker for diagnosis of Parkinson's disease (PD). Thus, it is critical to develop a simple method for the selective detection of α-syn oligomer with low cost as well as high sensitivity. In this paper, we reported the label-free detection of α-syn oligomer using a DNA aptamer as the bioreceptor with the techniques of gold nanoparticles (AuNPs)-based colorimetric assay, surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS). In the colorimetric assay, the aptamer adsorbed onto the surface of AuNPs to prevent the salt-induced aggregation of the nanoparticles. However, the specific binding of α-syn oligomer to aptamer prevented the absorption of aptamer onto the surface of AuNPs. As a result, the aggregation of AuNPs was triggered by high concentration of salt with a color change from red to blue. In the SPR- or EIS-based surface analysis, specific binding of α-syn oligomer to the aptamer immobilized onto the gold film or electrode surface led to an increase in the SPR dip shift or the electron-transfer resistance. The detection limits of the colorimetry, SPR and EIS were found to be 10 nM, 8 pM and 1 pM, respectively. The amenability of this method to α-syn oligomer analysis in a biological matrix was demonstrated by assay of α-syn oligomer in serum. [ABSTRACT FROM AUTHOR]

Soybean seed oil was valued in foods, animal feed and some industrial applications. Molecular marker-assisted selection (MAS) for high-oil-content cultivars was an important method for soybean breeders. The objective of this study was to identify quantitative trait loci (QTL) and epistatic QTL underlying the seed oil content of soybeans across two backcross (BC) populations (with one common male parent 'Dongnong47') and two different environments. Two molecular genetic maps were constructed. They encompassed 1046.8 cM [with an average distance of 6.75 cM in the 'Dongnong47' × 'Jiyu89' (DJ) population] and 846.10 cM [with an average distance of 5.76 cM in the 'Dongnong47' × 'Zaoshu18' (DZ) population]. Nine and seven QTL were identified to be associated with oil content in the DJ and DZ populations, respectively. The phenotypic variation explained by most of the QTL was usually less than 10%. Among the identified QTL, those stable ones across multiple environments and populations often had stronger additive effects. In addition, three stable QTL in the DZ populations were identified in the similar genomic region of the three QTL in the DJ population [qDJE and qDZE-1 were located near Satt151 of Chromosome 15 (Chr15), qDJA1 and qDZA1 were located near Satt200 of Chr15 (LG A1), and qDJD2-1 and qDZD2-1 were located near Sat365 of Chr17]. In conclusion, MAS will be able more effectively to combine beneficial alleles of the different donors to design new genotypes with higher soybean seed oil content using the BC populations. [ABSTRACT FROM AUTHOR]

We presented an antibody-free electrochemical technique for the determination of human chorionic gonadotropin (hCG) using silver nanoparticles (AgNPs) as the redox reporters and a hCG-specific binding peptide as the receptor. Peptide-induced AgNPs assembly was achieved on the electrode surface that was modified with the same sequence of peptide (recognition element) used in the AgNPs aggregation. As a result, a well-defined linear-sweep voltammetry (LSV) peak was observed. The attachment of hCG on the electrode surface made the peptide probe lose its ability to trigger the in situ formation of the AgNPs-based network architecture on the electrode surface, thus leading to a much attenuated LSV current. The current decreased with the increase of hCG concentration ranging from 1 mIU/mL to 0.2 IU/mL. Consequently, a detection limit of 0.4 mIU/mL was achieved. To demonstrate the amenability of our method, the contents of hCG in human serum/urine samples were determined. The results were consistent with those obtained by the enzyme linked immunosorbent assay (ELISA). Based on the well-defined and amplified electrochemical signal of the AgNPs-based network architecture, our work would also be valuable for the design of novel electrochemical sensors by marrying specific receptors. [ABSTRACT FROM AUTHOR]

We reported a general way to design electrochemical biosensors with peptide probes as the receptors of targets and the inducers of gold nanoparticles (AuNPs) assembly on electrode surface. To demonstrate the feasibility of our strategy, human chorionic gonadotropin (hCG) was first determined as a model analyte. Specifically, the hCG-binding peptide triggered the aggregation of AuNPs in solution; by modifying the electrode with the hCG-binding peptide, the peptide-induced AuNPs assembly was achieved on the electrode surface, resulting in the formation of a network of AuNPs and a significant fall of charge transfer resistance. The attachment of hCG onto the electrode surface through the probe-target interaction made the peptide lose its ability to trigger the formation of the AuNPs-based network architecture on electrode surface, thus leading to an increased charge transfer resistance. The electrochemical impedance technique allowed for the determination of hCG with a detection limit 0.6 mIU/mL. Furthermore, the method was used to the selective detection of amyloid-β oligomer (AβO, a reliable molecular biomarker and crucial target for the diagnosis and therapeutic intervention of Alzheimer's disease). Our result indicated that the AuNPs-based colorimetric assay can be developed into a corresponding electrochemical assay with significantly improving sensitivity and selectivity. Taking advantage of the simple principle and the unique physical and chemical properties of AuNPs, our work would be valuable for the design of novel electrochemical biosensors by marrying specific receptors. [ABSTRACT FROM AUTHOR]

This work presented a general way for in situ formation of citrate-capped silver nanoparticle (AgNP) aggregates as labels on an electrode surface. When the electrode surface was functionalised with a member of the o -diphenol family, 4-mercaptophenylboronic acid (MPBA) was anchored onto the electrode surface via a boronate ester covalent bond. The anchored MPBA captured AgNPs through Ag S interaction. The resulting surface-tethered AgNPs could recruit more MPBA molecules and AgNPs through the formation of an Ag S bond and the covalent interaction between the α-hydroxycarboxylate of the citrate and the boronate of the MPBA. This led to in situ formation of a network of AgNPs. The complexes formed between MBPA and citrate acid, as well as dopamine (a member of the o -diphenol family), were characterized by mass spectrometry. The MBPA-induced aggregation of citrate-capped AgNPs in solution was confirmed by UV–Vis spectrophotometry and transmission electron microscopy. The network of AgNPs formed on the diphenol-covered electrode surface was characterized by scanning electron microscopy. The electrochemical signal was measured based on the solid-state Ag/AgCl reaction of the AgNPs. To demonstrate the applications and analytical merits of our design, tyrosinase and protease (thrombin) were measured as model analytes. The proposed strategy is likely to lead to the development of sensors for the detection of other biomolecules. [ABSTRACT FROM AUTHOR]

A novel casting method was developed to grow β-Ga 2 O 3 bulk single crystals without using a seed crystal. After separation from the crucible and processing, 2-inch diameter single crystal β-Ga 2 O 3 ingots with (100) plane could be obtained and no large imperfection were observed. The 10 × 10 mm2 β-Ga 2 O 3 single crystals samples with different crystal orientation have good crystal quality with full width at half maximum less than 50″, surface roughness less than 0.5 nm and defect density at the magnitude of 104 cm−2. On the basis of the experimental phenomena, a numerical simulation model was proposed to explain the crystal growth process in the casting method. • β-Ga 2 O 3 bulk single crystals were grown by the innovative casting method. • Seed crystal was not used to grow β-Ga 2 O 3 crystal. • The defect density of the samples is similar to that of the EFG-grown crystal. • Numerical model was proposed to explain crystal growth process. [ABSTRACT FROM AUTHOR]

A novel casting method was developed to grow β-Ga 2 O 3 bulk single crystals without using a seed crystal. After separation from the crucible and processing, 2-inch diameter single crystal β-Ga 2 O 3 ingots with (100) plane could be obtained and no large imperfection were observed. The 10 × 10 mm2 β-Ga 2 O 3 single crystals samples with different crystal orientation have good crystal quality with full width at half maximum less than 50″, surface roughness less than 0.5 nm and defect density at the magnitude of 104 cm−2. On the basis of the experimental phenomena, a numerical simulation model was proposed to explain the crystal growth process in the casting method. • β-Ga 2 O 3 bulk single crystals were grown by the innovative casting method. • Seed crystal was not used to grow β-Ga 2 O 3 crystal. • The defect density of the samples is similar to that of the EFG-grown crystal. • Numerical model was proposed to explain crystal growth process. [ABSTRACT FROM AUTHOR]

Beta-amyloid (Aβ) peptides are the major constituents of senile plaques in the brains of Alzheimer’s disease (AD) patients. Aβ monomers (AβMs) can coalesce to form small, soluble oligomers (AβOs), followed by reorganization and assembly into long, thread-like fibrils (AβFs). Recently, soluble AβOs have been regarded as reliable molecular biomarkers for the diagnosis of AD because of their high toxicity for neuronal synapse and high concentration levels in the brains of AD patients. In this work, we reported a label-free, sensitive and selective method for visual and fluorescent detection of AβOs based on the inner filter effect (IFE) of gold nanoparticles (AuNPs) on the fluorescence of CdTe quantum dots (QDs). Specifically, the fluorescence of CdTe QDs was quenched significantly by AuNPs through the IFE. PrP(95–110), an AβOs-specific binding peptide from cellular prion protein, triggered the aggregation and color change of AuNPs suspension; thus, the IFE of AuNPs on the fluorescence of CdTe QDs was weakened and the fluorescence intensity was recovered. However, in the presence of AβOs, the specific interaction of AβOs and PrP(95–110) prevented the absorption of PrP(95–110) onto the surface of AuNPs. As a result, the aggregation of AuNPs was inhibited and the fluorescence intensity of CdTe QDs was quenched again. This label-free method is specific for detection of AβOs but not for AβMs and AβFs. The detection limits were found to be 0.5 nM for the visual assay and 0.2 nM for the fluorescent detection. We believe that this work would be valuable for many investigations related to AD diagnosis and drug discovery. [ABSTRACT FROM AUTHOR]

The authors describe an aptasensor for visual and fluorescent detection of lysozyme via an inner filter effect (IFE). The assay is based on the fact that red gold nanoparticles (AuNPs) act as powerful absorbers of the green fluorescence of CdTe because of spectral overlap. If the lysozyme-binding aptamer is adsorbed onto the surface of the AuNPs, the salt-induced aggregation of AuNPs (that leads to a color change from red to blue) does not occur and the IFE remains efficient. If lysozyme is present, it will bind the aptamer and thereby prevent its adsorption on the AuNPs. As a result, the salt-triggered aggregation of the AuNPs will occur. Consequently, color will change from red to blue, and green fluorescence will pop up because the IFE is suppressed. Under optimum conditions, fluorescence is linearly related to lysozyme concentration in the 1.0 nM to 20 nM concentration range, with a 0.55 nM limit of detection. The method is perceived to be of wider applicability in that it may be used to design other visual and fluorescent assays if appropriate aptamers are available. [ABSTRACT FROM AUTHOR]

This work, curcumin/β-cyclodextrin inclusion complex (CUR/β-CD IC) nanoparticles were successfully synthesized via flexible and efficient nanoprecipitation using absolute ethanol as precipitant. At the 1:2 and 1:1 M ratios of CUR/β-CD nanoparticles, the encapsulation efficiency reached more than 70%, and particle size was ∼200 nm. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) results validated the construction of CUR/β-CD nanoparticles. FT-IR results indicated that CUR remained in β-CD cavity, and the IC molecules aggregated to form nanoparticles via intermolecular hydrogen bonding. XRD results displayed the formation of new solid crystal phases in CUR/β-CD IC nanoparticles. As-synthesized CUR/β-CD IC nanoparticles exhibited excellent physicochemical stability compared to free CUR. Encapsulation of CUR within nanoparticles also improved its bioavailability. Therefore, nanoprecipitation is a promising approach to synthesize CD-based nanoparticles for delivery of CUR or other phytochemicals with enhanced stability and bioavailability. • CUR/β-CD IC nanoparticles were synthesized via efficient nanoprecipitation. • Physicochemical properties of CUR/β-CD IC nanoparticles were characterized. • CUR/β-CD IC nanoparticles exhibited excellent physicochemical stability. • CUR/β-CD IC nanoparticles enhance the bioavailability of CUR. • Nano-sized CD delivery systems have great potential in the future food industry. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes. [ABSTRACT FROM AUTHOR]

Amino terminal Cu(II)- and Ni(II)-binding (ATCUN) motif is included in a protein or peptide with a structural characterization comprising of a free NH 2 -terminus, a histidine residue in the third position and two intervening peptide nitrogens. We reported a signal-on electrochemical strategy for detection of protease based on the formation of ATCUN-Cu(II) on electrode surface. In the method, an amino residue in the native peptide substrate was replaced with a histidine. Cleavage of the sequence-specific peptide pre-immobilized on an electrode by the protease led to the presence of ATCUN motif and the formation of ATCUN-Cu(II) in the presence of Cu(II). Consequently, a voltammetric signal was observed. Contrarily, inhibition of protease by its potential inhibitor decreased the voltammetric response. To demonstrate the feasibility and sensitivity of our strategy, β-secretase was tested as a model protease. As a result, a detection limit of 0.08 nmol L −1 was achieved. The half-maximum inhibition value (IC 50 ) of a well-known β-secretase inhibitor was found to be 22.6 nmol L −1 , which is in agreement with the reported value. [ABSTRACT FROM AUTHOR]

This paper presented an electrochemical aptasensor for dopamine detection with high sensitivity and selectivity. The electrochemical signal was amplified by electrochemical-chemical redox cycling with tris(2-carboxyethyl)phosphine (TCEP) as the reducing reagent. Specifically, dopamine captured by the aptamer-covered gold nanoparticles-modified carbon glass electrode was cycled by TCEP after its electrochemical oxidization, enabling an increase in the anodic current. Because of the high specificity and strong binding affinity of aptamer to dopamine, the sensor is fairly selective in not responding to common interferences. The results of chronoamperometry indicated that this aptasensor allowed for the detection of dopamine in a linear concentration range of 5 nM to 0.5 μM. The detection limit was estimated to be 1.8 nM. Additionally, the aptasensor was successfully applied to determine dopamine spiked in the serum sample and gave recoveries ranging from 94.6 to 107.2%. This work would also be valuable for development of new types of electrochemical sensors for determination of other electroactive substances by marrying specific receptors and effective reducing or oxidizing reagents. [ABSTRACT FROM AUTHOR]

The enzyme cleaving the beta-site amyloid precursor protein (BACE1) is a prime therapeutic target for treatment of Alzheimer's disease (AD). Hence, improved high-throughput methods for probing the activity of BACE1 are crucial with respect to the discovery of novel drugs for treatment and prevention of AD. We describe a graphene oxide (GO)-based fluorescent platform for the determination of BACE1 activity and screening of its inhibitors. It is found that covalent linkage of the fluorescein isothiocyanate (FITC)-labeled enzyme substrate (of sequence GTEEISEVNLDAEFRHDSGYKK) to GO results in quenching of the FITC fluorescence, but that on peptide cleavage by BACE1, FITC is released from the GO surface and fluorescence is restored. In contrast to other fluorescent assays, the method presented here shows much higher quenching efficiency and sensitivity, and it can be used at pH value of 4.5 where BACE1 exhibits higher activity. The inhibition of BACE1 activity by a potential inhibitor results in retarded fluorescence recovery. The half-maximum inhibition value of a well-known BACE1 inhibitor was found to be 82.7 nM, which is in agreement with the value reported earlier. In our perception, this method represents a valuable tool for screening of BACE1 inhibitors and discovery of AD drugs in a high-throughput screening format using microplate readers. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Glutamate excitotoxicity contributes to the development of Parkinson's disease (PD) and pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) has beneficial anti-akinetic effects in animal models of PD; however, the mechanism by which these antagonists alleviate PD symptoms is largely unknown. In our study, the effects of mGluR5 inhibition on DNA damage were investigated in a rotenone-induced model of PD. We first found that the selective mGluR5 antagonist, 2-methyl-6- (phenylethynyl) pyridine, prevented rotenone-induced DNA damage in MN9D dopaminergic neurons through a mechanism involving the downregulation of intracellular calcium release which was associated with a reduction in endoplasmic reticulum stress and reactive oxygen species (ROS)-related mitochondrial dysfunction. Interestingly, the ROS-related mitochondrial dysfunction was accompanied by an increase in expression of the antioxidant protein, Trx2. Treatment of cells with the calcium chelating agent 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or the ROS scavenger N-acetyl-L-cysteine, also reduced rotenone-induced DNA damage, while transfection of a dominant-negative form of Trx2 increased it. In addition, mGluR5 inhibition altered the expression profiles of proteins involved in DNA repair activity. Specifically, the expression of phosphorylated ERK (p-ERK) and CREB, as well as APE1 and Rad51 were elevated after rotenone stimulation and were subsequently downregulated following blockade of mGluR5. These findings were confirmed in vivo in a rotenone-induced rat model of PD. Inhibition of mGluR5 protected against neurotoxicity by mitigating oxidative stress-related DNA damage associated with 8-hydroxy-2′-deoxyguanosine production and also reduced p-ERK activity and Trx2 expression. These findings provide a novel link between mGluR5 and DNA damage in a model of PD, and reveal a potential mechanism by which mGluR5 mediates DNA damage in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Soluble amyloid-β oligomer (AβO) is believed to be a reliable molecular biomarker for the diagnosis of Alzheimer's disease (AD) because of its high toxicity for neuronal synapse and higher concentration level in cerebrospinal fluid sample from AD patient than from control individual. At present, it is critical to develop a simple method for AβO detection with low cost as well as high sensitivity and selectivity. In this work, we reported an antibody-free electrochemical method for the detection of AβO based on the specific interaction between AβO and PrP(95–110) peptide, a segment of cellular prion protein. Specifically, cysteine-containing PrP(95–110) peptide was first immobilized on a gold electrode for the capture of AβO. Then, alkaline phosphatase-conjugated PrP(95–110) was used for the recognition of the captured AβO and the generation of electroactive species. Furthermore, an “outer-sphere to inner-sphere” electrochemical–chemical–chemical (ECC) redox cycling using ferrocene methanol as the redox mediator was employed to enhance the detection sensitivity. As a result, a detection limit of 3 pM for equivalent monomer was achieved. The amenability of this method to AβO analysis in a biological matrix was demonstrated by assays of AβO in serum samples. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular safety of inhaled long-acting β2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD. Methods: A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated. Results: There were 24 trials included in this meta-analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96). Conclusion: Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients. [ABSTRACT FROM AUTHOR]

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is an aspartic protease that promotes the production of beta-amyloid (Aβ) peptides from beta-site amyloid precursor protein. Pharmacological reduction of Aβ production by inhibiting BACE1 has emerged as a promising target for the treatment of Alzheimer's disease (AD). In this work, we reported a simple electrochemical method for detection of BACE1 and screening of its inhibitor. This method made use of an unlabeled peptide that comprises a segment of beta-site amyloid precursor protein with the Swiss mutation. The peptide–heme complex formed on the electrode surface showed strong electrocatalytic O 2 reduction. Cleavage of the peptide by BACE1 detached the heme-binding fragment from the electrode surface, leading to a remarkable decrease in the electrochemical signal. Suppression of BACE1 by the inhibitor yielded a larger voltammetric signal. The IC 50 of the inhibitor tested by this method (15.7 nM) was in agreement with that reported. The proposed method could serve as a promising alternative to the traditional methods for probing of BACE1 activity and screening of BACE1 inhibitor owing to its simplicity, high sensitivity and low assay cost. [ABSTRACT FROM AUTHOR]

Graphene has sparked tremendous interests across many fields such as biosensors, electrochemical energy storage, and electronics due to its extraordinary physicochemical and structural properties. The redox mediator-functionalized graphene composites may obtain highly electroactive materials with better conductivity, dispersion, and compatibility. Ferrocene and hemin, two iron-organic complexes, are the well-known mediators in view of their various properties, including reversibility, regeneration at low potential, and generation of stable redox states. Recently, it has been demonstrated that the use of ferrocene or hemin coupled with graphene can further improve the electrochemical performances of the developed sensors. In this contribution, we, for the first time, reviewed the preparation and applications of ferrocene/graphene and hemin/graphene nanocomposites in electrochemical sensing. [ABSTRACT FROM AUTHOR]

MicroRNAs (MiRNAs) have been regarded as clinically important biomarkers and drug discovery targets. In this work, we reported a simple and ultrasensitive electrochemical method for miRNAs detection based on single enzyme amplification and electrochemical–chemical–chemical (ECC) redox cycling. Specifically, upon contact with the target miRNAs, the hairpin structure of biotinylated DNA immobilized on gold electrode was destroyed and the biotin group in DNA was forced away from the electrode surface, allowing for the coupling of streptavidin-conjugated alkaline phosphatase (SA-ALP). Then, ascorbic acid (AA, the enzymatic product of ALP) triggered the ECC redox cycling with ferrocene methanol (FcM) and tris(2-carboxyethyl)phosphine (TCEP) as the redox mediator and the chemical reducing reagent, respectively. The method was more sensitive than that with horseradish peroxidase (HRP) or glucose oxidase (GOx) triggered recycling since one ALP molecule captured by one target miRNA molecule promoted the production of thousands of AA. Analytical merits ( e.g. , detection limit, dynamic range, specificity, regeneration and reproducibility) were evaluated. The feasibility of the method for analysis of miRNA-21 in human serum has also been demonstrated. [ABSTRACT FROM AUTHOR]

We reported a new approach for the immobilization of acetylcholinesterase (AChE) on glass carbon electrode by employing ferrocene (Fc)-phenylalanine (denoted as Fc-F) hydrogels. To demonstrate the application of the modified electrode, chlorpyrifos, an AChE inhibitor, was determined. Specifically, with the addition of substrate acetylthiocholine, the enzymatic conversion from acetylthiocholine to thiocholine by AChE proceeded. The AChE/Fc-F modified electrode exhibited good electro-catalytic performance for the oxidation of the enzymatically produced thiocholine. In this process, the oxidized forms of Fc (Fc + ) in the hydrogels were reduced by thiocholine, resulting in an increase in the anodic current of Fc. Based on the inhibition of the AChE activity, chlorpyrifos was determined with a detection limit of 3 nM. Analytical merits (e.g. stability, dynamic range, reproducibility, detection level, selectivity and regeneration) were also evaluated. [ABSTRACT FROM AUTHOR]