CREB: A Promising Therapeutic Target for Treating Psychiatric Disorders.

Psychiatric disorders are complex, multifactorial illnesses. It is challenging for us to understand the underlying mechanism of psychiatric disorders. In recent years, the morbidity of psychiatric disorders has increased yearly, causing huge economic losses to the society. Although some progress, such as psychotherapy drugs and electroconvulsive therapy, has been made in the treatment of psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive and autism spectrum disorders, antidepressants and psychotropic drugs have the characteristics of negative effects and high rate of relapse. Therefore, researchers continue to seek suitable interventions. cAMP response element binding protein (CREB) belongs to a protein family and is widely distributed in the majority of brain cells that function as a transcription factor. It has been demonstrated that CREB plays an important role in neurogenesis, synaptic plasticity, and neuronal growth. This review provides a 10-year update of the 2013 systematic review on the multidimensional roles of CREB-mediated transcriptional signaling in psychiatric disorders. We also summarize the classification of psychiatric disorders and elucidate the involvement of CREB and related downstream signalling pathways in psychiatric disorders. Importantly, we analyse the CREB-related signal pathways involving antidepressants and antipsychotics to relieve the pathological process of psychiatric disorders. This review emphasizes that CREB signalling may have a vast potential to treat psychiatric disorders like depression. Furthermore, it would be helpful for the development of potential medicine to make up for the imperfection of current antidepressants and antipsychotics.

Chinese expert consensus on the diagnosis and treatment of coronary microvascular diseases (2023 Edition).

Since the four working groups of the Chinese Society of Cardiology issued first expert consensus on coronary microvascular diseases (CMVD) in 2017, international consensus documents on CMVD have increased rapidly. Although some of these documents made preliminary recommendations for the diagnosis and treatment of CMVD, they did not provide classification of recommendations and levels of evidence. In order to summarize recent progress in the field of CMVD, standardize the methods and procedures of diagnosis and treatment, and identify the scientific questions for future research, the four working groups of the Chinese Society of Cardiology updated the 2017 version of the Chinese expert consensus on CMVD and adopted a series of measures to ensure the quality of this document. The current consensus has raised a new classification of CMVD, summarized new epidemiological findings for different types of CMVD, analyzed key pathological and molecular mechanisms, evaluated classical and novel diagnostic technologies, recommended diagnostic pathways and criteria, and therapeutic strategies and medications, for patients with CMVD. In view of the current progress and knowledge gaps of CMVD, future directions were proposed. It is hoped that this expert consensus will further expedite the research progress of CMVD in both basic and clinical scenarios.

Hydrogenation induced high-temperature superconductivity in two-dimensional W2C3.

The discovery of highly crystalline two-dimensional (2D) superconductors provides a new alluring branch for exploring the fundamental significances. Based on first-principles calculations, we predict a new kind of 2D stable material W2C3, which is a semimetal but not a superconductor because of the weak electron-phonon coupling (EPC) strength. After hydrogenation, W2C3H2 possesses the intrinsic metallic properties with a large density of states (DOS) at the Fermi energy (EF). More interestingly, the EPC strength is greatly enhanced after hydrogenation and the calculated critical temperature (Tc) is 40.5 K. Furthermore, the compressive strain can obviously soften the low-frequency phonons and enhance the EPC strength. Then, the Tc of W2C3H2 can be increased from 40.5 K to 49.1 K with -4% compressive strain. This work paves the way for providing a new platform for 2D superconductivity.

Superconductivity of monolayer functionalized biphenylene with Dirac cones.

Monolayer biphenylene is a new two-dimensional (2D) carbon allotrope, which has been experimentally synthesized and theoretically predicted to show superconductivity. In this work, we investigate functionalized biphenylene with the adsorption of Li. The superconducting critical temperature (Tc) can be pushed from 0.59 K up to 3.91 K after Li adsorption. Our calculations confirm that the adsorption pushes the peak showing a high electronic density of states closer to the Fermi level, which usually leads to a larger Tc. Furthermore, the application of biaxial tensile strain can soften phonons and further enhance the Tc up to 15.86 K in Li-deposited biphenylene. Interestingly, a pair of type-II Dirac cones below the Fermi level has been observed, expanding the range of Dirac materials. It suggests that monolayer biphenylene deposited with Li may be a material with potential applications and improves the understanding of Dirac-type superconductors.

Mesoporous Gold Nanostructures: Synthesis and Beyond.

Mesoporous metal nanostructures have offered multiple advantages that cannot be realized elsewhere. These materials have been attracting more research attention in catalysis and electrocatalysis owing to their functional structures and compositions. Of the various mesoporous metals available, mesoporous gold (mesoAu) nanostructures are of special interest in surface-enhanced Raman scattering (SERS) and related applications because of their strong electromagnetic field (localized surface plasmon resonance). In the last few decades, various synthesis strategies have been developed to prepare mesoAu nanostructures with controllable morphologies that exhibit fascinating physicochemical properties and increase applications in SERS, catalysis, and electrocatalysis. In this Perspective, we systematically summarize recent advances in synthesis and applications of mesoAu nanostructures. Four synthesis strategies, including dealloying, nanocasting, electrochemical deposition, and intermediate template, are discussed in detail. Moreover, physicochemical properties and promising applications of mesoAu nanostructures are presented. Finally, we describe current challenges and give a general outlook to explore further directions in synthesis and applications of mesoAu nanostructures.

Tongxinluo May Alleviate Inflammation and Improve the Stability of Atherosclerotic Plaques by Changing the Intestinal Flora.

Intestinal flora plays an important role in atherosclerosis. Tongxinluo, as a multi-target Chinese medicine to improve atherosclerosis, whether it can improve atherosclerosis by affecting the intestinal flora is worth exploring. We established a vulnerable plaque model of atherosclerosis in New Zealand white rabbits by high cholesterol diet and balloon injury (HCB), and performed Tongxinluo intervention. We detected the level of inflammation by immunohistochemistry, Western Blot, and ELISA, analyzed plaque characteristics by calculating the vulnerability index, and analyzed the changes of gut microbiota and metabolites by 16S rRNA gene sequencing and untargeted metabolomic sequencing. The results showed that Tongxinluo intervention improved plaque stability, reduced inflammatory response, inhibited NLRP3 inflammatory pathway, increased the relative abundance of beneficial bacteria such as Alistipes which reduced by HCB, and increased the content of beneficial metabolites such as trans-ferulic acid in feces. Through correlation analysis, we found that some metabolites were significantly correlated with some bacteria and some inflammatory factors. In particular, the metabolite trans-ferulic acid was also significantly positively correlated with plaque stability. Our further studies showed that trans-ferulic acid could also inhibit the NLRP3 inflammatory pathway. In conclusion, Tongxinluo can improve plaque stability and reduce inflammation in atherosclerotic rabbits, which may be achieved by modulating intestinal flora and intestinal metabolism. Our study provides new views for the role of Tongxinluo in improving atherosclerotic vulnerable plaque, which has important clinical significance.

Phonon-mediated superconductivity in two-dimensional hydrogenated phosphorus carbide: HPC3.

In recent years, three-dimensional (3D) high-temperature superconductors at ultrahigh pressure have been reported, typical examples are the polyhydrides H3S, LaH10, YH9, etc. To find high-temperature two-dimensional (2D) superconductors at atmospheric pressure is another research hotspot. Here, we investigated the possible superconductivity in a hydrogenated monolayer phosphorus carbide based on first-principles calculations. The results reveal that monolayer PC3 transforms from a semiconductor to a metal after hydrogenation. Interestingly, the C-π-bonding band contributes most to the states at the Fermi level. Based on the electron-phonon coupling mechanism, it is found that the electron-phonon coupling constant of HPC3 is 0.95, which mainly originates from the coupling of C-π electrons with the in-plane vibration modes of C and H. The calculated critical temperature Tc is 31.0 K, which is higher than those in most 2D superconductors. By further applying a biaxial tensile strain of 3%, the Tc can be boosted to 57.3 K, exceeding the McMillan limit. Thus, hydrogenation and strain are effective ways for increasing the superconducting Tc of 2D materials.

Association Between Stent Implantation and Progression of Nontarget Lesions in a Rabbit Model of Atherosclerosis.

BACKGROUND: Progression of nontarget lesions (NTLs) after percutaneous coronary intervention (PCI) has been reported. However, it remains unknown whether progression of NTLs was causally related to stenting. This study was undertaken to test the hypothesis that stent implantation triggers acute phase response and systemic inflammation which may be associated with progression of NTLs. METHODS: Thirty New Zealand rabbits receiving endothelial denudation and atherogenic diet were randomly divided into stenting, sham, and control groups. Angiography and intravascular ultrasonography were performed in the stenting and sham groups, and stent implantation performed only in the stenting group. Histopathologic study was conducted and serum levels of APPs (acute phase proteins) measured in all rabbits. Proteomics analysis was performed to screen the potential proteins related to NTLs progression after stent implantation. The serum levels of APPs and inflammatory cytokines were measured in 147 patients undergoing coronary angiography or PCI. RESULTS: Plaque burden in the NTLs was significantly increased 12 weeks after stent implantation in the stenting group versus sham group. Serum levels of APPs and their protein expression in NTLs were significantly increased and responsible for stenting-triggered inflammation. In patients receiving PCI, serum levels of SAA-1 (serum amyloid A protein 1), CRP (C-reactive protein), TNF (tumor necrosis factor)-α, and IL (interleukin)-6 were substantially elevated up to 1 month post-PCI. CONCLUSIONS: In a rabbit model of atherosclerosis, stent implantation triggered acute phase response and systemic inflammation, which was associated with increased plaque burden and pathological features of unstable plaque in NTLs. The potential mechanism involved vessel injury-triggered acute phase response manifested as increased serum levels of SAA-1, CRP, and LBP (lipopolysaccharide-binding protein) and their protein expression in NTLs. These findings provided a new insight into the relation between stent implantation and progression of NTLs, and further studies are warranted to clarify the detailed mechanism and clinical significance of these preliminary results. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900026393. Graphic Abstract: A graphic abstract is available for this article.

Ginsenoside Rb1 Enhances Plaque Stability and Inhibits Adventitial Vasa Vasorum via the Modulation of miR-33 and PEDF.

Background: Atherosclerosis is closely associated with proliferation of the adventitial vasa vasorum, leading to the atherosclerotic plaque progression and vulnerability. In this report, we investigated the role of Ginsenoside Rb1 (Rb1) on atherosclerotic plaque stabilization and adventitial vasa vasorum (VV) along with the mechanisms involved. Methods and Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed with a high-fat diet for 20 weeks, and then Ginsenoside Rb1 (50 mg/kg/d, intraperitoneal) was given for 4 weeks. Rb1 treatment significantly inhibited adventitial VV proliferation, alleviated inflammation, decreased plaque burden, and stabilized atherosclerotic plaques in apoE-/- mice. However, the beneficial effects of Rb1 on atherosclerotic lesion was attenuated by overexpression of miR-33. The analysis from atherosclerotic plaque revealed that Rb1 treatment could result in an induction of Pigment epithelium-derived factor (PEDF) expression and reduction of the miR-33 generation. Overexpression of miR-33 significantly reverted the Rb1-mediated elevation of PEDF and anti-angiogenic effect. Conclusions: Ginsenoside Rb1 attenuates plaque growth and enhances plaque stability partially through inhibiting adventitial vasa vasorum proliferation and inflammation in apoE-/- mice. The anti-angiogenic and anti-inflammation effects of Rb1 are exerted via the modulation of miR-33 and its target gene PEDF.

A phase Ⅲ randomized controlled study of a domestic endoscopic robot used in radical prostatectomy / 中华泌尿外科杂志

Objective:To evaluate the safety and efficacy of Toumai ? endoscopic robotic system in radical prostatectomy. Methods:This study was a single-center phase Ⅲ randomized controlled study. From June 2020 to January 2021, patients with prostate cancer who met the inclusion criteria in Changhai Hospital Affiliated to Naval Military Medical University were divided into the experimental group and the control group by random table method. Inclusion criteria included aged 18 to 80 years, pathologically diagnosed as prostate cancer, clinical stage ≤T 2N 0M 0. Exclusion criteria included patients requiring emergency surgery, having serious cardiovascular diseases and cannot tolerate surgery, having participated in other investigational drug or device clinical trials within the last 3 months. The experimental group used Toumai ? laparoscopic robotic system, and the continence group used the Da Vinci robotic system. The patients in both groups underwent radical prostatectomy via a transabdominal approach, which was performed by two surgeons. The clinical characteristics between the two groups were compared, related adverse events were recorded, and PSA and urinary continence were followed up one month after the operation. Results:A total of 44 patients were enrolled in this study, including 22 cases in the experimental group and 22 cases in the control group. The mean age of patients in the trial group and the control group was (67.7±7.5) years and (66.4±6.3) years, respectively. The median PSA at diagnosis was 10.5 (7.7, 23.7) ng/ ml and 13.5 (8.9, 24.7) ng/ ml, respectively. Biopsy Gleason score of 6, 7, 8 and 9 in experimental group were 13.6% (3/22), 68.2% (15/22), 4.5% (1/22) and 13.6% (3/22), respectively, and in the control group were 4.5% (1/22), 59.1% (13/22), 22.7% (5/22) and 13.6% (3/22) respectively. The middle risk and high risk group in the experimental group was 50.0% (11/22), 50.0% (11/22), and the control group was 36.4% (8/22), 63.6% (14/22). There was no statistical difference between the two groups.The operations in both groups were successfully performed. There were no conversions to open or laparoscopic surgeries, and no Clavien-Dindo grade Ⅲcomplications. There was no significant difference in the estimated blood loss during the operation [(109.1±51.6)ml vs.(94.5±51.6)ml] and the blood transfusion rate [9.1%(2/22)vs. 4.5%(1/22)] in both groups. The operation time was significantly higher in the experimental group than that in the control group [164.5(130.5, 214.3) min vs. 88.0(65.3, 110.5)min, P<0.001]. The positive rate of surgical margin was 13.6% (3/22) in the experimental group and 36.4% (8/22) in the control group, respectively, showing no significant difference. The pathologic stages of pT 2, pT 3a and pT 3bin experimental group were 63.6% (14/22), 13.6% (3/22) and 22.7% (5/22), respectively, while those in control group were 36.3% (8/22), 40.9% (9/22) and 22.7% (5/22), respectively, showing no significant difference. The recovery rates of urine control in the experimental group and the control group were 22.7% (5/22) and 22.7% (5/22), respectively. The median PSA in the experimental group and the control group were 0.055 (0.021, 0.103) ng/ ml and 0.032 (0.010, 0.089) ng/ ml, respectively, with no statistical difference. Conclusions:The Toumai ? endoscopic robotic system can successfully perform radical prostatectomy, based on insignificant difference from Da Vinci robotic system in safety and efficacy. The short-term follow-up showed that tumor control and urinary continence have recovered well in the test group. The long-term effect of the new system on tumor control and functional recovery after radical prostatectomy needs further multi-center studies.

Substituent control of photophysical properties for excited-state intramolecular proton transfer (ESIPT) of o-LHBDI derivatives: a TD-DFT investigation.

The substituted effect on excited-state intramolecular proton transfer (ESIPT) of o-LHBDI derivatives (4R-o-LHBDI) was investigated by DFT and TD-DFT methods. The structures of 4R-o-LHBDI (R: OH, NH2, CN, NO2, CF3) were fully optimized, and the H-bond distances, bond angles, and infrared spectra of the atoms involved in PT process in the S0 and S1 states were analyzed. The absorption and fluorescence spectra were calculated, and the potential energy curves in both S0 and S1 states were constructed. Moreover, the effects of different substituents on the ESIPT mechanism of 4R-o-LHBDI (R: OH, NH2, CN, NO2, CF3) were studied. The results indicate that ESIPT in the 4R-o-LHBDI is a little harder to proceed than that in o-LHBDI since the ESIPT barrier of 4R-o-LHBDI is slightly bigger than that value of o-LHBDI. When the substituent has stronger electron-withdrawing ability or weaker electron-donating ability, the ESIPT process has the smaller potential barrier. Graphical abstract.

Impact of intracoronary nicorandil before stent deployment in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

The present study aimed to clarify the effect of bolus intracoronary nicorandil on inflammatory, oxidative and adherent indicators in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This randomized controlled trial (RCT) was performed to detect the inflammation and oxidative stress in intracoronary blood both before and after PCI. In total, 65 consecutive patients undergoing PCI were classified into a nicorandil therapy group (n=32) or a placebo group (n=33). All procedures were performed at Shandong University Qilu Hospital, China, during the period from March, 2016 to May, 2017. Intracoronary blood from patients who received nicorandil therapy during PCI showed no change in soluble CD40 ligand (sCD40L) concentration (1.86±0.08 vs. 1.90±0.09 ng/ml, P=0.12) but a significant increase was noted in the control group (1.87±0.17 vs. 2.82±0.26 ng/ml, P<0.01). This indicated a relative reduction in sCD40L level after PCI in the nicorandil group. We further demonstrated an increase in superoxide dismutase (SOD) activity (29.37±0.81 vs. 31.03±0.60 U/ml, P<0.001) and a reduction in lipid peroxidation (3.84±0.99 vs. 4.23±0.13 U/ml, P=0.001) in the nicorandil group but observed no change in the placebo group. ICAM-1 levels showed no change in the nicorandil group (69.54±6.89 vs. 72.01±8.25 ng/ml, P=0.83) but a significant increase in the control group after PCI in intracoronary blood (56.57±4.96 vs. 76.81±6.88 ng/ml, P=0.002). No changes were found in hs-CRP, TNFα and sVCAM-1 levels in coronary blood for both groups before and after PCI in ACS patients. Our findings demonstrate that intracoronary bolus nicorandil therapy has a significant effect on the inhibition of inflammatory indicators and oxidative stress in patients with ACS during PCI. This suggests a possible medical application of nicorandil for reducing inflammation and oxidative stress.

G-CSF Inhibits Growths of Osteoblasts and Osteocytes by Upregulating Nitric Oxide Production in Neutrophils.

OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is the critical regulator of the proliferation, differentiation, and survival of granulocytes. Recently, it has been shown that G-CSF can adversely affect bone health in both animal models and patients. Here, the authors aimed to investigate whether G-CSF could inhibit the growth of osteoblasts and osteocytes by regulating nitric oxide. METHODS: The C57BL/6 mice were divided into the control group, G-CSF treatment group and recovery group (G-CSF+L-NAME). The morphology of femurs was assessed by histology and immunohistochemistry. The expression of apoptosis-related molecules in femurs was detected by immunohistochemistry and quantitative RT-PCR, respectively. To examine if neutrophil-secreted factors can induce apoptosis in osteoblasts, Gr1-positive (Gr1+) neutrophils from the bone marrow of wild-type mice were sorted and co-cultured with MC3T3 pre-osteoblasts for 2 days. RESULTS: The number of osteoblasts and newly embedding osteocytes significantly decreased and markers related to osteoblasts and osteocytes were downregulated in the G-CSF treatment compared to the control group. Moreover, G-CSF treatment did not change proliferation markers but induced apoptosis in osteoblast-lineage cells. The combined treatment of mice with G-CSF and a nitric oxide inhibitor partially restored the number of osteoblasts and osteocyte parameters. CONCLUSIONS: The G-CSF can inhibit osteoblasts and osteocytes by upregulating nitric oxide.

Deficiency of NONO is associated with impaired cardiac function and fibrosis in mice.

Non-POU-domain-containing octamer-binding protein (NONO), a component of multifunctional Drosophila behavior/human splicing (DBHS) family, plays an important role in regulating glucose and fat metabolism, circadian cycles, cell division, collagen formation and fibrosis. Dysfunctional variants of NONO have been described as the cause of congenital heart defects in males. However, the effects of NONO deficiency on the ventricular function and cardiac fibrosis as well as the related mechanisms are not clear. In the present study, we aimed to reveal the overall phenotypes, cardiac function and fibroblasts in NONO knockout (NONO KO) mice compared with the wild-type (WT) male littermates. The results showed that the birth rate of NONOgt/0 mice was much lower than their WT male littermates at the time of weaning. The body weight of NONOgt/0 mice was 19% lower than that of WT male littermates (27.2 ±â€¯1.49 g vs. 22.01 ±â€¯1.20 g, P < .001). NONO KO mice exhibited continuous higher mortality from birth to a year later (P < .05). Compared with those in the WT mice, the heart weight was lower(142.0 ±â€¯8.7 mg vs. 179.0 ±â€¯10.4 mg, P < .001), the heart weight to body weight ratio (HW/BW) was similar, the E/A ratio was higher (1.80 ±â€¯0.47 vs. 1.44 ±â€¯0.26, P < .05), and the left ventricular end diastolic diameter (LVEDd) was significantly lower (2.72 ±â€¯0.51 mm vs.3.54 ±â€¯0.43 mm, P < .001) in the NONO KO mice. We also found excessive matrix deposition in vivo. In vitro, NONO deficiency led to fibroblasts hyperproliferation, while migration was inhibited, which would induce collagen maturation and deposition. Conversely, overexpression of NONO inhibited fibroblasts proliferation and increased migration which reduced collagen deposition. RNA-seq of cardiac fibroblasts further indicated that NONO deficiency upregulated the cell cycle regulators, which included cyclin B2, the origin recognition complex 1 (ORC1) and cell division cycle 6 (CDC6), while downregulated the migration regulators, which included myosins, integrin and coagulation factor II. Overexpression of NONO further verified the effects of these indicators. In conclusion, our study demonstrated that NONO deficiency was associated with developing heart defects in mice. Hyperproliferation of cardiac fibroblasts with dramatically excessive collagen secretion might be the cause of heart defects of NONO KO mice.

Tongxinluo may stabilize atherosclerotic plaque via multiple mechanisms scanning by genechip.

BACKGROUND: Chinese traditional medicine Tongxinluo capsule (TXL) has been widely used for cardiovascular diseases. Both clinical and basic studies showed that TXL had effective effects on atherosclerosis. However, the mechanism researches were relatively scattered. This study was aimed to fully evaluate the potential mechanisms of TXL on atherosclerosis as a whole. METHOD: One hundred apoE-/- mice (male, 12 weeks old) were randomly divided into five groups (n = 20 each group) Mice in the control group were fed normal diet and mice in the other four groups (intervention groups) were fed high fat diet. The intervention groups were randomly divided into normal saline (NS) group and TXL treatment groups, and the latter were further divided into three subgroups: low-dose TXL (TXL-L), medium-dose TXL (TXL-M) and high-dose TXL (TXL-H), with TXL dosage at 0.38, 0.75, 1.5 g/kg/d by gavage, respectively. After sixteen weeks of intervention, all mice underwent euthanasia. Gene expression profiles with aortic tissues were determined by genechip. A Gene Ontology (GO) analysis was performed to interpret the functional implications of altered genes. RESULT: Histological and morphological analysis demonstrated that TXL at different doses all reduced plaque burden and plaque size. The expressions of IL-6, TNF-ɑ and MMP-2 were significantly decreased in the TXL intervention groups compared with control. In atherosclerotic lesions of TXL groups 3284 genes altered compared with control, and 632 genes changed in the TXL-H group compared with the NS group. Of these genes, 48 showed a decrease which were high in atherosclerosis, and 56 showed a increase which were low in atherosclerosis after TXL intervention. Significantly altered genes were found to be involved in the aspects of hormone secretion, protein binding, lipid metabolic, fatty acid metabolic immune system process, and inflammatory response. CONCLUSION: TXL has effects on inhibiting atherosclerosis development and stablizing plaque. The comprehensive mechanisms, in addition to inflammation and lipid metabolism, might also involve cell physical function, hormone secretion, protein binding, and immune response process.

Overexpression of tissue factor induced atherothrombosis in apolipoprotein E-/- mice via both enhanced plaque thrombogenicity and plaque instability.

The mechanisms leading to atherothrombosis from "vulnerable plaque" are more complex than initially proposed. We aimed to clarify whether plaque thrombogenicity is critical in atherothrombosis in mice. In a murine model of plaque destabilization, we enhanced plaque thrombogenicity by systemically overexpressing murine tissue factor (TF) by adenovirus-mediated gene transfer. The potential effects and mechanisms of TF on plaque destabilization were examined in cultured human aortic smooth muscle cells (HASMCs), RAW264.7 cells and human umbilical vein endothelial cells (HUVECs). To elucidate the TF noncoagulant effects on plaque destabilization, TF-overexpressed mice were treated with the protease-activated receptor 2 (PAR-2) antagonist ENMD-1068. In TF-overexpressing apolipoprotein (E)-deficient (ApoE-/-) mice, 67% (8 of 12) of carotid plaques exhibited plaque disruption and atherothrombosis. Moreover, 58% (7 of 12) showed plaque hemorrhage, including 1 due to plaque disruption, 4 neovascularization and 2 both. In contrast, only 17% (2 of 12) of control mice showed atherothrombosis, both with plaque hemorrhage but no neovascularization. On PCR, TF overexpression increased the expression of inflammatory factors. In cultured cells, the TF-FVIIa complex enhanced the expression of inflammatory factors and a vicious cycle of inflammation. Also, TF-FVIIa complex induced intra-plaque angiogenesis via PAR-2. ENMD-1068 treatment significantly inhibited the expression of inflammatory factors and neovascularization, and the incidence of intra-plaque hemorrhage decreased in TF-overexpressing mice. In conclusions, TF overexpression enhanced plaque thrombogenicity, which played a pivotal role in atherothrombosis in ApoE-/- mice. In addition, TF promoted plaque instability by activating inflammatory and proangiogenic effects via TF-FVIIa/PAR-2 signaling.

Synthesis of Biomass-Derived Carbon Induced by Cellular Respiration in Yeast for Supercapacitor Applications.

Because activated carbon is extensively used in supercapacitors, optimization of its precursors and synthetic strategies are crucial. Inspired by the rich sugar content of banana peel waste, which can be transformed through the respiration of yeast into alcohol with the release of CO2 , we developed an environmentally benign and highly efficient process for the production of renewable heteroatom-doped hierarchical porous carbon materials (yeast-treated banana-peel-based carbon, denoted as YBP) without any additional templates or activation agents. The resulting biologically activated carbon was characterized by near-edge X-ray absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, and other physical methods. The biologically activated carbon achieved a maximum gravimetric specific capacitance of 476 F g-1 in 1 m H2 SO4 electrolyte. Remarkably, with a moderate specific surface area of 1084 m2 g-1 , the as-obtained activated carbon was found to have a high packing density. With enriched pseudocapacitance sites, the YBP symmetric supercapacitor has a high volumetric specific capacitance and energy density (maximum values of 264 F cm-3 and 23.5 Wh L-1 , respectively). The supercapacitor showed superior cyclic stability, with 94 % capacitance retention for voltage values up to 1.6 V after 10 000 cycles, which confirmed the promising application of this supercapacitor in miniature electronic devices.

Serum endocan and circadian heart rate variability in non-dialysis stage 5 chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that elevated heart rate (HR) is a risk factor for cardiovascular mortality. We investigated the link between serum endocan and circadian heart rate variability in non-dialysis stage 5 CKD patients. METHODS: In a cross-sectional study, we enrolled 54 prevalent n non-dialysis stage 5 CKD patients (32 males, aged 48.2 ± 14.92 years). HR was measured with an automatic system. Serum endocan level was analyzed by ELISA. RESULTS: Night/day HR ratio was independently predicted by serum endocan level (P < 0.01) and hypertension history (P < 0.05). Adjusted R2 of the model was 0.222. CONCLUSION: Increased serum endocan is significantly associated with circadian heart rate variability in non-dialysis stage 5 CKD patients. Further investigation is needed to explore the potential benefits of serum endocan lowering therapy in this patient group.

Validation of the China-PAR Equations for Cardio-cerebrovascular Risk Prediction in the Inner Mongolian Population.

The objective of this study was to evaluate the usefulness of the China-PAR equations in predicting the 10-year risk of cardiovascular disease (CVD) in the Inner Mongolians population. A population-based, prospective cohort of 2,589 Mongolians were followed up from 2003 to 2012. Participants were categorized into 4 subgroups according to their 10-year CVD risks calculated using the China-PAR equations: < 5%, 5%-9.9%, 10%-19.9%, and ⪖ 20%. The China-PAR equations discriminated well with good C statistics (range, 0.76-0.86). The adjusted hazard ratios for CVD showed an increasing trend among the 4 subgroups (P for trend < 0.01). However, the China-PAR equations underestimated the 10-year CVD risk in Mongolians, and the calibration was unsatisfactory (Hosmer-Lemeshow χ2 = 19.98, P < 0.01 for men, χ2 = 46.58, P < 0.001 for women). The performance of the China-PAR equations warrants further validation in other ethnic groups in China.