A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Morphology Control of Au-Ni Hybrid Nanoparticles: Exploring Heterostructures and Optical Tuning.

Hybrid nanoparticles (NPs) have attracted considerable attention because of their ability to provide diverse properties by integrating the inherent properties of multiple components; however, synthetic strategies to control their morphology remain unexplored. In this study, a new method was used to control the morphology and optical properties of Au-Ni heterostructure (ANH) NPs. Unique morphological changes were observed by varying the Au/Ni precursor ratio from 2:1 to 1:4, exhibiting a shape transformation from dumbbell-like to quasi-spherical owing to the Ni NP size expansion, whereas the Au NP maintained their size. Moreover, increasing the Ni ratio induced plasmonic band broadening and wavelength redshift, resulting in color changes from red to navy and black. In terms of the structure, the atomic orientation of the crystallite showed that even a large lattice mismatch can result in heterojunctions at the NPs. In addition, the reaction aliquots uncovered heterogeneous nucleation and growth of ANH NPs in the colloidal system, demonstrating Ni reduction on the preformed Au NP owing to the reduction in potential gap. This study provides new insights into controlling the morphology of hybrid NPs using colloidal synthesis and the design of optimized materials for various applications.

High Doses of ANA12 Improve Phenobarbital Efficacy in a Model of Neonatal Post-Ischemic Seizures.

Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are resistant to PB. Previous animal studies have shown that in postnatal day P7 mice pups with ischemic stroke induced by unilateral carotid ligation, the tyrosine receptor kinase B (TrkB) antagonist ANA12 (N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide, 5 mg/kg) improved the efficacy of PB in reducing seizure occurrence. To meet optimal standards of effectiveness, a wider range of ANA12 doses must be tested. Here, using the unilateral carotid ligation model, we tested the effectiveness of higher doses of ANA12 (10 and 20 mg/kg) on the ability of PB to reduce seizure burden, ameliorate cell death (assessed by Fluoro-Jade staining), and affect neurodevelopment (righting reflex, negative geotaxis test, open field test). We found that a single dose of ANA12 (10 or 20 mg/kg) given 1 h after unilateral carotid ligation in P7 pups reduced seizure burden and neocortical and striatal neuron death without impairing developmental reflexes. In conclusion, ANA12 at a range of doses (10-20 mg/kg) enhanced PB effectiveness for the treatment of perinatal ischemia-related seizures, suggesting that this agent might be a clinically safe and effective adjunctive agent for the treatment of pharmacoresistant neonatal seizures.

Body-Centered-Cubic-Kernelled Ag15Cu6 Nanocluster with Alkynyl Protection: Synthesis, Total Structure, and CO2 Electroreduction.

While atomically monodisperse nanostructured materials are highly desirable to unravel the size- and structure-catalysis relationships, their controlled synthesis and the atomic-level structure determination pose challenges. Particularly, copper-containing atomically precise alloy nanoclusters are potential catalyst candidates for the electrochemical CO2 reduction reaction (eCO2RR) due to high abundance and tunable catalytic activity of copper. Herein, we report the synthesis and total structure of an alkynyl-protected 21-atom AgCu alloy nanocluster [Ag15Cu6(C≡CR)18(DPPE)2]-, denoted as Ag15Cu6 (HC≡CR: 3,5-bis(trifluoromethyl)phenylacetylene; DPPE: 1,2-bis(diphenylphosphino)ethane). The single-crystal X-ray diffraction reveals that Ag15Cu6 consists of an Ag11Cu4 metal core exhibiting a body-centered cubic (bcc) structure, which is capped by 2 Cu atoms, 2 Ag2DPPE motifs, and 18 alkynyl ligands. Interestingly, the Ag15Cu6 cluster exhibits excellent catalytic activity for eCO2RR with a CO faradaic efficiency (FECO) of 91.3% at -0.81 V (vs the reversible hydrogen electrode, RHE), which is much higher than that (FECO: 48.5% at -0.89 V vs RHE) of Ag9Cu6 with bcc structure. Furthermore, Ag15Cu6 shows superior stability with no significant decay in the current density and FECO during a long-term operation of 145 h. Density functional theory calculations reveal that the de-ligated Ag15Cu6 cluster can expose more space at the pair of AgCu dual metals as the efficient active sites for CO formation.

Copper Doping Boosts Electrocatalytic CO2 Reduction of Atomically Precise Gold Nanoclusters.

Unraveling the atomistic synergistic effects of nanoalloys on the electrocatalytic CO2 reduction reaction (eCO2RR), especially in the presence of copper, is of paramount importance. However, this endeavor encounters significant challenges due to the lack of the crystallographically determined atomic-level structure of appropriate monometallic and bimetallic analogues. Herein, we report a one-pot synthesis and structure characterization of a AuCu nanoalloy cluster catalyst, [Au15Cu4(DPPM)6Cl4(C≡CR)1]2+ (denoted as Au15Cu4). Single-crystal X-ray diffraction analysis reveals that Au15Cu4 comprises two interpenetrating incomplete, centered icosahedra (Au9Cu2 and Au8Cu3) and is protected by six DPPM, four halide, and one alkynyl ligand. The Au15Cu4 cluster and its closest monometal structural analogue, [Au18(DPPM)6Br4]2+ (denoted as Au18), as model systems, enable the elucidation of the atomistic synergistic effects of Au and Cu on eCO2RR. The results reveal that Au15Cu4 is an excellent eCO2RR catalyst in a gas diffusion electrode-based membrane electrode assembly (MEA) cell, exhibiting a high CO Faradaic efficiency (FECO) of >90%, and this efficiency is substantially higher than that of the undoped Au18 (FECO: 60% at -3.75 V). Au15Cu4 exhibits an industrial-level CO partial current density of up to -413 mA/cm2 at -3.75 V with the gas CO2-fed MEA, which is 2-fold higher than that of Au18. The density functional theory (DFT) calculations demonstrate that the synergistic effects are induced by Cu doping, where the exposed pair of AuCu dual sites was suggested for launching the eCO2RR process. Besides, DFT simulations reveal that these special dual sites synergistically coordinate a moderate shift in the d-state, thus enhancing its overall catalytic performance.

Probing Cation Effects on *CO Intermediates from Electroreduction of CO2 through Operando Raman Spectroscopy.

Cations in an electrolyte modulate microenvironments near the catalyst surface and affect product distribution from an electrochemical CO2 reduction reaction, and thus, their interaction with intermediate states has been tried to be probed. Herein, we directly observed the cation effect on *CO intermediates on the Cu(OH)2-derived catalyst in real time through operando surface-enhanced Raman spectroscopy at high overpotentials (-1.0 VRHE). Atop *CO peaks are composed of low-frequency binding *CO (*COLFB) and high-frequency binding *CO (*COHFB) because of their adsorption sites. These two *CO intermediates are found to have different sensitivities to the cation-induced field, and each *CO is proposed to be suitably stabilized for efficient C-C coupling. The proportions between *COHFB and *COLFB are dependent on the type of alkali cations, and the increases in the *COHFB ratio have a high correlation with selective C2H4 production under K+ and Cs+, indicating that *COHFB is the dominant and fast active species. In addition, as the hydrated cation size decreases, *COLFB is more sensitively red-shifted than *COHFB, which promotes C-C coupling and suppresses C1 products. Through time-resolved operando measurements, dynamic changes between the two *CO species are observed, showing the rapid initial adsorption of *COHFB and subsequently reaching a steady ratio between *COLFB and *COHFB.

Three-dimensional imaging performance of photoelectrochemical cells.

A photoelectrochemical (PEC) cell produces hydrogen energy using solar energy and an electrochemical reaction. In the hydrogen production process with water decomposition, electrons move from the anode to the cathode, and by measuring the current value at this time, the PEC cell can generate hydrogen and function as an image sensor at the same time. Due to the characteristics of the PEC cell that can perform both functions simultaneously, it can be applied as a device that can detect and respond to the surrounding environment without the need for an observation system such as a camera. We present the imaging performance of PEC cells. The effectiveness of the experiment was confirmed by applying the PEC cells to integral imaging, one of the three-dimensional (3D) imaging techniques.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Nucleus-targeted delivery of nitric oxide in human mesenchymal stem cells enhances osteogenic differentiation.

Nitric oxide (NO) is an important gaseous signaling molecule in various physiological processes, which functions through interactions with its acceptor molecules located in organelles. NO has an extremely short half-life, making it challenging to experimentally achieve effective NO levels in organelles to study these interactions. Here we developed an organelle-specific, peptide-based NO delivery material that targets the nucleus. NO was attached to the SH group of a cysteine residue inserted into the N-terminus of a cell-penetrating peptide (CPP) conjugated to varying repeats of the nuclear localization signal (NLS), which we denoted NO-CysCPP-NLS, through S-nitrosylation. NO-CysCPP-NLS strongly induced osteogenic differentiation of mesenchymal stem cells. This delivery concept can be extended to cells other than stem cells to elucidate the effects of NO release in the nucleus. Furthermore, conjugation of NO to CysCPP fused to mitochondria- or lysosome-targeting signals can be used to deliver NO to other organelles such as mitochondria and lysosomes, respectively.

Dietary quality and the gut microbiome in early-stage Parkinson's disease patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition. METHODS: This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences. RESULTS: Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls. CONCLUSIONS: Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed.

Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways.

Sarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice. Oral administration of Lp, Bb, or their mix (LB) increased grip strength and treadmill running distance and time. They significantly increased muscle weight in aged mice. They also increased AKT activation, PGC1α, SIRT1, and myosin heavy chain (MyHC) expression, MyHC-positive cell population, and cell size in the gastrocnemius (GA) muscle, while FOXO3a and NF-κB activation, MuRF1, muscle atrophy F-box, and p16 expression, and NF-κB+CD11c+ cell population decreased. Furthermore, they reduced cognitive impairment-like behavior, IL-6 expression, FOXO3a activation, and NF-κB-positive cell population in the hippocampus, GA, and colon, while hippocampal brain-derived neurotropic factor expression increased. They shifted gut microbiota composition in aged mice: they increased Akkermansiaceae and Bacteroidaceae populations, which were positively correlated with total muscle weight and MyHC expression, and decreased Odoribacteraceae and Deferribacteriaceae populations, which were positively correlated with MuRF1 and IL-6 expression. LB alleviated sarcopenia- and cognitive impairment-like symptoms more potently than Lp or Bb alone. Based on these findings, probiotics, particularly Lp, Bb, and LB, can alleviate aging-dependent sarcopenia and cognitive impairment by regulating gut microbiota-mediated AKT, NF-κB, and/or FOXO3a signaling pathways.

Far-Infrared Irradiation Decreases Proliferation in Basal and PDGF-Stimulated VSMCs Through AMPK-Mediated Inhibition of mTOR/p70S6K Signaling Axis.

BACKGROUND: Far-infrared (FIR) irradiation has been reported to improve diverse cardiovascular diseases, including heart failure, hypertension, and atherosclerosis. The dysregulated proliferation of vascular smooth muscle cells (VSMCs) is well established to contribute to developing occlusive vascular diseases such as atherosclerosis and in-stent restenosis. However, the effects of FIR irradiation on VSMC proliferation and the underlying mechanism are unclear. This study investigated the molecular mechanism through which FIR irradiation inhibited VSMC proliferation. METHODS: We performed cell proliferation and cell death assay, adenosine 5'-triphosphate (ATP) assay, inhibitor studies, transfection of dominant negative (dn)-AMP-activated protein kinase (AMPK) α1 gene, and western blot analyses. We also conducted confocal microscopic image analyses and ex vivo studies using isolated rat aortas. RESULTS: FIR irradiation for 30 minutes decreased VSMC proliferation without altering the cell death. Furthermore, FIR irradiation accompanied decreases in phosphorylation of the mammalian target of rapamycin (mTOR) at Ser2448 (p-mTOR-Ser2448) and p70 S6 kinase (p70S6K) at Thr389 (p-p70S6K-Thr389). The phosphorylation of AMPK at Thr172 (p-AMPK-Thr172) was increased in FIR-irradiated VSMCs, which was accompanied by a decreased cellular ATP level. Similar to in vitro results, FIR irradiation increased p-AMPK-Thr172 and decreased p-mTOR-Ser2448 and p-p70S6K-Thr389 in isolated rat aortas. Pre-treatment with compound C, a specific AMPK inhibitor, or ectopic expression of dn-AMPKα1 gene, significantly reversed FIR irradiation-decreased VSMC proliferation, p-mTOR-Ser2448, and p-p70S6K-Thr389. On the other hand, hyperthermal stimulus (39°C) did not alter VSMC proliferation, cellular ATP level, and AMPK/mTOR/p70S6K phosphorylation. Finally, FIR irradiation attenuated platelet-derived growth factor (PDGF)-stimulated VSMC proliferation by increasing p-AMPK-Thr172, and decreasing p-mTOR-Ser2448 and p-p70S6K-Thr389 in PDGF-induced in vitro atherosclerosis model. CONCLUSION: These results show that FIR irradiation decreases the basal and PDGF-stimulated VSMC proliferation, at least in part, by the AMPK-mediated inhibition of mTOR/p70S6K signaling axis irrespective of its hyperthermal effect. These observations suggest that FIR therapy can be used to treat arterial narrowing diseases, including atherosclerosis and in-stent restenosis.

Inhibition Effect of Adipogenesis and Lipogenesis via Activation of AMPK in Preadipocytes Treated with Canavalia gladiata Extract.

The aim of this study was to investigate the effect of Canavalia gladiata extract (CGE) on the regulation of AMP-activated protein kinase (AMPK) in 3T3-L1 preadipocytes and evaluate the adipogenesis and lipogenesis mechanisms. In 3T3-L1 preadipocytes, lipid accumulation and differentiation were suppressed by 1.1, 1.3, and 1.4 times under the CGE treatment at 0.25, 0.5, and 1.0 mg/mL, respectively. The expression of the main genes involved in the inhibition of adipogenesis was evaluated at the mRNA level via a transcription-polymerase chain reaction. The extract at 1.0 mg/mL increased the mRNA expressions of AMPK and carnitine palmitoyl transferase-1 (CPT-1) by 1.9 and 1.2 times, respectively, while it decreased the expression of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α), and fatty acid synthase (FAS) by 1.1, 1.2, 1.8, and 1.5 times, respectively, indicating inhibition of the adipogenesis and lipogenesis potential of CGE. Gallic acid (4.02 mg/g) was identified as the main component of the CGE via LC-MS/MS and HPLC analysis. The results of this study suggested that CGE can be utilized as an anti-obesity food additive or medication by activating the AMPK-induced regulation and suppressing adipogenesis transcription factors.

Effect of Home-Based Self-Management Intervention for Community-Dwelling Patients with Early Parkinson's Disease: A Feasibility Study.

PURPOSE: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). DESIGN: A randomized-controlled design. METHODS: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. FINDINGS: Physical activity and non-motor symptoms improved more in the intervention group than in the control group. CONCLUSION: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. CLINICAL EVIDENCE: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.

Valproic acid decreases vascular smooth muscle cell proliferation via protein phosphatase 2A-mediated p70 S6 kinase inhibition.

Valproic acid (VPA) has been used to treat epilepsy and bipolar disorder. Although the abnormal proliferation of vascular smooth muscle cells (VSMCs) is a well-established contributor to the development of various vascular diseases including atherosclerosis, the effect of VPA on VSMC proliferation and its mechanism of action have not been fully revealed. Herein, we investigated the molecular mechanism by which VPA inhibits rat VSMC proliferation. VPA dose-dependently decreased VSMC proliferation, which was accompanied by the dose-dependent decrease in phosphorylation of p70 S6 kinase (p70S6K) at Thr389 (p-p70S6K-Thr389), and overexpression of the p70S6K-T389E mutant gene significantly reversed VPA-inhibited VSMC proliferation. Co-treatment with okadaic acid, a specific protein phosphatase 2A (PP2A) inhibitor, significantly restored p-p70S6K-Thr389. Furthermore, knockdown of PP2Ac gene expression by siRNA significantly reversed VPA-inhibited p-p70S6K-Thr389 and VSMC proliferation. Confocal microscopic analyses and co-immunoprecipitation results clearly showed that the physical binding of p70S6K and PP2Ac was promoted by VPA. Valpromide, a VPA's structural derivative with no histone deacetylase (HDAC) inhibition activity, as well as VPA and sodium butyrate, an HDAC inhibitor similar to VPA, decreased VSMC proliferation and p-p70S6K-Thr389, indicating that HDAC is not involved in VPA-inhibited VSMC proliferation. Finally, the inhibitory effects of VPA on p-p70S6K-Thr389 and VSMC proliferation were reiterated in a platelet-derived growth factor (PDGF)-induced in vitro atherosclerosis model. In conclusion, our results demonstrate that VPA decreased cell proliferation via PP2A-mediated inhibition of p-p70S6K-Thr389 in basal and PDGF-stimulated VSMCs. The results suggest that VPA could be used in the treatment and prevention of atherosclerosis and in-stent restenosis.

Acute disseminated encephalomyelitis with bilateral optic neuritis following ChAdOx1 COVID-19 vaccination.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus. CASE PRESENTATION: A 36-year-old female presented with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine. Initial MRI Brain showed evidence of demyelination within the subcortical white matter, with no radiological involvement of the optic nerves. Visual evoked potentials were consistent with bilateral optic neuritis which was confirmed radiologically on follow up MRI. She was treated with intravenous steroids with improvement both in symptoms and radiological appearance. A pseudo-relapse occurred which was treated with a further course of intravenous steroids followed by an oral taper. The clinical, radiological and serological results were most consistent with diagnosis of ADEM. CONCLUSIONS: ADEM is an exceedingly rare complication of ChAdOx1 vaccine despite millions of doses. While it is imperative clinicians remain aware of neurological complications of vaccines, the importance of vaccination to control a pandemic should not be undermined.

Electrochemical conversion of CO2 to value-added chemicals over bimetallic Pd-based nanostructures: Recent progress and emerging trends.

Electrochemical conversion of CO2 to fuels and chemicals as a sustainable solution for waste transformation has garnered tremendous interest to combat the fervent issue of the prevailing high atmospheric CO2 concentration while contributing to the generation of sustainable energy. Monometallic palladium (Pd) has been shown promising in electrochemical CO2 reduction, producing formate or CO depending on applied potentials. Recently, bimetallic Pd-based materials strived to fine-tune the binding affinity of key intermediates is a prominent strategy for the desired product formation from CO2 reduction. Herein, the recent emerging trends on bimetallic Pd-based electrocatalysts are reviewed, including fundamentals of CO2 electroreduction and material engineering of bimetallic Pd-electrocatalysts categorized by primary products. Modern analytical techniques on these novel electrocatalysts are also thoroughly studied to get insights into reaction mechanisms. Lastly, we deliberate over the challenges and prospects for Pd-based catalysts for electrochemical CO2 conversion.

Metabolomic analysis of amino acids and organic acids in aging mouse eyes using gas chromatography-tandem mass spectrometry.

This is a metabolomics study for monitoring altered amino acid (AA) and organic acid (OA) metabolism of in eyes from aging an mouse model at 8 and 18 weeks and 18 months. Simultaneous metabolic profiling analysis of OAs and AAs was performed as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-tandem mass spectrometry. A total of 42 metabolites-24 AAs and 18 OAs-were determined and their composition values were normalized to the corresponding mean values of 8-week-old mice as the control group. Then their normalized values were plotted as star graphs, which were distorted and readily distinguishable for each age-related group. Among the 42 metabolites, 18 AAs and 11 OAs were age dependent and significantly different (p < 0.05). Principal component analysis and partial least squares discriminant analysis showed unclear separation between 8- and 18-week-old mice but clear separation between these and 18-month-old mice. In particular, the variable importance in projection scores of 4-hydroxyproline, cis-aconitic acid, glycine, isocitric acid, leucine, pipecolic acid and lysine from partial least-squares-discriminant analysis were higher than 1.3. A heatmap for the classification and visualization of 42 metabolites showed differences in metabolite changes with aging. Altered AA and OA profiles were monitored, which may explain the metabolic disturbance of AA and OA. These findings are related to mitochondrial dysfunctions related to energy metabolism and the impaired antioxidant system in the aging eye. Therefore, the present metabolomics results of the association between physiological states and altered metabolism of AA and OA will be useful for understanding the aging eye and related diseases.

Effect of mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease: Randomized controlled trial.

OBJECTIVES: To evaluate the effects of a mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease. METHODS: A randomized controlled design was used. The participants were randomly assigned to an intervention or a control group. The intervention group (n = 20) received mobile health intervention comprising mobile applications, smartwatches, smartphone-based short text messages and information, and telephone counselling; whereas the control group (n = 23) received short text messages and telephone counselling for 16 weeks. RESULTS: After 16 weeks, self-efficacy and non-motor symptom scores in the intervention group significantly improved compared to those in the control group. However, no significant differences were observed in the motor symptoms, self-management, and quality of life between the groups. CONCLUSIONS: The mobile health intervention for self-management is effective for self-efficacy and non-motor symptoms in people with Parkinson's disease.

Odontogenic Effect of Icariin on the Human Dental Pulp Cells.

Background and Objectives: Human dental pulp cells (HDPCs) can be used for dentin regeneration due to its odontogenic differentiation property. Icariin can induce osteogenic differentiation of stem cells. However, its potential to induce odontogenic differentiation of HDPCs remains unclear. Thus, the aim of this study was to evaluate the capacity of icariin to induce odontogenic differentiation of HDPCs and investigate the underlying molecular mechanism. Materials and Methods: Cell viability assay was used to detect the cytotoxicity of icariin to HDPCs. Effect of icariin on HDPCs chemotaxis was measured by scratch migration assay. The mineralized and odontogenic differentiation of HDPCs was assessed by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, real-time PCR, and Western blot of dentin matrix protein 1 (DMP 1) and dentin sialophosphoprotein (DSPP). In addition, Mitogen-activated protein kinase (MAPK) signaling pathway of icariin-induced biomineralization was investigated by Western blot. Results: Cells treated with icariin at all concentrations tested maintained viability, indicating that icariin was biocompatible. Icariin accelerated HDPCs chemotaxis (p < 0.05). Expression levels of related odontogenic markers were increased in the presence of icariin (p < 0.05). Icariin-induced odontogenic differentiation occurred via activation of the MAPK signaling pathway. Furthermore, MAPK inhibitors suppressed expression levels of DSPP and DMP 1 protein, ALP activity, and mineralization of HDPCs. Conclusions: Icariin can upregulate odontogenic differentiation of HDPCs by triggering the MAPK signaling pathway.