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Theaflavins (TFs), as the major polyphenolic components of fermented tea, possess beneficial effects on human health. In this study, the effervescent tablets based on theaflavins were developed. The optimal formulation of TF effervescent tablets was obtained by response surface methodology with the Box-Behnken design. Then, the physiochemical properties were evaluated, including hardness, friability, effervescent time and pH of the solution. At last, the antioxidant ability of TF effervescent tablets was studied through DPPH and ABTS radical scavenging assay. According to the results, the optimal formulation of the tablets contained TF powder 9.09%, disintegrating agent 43.80% (the weight ratio of citric acid and sodium bicarbonate was 1:1), aspartame 1.86%, PEG-600 3%, and mannitol in balance. With the wet granulation method, the TF effervescent tablets displayed suitable hardness, fast disintegration time, good color, pleasant taste and high antioxidant activity. This study demonstrated that the TF effervescent tablets could be a valuable product for the supplement market and contribute to promoting practical application of TFs. [ABSTRACT FROM AUTHOR]

In this study, a novel Euc functionalized zinc metal--organic framework (Eu@Zn-MOF) probe has been prepared by the post-synthetic modification method. Eu@Zn-MOF exhibited a strong blue fluorescence emission band of the Zn-MOF and a weak characteristic emission of Eu3+ under 390 nm excitation, which were innovatively used to construct a ratiometric fluorescent probe for tetracycline detection. Upon addition of tetracycline, the fluorescence of the Zn-MOF was quenched because of the inner filter effect between tetracycline and Eu@Zn-MOF, while the fluorescence of Eu3+ was enhanced owing to the ''antenna'' effect between tetracycline and Eu3+. Based on the ratio of fluorescence intensities, efficient detection of tetracycline was achieved. The results indicated that the ratiometric fluorescent probe has an excellent selectivity toward tetracycline over various interferents. It was found that there is a good linear relationship between the fluorescence intensity ratio (F618/F430) and the concentration of tetracycline ranging from 0.1 to 22.5 mM with a detection limit of 33 nM. Meanwhile, the color change of the solution from blue to light pink under an ultraviolet lamp can be observed by the naked eye. The assay was successfully used to detect tetracycline in tap water samples with a recovery of 97.1-100.6%. [ABSTRACT FROM AUTHOR]

Zr(IV) can form phosphate and Zr(IV) (-PO32--Zr4+-) complex owing to the high affinity between Zr(IV) with phosphate. Zr(IV) can induce the aggregation of gold nanoparticles (AuNPs), while adenosine triphosphate(ATP) can prevent Zr(IV)-induced aggregation of AuNPs. Herein, a visual and plasmon resonance absorption (PRA)sensor for ATP have been developed using AuNPs based on the high affinity between Zr(IV)with ATP. AuNPs get aggregated in the presence of certain concentrations of Zr(IV). After the addition of ATP, ATP reacts with Zr(IV) and prevents AuNPs from aggregation, enabling the detection of ATP. Because of the fast interaction of ATP with Zr(IV), ATP can be detected with a detection limit of 0.5 µM within 2 min by the naked eye. Moreover, ATP can be detected by the PRA technique with higher sensitivity. The A520nm/A650nm values in PRA spectra increase linearly with the concentrations of ATP from 0.1 µM to 15 µM (r = 0.9945) with a detection limit of 28 nM. The proposed visual and PRA sensor exhibit good selectivity against adenosine, adenosine monophosphate, guanosine triphosphate, cytidine triphosphate and uridine triphosphate. The recoveries for the analysis of ATP in synthetic samples range from 95.3% to 102.0%. Therefore, the proposed novel sensor for ATP is promising for real-time or on-site detection of ATP. [ABSTRACT FROM AUTHOR]

Chromatin remodelling is critical for repairing DNA damage and maintaining genomic integrity. Previous studies have reported that histone acetyltransferase p300 and ATP-dependent chromatin remodeler chromodomain helicase DNA-binding protein 4 (CHD4) functions, respectively, in DNA double-strand breaks (DSBs) repair. But the physiological significance of their interaction remains elusive. Here, we showed that p300 and CHD4 were both recruited to the sites of DSBs. Their ablation led to impaired DSBs repair and sensitised cells to laser and the anti-cancer drug, etoposide. Using DR-GFP and EJ5-GFP reporter systems, we found that knockdown of p300 or CHD4 impaired the homologous recombination (HR) repair but no the non-homologous end joining (NHEJ) repair. Furthermore, p300 or CHD4 knockdown respectively suppressed the recruitment of replication protein A (RPA), a key protein for HR, to the DSB sites. In addition, immunofluorescence results showed that knockdown of p300 reduced the recruitment of CHD4 at DSB sites. In turn, CHD4 knockdown also decreased p300 assembly. Moreover, immunoprecipitation and purified protein pull down assay revealed that p300 physically interacted with CHD4 at DNA damage sites, and this interaction was dependent on the chromodomain and ATPase/helicase domain of CHD4 and the CH2, Bd and HAT domains of p300. These results indicate that p300 and CHD4 could function cooperatively at DSB sites and provide a new insight into the detailed crosstalk among the chromatin remodelling proteins. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the protein expression, in addition to the clinical value of the expression, of estrogen receptor α (ERα), progesterone receptor (PR) and epidermal growth factor receptor (EGFR) in papillary thyroid carcinoma (PTC). The expression of ERα, PR and EGFR was examined immunohistochemically on paraffin-embedded thyroid tissues obtained from 64 patients with PTC and 14 patients with nodular thyroid goiter (NTG). The expression level of ERα, PR and EGFR was found to be significantly elevated in the PTC tissues compared with the NTG tissues. In addition, the expression of ERα was found to be correlated with the size of PTC tumors. However, there was no significant difference between the expression levels of ERα, PR and EGFR in males and females with PTC. Thus, immunohistochemical evaluation of ERα, PR and EGFR expression in patients with PTC may aid in the prediction of the prognosis of patients with PTC. [ABSTRACT FROM AUTHOR]

DNA double-strand breaks (DSBs) are a type of lethal DNA damage. The repair of DSBs requires tight coordination between the factors modulating chromatin structure and the DNA repair machinery. BRG1, the ATPase subunitof the chromatin remodelling complex Switch/Sucrose non-fermentable (SWI/SNF), is often linked to tumorigenesis and genome instability, and its role in DSB repair remains largely unclear. In the present study, we show that BRG1 is recruited to DSB sites and enhances DSB repair. Using DR-GFP and EJ5-GFP reporter systems, we demonstrate that BRG1 facilitates homologous recombination repair rather than nonhomologous end-joining (NHEJ) repair. Moreover, the BRG1-RAD52 complex mediates the replacement of RPA with RAD51 on single-stranded DNA (ssDNA) to initiate DNA strand invasion. Loss of BRG1 results in a failure of RAD51 loading onto ssDNA, abnormal homologous recombination repair and enhanced DSB-induced lethality. Our present study provides a mechanistic insight into how BRG1, which is known to be involved in chromatin remodelling, plays a substantial role in the homologous recombination repair pathway in mammalian cells. [ABSTRACT FROM AUTHOR]

Wireless electrochemiluminescence system based on the wireless energy transmission technique has been demonstrated for the first time. It has a disposable transmitter and a coiled energy receptor. The coiled energy receptor is smartly used as the electrode. The wireless electrochemiluminescence system has been used to detect hydrogen peroxide with good sensitivity, featuring advantages of easy manipulation, low cost, and small size. The handy and cheap wireless electrochemiluminescence device can use laptops as a power supply. It is promising for the development of portable or disposable electrochemiluminescence devices for various applications (e.g., such as point of care testing, field analysis, scientific research, and chemical education). These advantages enable one to integrate many wireless electrochemiluminescence minidevices with screen printing coiled electrode arrays in microwell plates and charge-coupled devices (CCD) cameras to develop electrochemiluminescence high-throughput screening systems with broad applications in clinical analysis, drug screening, and biomolecular interaction studies. [ABSTRACT FROM AUTHOR]

Both the electrochemiluminescence (ECL) method for sensitive detection of ozone and the ECL resonance energy transfer (ECRET) using ozone have been reported for the first time. It is based on the ECRET of Ru(phen)32+-doped silica nanoparticles (RuSiNPs) to indigo carmine. In the absence of ozone, the ECL of RuSiNPs is quenched as a result of the ECRET of RuSiNPs to indigo carmine. In the presence of ozone, the ECL of the system is "turned on" because ozone can oxidize indigo carmine and interrupt the ECRET from RuSiNPs to indigo carmine. In this way, it provides a simple ECL sensing of ozone via the proposed RuSiNP-based ECRET strategy with a linear range from 0.05-3.0 μM and a limit of detection (LOD) of 30 nM. The detection takes less than 5 min. This method is also successfully applied in the analysis of ozone in human serum samples and atmospheric samples. [ABSTRACT FROM AUTHOR]

In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells. [ABSTRACT FROM AUTHOR]

Ozone unexpectedly dramatically suppresses the electrochemiluminescence (ECL) of Ru(phen)³2+/glyoxal at an ozone/glyoxal ratio of less than 0.5%. Moreover, a sensitive, simple and fast ECL method for ozone detection is developed, with a detection time within 1 min and a limit of detection of 20 nM. [ABSTRACT FROM AUTHOR]

Discs large membrane-associated guanylate kinase (MAGUK) scaffold protein 1 (DLG1) plays important roles in cell contact and migration, but its role in antiviral innate immunity is not clear. In this study, the role of DLG1 in the antiviral innate immune response and its impact on type-I interferon (IFN-I) signaling were investigated. DLG1 plays a critical role in promoting the IFN-I response by inhibiting the autophagic degradation of the innate immune adaptor IκB kinase epsilon (IKKε). As a result, DLG1 effectively suppresses negative-stranded RNA virus replication, including that of viruses such as vesicular stomatitis virus, Sendai virus, and bovine ephemeral fever virus. DLG1 was found to enhance the production of IFN-β and IFN-stimulated genes, leading to the attenuation of virus propagation. Mechanistically, DLG1 competitively binds to the E3 ubiquitin ligase March2, preventing the ubiquitination and subsequent degradation of IKKε. Notably, March2 specifically catalyzes K27-linked polyubiquitination of IKKε. The interaction between March2 and IKKε is mediated by the transmembrane domain of March2 and the C-terminal domain of IKKε. Furthermore, p62 acts as a cargo receptor, recognizing ubiquitinated IKKε for eventual autophagic degradation, whereas the process is blocked by DLG1. Additionally, the results demonstrated a significant decrease in DLG1 mRNA and protein levels upon negative-stranded RNA virus infection. Overall, these findings provide insights into the molecular mechanisms by which DLG1 promotes IFN-I production by regulating IKKε expression to inhibit viral replication. [ABSTRACT FROM AUTHOR]

Retromer is an evolutionarily conserved multiprotein complex that orchestrates the endocytic recycling of integral membrane proteins. Here, we demonstrate that retromer is also required to maintain lysosomal amino acid signaling through mTORC1 across species. Without retromer, amino acids no longer stimulate mTORC1 translocation to the lysosomal membrane, which leads to a loss of mTORC1 activity and increased induction of autophagy. Mechanistically, we show that its effect on mTORC1 activity is not linked to retromer’s role in the recycling of transmembrane proteins. Instead, retromer cooperates with the RAB7-GAP TBC1D5 to restrict late endosomal RAB7 into microdomains that are spatially separated from the amino acid–sensing domains. Upon loss of retromer, RAB7 expands into the ragulator-decorated amino acid–sensing domains and interferes with RAG-GTPase and mTORC1 recruitment. Depletion of retromer in Caenorhabditis elegans reduces mTORC1 signaling and extends the lifespan of the worms, confirming an evolutionarily conserved and unexpected role for retromer in the regulation of mTORC1 activity and longevity. [ABSTRACT FROM AUTHOR]

Correlative evidence links stress, accumulation of oxidative cellular damage, and aging in several species. Genetic studies in species ranging from yeast to mammals revealed several pathways regulating stress response and life span, including caloric intake, mitochondrial respiration, insulin/IGF-1 (IIS), and JNK (c-Jun N-terminal kinase) signaling. How IIS and JNK signaling cross-talk to defend against diverse stressors contributing to aging is of critical importance but, so far, only poorly understood. In this study, we demonstrate that the adaptor protein SHC-1, the Caenorhabditis elegans homolog of human p52Shc, coordinates mechanisms of stress response and aging. Using genetic and biochemical approaches, we discover that SHC-1 not only opposes IIS but also activates JNK signaling. Loss of shc-1 function results in accelerated aging and enhanced sensitivity to heat, oxidative stress, and heavy metals, whereas expression of human p52Shc rescues the shc-1 mutant phenotype. SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2. Moreover, SHC-1 activates JNK signaling by binding to MEK-1 kinase. Both aspects converge on controlling the nuclear translocation and activation of the FOXO transcription factor DAF-16. Our findings establish C. elegans SHC-1 as a critical scaffold that directly cross-connects the two parallel JNK and IIS pathways and help to explain how these signaling cascades cooperate to ascertain normal stress response and life span in C. elegans. [ABSTRACT FROM AUTHOR]

In China there are approximately 100 pig breeds, which show great diversity in their appearance. However, information on genome selection signatures, such as spine curvature, is scarce. Therefore, we used the fixation index (FST) and cross‐population extended haplotype homozygosity (XPEHH) methods to explore the genome selection signatures of spine curvature in six breeds of Chinese indigenous pig. We identified 396 and 389 single nucleotide polymorphisms using the FST and XPEHH methods, respectively. We detected 19 selection signatures and 28 genes located in the selected regions. Five candidate genes (MAP3K7, CUX1, GRIN2B, ALPL and MACF1) were identified in the selection signatures. Additionally, 719 high‐frequency runs of homozygosity regions, 17 unique runs of homozygosity regions, 78 genes and 27 pathways were identified in the runs of homozygosity analysis. The TGF‐beta signaling pathway and eight genes related to the spine formation, spine defects and intervertebral disk degeneration were identified, comprising ACVR1, FMOD, ITGA4, MAPK8, PDGF, RPL3, SULF1 and UBE2D1. In summary, we identified 13 candidate genes related to spine curvature in Chinese indigenous pigs. [ABSTRACT FROM AUTHOR]

Both a wireless electrochemiluminescence (ECL) electrode microarray chip and the dramatic increase in ECL by embedding a diode in an electromagnetic receiver coil have been first reported. The newly designed device consists of a chip and a transmitter. The chip has an electromagnetic receiver coil, a mini-diode, and a gold electrode array. The mini-diode can rectify alternating current into direct current and thus enhance ECL intensities by 18 thousand times, enabling a sensitive visual detection using common cameras or smart phones as low cost detectors. The detection limit of hydrogen peroxide using a digital camera is comparable to that using photomultiplier tube (PMT)-based detectors. Coupled with a PMT-based detector, the device can detect luminol with higher sensitivity with linear ranges from 10 nM to 1 mM. Because of the advantages including high sensitivity, high throughput, low cost, high portability, and simplicity, it is promising in point of care testing, drug screening, and high throughput analysis. [ABSTRACT FROM AUTHOR]

Background: Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively.Methods: Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype.Results: The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls.Conclusions: In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)- associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ). Objective: We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers. Methods: Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time. Results: The CSF tau/A ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10--6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations). Conclusion: Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/A ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/A ratio was largely driven by increases in tau levels. Futurework should determine the functional/prognostic significance of these perioperative CSF tau elevations. [ABSTRACT FROM AUTHOR]

Luminol electrochemiluminescence is dramatically increased by about five hundred times by taking full advantage of both electrochemical reduction and electrochemical oxidation using simple linear sweep voltammetry, leading to sensitive detection. [ABSTRACT FROM AUTHOR]