Dynamic Design of a Quad-Stable Piezoelectric Energy Harvester via Bifurcation Theory.

The parameter tuning of a multi-stable energy harvester is crucial to enhancing harvesting efficiency. In this paper, the bifurcation theory is applied to quantitatively reveal the effects of structural parameters on the statics and dynamics of a quad-stable energy harvester (QEH). Firstly, a novel QEH system utilizing the geometric nonlinearity of springs is proposed. Static bifurcation analysis is carried out to design quad-stable working conditions. To investigate the cross-well and high-energy vibration, the complex dynamic frequency (CDF) method, suitable for both weakly and strongly nonlinear dynamic problems, is then applied to deduce the primary response solution. By using the unfolding analysis in singularity theory, four steady-state properties and dozens of primary resonance modes are demonstrated. Based on the transition set, the effective bandwidth for energy harvesting can be customized to adapt well to various vibration environments by parametric adjustment. Finally, the experimental tests verify that the output power can reach up to 1 mW. The proposed QEH and its mechanics optimization can guide energy supply for next-generation wireless systems and low-power sensors under magnetic forbidding environments.

Hypha essential genes in Candida albicans pathogenesis of oral lichen planus: an in-vitro study.

BACKGROUND: Hypha essential genes (HEGs) of Candida Albicans have been emerging into scholar's attention, little known about their functions in oral lichen planus (OLP) with an uncovered etiology. This research aimed to observe necessary genes in biphasic C. albicans from OLP and study their relevance in pathogenesis, so as to evaluate possible roles of morphologic switching in etiology of OLP. METHODS: Samples were collected from OLP lesions of patients, mycelia were cultured and total RNA was extracted then subjected to reverse transcription-PCR and real-time PCR. RESULTS: HWP1 and HGC1 were significantly expressed in hyphae phase and weakly detected in yeast phase, while there was no significant difference of EFG1, ALS3, and ECE1 between in yeast and mycelia. CONCLUSION: HGC1 and HWP1 were confirmed to be hypha essential genes, with HGC1 for hypha morphogenesis and HWP1 for adhesion invasion in pathogenesis of C. albicans in OLP. ALS3, ECE1 and EFG1 played minor roles in hyphae maintenance and adhesion for hyphae. These might be deemed as hints for the etiology of OLP and indicate HGC1 and HWP1 to be a priority of potential drug target.

Lanostane Triterpenoids from the Fruiting Bodies of Fomes officinalis and Their Anti-Inflammatory Activities.

In the current study, further chemical investigation of the fruiting bodies of Fomes officinalis led to isolate seven new 24-methyl-lanostane triterpenoids, named officimalonic acids I-O (1-7). Their structures were elucidated based on the analysis of spectroscopic data (HR-MS, 1D and 2D NMR, UV, IR). Compounds 1-3 possessed an unusual C-23 spirostructure moiety, while compounds 4-7 had 23,26-lactone unit. Anti-inflammatory assay revealed that compounds 3 and 5 exhibited significant inhibitory activities against NO production in LPS-induced RAW 264.7 cells and cyclooxygenase (COX-2).

Triterpenoid Saponin and Lignan Glycosides from the Traditional Medicine Elaeagnus angustifolia Flowers and Their Cytotoxic Activities.

A new triterpenoid saponin, named terpengustifol A (1), and two new lignan glucosides, phengustifols A and B (2 and 3), were isolated from the flowers of Elaeagnus angustifolia. Their structures were determined by the extensive analysis of the spectroscopic data (including NMR and HRMS) and ECD calculations. Compound 1 possesses an unusual monoterpene (Z)-6-hydroxy-2,6-dimethylocta-2,7-dienoyl unit at C-21. Compounds 2 and 3 are a pair of diastereoisomers, while their aglycones are a pair of enantiomers. Compounds 1 and 2 exhibited moderate cytotoxic activities against A375 cell lines with IC50 values at 12.1 and 15.6 µM, respectively. This is firstly reported the triterpenoid saponin and lignans isolated from the Elaeagnus angustifolia flowers.

Mechanical Behaviors Research and the Structural Design of a Bipolar Electrostatic Actuation Microbeam Resonator.

A class of bipolar electrostatically actuated micro-resonators is presented in this paper. Two parametric equations are proposed for changing the microbeam shape of the upper and lower sections. The mechanical properties of a micro-resonator can be enhanced by optimizing the two section parameters. The electrostatic force nonlinearity, neutral surface tension, and neutral surface bending are considered in the model. First, the theoretical results are verified with finite element results from COMSOL Multiphysics simulations. The influence of section variation on the electrostatic force, pull-in behaviors and safe working area of the micro-resonator are studied. Moreover, the impact of residual stress on pull-in voltage is discussed. The multi-scale method (MMS) is used to further study the vibration of the microbeam near equilibrium, and the relationship between the two section parameters of the microbeam under linear vibration was determined. The vibration amplitude and resonance frequency are investigated when the two section parameters satisfy the linear vibration. In order to research dynamic analysis under the case of large amplitude. The Simulink dynamics simulation was used to study the influence of section variation on the response frequency. It is found that electrostatic softening increases as the vibration amplitude increases. If the nonlinearity initially shows hardening behavior, the frequency response will shift from hardening to softening as the amplitude increases. The position of softening-hardening transition point decreases with the increase of residual stress. The relationship between DC voltage, section parameters, and softening-hardening transition points is presented. The accuracy of the results is verified using theoretical, numerical, and finite element methods.

[Chemical constituents from traditional Uighur herbal medicine Elaeagnus angustifolia flowers].

Seven aromatic glycosides (1-7), including four phenylethanol glycosides, one phenylmethanol glycoside, one phenylpropane glycoside and one benzoside, were isolated from the methanolic extract of Uighur Medicine Elaeagnus angustifolia flowers. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Compound 1 is a new compound, named as angustifol A. Six known compounds were identified as 2-phenylethyl-O-ß-D-glucopyranoside(2), salidroside (3), vanillic acid 4-O-ß-D-glucopyranoside(4), vanilloloside (5), (Z)-isoconiferin (6), 2-phenylethyl-6-O-α-L-arabinofuranosyl-ß-D-glucopyranoside (7). Compounds 2-7 were isolated from the genus Elaeagnus for the first time. In vitro anti-inflammatory assays revealed that none of these compounds showed good COX inhibitory activities.

[Two new triterpenoid acids from Uighur medicine Fomes officinalis].

Two new lanostane triterpenoid acids, 12ß, 15α-dihydroxy-24-methyl-3,23-dioxo-lanosta-7,9(11)-dien-26-oic acid (1), and 3α, 12ß-dihydroxy-24-methyl-7,23-dioxo-lanosta-8-en-26-oic acid (2), were isolated from the methanolic extract of Uighur medicine Fomes officinalis. Their structures were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Anti-inflammatory and cytotoxicity assays revealed that both compound 1 and 2 show no inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 cells, and no cytotoxicity activities against HepG2 cells.

Intervention of Grape Seed Proanthocyanidin Extract on the Subchronic Immune Injury in Mice Induced by Aflatoxin B1.

The aim was to investigate the prevention of grape seed proanthocyanidin extract (GSPE) on the subchronic immune injury induced by aflatoxin B1 (AFB1) and the possible ameliorating effect of GSPE in mice. The subchronic AFB1-induced immune injury mice model was set up with the continuous administration of 100 µg/kg body weight (BW) AFB1 for six weeks by intragastric administration. Then, intervention with different doses (50 and 100 mg/kg BW) of GSPE was conducted on mice to analyze the changes of body weight, immune organ index, antioxidant capability of spleen, serum immunoglobulin content, and the expression levels of inflammatory cytokines. The prevention of GSPE on the immune injury induced by AFB1 was studied. The GSPE could relieve the AFB1-induced reduction of body weight gain and the atrophy of the immune organ. The malondialdehyde (MDA) level of the spleen in the AFB1 model group significantly increased, but levels of catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-P(X)), and superoxide dismutase (SOD) significantly decreased. The GSPE could significantly inhibit the oxidative stress injury of the spleen induced by AFB1. AFB1 exposure could not significantly change the contents of IgA, IgG, or IgM. AFB1 significantly improved the expression of interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Additionally, GSPE could decrease the expression of these four proinflammatory factors to different degrees and inhibit the inflammatory reaction of mice. The results suggest that GSPE alleviates AFB1-induced oxidative stress and significantly improves the immune injury of mice induced by AFB1.

The Protective Effect of Grape-Seed Proanthocyanidin Extract on Oxidative Damage Induced by Zearalenone in Kunming Mice Liver.

Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway.

The discovery of potent agonists for GPR88, an orphan GPCR, for the potential treatment of CNS disorders.

Modulating GPR88 activity is suggested to have therapeutic utility in the treatment of CNS disorders, such as schizophrenia. This Letter will describe the discovery and SAR development of a class of potent GPR88 agonists.

Design, synthesis, and evaluation of phenylglycinols and phenyl amines as agonists of GPR88.

Small molecule modulators of GPR88 activity (agonists, antagonists, or modulators) are of interest as potential agents for the treatment of a variety of psychiatric disorders including schizophrenia. A series of phenylglycinol and phenylamine analogs have been prepared and evaluated for their GPR88 agonist activity and pharmacokinetic (PK) properties.

Zein-Based Nanoparticles Improve the Therapeutic Efficacy of a TrkB Agonist toward Alzheimer's Disease.

The brain-derived neurotrophic factor (BDNF)/TrkB pathway plays a crucial role in neural plasticity and neuronal survival but is often deficient in neurodegenerative diseases like Alzheimer's disease (AD). CF3CN acts as a specific TrkB agonist that displays therapeutic effects in the AD mouse model, but its brain/plasma ratio (B/P ratio) distribution is not satisfactory. To increase its brain exposure, we synthesized several derivatives and employed nanoparticle (NP) formulation to optimize the most potent #2 derivative's in vivo PK profiles. We generated stable #2-loaded zein/lactoferrin composite NPs (#2/zein/LF) using the antisolvent co-precipitation method. In vivo PK studies revealed that nanoencapsulation improved #2's oral bioavailability by approximately 2-fold and significantly enhanced its plasma Cmax and t1/2, but the brain profiles were comparable. Pharmacodynamics showed that #2/zein/LF activates TrkB signaling that phosphorylates asparagine endopeptidase (AEP) T322 and decreases its enzymatic activity, resulting in reduced AEP-cleaved amyloid precursor protein and Tau fragments in the brains of AD mice, correlating with its PK profiles. After 3 months of treatment in 3xTg mice, #2/zein/LF decreased AD pathologies and alleviated cognitive dysfunction. Hence, zein/LF composite nanoencapsulation is a promising drug delivery method for improving the PK profiles of a potential preclinical candidate for treating neurodegenerative diseases.

4,4'-Dimethoxychalcone protects the skin from AAPH-induced senescence and UVB-induced photoaging by activating autophagy.

Aging can lead to the occurrence of many degenerative diseases, and the most intuitive consequences are mainly manifested on the skin, which is affected by both endogenous and exogenous aging factors and can be used as an ideal model organ for studying aging. 4,4'-Dimethoxychalcone (DMC), a natural flavonoid compound from Angelica sinensis, has been proven to prolong the lifespan of multiple species. However, it is not clear whether it has the effect of delaying skin aging. This study aimed to establish a skin senescent cell model induced by oxidative stress, and further, to analyze the inhibitory effect of DMC on cellular senescence, and explore its molecular mechanisms. We found that treatment of HaCaT cells with 1 mM 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) for 48 h showed significant senescent characteristics, which could be effectively alleviated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). DMC significantly inhibited AAPH-induced senescence, and further mechanism studies showed that the activation of autophagy which depended on the phosphorylation of ULK1 at Ser555 was necessary for DMC to alleviate senescence of HaCaT cells. In addition, the mitogen-activated protein kinase (MAPK) signal pathway was also involved in the regulation of autophagy induced by DMC. These results were also validated in UVB-induced photoaging mice. In conclusion, we successfully establish a skin senescent cell model and prove that DMC can be used as a potential therapeutic agent to intervene in skin aging.

Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7,8-dihydroxyflavone in female mice.

OBJECTIVE: 7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. METHODS: For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro, the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. RESULTS: Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. CONCLUSIONS: These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women.

7,8-Dihydroxyflavone modulates bone formation and resorption and ameliorates ovariectomy-induced osteoporosis.

Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/ß-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3ß (p-GSK3ß), ß-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of ß-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

Biomarkers, oxidative stress and autophagy in skin aging.

Aging is a major cause of many degenerative diseases. The most intuitive consequence of aging is mainly manifested on the skin, resulting in cumulative changes in skin structure, function and appearance, such as increased wrinkles, laxity, elastosis, telangiectasia, and aberrant pigmentation of the skin. Unlike other organs of the human body, skin is not only inevitably affected by the intrinsic aging process, but also affected by various extrinsic environmental factors to accelerate aging, especially ultraviolet (UV) radiation. Skin aging is a highly complex and not fully understood process, and the lack of universal biomarkers for the definitive detection and evaluation of aging is also a major research challenge. Oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to lipid, protein, nucleic acid and organelle damage, thus leading to the occurrence of cellular senescence, which is one of the core mechanisms mediating skin aging. Autophagy can maintain cellular homeostasis when faced with different stress conditions and is one of the survival mechanisms of cell resistance to intrinsic and extrinsic stress. Autophagy and aging have many features in common and may be associated with skin aging mediated by different factors. Here, we summarize the changes and biomarkers of skin aging, and discuss the effects of oxidative stress and autophagy on skin aging.

Inhibiting roles of farnesol and HOG in morphological switching of Candida albicans.

Candida albicans is a major opportunistic fungal pathogen of humans, especially in the oral cavity it involves in precancerous lesions. Numerous transcriptional regulators and hypha-specific genes involved in the morphogenesis mechanisms have been identified. Its virulence is predominantly attributed to the potentiality of morphological switching from yeast and pseudohyphae to hyphal growth. Giving attention in farnesol for prevention or intervention of its virulence sense and possible etiologic role in some uncovered premalignant diseases, in addition, to be a quorum-sensing signal molecule and relationship with HOG pathway, although its morphological switching inhibiting function has attracted high attention and got great progress in being elucidated, their exact mode of action is not completely understood. This report provides a review of characteristic aspects of farnesol signaling and HOG pathway during hyphal development. It also includes other associated pathways, molecules, and novel drug development based on the latest researches over the last decade. Furthermore, farnesol as immunomodulatory to host is an important inferring.

Protective effect of a dietary flavonoid-rich antioxidant from bamboo leaves against internal exposure to acrylamide and glycidamide in humans.

Polyphenolic antioxidants may effectively reduce acrylamide contents in processed foods. However, few studies focused on their detoxification effects via estimating the profile change of internal exposure biomarkers. Here we showed the protective effect of a water-soluble flavone-C-glycoside-rich antioxidant from bamboo leaves (AOB-w) against acrylamide-induced toxicity in college students. The participants were randomly assigned to either the AOB-w or control group and served potato chips, corresponding to 12.6 µg per kg·bw of dietary exposure to acrylamide, followed by capsules containing 350 mg AOB-w or equivalent placebo. The kinetics of acrylamide, glycidamide, and mercapturic acid metabolites was profiled, and their hemoglobin adducts were measured. The toxicokinetic study showed that AOB-w promoted the excretion of acrylamide and shortened the distribution but prolonged the excretion of N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine. The intervention with AOB-w reduced the peak concentration and area under curve of AAMA by 42.1% and 49.8%, respectively. Besides, AOB-w gender-dependently altered the toxicokinetic profile and reduced the amount of a human-specific urinary biomarker, N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide in women. AOB-w accelerated the metabolism of hemoglobin adducts of acrylamide and glycidamide in blood of women. Compared with the baseline levels on the beginning day, we observed a significant enhancement of hemoglobin adducts on the 10th day after serving them potato chips, showing 54.5% and 20.9% higher levels of the hemoglobin adducts of acrylamide and glycidamide, respectively, which thus indicated a lower level of glycidamide-to-acrylamide ratio in blood of participants. Overall AOB-w could effectively reduce the internal exposure to acrylamide in college students, which provides advanced insights into protective functions of natural antioxidants against in vivo toxicity of chemical contaminants from diet.

Dynamic Analysis of a Micro Beam-Based Tactile Sensor Actuated by Fringing Electrostatic Fields.

A new kind of fringing electrostatic actuation mode is developed. In this new actuation mode, the expression of fringing electrostatic force is found. The nonlinear dynamic analysis of this new actuation mode is presented by using the Method of Multiple Scales. An experiment is designed to observe the dynamic behaviors of this structure. It is observed that the resonance frequency rises with the increase of the initial displacement and the decrease of the slit gap; a smaller slit gap makes marked change of the resonance frequency in the same range of the initial displacement; the increase of the vibration amplitude is linear with the increase of the initial displacement; the fringing electrostatic force has a larger impact on the frequency response of the nonlinear vibration when the initial displacement, the beam length and the actuated voltage are larger. This new fringing electrostatic actuation mode can be used in a micro tactile sensor. The results of dynamic analysis can provide support for sensor design. Based on the dynamic investigations into the micro cantilevered beam actuated by fringing electrostatic force; three usage patterns of the sensor are introduced as follows. Firstly, measuring resonance frequency of the micro beam can derive the initial displacement. Second, the initial displacement can be derived from vibration amplitude measurement. Third, jump phenomenon can be used to locate the initial displacement demand.

Prophylactic effect and mechanism of p-coumaric acid against hypoxic cerebral edema in mice.

Our previous study found that the anti-hypoxia effect of Tibetan turnip (Brassica rapa ssp. rapa) is directly related to its p-Coumaric acid (CA) and glucoside (pCoumaric acid-beta-d-glucopyranoside, CAG) contents. The present study aimed to investigate the role and mechanism of CA against hypoxic cerebral edema. Male mice were randomly divided into one normoxia group and three hypoxia groups, which were gavaged with sterilized water, CA, or dexamethasone, respectively, once daily for 4 days. The mice were then exposed to normoxia or hypoxia (9.5% O2) for 24 h. The results showed that the brain water content (BWC) and blood-brain-barrier permeability were significantly lower in the CA treatment group than in the hypoxia vehicle group. Mice in the CA treatment group showed good blood-brain-barrier integrity; increased Na+-K+-ATPase activity and mitochondrial membrane potential; decreased oxidative stress and inflammation; and increased occludin protein levels. Prophylactic administration of CA and dexamethasone exerted similar effects against hypoxic cerebral edema. The mechanism involved improving the integrity of the blood-brain-barrier, and inhibiting oxidative stress and inflammation.