Brain microglia activation and peripheral adaptive immunity in Parkinson's disease: a multimodal PET study.

BACKGROUND: Abnormal activation of immune system is an important pathogenesis of Parkinson's disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear. OBJECTIVES: To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity. METHODS: In this case-control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson's disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET. RESULTS: Compared to healthy controls, patients with Parkinson's disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson's disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed. CONCLUSION: Parkinson's disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.

Wearable Sweat Band for Noninvasive Levodopa Monitoring.

Levodopa is the standard medication clinically prescribed to patients afflicted with Parkinson's disease. In particular, the monitoring and optimization of levodopa dosage are critical to mitigate the onset of undesired fluctuations in the patients' physical and emotional conditions such as speech function, motor behavior, and mood stability. The traditional approach to optimize levodopa dosage involves evaluating the subjects' motor function, which has many shortcomings due to its subjective and limited quantifiable nature. Here, we present a wearable sweat band on a nanodendritic platform that quantitatively monitors levodopa dynamics in the body. Both stationary iontophoretic induction and physical exercise are utilized as our methods of sweat extraction. The sweat band measures real-time pharmacokinetic profiles of levodopa to track the dynamic response of the drug metabolism. We demonstrated the sweat band's functionalities on multiple subjects with implications toward the systematic administering of levodopa and routine management of Parkinson's disease.

Intravenously Delivered Allogeneic Mesenchymal Stem Cells Bidirectionally Regulate Inflammation and Induce Neurotrophic Effects in Distal Middle Cerebral Artery Occlusion Rats Within the First 7 Days After Stroke.

BACKGROUND/AIMS: Neurotrophic effects and immunosuppression are the main therapeutic mechanisms of mesenchymal stem cells (MSCs) in stroke treatment. Neurotrophins are produced by graft cells, host neurons, astrocytes, and even microglia/macrophages. Meanwhile, MSCs can increase inflammation if they are not sufficiently induced by pro-inflammatory cytokines. We examined whether intravenously transplanted bone marrow MSCs (BM-MSCs) increase inflammation in distal middle cerebral artery occlusion (dMCAO) rats, how long the increased inflammation effect persists for, and what the final therapeutic outcomes will be. We also tested the neurotrophic role of BM-MSCs and attempted to identify the neurotrophin-producing cells. METHODS: At 1 h after dMCAO was performed on Sprague-Dawley rats, allogeneic BM-MSCs were transplanted intravenously. The infarct volume was examined by Tetrazolium Red staining at 2 days (day 2), and the behavioral tests (cylinder test and grid walking test) were performed at 2, 4 (day 4) and 7 days (day 7) after transplantation. The concentrations of inflammation related cytokines and neurotrophins in the ischemic cortex, ipsilateral striatum, and serum, were measured using ELISA at days 2-7. The cell source of neurotrophins was observed by immunohistochemistry. RESULTS: The transplanted cells were mainly found in the infarct border zone (IBZ) of the brain. Infarct volume was reduced and behavioral outcomes were improved at 2 days after ischemia. In the striatum and circulation, BM-MSC transplantation increased inflammation at day 2 and decreased it at day 7. At days 2-7, insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) concentrations in the ischemic core of the cortex were significantly higher in the BM-MSC group than in the ischemia vehicle group. IGF-1 and BDNF were derived mainly from host microglia/macrophages in the ischemic core, and transplanted cells in the IBZ. At day 2, BM-MSC transplantation significantly increased the number of IGF-1+CD68+ and BDNF+Iba-1+ double positive cells in the ischemic core cortex. CONCLUSIONS: Although increased inflammation, BM-MSCs were still beneficial to dMCAO recovery at day 2. The immunopromoting effect of MSCs was transient and shifted to an immunosuppressive action at day 7. The neurotrophic factors IGF-1 and BDNF, which were mainly derived from transplanted BM-MSCs and host microglia/macrophages, contributed to the therapeutic effects from day 2 to day 7.

Multiparameter Characterization Confirms Apoptosis as the Primary Cause of Reduced Self-renewal Capacity in Cultured Human Fetal Neural Stem Cells.

BACKGROUND: Human fetal striatum-derived neural stem cells (hfsNSCs) are important in regenerative medicine; however, their ability to self-renew diminishes quickly following passages in culture. Typically when hfsNSC-derived neurospheres are dissociated by accutase, more than 90% of the cells survive, but only 6-8% of the cells are able to form secondary neurospheres. Our hypothesis is that the hfsNSCs that are unable to form new neurospheres become apoptotic. METHODS/RESULTS: Because the NSC apoptosis process has never been characterized in detail, we characterized hfsNSC apoptosis using multiparameter analysis and determined that the majority of hfsNSCs undergo apoptosis after passaging, which leads to a reduction in self-renewal. The replacement of trituration with vortexing decreases apoptosis, increases self-renewal, and does not affect NSC differentiation. When we used live cell staining with Annexin V, Hoechst 33342, and PI together, the apoptotic index was in agreement with what could be obtained using fixed-cell staining methods, including TUNEL and activated caspase-3 immunocytochemistry. NSC apoptosis could be divided into 9 stage types based on our live cell assay. Several types during early and late stages had similar staining profiles that could be further discriminated based on cell size. CONCLUSION: Apoptosis largely contributes to the low self-renewal of neurospheres, and replacing trituration with vortexing aided in alleviating NSC apoptosis. Multiparameter analysis is required for the identification of NSC apoptosis, particularly when live cell staining is used.

Direct writing of half-meter long CNT based fiber for flexible electronics.

Rapid construction of flexible circuits has attracted increasing attention according to its important applications in future smart electronic devices. Herein, we introduce a convenient and efficient "writing" approach to fabricate and assemble ultralong functional fibers as fundamental building blocks for flexible electronic devices. We demonstrated that, by a simple hand-writing process, carbon nanotubes (CNTs) can be aligned inside a continuous and uniform polymer fiber with length of more than 50 cm and diameters ranging from 300 nm to several micrometers. The as-prepared continuous fibers exhibit high electrical conductivity as well as superior mechanical flexibility (no obvious conductance increase after 1000 bending cycles to 4 mm diameter). Such functional fibers can be easily configured into designed patterns with high precision according to the easy "writing" process. The easy construction and assembly of functional fiber shown here holds potential for convenient and scalable fabrication of flexible circuits in future smart devices like wearable electronics and three-dimensional (3D) electronic devices.

Buckled Tin Oxide Nanobelt Webs as Highly Stretchable and Transparent Photosensors.

Stretchable and transparent inorganic semiconductors play a key role for the next generation of wearable optoelectronics. Achieving stretchability in intrinsically rigid inorganic materials is far more challenging than in polymers and metals. Here, we present a low-cost and scalable strategy to engineer inorganic semiconductors into a buckling open-mesh configuration, by which extraordinary stretchability (≈160%) as well as high optical transparency (>86% at 550 nm) can be realized simultaneously in SnO2 nanofiber webs. Moreover, the mechanical stretchability of SnO2 nanowebs can be further improved along with the optical transparency by precisely controlling the nanofiber density. The as-prepared freestanding nanowebs can be laminated onto curved surfaces by conformal contact. It is demonstrated that the fully exposed SnO2 nanowebs can be used as wearable UV photodetectors, showing reliable optoelectronic performance and remarkable tolerance to repeated complex deformations with body movements.

Ischemia, immunosuppression, and SSEA-1-negative cells all contribute to tumors resulting from mouse embryonic stem cell-derived neural progenitor transplantation.

Neural progenitor cells (NPCs) derived from mouse embryonic stem (mES) cells can lead to tumors after transplantation. The cellular source of such tumors remains under debate. We investigated the tumor formation resulting from mES cell-derived NPCs in a rat stroke model and in nude mice. After 2 hr of ischemia and 48 hr of reperfusion, the NPCs were transplanted into the ischemic core of the xenogeneic rats. Four weeks after transplantation, the grafted cells were found to be viable at the border of the necrosis and had differentiated into neurons. Transplanted rats did not exhibit any behavioral improvement, because tumor formed in 90% of the animals. Immunosuppression facilitated tumor formation. Tumors were observed in 40% of normal rats after NPC transplantation when cyclosporin A was administered. Meanwhile, no tumor formation was observed without cyclosporin A. Ischemic damage also facilitated tumor formation, because NPCs gave rise to tumors in 90% of ischemic rats, a percentage significantly higher than that in intact rats, which was 40%. The SSEA-1-positive cells isolated from stage 4 are not exactly undifferentiated ES cells. They exhibited a marker gene transcription profile different from that of ES cells and did not form tumors in transplanted nude mice. The undifferentiated ES cells remaining after differentiation did not contribute to tumors either. First, the tumor formation rate resulting from undifferentiated ES cells in the brains of normal rats is 0%, significantly lower than that of NPCs. Second, transplanted NPCs that led to 100% tumors in nude mice contained approximately 1.5 × 10(3) Oct-4-positive cells; however, even 5 × 10(5) undifferentiated ES cells formed neoplasm only in 40% nude mice.

Precursor-Confined Chemical Vapor Deposition of 2D Single-Crystalline SexTe1-x Nanosheets for p-Type Transistors and Inverters.

Two-dimensional (2D) tellurium (Te) is emerging as a promising p-type candidate for constructing complementary metal-oxide-semiconductor (CMOS) architectures. However, its small bandgap leads to a high leakage current and a low on/off current ratio. Although alloying Te with selenium (Se) can tune its bandgap, thermally evaporated SexTe1-x thin films often suffer from grain boundaries and high-density defects. Herein, we introduce a precursor-confined chemical vapor deposition (CVD) method for synthesizing single-crystalline SexTe1-x alloy nanosheets. These nanosheets, with tunable compositions, are ideal for high-performance field-effect transistors (FETs) and 2D inverters. The preformation of Se-Te frameworks in our developed CVD method plays a critical role in the growth of SexTe1-x nanosheets with high crystallinity. Optimizing the Se composition resulted in a Se0.30Te0.70 nanosheet-based p-type FET with a large on/off current ratio of 4 × 105 and a room-temperature hole mobility of 120 cm2·V-1·s-1, being eight times higher than thermally evaporated SexTe1-x with similar composition and thickness. Moreover, we successfully fabricated an inverter based on p-type Se0.30Te0.70 and n-type MoS2 nanosheets, demonstrating a typical voltage transfer curve with a gain of 30 at an operation voltage of Vdd = 3 V.

Co-Ni layered double hydroxides for water oxidation in neutral electrolyte.

The electrochemical properties of Co-Ni layered double hydroxides (LDHs) as efficient electrocatalysts for water oxidation were investigated in potassium phosphate electrolyte under neutral pH condition. The Co-Ni LDHs with a core-shell structure were fabricated using a facile route from a Co-Ni hydroxide precursor with iodine as a topotactic oxidizer. The unique core-shell morphology is likely due to the enrichment of Co(III) hydroxide in the inner core indicated by selected area electron diffraction and energy-dispersive spectroscopy. Through a self-assembling process at the organic/inorganic interface and dip-coating, the Co-Ni LDHs were deposited onto FTO glass substrates to prepare composite electrodes. Low over-potential and high current density was achieved in the oxygen evolution reaction. The excellent electrocatalytic activity of Co-Ni LDHs may be attributed to more accessible Co active sites and rapid movement of interlayer ions within their layered structure.

α-Synuclein aggregation causes muscle atrophy through neuromuscular junction degeneration.

BACKGROUND: Sarcopenia is common in patients with Parkinson's disease (PD), showing mitochondrial oxidative stress in skeletal muscle. The aggregation of α-synuclein (α-Syn) to induce oxidative stress is a key pathogenic process of PD; nevertheless, we know little about its potential role in regulating peripheral nerves and the function of the muscles they innervate. METHODS: To investigate the role of α-Syn aggregation on neuromuscular system, we used the Thy1 promoter to overexpress human α-Syn transgenic mice (mThy1-hSNCA). hα-Syn expression was evaluated by western blot, and its localization was determined by confocal microscopy. The impact of α-Syn aggregation on the structure and function of skeletal muscle mitochondria and neuromuscular junctions (NMJs), as well as muscle mass and function were characterized by flow cytometry, transmission electron microscopy, Seahorse XF24 metabolic assay, and AAV9 in vivo injection. We assessed the regenerative effect of mitochondrial-targeted superoxide dismutase (Mito-TEMPO) after skeletal muscle injury in mThy1-hSNCA mice. RESULTS: Overexpressed hα-Syn protein localized in motor neuron axons and NMJs in muscle and formed aggregates. α-Syn aggregation increased the number of abnormal mitochondrial in the intramuscular axons and NMJs by over 60% (P < 0.01), which inhibited the release of acetylcholine (ACh) from presynaptic vesicles in NMJs (P < 0.05). The expression of genes associated with NMJ activity, neurotransmission and regulation of reactive oxygen species (ROS) metabolic process were significantly decreased in mThy1-hSNCA mice, resulting in ROS production elevated by ~220% (P < 0.05), thereby exacerbating oxidative stress. Such process altered mitochondrial spatial relationships to sarcomeric structures, decreased Z-line spacing by 36% (P < 0.05) and increased myofibre apoptosis by ~10% (P < 0.05). Overexpression of α-Syn altered the metabolic profile of muscle satellite cells (MuSCs), including basal respiratory capacity (~170% reduction) and glycolytic capacity (~150% reduction) (P < 0.05) and decreased cell migration and fusion during muscle regeneration (~60% and ~40%, respectively) (P < 0.05). We demonstrated that Mito-TEMPO treatment could restore the oxidative stress status (the complex I/V protein and enzyme activities increased ~200% and ~150%, respectively), which caused by α-Syn aggregation, and improve the ability of muscle regeneration after injury. In addition, the NMJ receptor fragmentation and ACh secretion were also improved. CONCLUSIONS: These results reveal that the α-synuclein aggregation plays an important role in regulating acetylcholine release from neuromuscular junctions and induces intramuscular mitochondrial oxidative stress, which can provide new insights into the aetiology of muscle atrophy in patients with Parkinson's disease.

Analysis of Strain and Defects in Tellurium-WSe2 Moiré Heterostructures Using Scanning Nanodiffraction.

In recent years, there has been an increasing focus on 2D nongraphene materials that range from insulators to semiconductors to metals. As a single-elemental van der Waals semiconductor, tellurium (Te) has captivating anisotropic physical properties. Recent work demonstrated growth of ultrathin Te on WSe2 with the atomic chains of Te aligned with the armchair directions of the substrate using physical vapor deposition (PVD). In this system, a moiré superlattice is formed where micrometer-scale Te flakes sit on top of the continuous WSe2 film. Here, we determined the precise orientation of the Te flakes with respect to the substrate and detailed structure of the resulting moiré lattice by combining electron microscopy with image simulations. We directly visualized the moiré lattice using center of mass-differential phase contrast (CoM-DPC). We also investigated the local strain within the Te/WSe2 layered materials using scanning nanodiffraction techniques. There is a significant tensile strain at the edges of flakes along the direction perpendicular to the Te chain direction, which is an indication of the preferred orientation for the growth of Te on WSe2. In addition, we observed local strain relaxation regions within the Te film, specifically attributed to misfit dislocations, which we characterize as having a screw-like nature. The detailed structural analysis gives insight into the growth mechanisms and strain relaxation in this moiré heterostructure.

Association of plasma apolipoproteins and levels of inflammation-related factors with different stages of Alzheimer's disease: a cross-sectional study.

OBJECTIVE: Blood-based biomarkers for the early diagnosis of Alzheimer's disease (AD) are a 'Holy Grail' of AD research. Growing evidence shows that levels of apolipoproteins and various inflammation-related factors are altered in the peripheral blood of patients with AD. The purpose of this study was to clear and definite whether these biomarkers are differentially expressed at the early stages of AD, and could be a biomarker as an early diagnosis of the disease. DESIGN: Observation study. SETTING: This study was a part of the Sino Longitudinal Study on Cognitive Decline, an ongoing prospective cohort study (ClinicalTrials.gov identifier: NCT03370744) that centres on Xuanwu Hospital (Beijing, China) in cooperation with an alliance of 94 hospitals from 50 cities across China. PARTICIPANTS: In the present study, 416 right-handed Chinese Han subjects were recruited through standardised public advertisements from 2014 to 2019. OUTCOME MEASURES: Concentrations of plasma apolipoprotein A1, apolipoprotein CIII (ApoCIII), apolipoprotein E (ApoE), A-2-macroglobulin (A2M), complement C3 (C3) and complement factor H (FH) were determined using a commercial multiplex Luminex-based panel in normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment and AD groups. RESULTS: For individual analysis, pairwise comparisons showed that: (1) For SCD versus NC, no biomarker showed significant difference; (2) For amnestic mild cognitive impairment (aMCI) versus NC, levels of ApoCIII, ApoE, A2M, C3 and FH increased significantly; and (3) For AD versus NC, amounts of C3 increased. For models differentiating clinical groups, discriminant analysis was performed by including all protein markers, age, sex, genotype and education level in the model. This approach could distinguish between patients with aMCI (area under the curve (AUC): 0.743) and AD (AUC: 0.837) from NC. CONCLUSION: Our results suggest that concentrations of certain apolipoproteins and inflammation-related factors are altered at the early stage of AD, and could be useful biomarkers for early diagnosis. TRIAL REGISTRATION NUMBER: NCT03370744.

Serum factor(s) from lung adenocarcinoma patients regulates the molecular clock expression.

Lung cancer is a leading cause of cancer-associated deaths worldwide. Lung cancer may lead to circadian disruption, which could contribute to the development of lung cancer. Recently, several studies using animal models indicated that tumors influence systemic circadian homeostasis in remote tissues. However, it is unclear whether carcinoma of the lungs influences remote circadian rhythm, whether this effect exists in humans, and whether signals from the tumor travel through the blood. In this study, we used a cell-based assay to determine whether serum from patients with lung adenocarcinoma could modulate the molecular clock. We found that the daily oscillation period of Bmal1 was significantly lengthened following treatment with serum from untreated lung adenocarcinoma patients. In addition, heat inactivation of this serum abolished the effect, suggesting that a heat-sensitive circulating factor(s) is present in the serum of untreated lung adenocarcinoma patients. Using real-time PCR, we also examined the mRNA abundance of Bmal1, Cry1, and Per1 in human osteosarcoma u2os cell line, HUVECs and A549 cell lines. The expression of Bmal1 was changed in A549 cells in the presence of sera from lung adenocarcinoma patients. Our study revealed a direct effect of serum from lung adenocarcinoma patients on the molecular clock.

Tellurium Single-Crystal Arrays by Low-Temperature Evaporation and Crystallization.

Thermally evaporated tellurium possesses an intriguing crystallization behavior, where an amorphous to crystalline phase transition happens at near-ambient temperature. However, a comprehensive understanding and delicate control of the crystallization process for the evaporated Te films is lacking. Here, the kinetics and dynamics of the crystallization of thermally evaporated Te films is visualized and modeled. Low-temperature processing of highly crystalline tellurium films with large grain size and preferred out-of-plane orientation ((100) plane parallel to the surface) is demonstrated by controlling the crystallization process. Tellurium single crystals with a lateral dimension of up to 6 µm are realized on various substrates including glass and plastic. Field-effect transistors based on 5 °C crystallized Te single grains (6-nm-thick) exhibit an average effective hole mobility of ≈100 cm2 V-1 s-1 , and on/off current ratio of ≈3 × 104 .

Peripheral Circulation and Astrocytes Contribute to the MSC-Mediated Increase in IGF-1 Levels in the Infarct Cortex in a dMCAO Rat Model.

MATERIALS AND METHODS: Ischemic brain injury was induced by dMCAO in Sprague-Dawley rats. The transplantation group received MSC infusion 1 h after dMCAO. Expression of IGF-1 in GFAP+ astrocytes, Iba-1+ microglia/macrophages, CD3+ lymphocytes, Ly6C+ monocytes/macrophages, and neutrophil elastase (NE)+ neutrophils was examined to determine the contribution of these cells to the increase of IGF-1. ELISA was performed to examine IGF-1 levels in blood plasma at days 2, 4, and 7 after ischemia onset. RESULTS: In total, only 5-6% of Iba-1+ microglia were colabeled with IGF-1 in the infarct cortex, corpus callosum, and striatum at day 2 post-dMCAO. MSC transplantation did not lead to a higher proportion of Iba-1+ cells that coexpressed IGF-1. In the infarct cortex, all Iba-1+/IGF-1+ double-positive cells were also positive for CD68. In the infarct, corpus callosum, and striatum, the majority (50-80%) of GFAP+ cells were colabeled with ramified IGF-1 signals. The number of GFAP+/IGF-1+ cells was further increased following MSC treatment. In the infarct cortex, approximately 15% of IGF-1+ cells were double-positive for CD3. MSC treatment reduced the number of infiltrated CD3+/IGF-1+ cells by 70%. In the infarct, few Ly6C+ monocytes/macrophages or NE+ neutrophils expressed IGF-1, and MSC treatment did not induce a higher percentage of these cells that coexpressed IGF-1. The IGF-1 level in peripheral blood plasma was significantly higher in the MSC group than in the ischemia control group. CONCLUSION: The MSC-mediated increase in IGF-1 levels in the infarct cortex mainly derives from two sources, astrocytes in brain and blood plasma in periphery. Manipulating the IGF-1 level in the peripheral circulation may lead to a higher level of IGF-1 in brain, which could be conducive to recovery at the early stage of dMCAO.

Evaporated Sex Te1- x Thin Films with Tunable Bandgaps for Short-Wave Infrared Photodetectors.

Semiconducting absorbers in high-performance short-wave infrared (SWIR) photodetectors and imaging sensor arrays are dominated by single-crystalline germanium and III-V semiconductors. However, these materials require complex growth and device fabrication procedures. Here, thermally evaporated Sex Te1- x alloy thin films with tunable bandgaps for the fabrication of high-performance SWIR photodetectors are reported. From absorption measurements, it is shown that the bandgaps of Sex Te1- x films can be tuned continuously from 0.31 eV (Te) to 1.87 eV (Se). Owing to their tunable bandgaps, the peak responsivity position and photoresponse edge of Sex Te1- x film-based photoconductors can be tuned in the SWIR regime. By using an optical cavity substrate consisting of Au/Al2 O3 to enhance its absorption near the bandgap edge, the Se0.32 Te0.68 film (an optical bandgap of ≈0.8 eV)-based photoconductor exhibits a cut-off wavelength at ≈1.7 µm and gives a responsivity of 1.5 AW-1 and implied detectivity of 6.5 × 1010 cm Hz1/2 W-1 at 1.55 µm at room temperature. Importantly, the nature of the thermal evaporation process enables the fabrication of Se0.32 Te0.68 -based 42 × 42 focal plane arrays with good pixel uniformity, demonstrating the potential of this unique material system used for infrared imaging sensor systems.

Evaporated tellurium thin films for p-type field-effect transistors and circuits.

There is an emerging need for semiconductors that can be processed at near ambient temperature with high mobility and device performance. Although multiple n-type options have been identified, the development of their p-type counterparts remains limited. Here, we report the realization of tellurium thin films through thermal evaporation at cryogenic temperatures for fabrication of high-performance wafer-scale p-type field-effect transistors. We achieve an effective hole mobility of ~35 cm2 V-1 s-1, on/off current ratio of ~104 and subthreshold swing of 108 mV dec-1 on an 8-nm-thick film. High-performance tellurium p-type field-effect transistors are fabricated on a wide range of substrates including glass and plastic, further demonstrating the broad applicability of this material. Significantly, three-dimensional circuits are demonstrated by integrating multi-layered transistors on a single chip using sequential lithography, deposition and lift-off processes. Finally, various functional logic gates and circuits are demonstrated.

Aging, rather than Parkinson's disease, affects the responsiveness of PBMCs to the immunosuppression of bone marrow mesenchymal stem cells.

Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrow­derived mesenchymal stem cell (BM­MSCs) and which cytokines are more effective in inducing BM­MSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 26­35), healthy middle­aged (age 56­60) and middle­aged PD­affected individuals. All the recruits were male. The mitogen­stimulated PBMCs and proinflammatory cytokine­pretreated BM­MSCs were co­cultured. The PBMC proliferation was measured using Cell Counting Kit­8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BM­MSCs was confirmed in young healthy, middle­aged healthy and middle­aged PD­affected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middle­aged healthy and middle­aged PD­affected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middle­aged healthy subjects. Interferon (IFN)­Î³ synergized with tumor necrosis factor (TNF)­α, interleukin (IL)­1α or IL­1ß was more effective than either one alone, and the combinations of IFN­Î³ + IL­1α and IFN­Î³ + IL­1ß were more effective than IFN­Î³ + TNF­α in inducing BM­MSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BM­MSC, at least in middle­aged males. Patients with PD aged 56­60 remain eligible for anti­inflammatory BM­MSC­based therapy. Treatment of BM­MSCs with IFN­Î³ + IL­1α or IFN­Î³ + IL­1ß prior to transplantation may result in improved immunosuppressive effects.

Enhanced cycling performance of nanostructure LiFePO4/C composites with in situ 3D conductive networks for high power Li-ion batteries.

In this work, reduced nano-sized LiFePO4 precursor particles were fabricated via a green chemistry approach without the use of any organic solvent or surfactants by accelerating the feeding speed of ferrous sulfate. After carbon coating, a 4 nm thick high graphitic degree carbon layer was deposited uniformly on the surface of reduced nano-sized LiFePO4 particles and constructed in situ 3D conductive networks among the adjacent LiFePO4 particles, as a result of an elevated self-catalytic effect of the reduced nano-size LiFePO4 particles that promoted the formation of the conductive networks. The reduced nano-size LiFePO4/C particles with in situ 3D conductive networks were shown to have an excellent high rate discharge capacity and long cycle life, delivering a high initial reversible discharge capacity of 163 mA h g-1 at 0.2C and an even high rate discharge capacity of 104 mA h g-1 at 30C. Additionally, a capacity of 101.7 mA h g-1 with a capacity retention of 97% remained after 850 cycles at 30C. This work suggests that the enhanced electrochemical performance of the LiFePO4/C composite was improved via the combination of the reduced nano-sized and 3D conductive networks, facilitating the electron transfer efficiency and diffusion of lithium ions, especially over an extended cycling performance at a high rate.

Pyrosequencing analysis of methylation levels of clock genes in leukocytes from Parkinson's disease patients.

DNA methylation of neuronal PAS domain protein 2 (NPAS2) and cryptochrome circadian clock 1 (CRY1) promoters may be associated with Parkinson's disease (PD). However, there is no simple and cost-effective method to quantify DNA methylation in these regions. Additionally, it is not clear whether DNA methylation of NPAS2 and CRY1 promoters is altered in peripheral blood of PD patients, especially newly diagnosed drug-naïve PD patients, and thus can be used as a PD biomarker. In the present study, we utilized bisulfite pyrosequencing assays to examine DNA methylation levels of six CpG sites in the NPAS2 promoter and five CpG sites in the CRY1 promoter. We compared DNA methylation levels at these sites in leukocytes from 80 medicated PD patients, 30 drug-naïve PD patients, and 80 healthy controls. Our results indicate that NPAS2 hypomethylation occurs at the early stage of PD and is a moderate biomarker for distinguishing PD patients from healthy subjects.