Highly sensitive electrochemical sensing platform for the detection of L-dopa based on electropolymerizing glutathione disulfide and multi-walled carbon nanotube-modified electrodes

Afacile sensing platformfor the detection of L-dopa has been developed by electropolymerizing glutathione disulfide (PGSSG) on the surface of glass carbon electrodes (GCE) which were modified by multi-walled carbon nanotubes (MWCNTs). The electrochemical behaviour of the proposed electrodes were investigated via cyclic voltammetry (CV) and differential pulse voltammetry DPV). The morphology of the PGSSG and PGSSG/MWCNTs were characterized by scanning electron microscopy (SEM). Under the optimized experimental conditions, the sensing platform showed the linear response to L-Dopa in a range from 1.0 × 10–6 to 1.2 × 10–3 M with a detection limit of 3.3 × 10–7M (S/N = 3). Moreover, with the merits of high sensitivity and selectivity, good stability and reproducibility, the sensor was successfully applied for the determination of L-dopa in a real sample.Keywords: L-dopa, glutathione disulfide, multi-walled carbon nanotubes, electropolymerization, electrochemical determinatio

Enhanced Astrocytic Ca\u3csup\u3e2+\u3c/sup\u3e Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus.We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target

Association between salivary microbiota and renal function in renal transplant patients during the perioperative period

IntroductionRenal transplantation is an effective treatment for the end stage renal disease (ESRD). However, how salivary microbiota changes during perioperative period of renal transplant recipients (RTRs) has not been elucidated.MethodsFive healthy controls and 11 RTRs who had good recovery were enrolled. Saliva samples were collected before surgery and at 1, 3, 7, and 14 days after surgery. 16S rRNA gene sequencing was performed.ResultsThere was no significant difference in the composition of salivary microbiota between ESRD patients and healthy controls. The salivary microbiota of RTRs showed higher operational taxonomic units (OTUs) amount and greater alpha and beta diversity than those of ESRD patients and healthy controls, but gradually stabilized over time. At the phylum level, the relative abundance of Actinobacteria, Tenericutes and Spirochaetes was about ten times different from ESRD patients or healthy controls for RTRs overall in time. The relative abundance of Bacteroidetes, Fusobacteria, Patescibacteria, Leptotrichiaceae and Streptococcaceae was correlated with serum creatinine (Scr) after renal transplantation.DiscussionIn short, salivary microbiota community altered in the perioperative period of renal transplantation and certain species of salivary microbiota had the potential to be a biomarker of postoperative recovery

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling

Ocular fundus pathology and chronic kidney disease in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population.</p> <p>Methods</p> <p>This cross-sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m²and/or proteinuria was defined as CKD.</p> <p>Results</p> <p>Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes.</p> <p>Conclusions</p> <p>Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted.</p

Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity

Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs

An E-ARCH Model for the Term Structure of Implied Volatility of FX Options

this article, we contribute to the theoretical understanding of the volatility of option prices by studying empirically the dynamics of the term-structure of implied volatilities of currency options. We use a Principal Component Analysis (PCA) (Judge, 1988) combined with ARCH techniques to derive a statistical model for the evolution of the term structure of volatility. Thus, the present statistical analysis is not on the volatility of the underlying asset, as in traditional work (see Engle, 1994, 1995), but rather on the implied volatilities. The latter provide a &quot;dimensionless&quot; representation of the currency options market. Using historical data on the implied volatility of options on 13 currency pairs for the period Jan. 1, 1995 to July 30, 1996, we develop a three-factor term-structure model which appears to be applicable to all the studied currency pairs. A similar methodology was used by other authors in the study of term structure of interest-rates (Litterman and Scheinkman, 1991). There are, however, important structural differences between interest rates and implied volatilities. The main difference is that the term-structure of volatility is a stochastic process which is far from equilibrium. As an illustration of this, Figure 1 shows an &quot;equilibrium&quot; AR model fitted using least squares and maximum likelihood techniques compared against real data. One clearly observes more structure in the real data than in the equilibrium model, and unlike the latter, the real implied volatility data exhibits a trend. A formal test for non-stationarity or &quot;trend&quot; of time series is the unit root test (Enders, 1995). We apply this test to the term-structure of volatility, and the results 0 50 100 150 200 250 300 350 400 0 5 10 15 20 25 30 time 0 50 100 150 200 250 300 350 400..

蚂蚁金服：创新的边界在哪里？

本案例展示了蚂蚁金服利用数字技术在金融领域进行的创新过程和阶段性成果。这些创新成果不仅以普惠金融的形式弥补了传统金融服务的不足，还创造了诸如信用租之类的新市场，在对传统金融机构构成挑战的同时也帮助被挑战者提升了竞争力。不过，在取得这些成果的同时，蚂蚁金服也面临了诸多挑战：步入创新无人区的技术不确定性和监管盲区的挑战；来自竞争对手的挑战；界定创新边界的挑战。实际上，蚂蚁金服高层已经意识到这些挑战，2019年5月，他们专门召开了两天会议，议题就是持续创新和创新边界问题。“持续创新在今天到底意味着什么？如果有些事情，蚂蚁金服可以不做，那么究竟是哪些事情？又是为了什么？