Multifunctional sulfur doping in cobalt-based materials for high-energy density supercapacitors.

In this study, S-CCO@Co(OH)2('CCO' representing CuCo2O4/Cu2O; 'S-'representing sulfur doping) was synthesized by hydrothermal method followed by electrodeposition. The multiple effects of S doping were studied by S doping and constructing 3D core-shell structure. S doping induced the reduction of Cu2+and Co3+to Cu+and Co2+, respectively. Also, S partially replaces O and creates oxygen vacancies, which increases a number of active sites for the redox reaction enhancing the redox reaction activity. After the electrodeposition, S-Co bond is formed between the Co(OH)2shell and the S-CCO core, which suggests a synergistic effect between S doping and core-shell structure. The formation of S-Co bond is conducive to electron and ion transport, thus improving electrochemical performance. After modification, the specific capacitance of S-CCO@Co(OH)2is 4.28 times higher than CCO, up to 1730 Fg-1. Furthermore, the assembled S-CCO@Co(OH)2//activated carbon supercapacitor exhibits an energy density of 83.89 Whkg-1at 848.81 Wkg-1and a retention rate of 98.48% after 5000 charge and discharge cycles. Therefore, S doping and its mutual effect with the utilization of the core-shell structure considerably enhanced the electrochemical performance of the CCO-based electrodes, endowing its potential in further application.

Activation of MAPK-mediated immunity by phosphatidic acid in response to positive-strand RNA viruses.

Increasing evidence suggests that mitogen-activated protein kinase (MAPK) cascades play a crucial role in plant defense against viruses. However, the mechanisms that underlie the activation of MAPK cascades in response to viral infection remain unclear. In this study, we discovered that phosphatidic acid (PA) represents a major class of lipids that respond to Potato virus Y (PVY) at an early stage of infection. We identified NbPLDα1 (Nicotiana benthamiana phospholipase Dα1) as the key enzyme responsible for increased PA levels during PVY infection and found that it plays an antiviral role. 6K2 of PVY interacts with NbPLDα1, leading to elevated PA levels. In addition, NbPLDα1 and PA are recruited by 6K2 to membrane-bound viral replication complexes. On the other hand, 6K2 also induces activation of the MAPK pathway, dependent on its interaction with NbPLDα1 and the derived PA. PA binds to WIPK/SIPK/NTF4, prompting their phosphorylation of WRKY8. Notably, spraying with exogenous PA is sufficient to activate the MAPK pathway. Knockdown of the MEK2-WIPK/SIPK-WRKY8 cascade resulted in enhanced accumulation of PVY genomic RNA. 6K2 of Turnip mosaic virus and p33 of Tomato bushy stunt virus also interacted with NbPLDα1 and induced the activation of MAPK-mediated immunity. Loss of function of NbPLDα1 inhibited virus-induced activation of MAPK cascades and promoted viral RNA accumulation. Thus, activation of MAPK-mediated immunity by NbPLDα1-derived PA is a common strategy employed by hosts to counteract positive-strand RNA virus infection.

Thermally Activated Delayed Fluorescence (TADF)-active Coinage-metal Sulfide Clusters for High-resolution X-ray Imaging.

The study of facile-synthesis and low-cost X-ray scintillators with high light yield, low detection limit and high X-ray imaging resolution plays a vital role in medical and industrial imaging fields. However, the optimal balance between X-ray absorption, decay lifetime and excitonic utilization efficiency of scintillators to achieve high-resolution imaging is extremely difficult due to the inherent contradiction. Here two thermally activated delayed fluorescence (TADF)-actived coinage-metal clusters M6 S6 L6 (M=Ag or Cu) were synthesized by simple solvothermal reaction, where the cooperation of heavy atom-rich character and TADF mechanism supports strong X-ray absorption and rapid luminescent collection of excitons. Excitingly, Ag6 S6 L6 (SC-Ag) displays a high photoluminescence quantum yield of 91.6 % and scintillating light yield of 17420 photons MeV-1 , as well as a low detection limit of 208.65 nGy s-1 that is 26 times lower than the medical standard (5.5 µGy s-1 ). More importantly, a high X-ray imaging resolution of 16 lp/mm based on SC-Ag screen is demonstrated. Besides, rigid core skeleton reinforced by metallophilicity endows clusters M6 S6 L6 strong resistance to humidity and radiation. This work provides a new view for the design of efficient scintillators and opens the research door for silver clusters in scintillation application.

Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia.

Emerging evidence indicates that bile acids (BAs), which are signaling molecules that regulate metabolism and inflammation, appear to be dysregulated in schizophrenia (SZ). Further investigation is warranted to comprehensively characterize BA profiles in SZ. To address this, we analyzed serum BA profiles in 108 drug-free patients with SZ and in 108 healthy controls (HCs), divided into a discovery set (n = 119) and a validation set (n = 97), using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Forty serum BAs were detected and absolutely quantified using calibration curves. Global BA profiling showed differences in SZ and HC groups in both discovery and validation sets. The concentrations of chenodeoxycholic acid, ursodeoxycholic acid, 3ß-chenodeoxycholic acid, 7-ketolithocholic acid, 3-dehydrocholic acid, total BAs, and unconjugated BAs were significantly lower in patients with SZ compared with HCs in the two sample sets. The BA deconjugation potentials by gut microbiota and the affinity index of the farnesoid X receptor (FXR) were notably decreased in SZ patients compared to those of HCs. Conjugated BAs and BA deconjugation potentials differed in SZ patients with first versus recurrent episodes, although similar BA profiles were observed in both groups. In addition, a panel of 8 BA variables acted as a potential auxiliary diagnostic biomarker in discriminating SZ patients from HCs, with area under the curve values for receiver operating characteristic curves of 0.758 and 0.732 and for precision-recall curves of 0.750 and 0.714 in the discovery and validation sets, respectively. This study has provided compelling evidence of comprehensive characteristics of circulating BA metabolism in patients with SZ and promoted a deeper understanding of the role of BAs in the pathophysiology of this disease, possibly via the gut microbiota-FXR signaling pathway.

Impaired Membrane Lipid Homeostasis in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored. STUDY DESIGN: Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism. STUDY RESULTS: By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients. CONCLUSIONS: Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.

A Two-Layer IP Hopping-Based Moving Target Defense Approach to Enhancing the Security of Mobile Ad-Hoc Networks.

Mobile ad-hoc networks (MANETs) have great potential applications in military missions or emergency rescue due to their no-infrastructure, self-organizing and multi hop capability characteristics. Obviously, it is important to implement a low-cost and efficient mechanism of anti-invasion, anti-eavesdropping and anti-attack in MANETs, especially for military scenarios. The purpose of intruding or attacking a MANET is usually different from that of wired Internet networks whose security mechanism has been widely explored and implemented. For MANETs, moving target defense (MTD) is a suitable mechanism to enhance the network security, whose basic idea is to continuously and randomly change the system parameters or configuration to create inaccessibility for intruders and attackers. In this paper, a two-layer IP hopping-based MTD approach is proposed, in which device IP addresses or virtual IP addresses change or hop according to the network security status and requirements. The proposed MTD scheme based on the two-layer IP hopping has two major advantages in terms of network security. First, the device IP address of each device is not exposed to the wireless physical channel at all. Second, the two-layer IP hops with individual interval and rules to obtain enhanced security of MANET while maintaining relatively low computational load and communication cost for network control and synchronization. The proposed MTD scheme is implemented in our developed MANET terminals, providing three level of network security: anti-intrusion in normal environment, intrusion detection in offensive environment and anti-eavesdropping in a hostile environment by combining the data encryption technology.

Attenuated and delayed niacin skin flushing in schizophrenia and affective disorders: A potential clinical auxiliary diagnostic marker.

AIM: Schizophrenia and affective disorders all show high heterogeneity in clinical manifestations. A lack of objective biomarkers has long been a challenge in the clinical diagnosis of these diseases. In this study, we aimed to investigate the performance of niacin skin flushing in schizophrenia and affective disorders and determine its clinical potential as an auxiliary diagnostic marker. METHODS: In this case-control study, niacin skin-flushing tests were conducted in 613 patients (including 307 schizophrenia patients, 179 bipolar disorder patients, and 127 unipolar depression patients) and 148 healthy controls (HCs) with a modified method. Differences in niacin skin-flushing responses were compared with adjustment for gender, BMI, age, nicotine dependence, alcohol consumption and educational status. A diagnostic model was established based on a bivariate cut-off. RESULTS: Schizophrenia and affective disorders showed similar performance of niacin bluntness, characterized by attenuated flushing extent and reduced flushing rate. An innovative bivariate cut-off was established according to these two features, by which we could identify -patients with either schizophrenia or affective disorders from HCs with a sensitivity of 55.28%, a specificity of 83.56% and a positive predictive value of 93.66%. CONCLUSIONS: The niacin-induced skin flushing was prevalently blunted in patients with schizophrenia or affective disorders, indicating a promising potential as an auxiliary diagnostic marker in risk prediction and clinical management of these disorders. Additionally, the niacin-blunted subgroup implies a common biological basis in the investigated disorders, which provokes new thoughts in elucidating the pathological mechanisms.

Serum Metabolomic Profiling Based on Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry: Do the Dysfunctions of Metabolic Pathways Reveal a Universal Risk of Oxidative Stress in Schizophrenia?

Schizophrenia is a chronic, disabling, and complex mental illness, of which the pathogenesis remains elusive. To provide clues for the pathogenesis and etiology of schizophrenia, we performed serum metabolic profiling in 54 patients with schizophrenia and 54 matched healthy controls using Fourier transform-ion cyclotron resonance-mass spectrometry. Based on 94 differential metabolites identified, we discovered two dysregulated metabolic pathways in schizophrenia, including the upregulated arachidonic acid-related pathway and the downregulated aromatic amino acid-related pathway. Moreover, carnitine was identified as a promising diagnostic biomarker for schizophrenia with an area under the curve of 0.997. Given the antioxidant and pro-oxidant properties of these altered metabolites, these results pointed to an imbalance of the redox homeostasis in schizophrenia, which was further confirmed by a remarkable elevation of 8-hydroxydeoxyguanosine (8-OHdG), a reactive oxidative stress marker. Furthermore, correlation analyses demonstrated that 8-OHdG was negatively correlated with antioxidant biliverdin and positively related to oxidation products, 9-hydroxylinoleic acid and o-tyrosine, and that total antioxidant capacity was positively associated with antioxidant acetylcarnitine in schizophrenia. Our results lead to the hypothesis that the disturbed metabolic characteristics reveal enhanced oxidative stress, which in turn results in the damage of lipids, proteins, and DNA and ultimately promotes the development of schizophrenia.

An investigation of calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) in schizophrenia.

Evidence indicates that abnormal phospholipase A2 (PLA2) levels and niacin insensitivity are present in individuals with schizophrenia. This study was designed to determine whether differences in plasma calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) exist between those with schizophrenia and healthy controls, and to explore the correlation between PLA2s and the niacin skin reaction in schizophrenic patients. We performed ELISA experiments to measure the concentrations of plasma iPLA2 and cPLA2 and we conducted a series of niacin skin tests on schizophrenic patients from the Chinese Han population. In addition, a meta-analysis of the relationship between PLA2 and schizophrenia was conducted. The plasma concentration of iPLA2 in patients with schizophrenia was significantly higher than that in healthy controls while the plasma concentration of cPLA2 did not differ. The meta-analysis also revealed that the activity level of iPLA2 in individuals with schizophrenia was higher than that in healthy controls, whereas that of cPLA2 was not. Furthermore, a significant positive correlation was found between the concentration of iPLA2 and the score for the skin flushing response within 20 min. The abnormal plasma iPLA2 concentration and its relationship with the niacin skin test in schizophrenic patients has contributed to a deeper understanding of the pathology of schizophrenia, which may in turn provide new insights into the clinical diagnoses and treatment of schizophrenia.

CTX-II and YKL-40 in early diagnosis and treatment evaluation of osteoarthritis.

This study investigated the value of C-terminal telopeptides of collagen type II (CTX-II) and YKL-40 in early diagnosis and treatment evaluation of osteoarthritis (OA). A total of 90 patients with OA diagnosed and treated in The First Affiliated Hospital, Guangzhou Medical University from March 2015 to January 2018 were selected as the study group. At the same time, 50 healthy elderly were included as the control group. The study group was divided into three subgroups including group A (29 cases, 500 mg glucosamine sulfate), group B (29 cases, 50 mg diacerein) and group C (32 cases, 500 mg glucosamine sulfate and 50 mg diacerein). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess the severity and treatment of arthritis. Enzyme-linked immunosorbent assay was used to measure the concentration of CTX-II and YKL-40 in serum. WOMAC scores in the study A, B and C groups were significantly higher than those in the control group (P<0.001). Serum CTX-II and YKL-40 concentrations were higher in the study group than in the control group (P<0.001). Sensitivity of serum CTX-II combined with YKL-40 in the diagnosis of OA was 90% and the specificity was 78%. CTX-II and YKL-40 levels in different Kellgren Lawrence (K-L) grades were significantly different (P<0.001), and increased with the increase of K-L grade. Concentrations of serum CTX-II and YKL-40 before treatment in the study group was positively correlated with WOMAC score (P<0.001). At 3, 6 and 9 weeks after the beginning of treatment, serum concentrations of CTX-II and YKL-40 decreased significantly (P<0.001). At 3 weeks of treatment, CTX-II was positively correlated with YKL-40 concentration and WOMAC score (r=0.406, P<0.001; r=0.430, P<0.001); CTX-II was positively correlated with YKL-40 concentration and WOMAC score at 6 weeks of treatment (r=0.350, P<0.001; r=0.358, P<0.001); CTX-II was positively correlated with YKL-40 concentration and WOMAC score at 9 weeks after treatment (r=0.370, P<0.001; r=0.394, P<0.001). Combined detection of serum CTX-II and YKL-40 can improve the sensitivity of early OA diagnosis, and it has an important diagnostic value for early OA patients. Therefore, it can be used as a biological indicator for early OA diagnosis, severity assessment, and evaluation of treatment effects.

Secreted recombinant human IL-24 protein inhibits the proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro and in vivo.

Interleukin-24 (IL-24) displays cancer-specific apoptosis-inducing properties in a broad spectrum of human tumors without harmful effects on normal cells. The human IL-24 protein is secreted as a glycosylated protein and functions as a pro-Th1 cytokine and a potent antiangiogenic molecule. However, the function of secreted recombinant human IL-24 (srhIL-24) protein in esophageal squamous cell carcinoma (ESCC) cells has not been studied. In the present study, we prepared a stable site-specific-integrated cell line, Flp-InTMCHO/IL-24 (FCHO/IL-24), which secreted rhIL-24 at a higher level than three random-integrated cell lines. In vitro, we identified that the purified srhIL-24 inhibited proliferation and induced the apoptosis of ESCC Eca-109 cells and activated STAT3, which was related with the IL-20 receptors. In vivo, the tumorigenicity of Eca-109 cells was significantly inhibited by s.c. injection of FCHO/IL-24 cells. Decreased tumor microvessel density and an increased number of TUNEL-positive tumor cells were associated with tumor growth inhibition, indicating the presence of antiangiogenic activity and induction of apoptotic activity. In summary, the present study demonstrated that srhIL-24 induced growth inhibition and apoptosis in ESCC Eca-109 cells in vitro and in vivo, which may be mediated by the receptor pathway.

A novel human interleukin-24 peptide created by computer-guided design contributes to suppression of proliferation in esophageal squamous cell carcinoma Eca-109 cells.

Based on the three-dimensional modeling structure of human interleukin-24 (hIL-24) and its most likely active position predicted by solvent accessibility and apparent electrostatic properties, a novel hIL-24 peptide M1 was created by computer-guided molecular design. The cytotoxicity and cell selectivity of M1 were examined in three human carcinoma cell lines and one normal human embryo lung fibroblast cell line (HEL). MTT assay showed that M1 induced growth arrest in two IL-20 receptor complex-positive cancer cell lines (the esophageal squamous cell carcinoma cell line Eca-109 and the melanoma cell line A375), and antibodies against IL-24 or IL-20 receptor complexes significantly neutralized the inhibitory activity. Moreover, M1 had almost no cytotoxicity on the lung cancer A549 cell line, which lacks a full complement of the IL-20 receptor complexes, or on HEL cells that express the IL-20 receptor complexes. These findings demonstrate that M1 could act as an excellent candidate for the induction of growth arrest on receptor complex-positive cancer cells. In summary, the M1 peptide may represent a novel anticancer agent for esophageal squamous cell carcinoma therapy due to its cancer cell selectivity and its relatively low cytotoxicity to normal cells.