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The novel diketopiperazine alkaloid toxicocladine A (1), two new natural products cyclo(L-Phe-ΔAla) (2) and cyclo(L-Tyr-ΔAla) (3), and three known compounds protocatechuic acid (4), protocatechuic acid methyl ester (5) and ergosterol peroxide (6), were isolated from the fungus Toxicocladosporium sp. CYH-18 collected from the Haima cold seep. The structures and absolute configurations of the compounds were determined via NMR, MS, optical rotation, and X-ray diffraction analysis and by comparison with the literature. Structurally, compound 1 was a diketopiperazine with an unprecedented methylene sulfide bridge between C-5 and C-8, while compounds 2 and 3 were diketopiperazines with terminal olefins. Compounds 4 and 5 showed antioxidant activity. Compound 6 displayed antibacterial activity against Bacillus subtilis and Exiguobacterium profundum. [Display omitted] • Three new alkaloids were found in this study. • There was a methylene sulfide bridge in compound 1. • The absolute configuration of compound 1 was determined by X-ray diffraction. • Compounds 4 and 5 exhibited antioxidant activity. • Compound 6 showed inhibitory activity. [ABSTRACT FROM AUTHOR]

• Long-term exposure of peritoneal dialysate and chronic inflammation were risk factors of encapsulating peritoneal sclerosis. • The miRNA-based model could be useful to assist to determine the possibility of encapsulating peritoneal sclerosis. • 5 miRNAs were key regulators of TGF-β signal pathway in mesothelial-mesenchymal transition and immune systems. • The interaction network of miRNAs and compounds indicated these these miRNAs have the therapeutic potential targets. Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-β signaling pathway. The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three new isopimaric acid diterpenoids were isolated from the bark of Cryptomeria japonica. • Structures of these isolates were elucidated by spectroscopic methods. • Some isolates exhibited xanthine oxidase inhibitory activities. Three new isopimaric acid diterpenoids, 6-oxoisopimaric acid (1), 6α-hydroxyisopimaric acid (2), and isopimara-7,9(11),15-trien-18-oic acid (4), together with two known isopimaric acid diterpenoids, isopimaric acid (3), and 8(14),15-isopimaradien-18-oic acid (5), were isolated from the bark of Cryptomeria japonica D. Don. Their structures were determined by analysis of spectroscopic data and comparison with the spectral data of known analogues. At the concentration of 50 μM, compounds 1 – 5 inhibited xanthine oxidase activity by 17.3, 16.5, 2.6, 30.5, and 24.5 %, respectively. [ABSTRACT FROM AUTHOR]

The exploitation of high-quality borophosphate-based phosphor products is currently garnering a significant research focus in solid-state light source. The interest is due to its low-cost and environment-friendly synthesis. In this paper, a new La 7 O 6 (BO 3)(PO 4) 2 (LBP):Dy phosphor was developed via sintering at 1673 K for 3 h under an air atmosphere. Structural characterization indicates that all of the prepared products are the monoclinic phases with the space group P 2 1 /n. A comparison of the surface chemical states of the elemental compositions for the LBP host versus optimal LBP:13%Dy product was conducted via X-ray photoelectron spectroscopy. Optical characterization shows that the Dy-doped products exhibited visible light emissions of Dy3+ from 4F 9/2 to 6H 15/2 , 6H 13/2 , and 6H 11/2 upon exposure to 348 nm near-ultra violet irradiation. The dominant emission (yellow, 576 nm) belongs to the 4F 9/2 → 6H 13/2 transition. The best Dy content for doping was 13 mol%, and content quenching occurred due to dipole – dipole interaction. The measured decay lifetime and calculated chromatic properties together manifest that the optimal LBP:13%Dy phosphor shows potential as a yellow ingredient in solid-state lighting. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Three new 7-oxoabietane-type diterpenoids were isolated from the bark of Cryptomeria japonica. • Structures of these isolates were elucidated by spectroscopic methods. • Two 7-oxoabietane-type diterpenoids exhibited xanthine oxidase inhibitory activity. Abstract Three new 7-oxoabietane-type diterpenoids, 3-oxosugiol methyl ether (1), 18-hydroxysugiol (2), and 1β-hydroxysugiol (3), as well as two known 7-oxoabietane-type diterpenoids, 6α-hydroxysugiol (4) and 6α-acetoxysugiol (5), were isolated from the bark of Cryptomeria japonica D. Don. Their structures were elucidated mainly by NMR and HREIMS, as well as on comparison with the data of known analogues. At the concentration of 75 μM, compounds 2 and 5 exhibited 11.9 and 21.7% xanthine oxidase inhibitory activity, respectively. [ABSTRACT FROM AUTHOR]

Background/purpose: Emerging research findings suggest that long non-coding RNAs (lncRNAs) are key regulators to fibrosis formation. Nevertheless, the role of lncRNA GAS5-AS1 in the progression of precancerous oral submucous fibrosis (OSF) remains to be elucidated.Methods: Quantitative real-time PCR were used to examine the expression of GAS5-AS1 in OSF tissues. The activities of myofibroblasts, including collagen contractility and cell migration, as well as the marker α-smooth muscle actin (SMA) were assessed following overexpression of GAS5-AS1. Also, we analyzed the expression of Smad activity in order to gain insight into the downstream regulator.Results: The level of GAS5-AS1 was found significantly downregulated in the OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs). Ectopic expression of GAS5-AS1 significantly reduced the abilities of collagen gel contraction and migration in fBMFs or arecoline-treated BMFs. Moreover, we have shown that overexpression of GAS5-AS1 inhibited the expression of p-Smad and the marker of myofibroblasts.Conclusion: We showed the reduced expression of GAS5-AS1 in OSF tissues and demonstrated its effect on the myofibroblast activities and the level of p-Smad and α-SMA, indicating its potential contribution in OSF pathogenesis. [ABSTRACT FROM AUTHOR]

Background/purpose: With an increasing geriatric population, the need for effective management of chronic conditions and medication use in the elderly is growing. Medication use in the elderly presents significant challenges due to changes in pharmacodynamic and pharmacokinetic profiles. We aimed to examine the impact of a collaborative physician-pharmacist medication therapy management (MTM) program for polypharmacy elderly patients.Methods: Elderly patients with multiple chronic conditions on polypharmacy were enrolled in this prospective, randomized, and controlled study over 16 months of implementation. The intervention group consisted of patients randomized to a collaborative pharmacist-physician MTM program. They were monitored continuously by a clinical pharmacist, while patients in the control group received only usual care with follow-up assessment. Primary outcome was economic differences, measured in total medical expenditure. Secondary outcomes of clinical and humanistic effects were compared between the two groups.Results: The total number of enrolled patients was 87 and 91 in the MTM and usual groups, respectively. The difference-in-difference estimate on medical expenditure during the 16-month implementation period was $3,758,373 New Taiwan Dollars ($127,015 US Dollars) less than the usually care group. Impact was also seen in humanistic outcomes while lipid profiles and mortality trended toward improvement.Conclusion: The pharmacist-physician collaborative MTM program for polypharmacy elderly had significant cost savings and improvement in humanistic measures, demonstrating the importance of clinical pharmacists and MTM programs for elderly patients in Taiwan. The results suggest the possibility of clinical benefits, but the study was not substantially powered to find a statistical difference. [ABSTRACT FROM AUTHOR]

Visualization has been extensively applied in many areas, especially for the management of massive data and the display interface area. However, the complexity of grid connections in a large-scale power system is a challenging issue. For an efficient power system operation, it is necessary for electrical engineers and operators to analyze huge amount of data. Additionally, providing real-time operating status and visualization to system operators is also significant. This work reviews different types of power system visualization techniques, including power-flow visualization, trend charts, pie chart, area chart, and warnings in colors. This work also developed a visualization interface that displays the transmission system congestions for N-0 steady state and N-1 contingency analyses. The developed visualization interface has been applied to the Taiwan power system by considering real system parameters and operating conditions, and the developed visualization techniques include the plot for displaying real-time transmission system operation, status warning, and N-1 system contingencies. The developed visualization interface helps system operators understand the real-time operating conditions and determine the potential schedules for generation and transmission systems. [ABSTRACT FROM AUTHOR]

Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db-/- mice. The results demonstrate that EPA and DHA alleviate high glucose-mediated impairment of tubular formation in EPCs through a rescue of neovasculogenic capability. The molecular mechanisms underlying the effects of EPA and DHA include the activation of the extracellular signal-regulated kinase 1/2, Akt/endothelial nitric oxide synthase (eNOS) and AMP-activated kinase (AMPK) signaling cascades as well as the phosphorylation of the downstream FOXO3a protein in EPCs. Moreover, EPA and DHA up-regulate the expression of c-kit, erythroid 2-related factor and heme oxygenase-1 proteins. Daily consumption of FO at dosages of 4% and 6% (wt/wt) significantly increased the level of bone marrow-derived and circulating EPCs, induced a recovery of blood flow and prevented ischemic injuries in a T2D db-/- mouse model. The effects of FO consumption were exerted the activation of Akt/eNOS and AMPK signaling cascades without any effect on the plasma VEGF level in vivo. [ABSTRACT FROM AUTHOR]

Objective: Depression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.Methods: We conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.Results: We recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63±12years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8-14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p=0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69-9.72, p<0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.Conclusion: Qi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients' depression symptoms. [ABSTRACT FROM AUTHOR]

Purpose Topiramate is an effective anti-epileptic drug and can be associated with increased risk for urolithiasis because of its effects on acid–base profile. Evidences that supported an association of topiramate and urolithiasis were limited to case reports or series. We investigated the association of topiramate and urolithiasis in a nationwide population-based cohort study. Methods We analyzed 1377 patients receiving topiramate and 1377 age- and gender-matched control patients (not receiving topiramate) between 1997 and 2008. The risk of urolithiasis was analyzed using Kaplan–Meier analysis, followed by Cox proportional hazard regression. Results Of the 2754 patients, 79 (2.9%) patients developed urolithiasis in two (interquartile range: 1.2–4.2) years. The proportion of patients who developed urolithiasis in the patients receiving topiramate was not different from that of the control patients ( p = 0.138, χ 2 test). The urolithiasis free survival was not different between the patients receiving topiramate and the control patients ( p = 0.168) in Cox proportional hazard regression. The duration and total dosage of topiramate were not associated with risk of urolithiasis in patients receiving topiramate ( p = 0.482 and p = 0.751). Conclusion Topiramate may not increase the risk of urolithiasis. The duration and the total dosage of topiramate were not associated with urolithiasis risks. [ABSTRACT FROM AUTHOR]

Many studies have shown that chronic stress can cause neuronal damage and depression, but this exact mechanism still remains unknown. Neurons are vulnerable to lipid peroxidation-induced damage because the major part of neuronal cell membrane is polyunsaturated fatty acids that are substrate for reactive oxygen species. Since endogenous antioxidant defense systems normally eliminate production of reactive oxygen species, deficient antioxidant defense can cause oxidative stress-induced damage. In the present study, to understand the role of endogenous antioxidant defense in chronic stress-induced neuronal damage, we analyzed lipid peroxidation, total antioxidant capacity, and activities of catalase and glutathione peroxidase in frontal cortex, hippocampus and striatum of rats exposed to chronic unpredictable stress. We found that chronic unpredictable stress for four weeks in rats induced depressive-like behaviors such as anhedonia, despair and decreased exploration. Malondialdehyde, a lipid peroxidation product, is increased, but total antioxidant capacity, glutathione peroxidase activity and catalase activity are decreased in brain of rats exposed to chronic unpredictable stress. Our findings suggest that down regulation of endogenous antioxidant defense induces lipid peroxidation contributing a role to chronic stress and depression. [ABSTRACT FROM AUTHOR]

Two new compounds, derriscoumaronochromone ( 1 ) and cis -3,4′-dihydroxy- 5,7-dimethoxyflavan ( 2 ), as well as trans -4'- O -methylcatechin ( 3 ) were isolated from Derris laxiflora , The structures of these compounds were determined by analysis of their spectroscopic data. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two new labdane-type diterpenes were isolated and characterized from Cunninghamia konishii. [•] Four known labdane-type diterpenoids were isolated from C. konishii. [•] Structures of these isolates were elucidated by spectroscopic methods. [Copyright &y& Elsevier]

Neuromorphic electronics with two-dimensional van der Waals materials meet the ever-increasing demands of both the semiconductor industry and biological engineering, such as miniaturization, structure flexibility, multifunctionality, and low power consumption. However, the majority of reported electronic devices achieve multifarious memory storage states or synaptic plasticity through regulation of an electrical or an optical signal. Herein, we propose an innovative touch-modulated device based on an indium selenide/hexagonal boron nitride/graphene van der Waals heterostructure coupled with a triboelectric nanogenerator. The device is prepared utilizing a simple copper grid shadow mask instead of the expensive and cumbersome electron beam lithography process, exhibits high mobility of 829 cm2 V−1 s−1, low voltage, and low power consumption. Nonvolatile memory with self-writing power, durability and multibit data storage is achieved through mechanical modulation without an additional gate-voltage supply. Moreover, by adjusting the distance between the two friction layers, essential synaptic plasticity, including short-term and long-term potentiation/depression and paired-pulse facilitation/depression, are successfully imitated in the device. Most importantly, we achieve ultralow power consumption of 165 aJ in tribotronic synapses owing to the ultra-high mobility of InSe. Our tribotronic synapse with self-writing power has great potential to simulate the low-power-consuming neuromorphic bioelectronic devices with multiple functions and lays the foundation for future advanced neuromorphic systems and artificial intelligence. Touch-modulated van der Waals Heterostructure with Self-writing Power Switch for Synaptic Simulation , is demonstrated by an InSe floating-gate device, coupled with a triboelectric nanogenerator (TENG). We demonstrated a zero-writing-power nonvolatile memory with an on/off ratio of 104, excellent repeatability over 100 cycles, and diverse data storage, and the whole system has no additional electrical and optical signal input. When InSe transistor is normally/reversely connected with TENG, by adjusting the distance (D + / D −) between the two friction layers of TENG, excitatory/inhibitory plasticity behaviours with low-power consumption 165 aJ successfully simulated. [Display omitted] • The tribotronic synapses compose of a floating-gate transistor with van der Waals heterostructures integrated with a TENG. • The NVM features including diverse date storage, on/off resolution of 104 and repeatability over 100 cycles were achieved. • The excitatory/inhibitory diverse synaptic plasticity behaviors were successfully imitated. • The tribotronic synapse exhibited ultralow energy consumption of 165 aJ superior to other work. [ABSTRACT FROM AUTHOR]

Abstract: Equal-channel angular pressing (ECAP) was applied to the as-cast Mg–8wt.%Zn–5wt.%Al (ZA85) alloy to produce a fine-grained structure with fine and uniformly distributed Mg32 (Al, Zn)49 (τ-phase) particles. Experiments showed that the ZA85 alloy had an initial grain size of ∼150μm after casting and was significantly reduced to 4μm after six ECAP passes at 180°C. After annealing at 300°C for 1h, the average grain size merely increased to 7.1μm. This thermal stability of the fine-grained structure at temperatures at or below 325°C is attributed to the presence of the fine and well distributed τ-phase. It was demonstrated that ECAP processing greatly enhances ductility of the experimental alloy. By testing over a range of temperatures and strain rates, a maximum elongation to failure of 400% was obtained in the ECAP ZA85 alloy tested at 300°C (0.53 Tm ) with the initial strain rate of 1.0×10−4 s−1. The dominant deformation mechanism for the specimens tested at 300 and 350°C with the initial strain rates ranging from 1.0×10−4 s−1 to 1.0×10−3 s−1 is GBS controlled by grain boundary diffusion. At the higher testing temperature of 400°C, the deformation mechanism for the experimental alloy is dislocation creep. [Copyright &y& Elsevier]

Abstract: Preventive or therapeutic effects of caffeic acid in brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice against inflammatory injury were examined. Caffeic acid at 0.5, 1 or 2% was supplied either pre-intake or post-intake for 4weeks. Brain caffeic acid content was increased by caffeic acid pre-intake at 1 and 2%, and post-intake at 2% (P <0.05). MPTP treatment enhanced the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-4 and IL-10 (P <0.05). Pre-intake of caffeic acid decreased the production of test cytokines (P <0.05); however, post-intake only at 2% reduced the level of IL-1beta, IL-6 and TNF-alpha (P <0.05). MPTP treatment up-regulated mRNA expression of inducible nitric oxide synthase (iNOS), neuronal NOS, cyclooxygenase (COX)-2, glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1, and increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) (P <0.05). Caffeic acid pre-intake at test doses and post-intake at 2% declined the expression of iNOS, COX-2 and GFAP; and lowered the production of NO and PGE2 (P <0.05). MPTP treatment suppressed mRNA expression of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and tyrosine hydroxylase (TH), and lowered dopamine level (P <0.05). Caffeic acid pre-intake retained the expression of these factors, maintained TH activity and protein production, and dopamine synthesis (P <0.05). These results suggest that caffeic acid is a potent neuroprotective agent against the development of Parkinson''s disease. [Copyright &y& Elsevier]