Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.

Dopaminergic neurons in the substantia nigra pars compacta (SNpc) demonstrate regionally selective susceptibility in Parkinson's disease (PD) compared to those in the ventral tegmental area (VTA). However, the molecular mechanism for this distinct vulnerability remains unclear. Here, it is shown that Legumain, also known as asparagine endopeptidase (AEP), is activated in a subgroup of SRY-box transcription factor 6 /Aldehyde dehydrogenase 1 family member A1, (Sox6/ALDH1A1) neurons in the ventral tier of the SNpc and cleaves Sox6 and ALDH1A1, leading to repression of Special AT-rich sequence binding protein 1 (Satb1) that is a dimeric/tetrameric transcription factor specifically binding to AT-rich DNA sequences, and toxic dopamine metabolite accumulation.

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.

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.

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 , has been proven to prolong the lifespan of multiple species. However, it is not clear whether it has the effect of delaying skin aging.

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.

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.

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.

Inhibiting roles of farnesol and HOG in morphological switching of .

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.

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

In the current study, further chemical investigation of the fruiting bodies of led to isolate seven new 24-methyl-lanostane triterpenoids, named officimalonic acids I-O (-). Their structures were elucidated based on the analysis of spectroscopic data (HR-MS, 1D and 2D NMR, UV, IR). Compounds - possessed an unusual C-23 spirostructure moiety, while compounds - had 23,26-lactone unit.

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.

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.

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

A new triterpenoid saponin, named terpengustifol A (), and two new lignan glucosides, phengustifols A and B ( and ), were isolated from the flowers of . Their structures were determined by the extensive analysis of the spectroscopic data (including NMR and HRMS) and ECD calculations. Compound possesses an unusual monoterpene ()-6-hydroxy-2,6-dimethylocta-2,7-dienoyl unit at C-21.

Vertical 1T/2H-WS nanoflakes grown on 2D-CN: Multiple charge transfer channels designed for enhanced photocatalytic activity.

Two-dimensional (2D) sulfides have attracted much attention as a promising photocatalyst for the hydrogen evolution reaction. In this work, a highly active and stable vertical 1T/2H-WS nanoflakes grown on 2D-CN with multiple charge transfer channels through a simple and efficient colloidal strategy is reported. This three-dimensional (3D) composite presents the usual semiconducting 2H phase WS as well as the unusual distorted octahedral 1T phase WS, which vertically connect 2D-CN constructing an interesting 3D structure with more active sites.

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.

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.

Qualitative Identification of the Static Pull-In and Fundamental Frequency of One-Electrode MEMS Resonators.

This paper attempts to qualitatively identify the static pull-in position, pull-in voltage, and fundamental frequency of one-electrode microresonators from a physical perspective. During theoretical derivation, a generalized one-degree-of-freedom (1-DOF) model in nondimensional form derived using the differential quadrature method (DQM) is first introduced and then transformed for frequency normalization. Based on the deduced formulas, the upper and lower bounds of the static pull-in position and pull-in voltage are both deduced through mathematical proof.

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.

Vibration Identification of Folded-MEMS Comb Drive Resonators.

Natural frequency and frequency response are two important indicators for the performances of resonant microelectromechanical systems (MEMS) devices. This paper analytically and numerically investigates the vibration identification of the primary resonance of one type of folded-MEMS comb drive resonator. The governing equation of motion, considering structure and electrostatic nonlinearities, is firstly introduced.

Monostable Dynamic Analysis of Microbeam-Based Resonators via an Improved One Degree of Freedom Model.

Monostable vibration can eliminate dynamic bifurcation and improve system stability, which is required in many microelectromechanical systems (MEMS) applications, such as microbeam-based and comb-driven resonators. This article aims to theoretically investigate the monostable vibration in size-effected MEMS via a low dimensional model. An improved single degree of freedom model to describe electrically actuated microbeam-based resonators is obtained by using modified couple stress theory and Nonlinear Galerkin method.

p-Coumaric acid as a prophylactic measure against normobaric hypoxia induced pulmonary edema in mice.

Aims: Previous studies indicate that the anti-hypoxia effects of Tibetan Turnip (Brassica rapa ssp. rapa) were closely related to its characteristic components being p-coumaric acid (CA) and p-coumaric acid‑β‑d‑glucopyranoside (CAG). Since CAG would be converted to CA in vivo, this study aims to further examine the efficacy and mechanism of CA against pulmonary edema induced by normobaric hypoxia.

[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.

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

Two new lanostane triterpenoid acids, 12β, 15α-dihydroxy-24-methyl-3,23-dioxo-lanosta-7,9(11)-dien-26-oic acid (1), and 3α, 12β-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.

Cytotoxic lanostane triterpenoids from the fruiting bodies of Piptoporus betulinus.

Chemical investigation of a bioactive methanolic extract of the fruiting bodies of Piptoporus betulinus led to the isolation of five previously undescribed lanostane triterpenoids named piptolinic acids A-E, as well as five known lanostane triterpenoids. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic and HRESIMS analysis. Piptolinic acid A with an unusual moiety (3-hydroxy-4-methoxycarbonyl-3-methylbutyryloxy) at C-3 exhibited comparable cytotoxic activity against human promyelocytic leukemia cell line HL-60 (IC = 1.