Comparative study of reactive oxygen species and tetracycline degradation pathways in catalytic peroxodisulfate activation by asymmetric mesoporous TiO2 and the corresponding controlled-release materials.

The removal of trace amounts of antibiotics from water environments while simultaneously avoiding potential environmental hazards during the treatment is still a challenge. In this work, green, harmless, and novel asymmetric mesoporous TiO2 (A-mTiO2) was combined with peroxodisulfate (PDS) as active components in a controlled-release material (CRM) system for the degradation of tetracycline (TC) in the dark. The formation of reactive oxygen species (ROS) and the degradation pathways of TC during catalytic PDS activation by A-mTiO2 powder catalysts and the CRMs were thoroughly studied. Due to its asymmetric mesoporous structure, there were abundant Ti3+/Ti4+ couples and oxygen vacancies in A-mTiO2, resulting in excellent activity in the activation of PDS for TC degradation, with a mineralization rate of 78.6%. In CRMs, ROS could first form during PDS activation by A-mTiO2 and subsequently dissolve from the CRMs to degrade TC in groundwater. Due to the excellent performance and good stability of A-mTiO2, the resulting constructed CRMs could effectively degrade TC in simulated groundwater over a long period (more than 20 days). From electron paramagnetic resonance analysis and TC degradation experiments, it was interesting to find that the ROS formed during PDS activation by A-mTiO2 powder catalysts and CRMs were different, but the degradation pathways for TC were indeed similar in the two systems. In PDS activation by A-mTiO2, besides the free hydroxyl radical (·OH), singlet oxygen (1O2) worked as a major ROS participating in TC degradation. For CRMs, the immobilization of A-mTiO2 inside CRMs made it difficult to capture superoxide radicals (·O2-), and continuously generate 1O2. In addition, the formation of sulfate radicals (·SO4-), and ·OH during the release process of CRMs was consistent with PDS activation by the A-mTiO2 powder catalyst. The eco-friendly CRMs had a promising potential for practical application in the remediation of organic pollutants from groundwater.

Comparative study of the performance of controlled release materials containing mesoporous MnOx in catalytic persulfate activation for the remediation of tetracycline contaminated groundwater.

Controlled release materials (CRMs) are an emerging oxidant delivery technique for in-situ chemical oxidation (ISCO) that solve the problems of contaminant rebound, backflow and wake during groundwater remediation. CRMs were fabricated using ordered mesoporous manganese oxide (O-MnOx) and sodium persulfate (Na2S2O8) as active components, for the removal of antibiotic pollutants from groundwater. In both static and dynamic groundwater environments, persulfate can first be activated by O-MnOx within CRMs to form sulfate radicals and hydroxyl radicals, with these radicals subsequently dissolving out from the CRMs and degrading tetracycline (TC). Due to their excellent persulfate activation performance and good stability, the constructed CRMs could effectively degrade TC in both static and dynamic simulated groundwater systems over a long period (>21 days). The TC removal rate reached >80 %. Changing the added content of O-MnOx and persulfate could effectively regulate the performance of the CRMs during TC degradation in groundwater. The process and products of TC degradation in the dynamic groundwater system were the same as in the static groundwater system. Due to the strong oxidizing properties of sulfate radicals and hydroxyl radicals, TC molecules were completely mineralized within the groundwater systems, resulting in only trace levels of degradation products being detectable, with low- or non-toxicity. Therefore, the CRMs constructed in this study exhibited good potential for practical application in the remediation of organic pollutants from both static and dynamic groundwater environments.

Extract the Degradation Information in Squeezed States with Machine Learning.

In order to leverage the full power of quantum noise squeezing with unavoidable decoherence, a complete understanding of the degradation in the purity of squeezed light is demanded. By implementing machine-learning architecture with a convolutional neural network, we illustrate a fast, robust, and precise quantum state tomography for continuous variables, through the experimentally measured data generated from the balanced homodyne detectors. Compared with the maximum likelihood estimation method, which suffers from time-consuming and overfitting problems, a well-trained machine fed with squeezed vacuum and squeezed thermal states can complete the task of reconstruction of the density matrix in less than one second. Moreover, the resulting fidelity remains as high as 0.99 even when the antisqueezing level is higher than 20 dB. Compared with the phase noise and loss mechanisms coupled from the environment and surrounding vacuum, experimentally, the degradation information is unveiled with machine learning for low and high noisy scenarios, i.e., with the antisqueezing levels at 12 dB and 18 dB, respectively. Our neural network enhanced quantum state tomography provides the metrics to give physical descriptions of every feature observed in the quantum state with a single scan measurement just by varying the local oscillator phase from 0 to 2π and paves a way of exploring large-scale quantum systems in real time.

Invasive Blood Pressure Measurement and In-hospital Mortality in Critically Ill Patients With Hypertension.

Background: Invasive blood pressure (IBP) measurement is common in the intensive care unit, although its association with in-hospital mortality in critically ill patients with hypertension is poorly understood. Methods and Results: A total of 11,732 critically ill patients with hypertension from the eICU-Collaborative Research Database (eICU-CRD) were enrolled. Patients were divided into 2 groups according to whether they received IBP. The primary outcome in this study was in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) models were used to balance the confounding covariates. Multivariable logistic regression was used to evaluate the association between IBP measurement and hospital mortality. The IBP group had a higher in-hospital mortality rate than the no IBP group in the primary cohort [238 (8.7%) vs. 581 (6.5%), p < 0.001]. In the PSM cohort, the IBP group had a lower in-hospital mortality rate than the no IBP group [187 (8.0%) vs. 241 (10.3%), p = 0.006]. IBP measurement was associated with lower in-hospital mortality in the PSM cohort (odds ratio, 0.73, 95% confidence interval, 0.59-0.92) and in the IPTW cohort (odds ratio, 0.81, 95% confidence interval, 0.67-0.99). Sensitivity analyses showed similar results in the subgroups with high body mass index and no sepsis. Conclusions: In conclusion, IBP measurement was associated with lower in-hospital mortality in critically ill patients with hypertension, highlighting the importance of IBP measurement in the intensive care unit.

Phospholipase C inhibits apoptosis of porcine oocytes cultured in vitro.

Oocyte apoptosis can be used as an indicator of oocyte quality and development competency. Phospholipase C (PLC) is a critical enzyme that participates in phosphoinositide metabolic regulation and performs many functions, including the regulation of reproduction. In this study, we aimed to explore whether PLC participates in the regulation of apoptosis in porcine oocytes and investigated its possible mechanism. In porcine oocytes, 0.5 µM U73122 (the PLC inhibitor) was considered to be the best concentration to facilitate maturation, and 0.5 µM m-3M3FBS (the PLC activator) was regarded as the most appropriate concentration to inhibit maturation. The percentage of cleavage and blastocysts treated with 0.5 µM U73122 was lower than that of the control group. Furthermore, the percentage of cleavage and blastocysts treated with 0.5 µM m-3M3FBS was higher than that of the control group. The relative PLC messenger RNA (mRNA) expression tested by a quantitative real-time polymerase chain reaction was found to be inhibited by 0.5 µM U73122 or activated by 0.5 µM m-3M3FBS. The relative mRNA abundance of BAK, BAX, CASP3, CASP8, and TP53 and protein abundance of Bak, cleaved caspase-3, caspase-8, and P53 was activated by U73122 or inhibited by m-3M3FBS, while the relative mRNA and protein level of BCL6 showed the opposite trend. The intracellular Ca2+ concentration increased and the expression of PLCB1 protein also increased in porcine oocytes when they were cultured with 0.5 µM m-3M3FBS for 44 hours. The abundance of proteins PKCß and CAMKIIα and the expression of several downstream genes (CDC42, NFATc1, NFATc2, NFκB, and NLK) were activated by m-3M3FBS or inhibited by U73122. Our findings indicate that PLC inhibits apoptosis and maturation in porcine oocytes. The intracellular Ca2+ concentration, two Ca2+ -sensitive proteins, and several downstream genes were positively regulated by PLC.

Interplay between Alzheimer's disease and global glucose metabolism revealed by the metabolic profile alterations of pancreatic tissue and serum in APP/PS1 transgenic mice.

Increasing evidence suggests that there is a correlation between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD). Increased Aß polypeptide production in AD patients would promote metabolic abnormalities, insulin signaling dysfunction and perturbations in glucose utilization, thus leading to the onset of T2D. However, the metabolic mechanisms underlying the interplay between AD and its diabetes-promoting effects are not fully elucidated. Particularly, systematic metabolomics analysis has not been performed for the pancreas tissues of AD subjects, which play key roles in the glucose metabolism of living systems. In the current study, we characterized the dynamic metabolic profile alterations of the serum and the pancreas of APP/PS1 double-transgenic mice (an AD mouse model) using the untargeted metabolomics approaches. Serum and pancreatic tissues of APP/PS1 transgenic mice and wild-type mice were extracted and subjected to NMR analysis to evaluate the functional state of pancreas in the progress of AD. Multivariate analysis of principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to define the global and the local (pancreas) metabolic features associated with the possible initiation of T2D in the progress of AD. Our results showed the onset of AD-induced global glucose metabolism disorders in AD mice. Hyperglycemia and its accompanying metabolic disorders including energy metabolism down-regulation and oxidative stress were observed in the serum of AD mice. Meanwhile, global disturbance of branched-chain amino acid (BCAA) metabolism was detected, and the change of BCAA (leucine) was positively correlated to the alteration of glucose. Moreover, increased level of glucose and enhanced energy metabolism were observed in the pancreas of AD mice. The results suggest that the diabetes-promoting effects accompanying the progress of AD are achieved by down-regulating the global utilization of glucose and interfering with the metabolic function of pancreas. Since T2D is a risk factor for the pathogenesis of AD, our findings suggest that targeting the glucose metabolism dysfunctions might serve as a supplementary therapeutic strategy for Alzheimer's disease.

Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.

Nearly complete survival of an entangled biphoton through bound states in continuum in disordered photonic lattices.

Bound states in the continuum (BICs) of periodic lattices have been the recent focus in a variety of photonic nanostructures. Motivated by the recent results about the photons evolving in BIC structures, we investigate the quantum decay of entangled biphotons through disordered photonic lattices. We report that the persistence of bound states in disordered photonic lattices leads to an interplay between the BIC and disorder-induced Anderson localized states. We reveal a novel effect resulting from such an interplay: a nearly complete quantum survival for the entangled biphoton respecting the antisymmetric exchange symmetry. This is in contrast to the complete vanishment in a periodic photonic lattice.

An enhanced targeted identification strategy for the selective identification of flavonoid O-glycosides from Carthamus tinctorius by integrating offline two-dimensional liquid chromatography/linear ion-trap-Orbitrap mass spectrometry, high-resolution diagnostic product ions/neutral loss filtering and liquid chromatography-solid phase extraction-nuclear magnetic resonance.

Targeted identification of potentially bioactive molecules from herbal medicines is often stymied by the insufficient chromatographic separation, ubiquitous matrix interference, and pervasive isomerism. An enhanced targeted identification strategy is presented and validated by the selective identification of flavonoid O-glycosides (FOGs) from Carthamus tinctorius. It consists of four steps: (i) enhanced separation and detection by offline two-dimensional liquid chromatography/LTQ-Orbitrap MS (offline 2D-LC/LTQ-Orbitrap MS) using collision-induced dissociation (CID) and high-energy C-trap dissociation (HCD); (ii) improved identification of the major aglycones by acid hydrolysis and LC-SPE-NMR; (iii) simplified spectral elucidation by high-resolution diagnostic product ions/neutral loss filtering; and (iv) more convincing structural identification by matching an in-house library. An offline 2D-LC system configuring an Acchrom XAmide column and a BEH Shield RP-18 UPLC® column enabled much better separation of the easily co-eluting components. Combined use of CID and HCD could produce complementary fragmentation information. The intensity ratios of the aglycone ion species ([Y0-H]-/Y0- and [Y0-2H]-/Y0-) in the HCD-MS2 spectra were found diagnostic for discriminating the aglycone subtypes and characterizing the glycosylation patterns. Five aglycone structures (kaempferol, 6-hydroxykaempferol, 6-methoxykaempferol, carthamidin, and isocarthamidin) were identified based on the 1H-NMR data recorded by LC-SPE-NMR. Of the 107 characterized flavonoids, 80 FOGs were first reported from C. tinctorius. Unknown aglycones, pentose, and novel acyl substituents were discovered. A new compound thereof was isolated and fully identified, which could partially validate the MS-oriented identification. This integral strategy can improve the potency, efficiency, and accuracy in the detection of new compounds from medicinal herbs and other natural sources.

Melatonin modulates the functions of porcine granulosa cells via its membrane receptor MT2 in vitro.

Melatonin (N-acetyl-5-methoxytryptamine) is documented as a hormone involved in the circadian regulation of physiological and neuroendocrine function in mammals. Herein, the effects of melatonin on the functions of porcine granulosa cells in vitro were investigated. Porcine granulosa cells were cultivated with variable concentrations of melatonin (0, 0.001, 0.01, 0.1, 1.0, and 10ng/mL) for 48h. Melatonin receptor agonist (IIK7) and antagonist (Luzindole, 4P-PDOT) were used to further examine the action of melatonin. The results showed optimum cell viability and colony-forming efficiency of porcine granulosa cells at 0.01ng/mL melatonin for 48-h incubation period. The percentage of apoptotic granulosa cells was significantly reduced by 0.01 and 0.1ng/mL melatonin within the 48-h incubation period as compared with the rest of the treatments. Estradiol biosynthesis was significantly stimulated by melatonin supplementation and suppressed for the progesterone secretion; the minimum ratio of progesterone to estradiol was 1.82 in 0.01ng/mL melatonin treatment after 48h of cultivation. Moreover, the expression of BCL-2, CYP17A1, CYP19A1, SOD1, and GPX4 were up-regulated by 0.01ng/mL melatonin or combined with IIK7, but decreased for the mRNA levels of BAX, P53, and CASPASE-3, as compared with control or groups treated with Luzindole or 4P-PDOT in the presence of melatonin. In conclusion, the study demonstrated that melatonin mediated proliferation, apoptosis, and steroidogenesis in porcine granulosa cells predominantly through the activation of melatonin receptor MT2 in vitro, which provided evidence of the beneficial role of melatonin as well as its functional mechanism in porcine granulosa cells in vitro.

Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK.

Doxorubicin (DOX) is a wide spectrum antitumor drug, but its clinical application is limited by the cardiotoxicity. Ghrelin, a multi-functional peptide hormone with metabolic regulation in energy homeostasis, plays important roles in cardiovascular protection. Now, the underlying mechanisms of ghrelin against DOX-induced cardiomyocyte apoptosis and atrophy are still not clear. In the present study, we revealed an autophagy-dependent mechanism involved in ghrelin's protection against DOX-induced cardiomyocyte death and size decrease. We observed that DOX insult induced remarkable mortality and cardiac dysfunction in mice, and increase in LDH leakage, cardiomyocyte apoptosis and decrease in cell viability and size in mouse hearts and H9c2 cell cultures, which were effectively improved by ghrelin supplement. We further observed that the strong autophagy stirred by DOX exposure was paralleling with the serious apoptosis and size decrease in cardiomyocytes. Ghrelin, like an autophagy inhibitor, 3-MA, inhibited the DOX-induced autophagy and attenuated cardiomyocyte apoptosis and size decrease. Furthermore, ghrelin significantly reduced the intercellular oxidative stress level, a strong autophagy trigger, partly by augmenting the expression and activities of the endogenous anti-oxidative enzymes. After the further investigation in the post signaling pathways of ghrelin receptors in H9c2 cells, including ERK, p38/MAPK, JNK, AMPK and Akt, we observed that ghrelin supplement only reduced the DOX-activated AMPK and augmented the DOX-down regulated p38-MAPK and mTOR phosphorylation. Our results indicated that ghrelin effectively improved the cardiomyocyte survival and size maintenance by suppressing the excessive autophagy through both ROS inhibition and mTOR induction through suppressing AMPK activity and stimulating p38-MAPK activity.

Salidroside improves doxorubicin-induced cardiac dysfunction by suppression of excessive oxidative stress and cardiomyocyte apoptosis.

Doxorubicin (DOX) is a potent available antitumor drug; however, its clinical use is limited by the cardiotoxicity. Salidroside (SLD), with strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. Now, the protection and underlying mechanisms of SLD against DOX-induced cardiotoxicity are still unknown. In the present study, we revealed both antioxidative mechanism and Bcl2-dependent survival signaling involved in SLD's protection. We observed that DOX exposure induced mortality elevation, body weight loss, and cardiac dysfunction in mice, increased lactate dehydrogenase leakage and cardiomyocyte apoptosis, but decreased cell viability and size in cardiac tissues and cultured H9c2 cells, respectively, which were effectively antagonized by SLD supplement. We further observed that SLD significantly reduced the intercellular oxidative stress level, partly by inhibiting NOX1 expression and augmenting the expression and activities of the endogenous antioxidative enzymes, catalase, and manganese superoxide dismutase. In addition, SLD treatment upregulated the antiapoptotic Bcl2 and downregulated the proapoptotic Bax and inhibited a downstream pathway of Bcl2/Bax and caspase-3 activity. Our results indicated that SLD effectively protected the cardiomyocytes against DOX-induced cardiotoxicity by suppressing the excessive oxidative stress and activating a Bcl2-mediated survival signaling pathway.

Ghrelin protects against cobalt chloride-induced hypoxic injury in cardiac H9c2 cells by inhibiting oxidative stress and inducing autophagy.

Ghrelin is a multifunctional peptide that actively protects against cardiovascular ischemic diseases, but the underlying mechanisms are unclear. We used CoCl(2) to mimic hypoxic conditions in cardiac H9c2 cells in order to study the mechanism by which ghrelin protects cardiac myocytes against hypoxic injury by regulating the content of intracellular ROS and autophagy levels. Cell apoptosis and necrosis were evaluated by the flow cytometry assay, Hoechst staining, and LDH activity. Cell viability was detected by the WST-1 assay; ROS levels were assessed using DCFH2-DA; and Nox1, catalase and Mn-SOD were assayed by real-time PCR and activity assays. LC3II was measured by Western blot analysis. We observed that CoCl(2) induced apoptosis and death of H9c2 cells in a dose- and time-dependent manner. This was characterized by an increase in cell apoptosis, LDH activity, ROS content, Nox1 expression, and autophagy levels and a decrease in cell viability, catalase, and Mn-SOD activities. Ghrelin treatment significantly attenuated CoCl(2)-induced hypoxic injury by decreasing cell apoptosis, LDH activity, ROS content, and Nox1 expression and increasing cell viability, autophagy levels, catalase, and Mn-SOD mRNA levels and activities. Further experiments revealed that inhibiting autophagy using 3-MA or AMPK pathway with compound C almost abrogated the induction of ghrelin in autophagy. This was associated with a decrease in cell viability and an increase in LDH activity. Our results indicate that ghrelin protected cardiac myocytes against CoCl(2)-induced hypoxic injury by decreasing Nox1 expression, increasing the expression and activity of endogenous antioxidant enzymes, and inducing protective autophagy in an AMPK-dependent manner.

Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway.

Oxidative stress induces serious tissue injury in cardiovascular diseases. Salidroside, with its strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. We examined the pharmacological effects of salidroside on H9c2 rat cardiomyoblast cells under conditions of oxidative stress induced by hydrogen peroxide (H2O2) challenge. Salidroside attenuated H2O2-impaired cell viability in a concentration-dependent manner, and effectively inhibited cellular malondialdehyde production, lethal sarcolemmal disruption, cell necrosis, and apoptosis induced by H2O2 insult. Salidroside significantly augmented Akt phosphorylation at Serine 473 in the absence or presence of H2O2 stimulation; wortmannin, a specific inhibitor of PI3K, abrogated salidroside protection. Salidroside increased the intracellular mRNA expression and activities of catalase and Mn-superoxide dismutases in a PI3K-dependent manner. Our results indicated that salidroside protected cardiomyocytes against oxidative injury through activating the PI3K/Akt pathway and increasing the expression and activities of endogenous PI3K dependent antioxidant enzymes.

Construction of middle fragment deletion mutant with improved gene splicing by overlap extension / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To construct a phosphatidylinositol 4-kinase beta (PI4K-beta) mutant with the 325th to 373rd amino acid codons deleted, and try to develop a simple method for constructing middle fragment deletion mutant.</p><p><b>METHODS</b>In line with the mechanism of gene splicing by overlap extension(SOE), an additional PCR was used to get the PI4K-beta mutant in which the 325th to 373rd amino acid codons were deleted. Then the mutated gene was cloned into pCMV-Tag4A mammalian expression vector.</p><p><b>RESULTS</b>A mutant with the 325th to 373rd amino acid codons deleted was constructed successfully.</p><p><b>CONCLUSION</b>The improved SOE is a very effective and reliable method to construct middle fragment deletion mutant. It is worthy to be popularized.</p>