Electron and surface engineering of Ni2P/MnP4 heterojunction as high performance bifunctional electrocatalyst for amperage-level overall water splitting.

Producing hydrogen through electrocatalytic overall water splitting with ampere-level current density is still limited by the high cost and poor stability of electrocatalysts. In this work, a new type Ni2P/MnP4 heterojunction composite material was designed and prepared as bifunctional electrocatalyst. Based on XPS spectra and theoretical calculation, the formation of Ni2P/MnP4 heterojunction successfully modulates the local electronic structure of Ni2P and enhances the ionization of H and Ni by increasing the electron transfer rate. Moreover, the special nanovilli structure and superhydropholic/superaerophobic surface of Ni2P/MnP4 heterojunction accelerates the transfer of electrolyte and gaseous products. Benefiting from these advantages, the as-prepared Ni2P/MnP4/CF not only exhibits superior electrocatalytic performance, which can release 10 mA/cm2 current density with a low overpotential of 69 mV and 247 mV for HER and OER respectively, but also shows admirable stability of continuous overall water splitting to drive 1000 mA/cm2 for 180 h without notable activity degradation. We believe this material possesses outstanding potential for industrial applications, and our strategy may provide a new pathway to design relative materials.

Combined Lycium barbarum Polysaccharides with Plasmon-Activated Water Affect IFN-γ/TNF-α Induced Inflammation in Caco-2 Cells.

The effects of Lycium barbarum polysaccharides (LBP) and plasmon-activated water (PAW) against IFN-γ/TNF-α induced inflammation in human colon Caco-2 cells were investigated. Cells were divided into the control, induction, LBP treatment (100-500 µg/mL), and combination groups with PAW. Inflammation was induced 24 h with 10 ng/mL IFN-γ when cell confluency reached >90%, and various doses of LBP with or without PAW were treated for 3 h, and subsequently 50 ng/mL TNF-α was added for another 24 h to provoke inflammation. Combination of LBP with PAW significantly decreased the secretion of IL-6 and IL-8. Cyclooxygenase-2 and inducible NO synthase expression was attenuated in all LBP-treated groups with or without PAW. NLRP3 inflammasome and related protein PYCARD expression were inhibited by LBP at the highest dose (500 µg/mL). All doses of LBP alone significantly decreased p-ERK expression, but combination with PAW increased p-ERK expression compared to those without PAW. Additionally, 250 and 500 µg/mL of LBP with or without PAW inhibited procaspase-3/caspase-3 expression. Therefore, LBP possesses anti-inflammation and anti-apoptosis by inhibiting the secretion of inflammatory cytokines and the expression of NLRP3 inflammasome-related protein. The combination with PAW exerts additive or synergistic effect on anti-inflammation.

Plasmon-activated water as a therapeutic strategy in Alzheimer's disease by altering gut microbiota.

Gut microbiota (GM) are involved in the pathophysiology of Alzheimer's disease (AD) and might correlate to the machinery of the gut-brain axis. Alteration of the GM profiles becomes a potential therapy strategy in AD. Here, we found that plasmon-activated water (PAW) therapy altered GM profile and reduced AD symptoms in APPswe/PS1dE9 transgenic mice (AD mice). GM profile showed the difference between AD and WT mice. PAW therapy in AD mice altered GM profile and fecal microbiota transplantation (FMT) reproduced GM profile in AD mice. PAW therapy and FMT in AD mice reduced cognitive decline and amyloid accumulation by novel object recognition (NOR) test and amyloid PET imaging. Immunofluorescent staining and western blot analysis of ß-amyloid (Aß) and phosphorylated (p)-tau in the brain of AD mice were reduced in PAW therapy and FMT. The inflammatory markers, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α and pro-inflammatory indicator of arginase-1/CD86 ratio were also reduced. Furthermore, immunohistochemistry (IHC) analysis of occludin and claudin-5 in the intestine and AXL in the brain were increased to correlate with the abundant GM in PAW therapy and FMT. Our results showed the machinery of gut-brain axis, and PAW might be a potential therapeutic strategy in AD.

Capacitor-parallel-amplified decoupled photoelectrochemical/electrochromic dual-mode bioassay for sensitive detection of microRNA with high reliability.

To achieve sensitive detection of low-content microRNA, photoelectrochemical/electrochromic dual-mode sensor with intrinsically low background signal has been developed, but the two detection modules are usually designed with a series-connected structure, which may cause signal interference and thus affect the detection reliability. To solve the above problems, a decoupled dual-mode bioassay for sensitive miRNA-21 detection with high reliability is constructed in this work, by selecting two capacitors to realize parallel amplification for the two detection modules, supplemented with a 3D DNA nanoring photoelectrode signal amplification strategy. The complete decoupling of the two detection modes, photoelectrochemical and electrochromic, as well as the use of digital multimeter, improves the reliability and accuracy of the sensor, and also frees it from dependence on electrochemical workstation, making detection more intuitive and faster. With simple structure, low cost, good reproducibility, high sensitivity, and easy operation, the capacitor-parallel-amplified decoupled photoelectrochemical/electrochromic dual-mode bioassay has broad application prospect in on-site point-of-care detection of diseases and low-cost clinical diagnosis. The design idea of decoupled dual-mode detector can also be extended to the construction of other dual-mode methods.

HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson's disease.

Microglial activation-induced neuroinflammation contributes to onset and progression of sporadic and hereditary Parkinson's disease (PD). Activated microglia secrete pro-inflammatory and neurotoxic IL-1ß, IL-6 and TNF-α, which subsequently promote neurodegeneration. Formyl peptide receptor-1 (FPR1) of CNS microglia functions as pattern recognition receptor and is activated by N-formylated peptides, leading to microglial activation, induction of inflammatory responses and resulting neurotoxicity. In this study, it was hypothesized that FPR1 activation of microglia causes loss of dopaminergic neurons by activating inflammasome and upregulating IL-1ß, IL-6 or TNF-α and that FPR1 antagonist HCH6-1 exerts neuroprotective effect on dopaminergic neurons. FPR1 agonist fMLF induced activation of microglia cells by causing activation of NLRP3 inflammasome and upregulation and secretion of IL-1ß, IL-6 or TNF-α. Conditioned medium (CM) of fMLF-treated microglia cells, which contains neurotoxic IL-1ß, IL-6 and TNF-α, caused apoptotic death of differentiated SH-SY5Y dopaminergic neurons by inducing mitochondrial oxidative stress and activating pro-apoptotic signaling. FPR1 antagonist HCH6-1 prevented fMLF-induced activation of inflammasome and upregulation of pro-inflammatory cytokines in microglia cells. HCH6-1 co-treatment reversed CM of fMLF-treated microglia-induced apoptotic death of dopaminergic neurons. FPR1 antagonist HCH6-1 inhibited rotenone-induced upregulation of microglial marker Iba-1 protein level, cell death of dopaminergic neurons and motor impairment in zebrafish. HCH6-1 ameliorated rotenone-induced microglial activation, upregulation of FPR1 mRNA, activation of NLRP3 inflammasome, cell death of SN dopaminergic neurons and PD motor deficit in mice. Our results suggest that FPR1 antagonist HCH6-1 possesses anti-neuroinflammatory and neuroprotective effects on dopaminergic neurons by inhibiting microglial activation and upregulation of inflammasome activity and pro-inflammatory cytokines.

Arrhythmia Disease Diagnosis Based on ECG Time-Frequency Domain Fusion and Convolutional Neural Network.

Electrocardiogram (ECG) signals are often used to diagnose cardiac status. However, most of the existing ECG diagnostic methods only use the time-domain information, resulting in some obviously lesion information in frequency-domain of ECG signals are not being fully utilized. Therefore, we propose a method to fuse the time and frequency domain information in ECG signals by convolutional neural network (CNN). First, we adapt multi-scale wavelet decomposition to filter the ECG signal; Then, R-wave localization is used to segment each individual heartbeat cycle; And then, the frequency domain information of this heartbeat cycle is extracted via fast Fourier transform. Finally, the temporal information is spliced with the frequency domain information and input to the neural network for classification. The experimental results show that the proposed method has the highest recognition accuracy (99.43%) of ECG singles compared with state-of-the-art methods. Clinical and Translational Impact Statement- The proposed ECG classification method provides an effective solution for ECG interrogation to quickly diagnose the presence of arrhythmia in a patient from the ECG signal. It can increase the efficiency of the interrogating physician by aiding diagnosis.

Preparation of pure active water for auto-catalytic reactions performed in it.

In catalyzed electrochemical reactions, a general strategy is to modify electrode materials to increase the efficiency of the reaction. From the viewpoint of environmental protection, electrochemical reactions should be performed in an inert green water phase. In this study, we report active pure liquid water (named PV), which was collected from the condensed vapor of heated gold (Au)-containing plasmon-activated water (PAW) with a distinct structure of electron-doping and reduced hydrogen bonding (HB). The resulting PV also exhibited distinct properties of the formation of stronger intermolecular HB with alcohols, and notable activities in catalytic electrochemical reactions, compared to bulk deionized water (DIW). Moreover, the measured diffusion coefficients of water increased by ca. 30% in PV solutions. Two typical electrochemical reactions significantly increased peak currents observed in oxidation-reduction cycles (ORCs) with roughening of the Au substrate and in a model of reversible oxidation-reduction reactions on a platinum (Pt) substrate. Also, PV enhanced hydrogen evolution reactions (HERs) on catalytic Pt and inert stainless steel substrates in PV-based solutions at different pH values, compared to DIW. Moreover, these activities of PV were more marked, even better than those of PAW, when PV was collected under a higher heating rate used to heat PAW. Active pure PV has emerged as a promising green solvent applicable to various chemical reactions with more efficiency.

A metal-organic framework loaded paper-based chemiluminescence sensor for trace acetone detection in exhaled breath.

Trace acetone determination in breath can be regarded as a noninvasive method for diagnosis of diabetes. Here, a paper-based CL gas sensor combined with UiO-66 as the preconcentrator was established for sensitive detection of trace acetone in exhaled breath. UiO-66 with excellent adsorption performance and unique water stability was used for the adsorption and enrichment of acetone gas under high humidity conditions in exhaled breath. As acetone can remarkably increase the chemiluminescence (CL) of the 2,4-dinitrophenylhydrazine (DNPH)-potassium permanganate (KMnO4) system, a sensitive CL device based on a paper substrate for trace acetone detection was established and the detection limit was 0.03 ppm. The fabricated method was used to assess the content of trace acetone in exhaled breath with satisfactory recoveries of 90-110%. It is expected to realize the noninvasive determination of acetone for diabetic patients in exhaled breath.

Real-world treatment pattern and prognostic factors of stage IV lung squamous cell carcinoma patients.

Lung squamous cell carcinoma (LUSC) represents a minor proportion of nonsmall cell lung cancer (NSCLC) harboring a poor prognosis. Herein, retrospective medical record research was performed to investigate real-world treatment patterns and identify the prognostic factors among LUSC patients. A total of 173 patients with a median age of 68 years were enrolled for analysis. Males were predominant (n = 143, 83%) and current or ex-smokers contributed to 78% of the entire cohort. Pleura and lung were the most common metastatic sites, whereas brain metastasis was only 7%. After diagnosis, however, only 107 patients (62%) had received first-line chemotherapy. In the chemotherapy cohort, median progression-free survival (PFS) and overall survival (OS) were 3.9 and 11.1 months, respectively. After multivariable analysis, bone metastasis and the use of first-line single-agent chemotherapy independently predicted shorter PFS. For baseline characteristics, male sex, metastasis to lung, pleura, liver, and bone independently predicted worse OS. Regarding the treatment pattern, patients who had undergone standard first-line doublet therapy and employed targeted therapies after disease progression linked to longer OS. In the real world, even those who underwent chemotherapy still had poor outcome. The findings may help clinicians to orchestrate the treatment strategies for LUSC patients and provide further direction of large-scale studies.

Functional Plasmon-Activated Water Increases Akkermansia muciniphila Abundance in Gut Microbiota to Ameliorate Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with dysbiosis and intestinal barrier dysfunction, as indicated by epithelial hyperpermeability and high levels of mucosal-associated bacteria. Changes in gut microbiota may be correlated with IBD pathogenesis. Additionally, microbe-based treatments could mitigate clinical IBD symptoms. Plasmon-activated water (PAW) is known to have an anti-inflammatory potential. In this work, we studied the association between the anti-inflammatory ability of PAW and intestinal microbes, thereby improving IBD treatment. We examined the PAW-induced changes in the colonic immune activity and microbiota of mice by immunohistochemistry and next generation sequencing, determined whether drinking PAW can mitigate IBD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dysbiosis through mice animal models. The effects of specific probiotic species on mice with TNBS-induced IBD were also investigated. Experimental results indicated that PAW could change the local inflammation in the intestinal microenvironment. Moreover, the abundance of Akkermansia spp. was degraded in the TNBS-treated mice but elevated in the PAW-drinking mice. Daily rectal injection of Akkermansia muciniphila, a potential probiotic species in Akkermansia spp., also improved the health of the mice. Correspondingly, both PAW consumption and increasing the intestinal abundance of Akkermansia muciniphila can mitigate IBD in mice. These findings indicate that increasing the abundance of Akkermansia muciniphila in the gut through PAW consumption or other methods may mitigate IBD in mice with clinically significant IBD.

Post-crosslinking of conjugated microporous polymers using vinyl polyhedral oligomeric silsesquioxane for enhancing surface areas and organic micropollutants removal performance from water.

High-capacity and rapid adsorption of organic micropollutants (OMPs) from water by adsorbents remain a great significance in water treatment. Recently, porous organic polymers with high surface areas, tunable nanopores and easy-to-modify skeletons are promising new generation of adsorbents. Here, a series of silsesquioxane-crosslinked conjugated microporous polymers (PcCMPs) with high surface areas and well-defined nanopores are developed via a molecular expansion strategy for removing OMPs from water. Among these PcCMPs, PcCMP-2E exhibited the highest Brunauer-Emmett-Teller surface area up to 2518 m2 g-1. The maximum adsorption capacities of bisphenol A (BPA) of PcCMPs are ranging from 485.44 to 628.93 mg g-1. Specially, >93.5% of BPA could be removed even through a thin layer filtration device composed of PcCMPs, which can be regenerated well using a mild washing procedure. PcCMPs also exhibit extraordinary adsorption to a variety of OMPs, such as tetracycline (226.99 mg g-1), 1-naphthylamine (290.07 mg g-1), 2-naphthol (213.87 mg g-1), 2,4-dichlorophenol (183.85 mg g-1) and p-nitrophenol (360.24 mg g-1). This work provides a new strategy to design porous adsorbents with high adsorption capacity and fast adsorption rate for water treatment.

Fit to be good: Physical fitness is negatively associated with deviance.

While modern organizations generate economic value, they also produce negative externalities in terms of human physical fitness, such that workers globally are becoming physically unfit. In the current research, we focus on a significant but overlooked indirect cost that lack of physical fitness entails-deviance. In contrast to early (and methodologically limited) research in criminology, which suggests that physically fit people are more likely to behave in a deviant manner, we draw on self-control theory to suggest the opposite: That physically fit people are less likely to engage in deviance. In Study 1, we assembled a dataset on 50 metropolitan areas in the U.S. spanning a 9-year period, and found that physical fitness index of a metropolitan area is negatively related to deviance in that area in a concurrent as well as time-lagged fashion. We complemented this aggregate-level theory test with two studies testing the theory at the individual level. In Study 2, we collected multi-source data from 3,925 military recruits who underwent physical training and found that those who score higher on physical fitness test are less likely to engage in deviance. Study 3 conceptually replicated the effect with both concurrent and time-lagged models using a five-wave longitudinal design in a sample of employees working in service roles, and also found that ego depletion mediates the effect of physical activity on workplace deviance. We speculate on economic implications of the observed relationship between physical fitness and deviance and discuss its relevance for organizations and public policy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are 'true' totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes Zscan4s and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely 'cluster 3', as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population.

Our previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD patients had higher C allele frequency. CC and CT genotype significantly increased risk of PD compared with TT genotype. SNP rs17525453 within RAB35 gene promoter leads to formation of transcription factor TFII-I binding site. Results of EMSA and supershift assay indicated that TFII-I binds to rs17525453 sequence of RAB35 gene promoter. Luciferase reporter assays showed that rs17525453 variant of RAB35 gene promoter possesses an augmented transcriptional activity. Our results suggest that functional variant rs17525453 within RAB35 gene promoter is likely to enhance transcriptional activity and upregulate RAB35 protein, which could lead to increased risk of PD in Taiwanese population.

Transferring Plasmon Effect on a Biological System: Expression of Biological Polymers in Chronic Rejection and Inflammatory Rat Model.

The plasmon-activated water (PAW) that reduces hydrogen bonds is made of deionized reverse osmosis water (ROW). However, compared with ROW, PAW has a significantly higher diffusion coefficient and electron transfer rate constant in electrochemical reactions. PAW has a boiling point of97 °C and specific heat of0.94; the energy of PAW is also 1121 J/mol higher than ordinary water. The greater the force of hydrogen bonds between H2O, the larger the volume of the H2O cluster, and the easier it is to lose the original characteristics. The hydrogen bonding force of PAW is weak, so the volume of its cluster is small, and it exists in a state very close to a single H2O. PAW has a high permeability and diffusion rate, which can improve the needs of biological applications and meet the dependence of biological organisms on H2O when performing physiological functions. PAW can successfully remove free radicals, and efficiently reduce lipopolysaccharide (LPS)-induced monocytes to release nitric oxide. PAW can induce expression of the antioxidant gene Nrf2 in human gingival fibroblasts, lower amyloid burden in mice with Alzheimer's disease, and decrease metastasis in mice grafted with Lewis lung carcinoma cells. Because the transferring plasmon effect may improve the abnormality of physiological activity in a biological system, we aimed to evaluate the influence of PAW on orthotopic allograft transplantation (OAT)-induced vasculopathy in this study. Here, we demonstrated that daily intake of PAW lowered the progression of vasculopathy in OAT-recipient ACI/NKyo rats by inhibiting collagen accumulation, proliferation of smooth muscle cells and fibroblasts, and T lymphocyte infiltration in the vessel wall. The results showed reduced T and B lymphocytes, plasma cells, and macrophage activation in the spleen of the OAT-recipient ACI/NKyo rats that were administered PAW. In contrast to the control group, the OAT-recipient ACI/NKyo rats that were administered PAW exhibited higher mobilization and levels of circulating endothelial progenitor cells associated with vessel repair. We use the transferring plasmon effect to adjust and maintain the biochemical properties of water, and to meet the biochemical demand of organisms. Therefore, this study highlights the therapeutic roles of PAW and provides more biomedical applicability for the transferring plasmon effect.

Insight into an unsupervised two-step sparse transfer learning algorithm for speech diagnosis of Parkinson's disease.

Speech diagnosis of Parkinson's disease (PD) as a non-invasive and simple diagnosis method is particularly worth exploring. However, the number of samples of speech-based PD is relatively small, and there exist discrepancies in the distribution between subjects. In order to solve the two problems, a novel unsupervised two-step sparse transfer learning is proposed in this paper to tackle with PD speech diagnosis. In the first step, convolution sparse coding with the coordinate selection of samples and features is designed to learn speech structure from the source domain to replenish sample information of the target domain. In the second step, joint local structure distribution alignment is designed to maintain the neighbor relationship between the respective samples of the training set and test set, and reduce the distribution difference between the two domains at the same time. Two representative public PD speech datasets and one real-world PD speech dataset were exploited to verify the proposed method on PD speech diagnosis. Experimental results demonstrate that each step of the proposed method has a positive effect on the PD speech classification results, and it also delivers superior performance over the existing relative methods.

3D X-ray micro-computed tomography imaging for the microarchitecture evaluation of porous metallic implants and scaffolds.

As an advanced microscopy technology with strong sample adaptability and non-destructive three-dimensional (3D) characteristics, X-ray micro-computed tomography (Micro-CT) can establish the overall connection between various microarchitecture parameters and accelerate the research process of porous metallic implants and scaffolds. In this review, the Micro-CT based quantitative evaluation methods of microarchitecture and bone formation are investigated. To ensure reliability of the results, the Micro-CT setup is discussed briefly and the essential image processing algorithms are introduced in detail. The significance and limitations of Micro-CT are analyzed in the context of research on porous metallic implants. We also discuss the future development of Micro-CT technology in the field of biological tissue engineering.

(D620N) VPS35 causes the impairment of Wnt/ß-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model.

Patients with familial type 17 of Parkinson's disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson's disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/ß-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/ß-catenin pathway. Protein levels of Wnt1 and nuclear ß-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear ß-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/ß-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.